UniProtKB - P17405 (ASM_HUMAN)
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- BLAST
>sp|P17405|ASM_HUMAN Sphingomyelin phosphodiesterase OS=Homo sapiens OX=9606 GN=SMPD1 PE=1 SV=5 MPRYGASLRQSCPRSGREQGQDGTAGAPGLLWMGLVLALALALALALALSDSRVLWAPAE AHPLSPQGHPARLHRIVPRLRDVFGWGNLTCPICKGLFTAINLGLKKEPNVARVGSVAIK LCNLLKIAPPAVCQSIVHLFEDDMVEVWRRSVLSPSEACGLLLGSTCGHWDIFSSWNISL PTVPKPPPKPPSPPAPGAPVSRILFLTDLHWDHDYLEGTDPDCADPLCCRRGSGLPPASR PGAGYWGEYSKCDLPLRTLESLLSGLGPAGPFDMVYWTGDIPAHDVWHQTRQDQLRALTT VTALVRKFLGPVPVYPAVGNHESTPVNSFPPPFIEGNHSSRWLYEAMAKAWEPWLPAEAL RTLRIGGFYALSPYPGLRLISLNMNFCSRENFWLLINSTDPAGQLQWLVGELQAAEDRGD KVHIIGHIPPGHCLKSWSWNYYRIVARYENTLAAQFFGHTHVDEFEVFYDEETLSRPLAV AFLAPSATTYIGLNPGYRVYQIDGNYSGSSHVVLDHETYILNLTQANIPGAIPHWQLLYR ARETYGLPNTLPTAWHNLVYRMRGDMQLFQTFWFLYHKGHPPSEPCGTPCRLATLCAQLS ARADSPALCRHLMPDGSLPEAQSLWPRPLFC
- Align
Protein
Sphingomyelin phosphodiesterase
Gene
SMPD1
Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:
Annotation score:5 out of 5
<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>Select a section on the left to see content.
<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni
Converts sphingomyelin to ceramide (PubMed:1840600, PubMed:18815062, PubMed:27659707, PubMed:25920558). Also has phospholipase C activities toward 1,2-diacylglycerolphosphocholine and 1,2-diacylglycerolphosphoglycerol.Curated4 Publications
<p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More...</a></p> Manual assertion based on experiment ini
- Ref.1"Human acid sphingomyelinase. Isolation, nucleotide sequence and expression of the full-length and alternatively spliced cDNAs."
Schuchman E.H., Suchi M., Takahashi T., Sandhoff K., Desnick R.J.
J. Biol. Chem. 266:8531-8539(1991) [PubMed] [Europe PMC] [Abstract]Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, ALTERNATIVE SPLICING, VARIANTS 48-ALA-LEU-49 DEL; ILE-324 AND ARG-508. - Ref.12"Structural and functional analysis of the ASM p.Ala359Asp mutant that causes acid sphingomyelinase deficiency."
Acuna M., Castro-Fernandez V., Latorre M., Castro J., Schuchman E.H., Guixe V., Gonzalez M., Zanlungo S.
Biochem. Biophys. Res. Commun. 479:496-501(2016) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT NPDB ASP-359. - Ref.13"Epidemiological, clinical and biochemical characterization of the p.(Ala359Asp) SMPD1 variant causing Niemann-Pick disease type B."
Acuna M., Martinez P., Moraga C., He X., Moraga M., Hunter B., Nuernberg P., Gutierrez R.A., Gonzalez M., Schuchman E.H., Santos J.L., Miquel J.F., Mabe P., Zanlungo S.
Eur. J. Hum. Genet. 24:208-213(2016) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, SUBCELLULAR LOCATION, VARIANT NPDB ASP-359, CHARACTERIZATION OF VARIANT NPDB ASP-359. - Ref.34"Characterization of common SMPD1 mutations causing types A and B Niemann-Pick disease and generation of mutation-specific mouse models."
Jones I., He X., Katouzian F., Darroch P.I., Schuchman E.H.
Mol. Genet. Metab. 95:152-162(2008) [PubMed] [Europe PMC] [Abstract]Cited for: CHARACTERIZATION OF VARIANTS NPDA PRO-304 AND LEU-498, CHARACTERIZATION OF VARIANTS NPDB TYR-423 AND ARG-610 DEL, FUNCTION, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY.
Isoform 2 lacks residues that bind the cofactor Zn2+ and has no enzyme activity.Curated1 Publication
Manual assertion based on experiment ini
- Ref.1"Human acid sphingomyelinase. Isolation, nucleotide sequence and expression of the full-length and alternatively spliced cDNAs."
Schuchman E.H., Suchi M., Takahashi T., Sandhoff K., Desnick R.J.
J. Biol. Chem. 266:8531-8539(1991) [PubMed] [Europe PMC] [Abstract]Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, ALTERNATIVE SPLICING, VARIANTS 48-ALA-LEU-49 DEL; ILE-324 AND ARG-508.
Isoform 3 lacks residues that bind the cofactor Zn2+ and has no enzyme activity.Curated1 Publication
Manual assertion based on experiment ini
- Ref.1"Human acid sphingomyelinase. Isolation, nucleotide sequence and expression of the full-length and alternatively spliced cDNAs."
Schuchman E.H., Suchi M., Takahashi T., Sandhoff K., Desnick R.J.
J. Biol. Chem. 266:8531-8539(1991) [PubMed] [Europe PMC] [Abstract]Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, ALTERNATIVE SPLICING, VARIANTS 48-ALA-LEU-49 DEL; ILE-324 AND ARG-508.
Miscellaneous
There are two types of sphingomyelinases: ASM (acid), and NSM (neutral).
Caution
Variants Gln-294 and Val-485 have been originally reported as disease-causing mutations in NPDA and NPDB (PubMed:12369017, PubMed:15221801). These variants have been reclassified as benign polymorphisms (PubMed:23430512).3 Publications
Manual assertion based on experiment ini
- Ref.27"The demographics and distribution of type B Niemann-Pick disease: novel mutations lead to new genotype/phenotype correlations."
Simonaro C.M., Desnick R.J., McGovern M.M., Wasserstein M.P., Schuchman E.H.
Am. J. Hum. Genet. 71:1413-1419(2002) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS NPDB VAL-51; TRP-94; PRO-139; ARG-159; PRO-198; CYS-202; MET-227; CYS-230; ASP-234; SER-247; ARG-250; HIS-291; ALA-325; ARG-332; ASP-359; HIS-378; LEU-378; PRO-381; VAL-415; TYR-423; ARG-433; PRO-434; CYS-437; VAL-454; ASP-458; TRP-476; LEU-477; LEU-482; ASN-490; SER-496; CYS-498; GLN-516; VAL-517; ARG-535; PRO-551; ASN-578; HIS-602 AND PRO-602, VARIANT VAL-487. - Ref.29"Screening of 25 Italian patients with Niemann-Pick A reveals fourteen new mutations, one common and thirteen private, in SMPD1."
Ricci V., Stroppiano M., Corsolini F., Di Rocco M., Parenti G., Regis S., Grossi S., Biancheri R., Mazzotti R., Filocamo M.
Hum. Mutat. 24:105-105(2004) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS NPDA PRO-105; SER-247; LYS-248; HIS-315; PRO-452; LEU-477; LEU-498; HIS-498 AND CYS-519, VARIANT GLN-296. - Ref.43"The acid sphingomyelinase sequence variant p.A487V is not associated with decreased levels of enzymatic activity."
Rhein C., Naumann J., Muehle C., Zill P., Adli M., Hegerl U., Hiemke C., Mergl R., Moeller H.J., Reichel M., Kornhuber J.
JIMD Rep. 8:1-6(2013) [PubMed] [Europe PMC] [Abstract]Cited for: CHARACTERIZATION OF VARIANT NPDB ALA-325, CHARACTERIZATION OF VARIANT VAL-487.
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes the catalytic activity of an enzyme, i.e. the chemical reaction it catalyzes. This information usually correlates with the presence of an EC (Enzyme Commission) number in the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi
Sphingomyelin + H2O = N-acylsphingosine + phosphocholine.7 Publications
Manual assertion based on experiment ini
- Ref.1"Human acid sphingomyelinase. Isolation, nucleotide sequence and expression of the full-length and alternatively spliced cDNAs."
Schuchman E.H., Suchi M., Takahashi T., Sandhoff K., Desnick R.J.
J. Biol. Chem. 266:8531-8539(1991) [PubMed] [Europe PMC] [Abstract]Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, ALTERNATIVE SPLICING, VARIANTS 48-ALA-LEU-49 DEL; ILE-324 AND ARG-508. - Ref.8"Zn2+-stimulated sphingomyelinase is secreted by many cell types and is a product of the acid sphingomyelinase gene."
Schissel S.L., Schuchman E.H., Williams K.J., Tabas I.
J. Biol. Chem. 271:18431-18436(1996) [PubMed] [Europe PMC] [Abstract]Cited for: CATALYTIC ACTIVITY, COFACTOR, SUBCELLULAR LOCATION. - Ref.14"Structure of human acid sphingomyelinase reveals the role of the saposin domain in activating substrate hydrolysis."
Xiong Z.J., Huang J., Poda G., Pomes R., Prive G.G.
J. Mol. Biol. 428:3026-3042(2016) [PubMed] [Europe PMC] [Abstract]Cited for: X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 47-629 OF MUTANT SER-631 IN COMPLEX WITH ZINC, CATALYTIC ACTIVITY, GLYCOSYLATION AT ASN-88; ASN-177; ASN-337; ASN-397; ASN-505 AND ASN-522, DISULFIDE BONDS, SUBUNIT. - Ref.16"Molecular basis of acid sphingomyelinase deficiency in a patient with Niemann-Pick disease type A."
Ferlinz K., Hurwitz R., Sandhoff K.
Biochem. Biophys. Res. Commun. 179:1187-1191(1991) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT NPDA SER-579, CHARACTERIZATION OF VARIANT NPDA SER-579, CATALYTIC ACTIVITY. - Ref.32"Acid sphingomyelinase deficiency. Phenotype variability with prevalence of intermediate phenotype in a series of twenty-five Czech and Slovak patients. A multi-approach study."
Pavluu-Pereira H., Asfaw B., Poupctova H., Ledvinova J., Sikora J., Vanier M.T., Sandhoff K., Zeman J., Novotna Z., Chudoba D., Elleder M.
J. Inherit. Metab. Dis. 28:203-227(2005) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS NPDA ARG-168; LEU-186; HIS-230; VAL-243; ARG-250; GLU-253; ALA-280; HIS-291; LYS-294; PRO-343; HIS-378; TRP-476; ARG-535 AND SER-579, VARIANT ARG-508, CATALYTIC ACTIVITY, CHARACTERIZATION OF VARIANTS NPDA LEU-186; GLU-253; ALA-280; LYS-294; PRO-343 AND HIS-378. - Ref.34"Characterization of common SMPD1 mutations causing types A and B Niemann-Pick disease and generation of mutation-specific mouse models."
Jones I., He X., Katouzian F., Darroch P.I., Schuchman E.H.
Mol. Genet. Metab. 95:152-162(2008) [PubMed] [Europe PMC] [Abstract]Cited for: CHARACTERIZATION OF VARIANTS NPDA PRO-304 AND LEU-498, CHARACTERIZATION OF VARIANTS NPDB TYR-423 AND ARG-610 DEL, FUNCTION, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY. - Ref.46"Alleged detrimental mutations in the SMPD1 gene in patients with Niemann-Pick disease."
Rhein C., Muehle C., Kornhuber J., Reichel M.
Int. J. Mol. Sci. 16:13649-13652(2015) [PubMed] [Europe PMC] [Abstract]Cited for: CHARACTERIZATION OF VARIANT NPDB ALA-325, CHARACTERIZATION OF VARIANTS ALA-36; VAL-487 AND ARG-508, CATALYTIC ACTIVITY.
<p>This subsection of the ‘Function’ section provides information relevant to cofactors. A cofactor is any non-protein substance required for a protein to be catalytically active. Some cofactors are inorganic, such as the metal atoms zinc, iron, and copper in various oxidation states. Others, such as most vitamins, are organic.<p><a href='/help/cofactor' target='_top'>More...</a></p>Cofactori
Zn2+1 Publication
Manual assertion based on experiment ini
- Ref.8"Zn2+-stimulated sphingomyelinase is secreted by many cell types and is a product of the acid sphingomyelinase gene."
Schissel S.L., Schuchman E.H., Williams K.J., Tabas I.
J. Biol. Chem. 271:18431-18436(1996) [PubMed] [Europe PMC] [Abstract]Cited for: CATALYTIC ACTIVITY, COFACTOR, SUBCELLULAR LOCATION.
Manual assertion based on experiment ini
- Ref.8"Zn2+-stimulated sphingomyelinase is secreted by many cell types and is a product of the acid sphingomyelinase gene."
Schissel S.L., Schuchman E.H., Williams K.J., Tabas I.
J. Biol. Chem. 271:18431-18436(1996) [PubMed] [Europe PMC] [Abstract]Cited for: CATALYTIC ACTIVITY, COFACTOR, SUBCELLULAR LOCATION. - Ref.14"Structure of human acid sphingomyelinase reveals the role of the saposin domain in activating substrate hydrolysis."
Xiong Z.J., Huang J., Poda G., Pomes R., Prive G.G.
J. Mol. Biol. 428:3026-3042(2016) [PubMed] [Europe PMC] [Abstract]Cited for: X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 47-629 OF MUTANT SER-631 IN COMPLEX WITH ZINC, CATALYTIC ACTIVITY, GLYCOSYLATION AT ASN-88; ASN-177; ASN-337; ASN-397; ASN-505 AND ASN-522, DISULFIDE BONDS, SUBUNIT. - Ref.15"Human acid sphingomyelinase structures provide insight to molecular basis of Niemann-Pick disease."
Zhou Y.F., Metcalf M.C., Garman S.C., Edmunds T., Qiu H., Wei R.R.
Nat. Commun. 7:13082-13082(2016) [PubMed] [Europe PMC] [Abstract]Cited for: X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 47-629 OF APOENZYME AND IN COMPLEX WITH PHOSPHOCHOLINE AND ZINC, COFACTOR, GLYCOSYLATION AT ASN-88; ASN-177; ASN-337; ASN-397; ASN-505 AND ASN-522.
Sites
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| <p>This subsection of the ‘Function’ section indicates at which position the protein binds a given metal ion. The nature of the metal is indicated in the ‘Description’ field.<p><a href='/help/metal' target='_top'>More...</a></p>Metal bindingi | 208 | Zinc 1Combined sources <p>Manually validated information inferred from a combination of experimental and computational evidence.</p> <p><a href="/manual/evidences#ECO:0000244">More...</a></p> Manual assertion inferred from combination of experimental and computational evidencei 1 PublicationManual assertion based on experiment ini
| 1 | |
| Metal bindingi | 210 | Zinc 1; via tele nitrogenCombined sources Manual assertion inferred from combination of experimental and computational evidencei 1 PublicationManual assertion based on experiment ini
| 1 | |
| Metal bindingi | 280 | Zinc 1Combined sources Manual assertion inferred from combination of experimental and computational evidencei 1 PublicationManual assertion based on experiment ini
| 1 | |
| Metal bindingi | 280 | Zinc 2Combined sources Manual assertion inferred from combination of experimental and computational evidencei 1 PublicationManual assertion based on experiment ini
| 1 | |
| Metal bindingi | 320 | Zinc 2Combined sources Manual assertion inferred from combination of experimental and computational evidencei 1 PublicationManual assertion based on experiment ini
| 1 | |
| Metal bindingi | 427 | Zinc 2; via tele nitrogenCombined sources Manual assertion inferred from combination of experimental and computational evidencei 1 PublicationManual assertion based on experiment ini
| 1 | |
| Metal bindingi | 459 | Zinc 2; via pros nitrogenCombined sources Manual assertion inferred from combination of experimental and computational evidencei 1 PublicationManual assertion based on experiment ini
| 1 | |
| Metal bindingi | 461 | Zinc 1; via tele nitrogenCombined sources Manual assertion inferred from combination of experimental and computational evidencei 1 PublicationManual assertion based on experiment ini
| 1 |
<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni
- acid sphingomyelin phosphodiesterase activity Source: UniProtKB <p>Inferred from Direct Assay</p> <p>Used to indicate a direct assay for the function, process or component indicated by the GO term.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#ida">GO evidence code guide</a></p> Inferred from direct assayi
- hydrolase activity, acting on glycosyl bonds Source: UniProtKB-KW
- sphingomyelin phosphodiesterase activity Source: Reactome
- zinc ion binding Source: UniProtKBInferred from direct assayi
GO - Biological processi
- ceramide biosynthetic process Source: UniProtKBInferred from direct assayi
- glycosphingolipid metabolic process Source: Reactome
- negative regulation of MAP kinase activity Source: BHF-UCL <p>Inferred from Mutant Phenotype</p> <p>Describes annotations that are concluded from looking at variations or changes in a gene product such as mutations or abnormal levels and includes techniques such as knockouts, overexpression, anti-sense experiments and use of specific protein inhibitors.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#imp">GO evidence code guide</a></p> Inferred from mutant phenotypei
- nervous system development Source: ProtInc <p>Traceable Author Statement</p> <p>Used for information from review articles where the original experiments are traceable through that article and also for information from text books or dictionaries.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#tas">GO evidence code guide</a></p> Traceable author statementi
- positive regulation of apoptotic process Source: Ensembl
- positive regulation of protein dephosphorylation Source: BHF-UCLInferred from mutant phenotypei
- response to cocaine Source: Ensembl
- signal transduction Source: ProtIncTraceable author statementi
- sphingomyelin catabolic process Source: UniProtKBInferred from direct assayi
- sphingomyelin metabolic process Source: ProtIncTraceable author statementi
- termination of signal transduction Source: BHF-UCLInferred from mutant phenotypei
<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi
| Molecular function | Glycosidase, Hydrolase |
| Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
Reactome - a knowledgebase of biological pathways and processes More...Reactomei | R-HSA-1660662 Glycosphingolipid metabolism |
SIGNOR Signaling Network Open Resource More...SIGNORi | P17405 |
Chemistry databases
SwissLipids knowledge resource for lipid biology More...SwissLipidsi | SLP:000001748 |
<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi
| <p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi | Recommended name: Sphingomyelin phosphodiesterase (EC:3.1.4.126 PublicationsManual assertion based on experiment ini
Alternative name(s): Acid sphingomyelinase1 Publication <p>Manually curated information that is based on statements in scientific articles for which there is no experimental support.</p> <p><a href="/manual/evidences#ECO:0000303">More...</a></p> Manual assertion based on opinion ini
Short name: aSMase |
| <p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi | Name:SMPD1 Synonyms:ASM |
| <p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>Organismi | Homo sapiens (Human) |
| <p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri | 9606 [NCBI] |
| <p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineagei | cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo |
| <p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi |
|
Organism-specific databases
Eukaryotic Pathogen Database Resources More...EuPathDBi | HostDB:ENSG00000166311.9 |
Human Gene Nomenclature Database More...HGNCi | HGNC:11120 SMPD1 |
Online Mendelian Inheritance in Man (OMIM) More...MIMi | 607608 gene |
neXtProt; the human protein knowledge platform More...neXtProti | NX_P17405 |
<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi
Extracellular region or secreted
- Secreted 3 Publications
Manual assertion based on experiment ini
- Ref.8"Zn2+-stimulated sphingomyelinase is secreted by many cell types and is a product of the acid sphingomyelinase gene."
Schissel S.L., Schuchman E.H., Williams K.J., Tabas I.
J. Biol. Chem. 271:18431-18436(1996) [PubMed] [Europe PMC] [Abstract]Cited for: CATALYTIC ACTIVITY, COFACTOR, SUBCELLULAR LOCATION. - Ref.12"Structural and functional analysis of the ASM p.Ala359Asp mutant that causes acid sphingomyelinase deficiency."
Acuna M., Castro-Fernandez V., Latorre M., Castro J., Schuchman E.H., Guixe V., Gonzalez M., Zanlungo S.
Biochem. Biophys. Res. Commun. 479:496-501(2016) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT NPDB ASP-359. - Ref.13"Epidemiological, clinical and biochemical characterization of the p.(Ala359Asp) SMPD1 variant causing Niemann-Pick disease type B."
Acuna M., Martinez P., Moraga C., He X., Moraga M., Hunter B., Nuernberg P., Gutierrez R.A., Gonzalez M., Schuchman E.H., Santos J.L., Miquel J.F., Mabe P., Zanlungo S.
Eur. J. Hum. Genet. 24:208-213(2016) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, SUBCELLULAR LOCATION, VARIANT NPDB ASP-359, CHARACTERIZATION OF VARIANT NPDB ASP-359.
- Secreted 3 Publications
Lysosome
- Lysosome 2 Publications
Manual assertion based on experiment ini
- Ref.12"Structural and functional analysis of the ASM p.Ala359Asp mutant that causes acid sphingomyelinase deficiency."
Acuna M., Castro-Fernandez V., Latorre M., Castro J., Schuchman E.H., Guixe V., Gonzalez M., Zanlungo S.
Biochem. Biophys. Res. Commun. 479:496-501(2016) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT NPDB ASP-359. - Ref.34"Characterization of common SMPD1 mutations causing types A and B Niemann-Pick disease and generation of mutation-specific mouse models."
Jones I., He X., Katouzian F., Darroch P.I., Schuchman E.H.
Mol. Genet. Metab. 95:152-162(2008) [PubMed] [Europe PMC] [Abstract]Cited for: CHARACTERIZATION OF VARIANTS NPDA PRO-304 AND LEU-498, CHARACTERIZATION OF VARIANTS NPDB TYR-423 AND ARG-610 DEL, FUNCTION, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY.
- Lysosome 2 Publications
Endosome
Extracellular region or secreted
- extracellular exosome Source: UniProtKBInferred from high throughput direct assayi
- extracellular space Source: UniProtKBInferred from direct assayi
Lysosome
- lysosomal lumen Source: Reactome
- lysosome Source: UniProtKBInferred from direct assayi
Plasma Membrane
- plasma membrane Source: UniProtKBInferred from direct assayi
Other locations
- lamellar body Source: Ensembl
Keywords - Cellular componenti
Lysosome, Secreted<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi
<p>This subsection of the ‘Pathology and Biotech’ section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei
Niemann-Pick disease A (NPDA)18 PublicationsManual assertion based on experiment ini
- Ref.16"Molecular basis of acid sphingomyelinase deficiency in a patient with Niemann-Pick disease type A."
Ferlinz K., Hurwitz R., Sandhoff K.
Biochem. Biophys. Res. Commun. 179:1187-1191(1991) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT NPDA SER-579, CHARACTERIZATION OF VARIANT NPDA SER-579, CATALYTIC ACTIVITY. - Ref.17"Niemann-Pick disease: a frequent missense mutation in the acid sphingomyelinase gene of Ashkenazi Jewish type A and B patients."
Levran O., Desnick R.J., Schuchman E.H.
Proc. Natl. Acad. Sci. U.S.A. 88:3748-3752(1991) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT NPDA LEU-498. - Ref.19"Identification and expression of a common missense mutation (L302P) in the acid sphingomyelinase gene of Ashkenazi Jewish type A Niemann-Pick disease patients."
Levran O., Desnick R.J., Schuchman E.H.
Blood 80:2081-2087(1992) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT NPDA PRO-304. - Ref.21"Identification and expression of five mutations in the human acid sphingomyelinase gene causing types A and B Niemann-Pick disease. Molecular evidence for genetic heterogeneity in the neuronopathic and non-neuronopathic forms."
Takahashi T., Suchi M., Desnick R.J., Takada G., Schuchman E.H.
J. Biol. Chem. 267:12552-12558(1992) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT NPDA ILE-384, VARIANTS NPDB ARG-244 AND SER-385. - Ref.23"Two new mutations in the acid sphingomyelinase gene causing type A Niemann-pick disease: N389T and R441X."
Schuchman E.H.
Hum. Mutat. 6:352-354(1995) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT NPDA THR-391. - Ref.24"Identification and expression of a missense mutation (Y446C) in the acid sphingomyelinase gene from a Japanese patient with type A Niemann-Pick disease."
Takahashi T., Suchi M., Sato W., Ten S.B., Sakuragawa N., Desnick R.J., Schuchman E.H., Takada G.
Tohoku J. Exp. Med. 177:117-123(1995) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT NPDA CYS-448. - Ref.26"Two novel mutations in patients with atypical phenotypes of acid sphingomyelinase deficiency."
Pavluu H., Elleder M.
J. Inherit. Metab. Dis. 20:615-616(1997) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS NPDA LYS-294 AND PRO-343. - Ref.28"Seven novel Acid sphingomyelinase gene mutations in Niemann-Pick type A and B patients."
Sikora J., Pavluu-Pereira H., Elleder M., Roelofs H., Wevers R.A.
Ann. Hum. Genet. 67:63-70(2003) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS NPDA ARG-250; TYR-321; SER-465; LEU-477 AND HIS-539, VARIANTS NPDB SER-373 AND ARG-610 DEL. - Ref.29"Screening of 25 Italian patients with Niemann-Pick A reveals fourteen new mutations, one common and thirteen private, in SMPD1."
Ricci V., Stroppiano M., Corsolini F., Di Rocco M., Parenti G., Regis S., Grossi S., Biancheri R., Mazzotti R., Filocamo M.
Hum. Mutat. 24:105-105(2004) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS NPDA PRO-105; SER-247; LYS-248; HIS-315; PRO-452; LEU-477; LEU-498; HIS-498 AND CYS-519, VARIANT GLN-296. - Ref.32"Acid sphingomyelinase deficiency. Phenotype variability with prevalence of intermediate phenotype in a series of twenty-five Czech and Slovak patients. A multi-approach study."
Pavluu-Pereira H., Asfaw B., Poupctova H., Ledvinova J., Sikora J., Vanier M.T., Sandhoff K., Zeman J., Novotna Z., Chudoba D., Elleder M.
J. Inherit. Metab. Dis. 28:203-227(2005) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS NPDA ARG-168; LEU-186; HIS-230; VAL-243; ARG-250; GLU-253; ALA-280; HIS-291; LYS-294; PRO-343; HIS-378; TRP-476; ARG-535 AND SER-579, VARIANT ARG-508, CATALYTIC ACTIVITY, CHARACTERIZATION OF VARIANTS NPDA LEU-186; GLU-253; ALA-280; LYS-294; PRO-343 AND HIS-378. - Ref.34"Characterization of common SMPD1 mutations causing types A and B Niemann-Pick disease and generation of mutation-specific mouse models."
Jones I., He X., Katouzian F., Darroch P.I., Schuchman E.H.
Mol. Genet. Metab. 95:152-162(2008) [PubMed] [Europe PMC] [Abstract]Cited for: CHARACTERIZATION OF VARIANTS NPDA PRO-304 AND LEU-498, CHARACTERIZATION OF VARIANTS NPDB TYR-423 AND ARG-610 DEL, FUNCTION, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY. - Ref.36"Identification and characterization of SMPD1 mutations causing Niemann-Pick types A and B in Spanish patients."
Rodriguez-Pascau L., Gort L., Schuchman E.H., Vilageliu L., Grinberg D., Chabas A.
Hum. Mutat. 30:1117-1122(2009) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS NPDA SER-247; CYS-369; PHE-392 DEL; ARG-423; SER-469; GLU-484 AND THR-594 DEL, VARIANTS NPDB CYS-230; HIS-378; TRP-476; ALA-488 AND ARG-610 DEL. - Ref.37"Identification and characterization of eight novel SMPD1 mutations causing types A and B Niemann-Pick disease."
Desnick J.P., Kim J., He X., Wasserstein M.P., Simonaro C.M., Schuchman E.H.
Mol. Med. 16:316-321(2010) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS NPDA ARG-211 AND HIS-253, VARIANTS NPDB MET-314; ARG-427 AND HIS-525, CHARACTERIZATION OF VARIANTS NPDA ARG-211 AND HIS-253, CHARACTERIZATION OF VARIANTS NPDB MET-314; ARG-427 AND HIS-525. - Ref.40"Molecular genetic characterization of novel sphingomyelin phosphodiesterase 1 mutations causing niemann-pick disease."
Toth B., Erdos M., Szekely A., Ritli L., Bagossi P., Suemegi J., Marodi L.
JIMD Rep. 3:125-129(2012) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS NPDA ASP-247 AND LEU-572, CHARACTERIZATION OF VARIANTS NPDA ASP-247 AND LEU-572. - Ref.41"Acid sphingomyelinase (Asm) deficiency patients in The Netherlands and Belgium: disease spectrum and natural course in attenuated patients."
Hollak C.E., de Sonnaville E.S., Cassiman D., Linthorst G.E., Groener J.E., Morava E., Wevers R.A., Mannens M., Aerts J.M., Meersseman W., Akkerman E., Niezen-Koning K.E., Mulder M.F., Visser G., Wijburg F.A., Lefeber D., Poorthuis B.J.
Mol. Genet. Metab. 107:526-533(2012) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS NPDB HIS-91; PRO-105; PRO-163; CYS-230; SER-373; PRO-551 AND ARG-610 DEL, VARIANTS NPDA ARG-250; SER-465; LEU-477 AND HIS-539. - Ref.42"Identification of seven novel SMPD1 mutations causing Niemann-Pick disease types A and B."
Irun P., Mallen M., Dominguez C., Rodriguez-Sureda V., Alvarez-Sala L.A., Arslan N., Bermejo N., Guerrero C., Perez de Soto I., Villalon L., Giraldo P., Pocovi M.
Clin. Genet. 84:356-361(2013) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS NPDA ARG-228 AND ARG-387, VARIANTS NPDB CYS-230; SER-247; HIS-378; TRP-476; SER-492; PHE-599 AND ARG-610 DEL. - Ref.44"Spectrum of SMPD1 mutations in Asian-Indian patients with acid sphingomyelinase (ASM)-deficient Niemann-Pick disease."
Ranganath P., Matta D., Bhavani G.S., Wangnekar S., Jain J.M., Verma I.C., Kabra M., Puri R.D., Danda S., Gupta N., Girisha K.M., Sankar V.H., Patil S.J., Ramadevi A.R., Bhat M., Gowrishankar K., Mandal K., Aggarwal S. , Tamhankar P.M., Tilak P., Phadke S.R., Dalal A.
Am. J. Med. Genet. A 170:2719-2730(2016) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS ALA-36; PHE-510 AND GLY-605, VARIANTS NPDA ARG-216; CYS-230; SER-255; ARG-319; PRO-324; ARG-343; ARG-363; HIS-391; ARG-393; SER-426; ILE-494; HIS-498; ARG-535 AND HIS-602, VARIANTS NPDB PRO-105; PHE-282; ASP-320; CYS-369; SER-465; LEU-520 AND LYS-549. - Ref.45"SMPD1 mutation update: database and comprehensive analysis of published and novel variants."
Zampieri S., Filocamo M., Pianta A., Lualdi S., Gort L., Coll M.J., Sinnott R., Geberhiwot T., Bembi B., Dardis A.
Hum. Mutat. 37:139-147(2016) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS NPDB ILE-258; GLN-476; ASP-577; ARG-598 AND CYS-610, VARIANT NPDA PHE-482 DEL, REVIEW ON VARIANTS.
Ref.16
"Molecular basis of acid sphingomyelinase deficiency in a patient with Niemann-Pick disease type A."
Ferlinz K., Hurwitz R., Sandhoff K.
Biochem. Biophys. Res. Commun. 179:1187-1191(1991) [PubMed] [Europe PMC] [Abstract]
Ferlinz K., Hurwitz R., Sandhoff K.
Biochem. Biophys. Res. Commun. 179:1187-1191(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NPDA SER-579, CHARACTERIZATION OF VARIANT NPDA SER-579, CATALYTIC ACTIVITY.
Ref.17
"Niemann-Pick disease: a frequent missense mutation in the acid sphingomyelinase gene of Ashkenazi Jewish type A and B patients."
Levran O., Desnick R.J., Schuchman E.H.
Proc. Natl. Acad. Sci. U.S.A. 88:3748-3752(1991) [PubMed] [Europe PMC] [Abstract]
Levran O., Desnick R.J., Schuchman E.H.
Proc. Natl. Acad. Sci. U.S.A. 88:3748-3752(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NPDA LEU-498.
Ref.19
"Identification and expression of a common missense mutation (L302P) in the acid sphingomyelinase gene of Ashkenazi Jewish type A Niemann-Pick disease patients."
Levran O., Desnick R.J., Schuchman E.H.
Blood 80:2081-2087(1992) [PubMed] [Europe PMC] [Abstract]
Levran O., Desnick R.J., Schuchman E.H.
Blood 80:2081-2087(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NPDA PRO-304.
Ref.21
"Identification and expression of five mutations in the human acid sphingomyelinase gene causing types A and B Niemann-Pick disease. Molecular evidence for genetic heterogeneity in the neuronopathic and non-neuronopathic forms."
Takahashi T., Suchi M., Desnick R.J., Takada G., Schuchman E.H.
J. Biol. Chem. 267:12552-12558(1992) [PubMed] [Europe PMC] [Abstract]
Takahashi T., Suchi M., Desnick R.J., Takada G., Schuchman E.H.
J. Biol. Chem. 267:12552-12558(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NPDA ILE-384, VARIANTS NPDB ARG-244 AND SER-385.
Ref.23
"Two new mutations in the acid sphingomyelinase gene causing type A Niemann-pick disease: N389T and R441X."
Schuchman E.H.
Hum. Mutat. 6:352-354(1995) [PubMed] [Europe PMC] [Abstract]
Schuchman E.H.
Hum. Mutat. 6:352-354(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NPDA THR-391.
Ref.24
"Identification and expression of a missense mutation (Y446C) in the acid sphingomyelinase gene from a Japanese patient with type A Niemann-Pick disease."
Takahashi T., Suchi M., Sato W., Ten S.B., Sakuragawa N., Desnick R.J., Schuchman E.H., Takada G.
Tohoku J. Exp. Med. 177:117-123(1995) [PubMed] [Europe PMC] [Abstract]
Takahashi T., Suchi M., Sato W., Ten S.B., Sakuragawa N., Desnick R.J., Schuchman E.H., Takada G.
Tohoku J. Exp. Med. 177:117-123(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NPDA CYS-448.
Ref.26
"Two novel mutations in patients with atypical phenotypes of acid sphingomyelinase deficiency."
Pavluu H., Elleder M.
J. Inherit. Metab. Dis. 20:615-616(1997) [PubMed] [Europe PMC] [Abstract]
Pavluu H., Elleder M.
J. Inherit. Metab. Dis. 20:615-616(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPDA LYS-294 AND PRO-343.
Ref.28
"Seven novel Acid sphingomyelinase gene mutations in Niemann-Pick type A and B patients."
Sikora J., Pavluu-Pereira H., Elleder M., Roelofs H., Wevers R.A.
Ann. Hum. Genet. 67:63-70(2003) [PubMed] [Europe PMC] [Abstract]
Sikora J., Pavluu-Pereira H., Elleder M., Roelofs H., Wevers R.A.
Ann. Hum. Genet. 67:63-70(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPDA ARG-250; TYR-321; SER-465; LEU-477 AND HIS-539, VARIANTS NPDB SER-373 AND ARG-610 DEL.
Ref.29
"Screening of 25 Italian patients with Niemann-Pick A reveals fourteen new mutations, one common and thirteen private, in SMPD1."
Ricci V., Stroppiano M., Corsolini F., Di Rocco M., Parenti G., Regis S., Grossi S., Biancheri R., Mazzotti R., Filocamo M.
Hum. Mutat. 24:105-105(2004) [PubMed] [Europe PMC] [Abstract]
Ricci V., Stroppiano M., Corsolini F., Di Rocco M., Parenti G., Regis S., Grossi S., Biancheri R., Mazzotti R., Filocamo M.
Hum. Mutat. 24:105-105(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPDA PRO-105; SER-247; LYS-248; HIS-315; PRO-452; LEU-477; LEU-498; HIS-498 AND CYS-519, VARIANT GLN-296.
Ref.32
"Acid sphingomyelinase deficiency. Phenotype variability with prevalence of intermediate phenotype in a series of twenty-five Czech and Slovak patients. A multi-approach study."
Pavluu-Pereira H., Asfaw B., Poupctova H., Ledvinova J., Sikora J., Vanier M.T., Sandhoff K., Zeman J., Novotna Z., Chudoba D., Elleder M.
J. Inherit. Metab. Dis. 28:203-227(2005) [PubMed] [Europe PMC] [Abstract]
Pavluu-Pereira H., Asfaw B., Poupctova H., Ledvinova J., Sikora J., Vanier M.T., Sandhoff K., Zeman J., Novotna Z., Chudoba D., Elleder M.
J. Inherit. Metab. Dis. 28:203-227(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPDA ARG-168; LEU-186; HIS-230; VAL-243; ARG-250; GLU-253; ALA-280; HIS-291; LYS-294; PRO-343; HIS-378; TRP-476; ARG-535 AND SER-579, VARIANT ARG-508, CATALYTIC ACTIVITY, CHARACTERIZATION OF VARIANTS NPDA LEU-186; GLU-253; ALA-280; LYS-294; PRO-343 AND HIS-378.
Ref.34
"Characterization of common SMPD1 mutations causing types A and B Niemann-Pick disease and generation of mutation-specific mouse models."
Jones I., He X., Katouzian F., Darroch P.I., Schuchman E.H.
Mol. Genet. Metab. 95:152-162(2008) [PubMed] [Europe PMC] [Abstract]
Jones I., He X., Katouzian F., Darroch P.I., Schuchman E.H.
Mol. Genet. Metab. 95:152-162(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANTS NPDA PRO-304 AND LEU-498, CHARACTERIZATION OF VARIANTS NPDB TYR-423 AND ARG-610 DEL, FUNCTION, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY.
Ref.36
"Identification and characterization of SMPD1 mutations causing Niemann-Pick types A and B in Spanish patients."
Rodriguez-Pascau L., Gort L., Schuchman E.H., Vilageliu L., Grinberg D., Chabas A.
Hum. Mutat. 30:1117-1122(2009) [PubMed] [Europe PMC] [Abstract]
Rodriguez-Pascau L., Gort L., Schuchman E.H., Vilageliu L., Grinberg D., Chabas A.
Hum. Mutat. 30:1117-1122(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPDA SER-247; CYS-369; PHE-392 DEL; ARG-423; SER-469; GLU-484 AND THR-594 DEL, VARIANTS NPDB CYS-230; HIS-378; TRP-476; ALA-488 AND ARG-610 DEL.
Ref.37
"Identification and characterization of eight novel SMPD1 mutations causing types A and B Niemann-Pick disease."
Desnick J.P., Kim J., He X., Wasserstein M.P., Simonaro C.M., Schuchman E.H.
Mol. Med. 16:316-321(2010) [PubMed] [Europe PMC] [Abstract]
Desnick J.P., Kim J., He X., Wasserstein M.P., Simonaro C.M., Schuchman E.H.
Mol. Med. 16:316-321(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPDA ARG-211 AND HIS-253, VARIANTS NPDB MET-314; ARG-427 AND HIS-525, CHARACTERIZATION OF VARIANTS NPDA ARG-211 AND HIS-253, CHARACTERIZATION OF VARIANTS NPDB MET-314; ARG-427 AND HIS-525.
Ref.40
"Molecular genetic characterization of novel sphingomyelin phosphodiesterase 1 mutations causing niemann-pick disease."
Toth B., Erdos M., Szekely A., Ritli L., Bagossi P., Suemegi J., Marodi L.
JIMD Rep. 3:125-129(2012) [PubMed] [Europe PMC] [Abstract]
Toth B., Erdos M., Szekely A., Ritli L., Bagossi P., Suemegi J., Marodi L.
JIMD Rep. 3:125-129(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPDA ASP-247 AND LEU-572, CHARACTERIZATION OF VARIANTS NPDA ASP-247 AND LEU-572.
Ref.41
"Acid sphingomyelinase (Asm) deficiency patients in The Netherlands and Belgium: disease spectrum and natural course in attenuated patients."
Hollak C.E., de Sonnaville E.S., Cassiman D., Linthorst G.E., Groener J.E., Morava E., Wevers R.A., Mannens M., Aerts J.M., Meersseman W., Akkerman E., Niezen-Koning K.E., Mulder M.F., Visser G., Wijburg F.A., Lefeber D., Poorthuis B.J.
Mol. Genet. Metab. 107:526-533(2012) [PubMed] [Europe PMC] [Abstract]
Hollak C.E., de Sonnaville E.S., Cassiman D., Linthorst G.E., Groener J.E., Morava E., Wevers R.A., Mannens M., Aerts J.M., Meersseman W., Akkerman E., Niezen-Koning K.E., Mulder M.F., Visser G., Wijburg F.A., Lefeber D., Poorthuis B.J.
Mol. Genet. Metab. 107:526-533(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPDB HIS-91; PRO-105; PRO-163; CYS-230; SER-373; PRO-551 AND ARG-610 DEL, VARIANTS NPDA ARG-250; SER-465; LEU-477 AND HIS-539.
Ref.42
"Identification of seven novel SMPD1 mutations causing Niemann-Pick disease types A and B."
Irun P., Mallen M., Dominguez C., Rodriguez-Sureda V., Alvarez-Sala L.A., Arslan N., Bermejo N., Guerrero C., Perez de Soto I., Villalon L., Giraldo P., Pocovi M.
Clin. Genet. 84:356-361(2013) [PubMed] [Europe PMC] [Abstract]
Irun P., Mallen M., Dominguez C., Rodriguez-Sureda V., Alvarez-Sala L.A., Arslan N., Bermejo N., Guerrero C., Perez de Soto I., Villalon L., Giraldo P., Pocovi M.
Clin. Genet. 84:356-361(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPDA ARG-228 AND ARG-387, VARIANTS NPDB CYS-230; SER-247; HIS-378; TRP-476; SER-492; PHE-599 AND ARG-610 DEL.
Ref.44
"Spectrum of SMPD1 mutations in Asian-Indian patients with acid sphingomyelinase (ASM)-deficient Niemann-Pick disease."
Ranganath P., Matta D., Bhavani G.S., Wangnekar S., Jain J.M., Verma I.C., Kabra M., Puri R.D., Danda S., Gupta N., Girisha K.M., Sankar V.H., Patil S.J., Ramadevi A.R., Bhat M., Gowrishankar K., Mandal K., Aggarwal S. , Tamhankar P.M., Tilak P., Phadke S.R., Dalal A.
Am. J. Med. Genet. A 170:2719-2730(2016) [PubMed] [Europe PMC] [Abstract]
Ranganath P., Matta D., Bhavani G.S., Wangnekar S., Jain J.M., Verma I.C., Kabra M., Puri R.D., Danda S., Gupta N., Girisha K.M., Sankar V.H., Patil S.J., Ramadevi A.R., Bhat M., Gowrishankar K., Mandal K., Aggarwal S. , Tamhankar P.M., Tilak P., Phadke S.R., Dalal A.
Am. J. Med. Genet. A 170:2719-2730(2016) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ALA-36; PHE-510 AND GLY-605, VARIANTS NPDA ARG-216; CYS-230; SER-255; ARG-319; PRO-324; ARG-343; ARG-363; HIS-391; ARG-393; SER-426; ILE-494; HIS-498; ARG-535 AND HIS-602, VARIANTS NPDB PRO-105; PHE-282; ASP-320; CYS-369; SER-465; LEU-520 AND LYS-549.
Ref.45
"SMPD1 mutation update: database and comprehensive analysis of published and novel variants."
Zampieri S., Filocamo M., Pianta A., Lualdi S., Gort L., Coll M.J., Sinnott R., Geberhiwot T., Bembi B., Dardis A.
Hum. Mutat. 37:139-147(2016) [PubMed] [Europe PMC] [Abstract]
Zampieri S., Filocamo M., Pianta A., Lualdi S., Gort L., Coll M.J., Sinnott R., Geberhiwot T., Bembi B., Dardis A.
Hum. Mutat. 37:139-147(2016) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPDB ILE-258; GLN-476; ASP-577; ARG-598 AND CYS-610, VARIANT NPDA PHE-482 DEL, REVIEW ON VARIANTS.
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn early-onset lysosomal storage disorder caused by failure to hydrolyze sphingomyelin to ceramide. It results in the accumulation of sphingomyelin and other metabolically related lipids in reticuloendothelial and other cell types throughout the body, leading to cell death. Niemann-Pick disease type A is a primarily neurodegenerative disorder characterized by onset within the first year of life, mental retardation, digestive disorders, failure to thrive, major hepatosplenomegaly, and severe neurologic symptoms. The severe neurological disorders and pulmonary infections lead to an early death, often around the age of four. Clinical features are variable. A phenotypic continuum exists between type A (basic neurovisceral) and type B (purely visceral) forms of Niemann-Pick disease, and the intermediate types encompass a cluster of variants combining clinical features of both types A and B.
See also OMIM:257200| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| <p>This subsection of the ‘Sequence’ section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_060877 | 186 | P → L in NPDA; reduces enzyme activity; intermediate form with clinical features of both Niemann-Pick disease types A and B. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_068435 | 211 | W → R in NPDA; results in less than 0.5% of wild-type activity. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_077311 | 216 | L → R in NPDA. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_075324 | 228 | C → R in NPDA. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060883 | 230 | R → H in NPDA; intermediate form with clinical features of both Niemann-Pick disease types A and B. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060885 | 243 | A → V in NPDA; intermediate form with clinical features of both Niemann-Pick disease types A and B. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_075325 | 247 | G → D in NPDA; severe decrease in activity; the mutant is highly unstable. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060888 | 248 | E → K in NPDA. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060889 | 253 | D → E in NPDA; strongly reduces enzyme activity; intermediate form with clinical features of both Niemann-Pick disease types A and B. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_068436 | 253 | D → H in NPDA; results in loss of activity. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_077312 | 255 | P → S in NPDA. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060890 | 280 | D → A in NPDA; strongly reduces enzyme activity; intermediate form with clinical features of both Niemann-Pick disease types A and B. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060893 | 294 | Q → K in NPDA; strongly reduces enzyme activity; intermediate form with clinical features of both Niemann-Pick disease types A and B. 3 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_005060 | 304 | L → P in NPDA; in 23% of NPDA Ashkenazi Jewish patients; abolishes enzyme activity. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060895 | 315 | Y → H in NPDA. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_077314 | 319 | G → R in NPDA. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_015288 | 321 | H → Y in NPDA. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_077316 | 324 | T → P in NPDA; unknown pathological significance. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060898 | 343 | L → P in NPDA; strongly reduces enzyme activity; intermediate form with clinical features of both Niemann-Pick disease types A and B. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_077317 | 343 | L → R in NPDA. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_077318 | 363 | L → R in NPDA; unknown pathological significance. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060900 | 369 | Y → C in NPDA. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_075327 | 387 | C → R in NPDA. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_077319 | 391 | N → H in NPDA. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_005063 | 391 | N → T in NPDA. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060904 | 392 | Missing in NPDA. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_077320 | 393 | W → R in NPDA; intermediate form. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060906 | 423 | H → R in NPDA. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_077321 | 426 | G → S in NPDA. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_011388 | 448 | Y → C in NPDA. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060910 | 452 | L → P in NPDA. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_015291 | 465 | F → S in NPDA. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060913 | 469 | Y → S in NPDA. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_075329 | 482 | Missing in NPDA; unknown pathological significance. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060916 | 484 | A → E in NPDA. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_077322 | 494 | N → I in NPDA; intermediate form. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060922 | 498 | R → H in NPDA. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_005066 | 498 | R → L in NPDA; in 32% of NPDA Ashkenazi Jewish patients; nearly abolishes enzyme activity. 3 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060926 | 519 | Y → C in NPDA. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_015293 | 539 | Y → H in NPDA. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_075331 | 572 | F → L in NPDA; results in decreased activity; decreased stability. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_005067 | 579 | G → S in NPDA; impairs enzyme activity; also in patients with an intermediate form. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060931 | 594 | Missing in NPDA. 1 Publication Manual assertion based on experiment ini
| 1 |
Niemann-Pick disease B (NPDB)24 PublicationsManual assertion based on experiment ini
- Ref.12"Structural and functional analysis of the ASM p.Ala359Asp mutant that causes acid sphingomyelinase deficiency."
Acuna M., Castro-Fernandez V., Latorre M., Castro J., Schuchman E.H., Guixe V., Gonzalez M., Zanlungo S.
Biochem. Biophys. Res. Commun. 479:496-501(2016) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT NPDB ASP-359. - Ref.13"Epidemiological, clinical and biochemical characterization of the p.(Ala359Asp) SMPD1 variant causing Niemann-Pick disease type B."
Acuna M., Martinez P., Moraga C., He X., Moraga M., Hunter B., Nuernberg P., Gutierrez R.A., Gonzalez M., Schuchman E.H., Santos J.L., Miquel J.F., Mabe P., Zanlungo S.
Eur. J. Hum. Genet. 24:208-213(2016) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, SUBCELLULAR LOCATION, VARIANT NPDB ASP-359, CHARACTERIZATION OF VARIANT NPDB ASP-359. - Ref.18"Niemann-Pick type B disease. Identification of a single codon deletion in the acid sphingomyelinase gene and genotype/phenotype correlations in type A and B patients."
Levran O., Desnick R.J., Schuchman E.H.
J. Clin. Invest. 88:806-810(1991) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT NPDB ARG-610 DEL. - Ref.20"Identification of a missense mutation (S436R) in the acid sphingomyelinase gene from a Japanese patient with type B Niemann-Pick disease."
Takahashi T., Desnick R.J., Takada G., Schuchman E.H.
Hum. Mutat. 1:70-71(1992) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT NPDB ARG-438. - Ref.21"Identification and expression of five mutations in the human acid sphingomyelinase gene causing types A and B Niemann-Pick disease. Molecular evidence for genetic heterogeneity in the neuronopathic and non-neuronopathic forms."
Takahashi T., Suchi M., Desnick R.J., Takada G., Schuchman E.H.
J. Biol. Chem. 267:12552-12558(1992) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT NPDA ILE-384, VARIANTS NPDB ARG-244 AND SER-385. - Ref.22"A family with visceral course of Niemann-Pick disease, macular halo syndrome and low sphingomyelin degradation rate."
Sperl W., Bart G., Vanier M.T., Christomanou H., Baldissera I., Steichensdorf E., Paschke E.
J. Inherit. Metab. Dis. 17:93-103(1994) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT NPDB GLY-393. - Ref.25"Identification of three novel mutations in the acid sphingomyelinase gene of Japanese patients with Niemann-Pick disease type A and B."
Ida H., Rennert O.M., Maekawa K., Eto Y.
Hum. Mutat. 7:65-67(1996) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT NPDB GLN-248. - Ref.27"The demographics and distribution of type B Niemann-Pick disease: novel mutations lead to new genotype/phenotype correlations."
Simonaro C.M., Desnick R.J., McGovern M.M., Wasserstein M.P., Schuchman E.H.
Am. J. Hum. Genet. 71:1413-1419(2002) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS NPDB VAL-51; TRP-94; PRO-139; ARG-159; PRO-198; CYS-202; MET-227; CYS-230; ASP-234; SER-247; ARG-250; HIS-291; ALA-325; ARG-332; ASP-359; HIS-378; LEU-378; PRO-381; VAL-415; TYR-423; ARG-433; PRO-434; CYS-437; VAL-454; ASP-458; TRP-476; LEU-477; LEU-482; ASN-490; SER-496; CYS-498; GLN-516; VAL-517; ARG-535; PRO-551; ASN-578; HIS-602 AND PRO-602, VARIANT VAL-487. - Ref.28"Seven novel Acid sphingomyelinase gene mutations in Niemann-Pick type A and B patients."
Sikora J., Pavluu-Pereira H., Elleder M., Roelofs H., Wevers R.A.
Ann. Hum. Genet. 67:63-70(2003) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS NPDA ARG-250; TYR-321; SER-465; LEU-477 AND HIS-539, VARIANTS NPDB SER-373 AND ARG-610 DEL. - Ref.30"Acid sphingomyelinase: identification of nine novel mutations among Italian Niemann Pick type B patients and characterization of in vivo functional in-frame start codon."
Pittis M.G., Ricci V., Guerci V.I., Marcais C., Ciana G., Dardis A., Gerin F., Stroppiano M., Vanier M.T., Filocamo M., Bembi B.
Hum. Mutat. 24:186-187(2004) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS NPDB PRO-105; PRO-227; CYS-246; THR-283; LYS-294 AND ILE-384. - Ref.31"Functional in vitro characterization of 14 SMPD1 mutations identified in Italian patients affected by Niemann Pick type B disease."
Dardis A., Zampieri S., Filocamo M., Burlina A., Bembi B., Pittis M.G.
Hum. Mutat. 26:164-164(2005) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS NPDB ALA-132 AND TYR-565, CHARACTERIZATION OF VARIANTS NPDB PRO-105; ALA-132; PRO-227; CYS-246; THR-283; TYR-565; HIS-602 AND PRO-602. - Ref.33"Clinical findings in Niemann-Pick disease type B."
Muessig K., Harzer K., Mayrhofer H., Kraegeloh-Mann I., Haering H.-U., Machicao F.
Intern. Med. J. 36:135-136(2006) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS NPDB ARG-168 AND ASN-178, VARIANT GLY-507. - Ref.34"Characterization of common SMPD1 mutations causing types A and B Niemann-Pick disease and generation of mutation-specific mouse models."
Jones I., He X., Katouzian F., Darroch P.I., Schuchman E.H.
Mol. Genet. Metab. 95:152-162(2008) [PubMed] [Europe PMC] [Abstract]Cited for: CHARACTERIZATION OF VARIANTS NPDA PRO-304 AND LEU-498, CHARACTERIZATION OF VARIANTS NPDB TYR-423 AND ARG-610 DEL, FUNCTION, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY. - Ref.35"A novel missense mutation of the SMPD1 gene in a Taiwanese patient with type B Niemann-Pick disease."
Lan M.Y., Lin S.J., Chen Y.F., Peng C.H., Liu Y.F.
Ann. Hematol. 88:695-697(2009) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS NPDB ARG-332 AND ASP-453. - Ref.36"Identification and characterization of SMPD1 mutations causing Niemann-Pick types A and B in Spanish patients."
Rodriguez-Pascau L., Gort L., Schuchman E.H., Vilageliu L., Grinberg D., Chabas A.
Hum. Mutat. 30:1117-1122(2009) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS NPDA SER-247; CYS-369; PHE-392 DEL; ARG-423; SER-469; GLU-484 AND THR-594 DEL, VARIANTS NPDB CYS-230; HIS-378; TRP-476; ALA-488 AND ARG-610 DEL. - Ref.37"Identification and characterization of eight novel SMPD1 mutations causing types A and B Niemann-Pick disease."
Desnick J.P., Kim J., He X., Wasserstein M.P., Simonaro C.M., Schuchman E.H.
Mol. Med. 16:316-321(2010) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS NPDA ARG-211 AND HIS-253, VARIANTS NPDB MET-314; ARG-427 AND HIS-525, CHARACTERIZATION OF VARIANTS NPDA ARG-211 AND HIS-253, CHARACTERIZATION OF VARIANTS NPDB MET-314; ARG-427 AND HIS-525. - Ref.38"PAS-positive macrophages--not always infection."
Meersseman W., Verschueren P., Tousseyn T., De Vos R., Cassiman D.
Lancet 377:1890-1890(2011) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT NPDB PRO-163. - Ref.41"Acid sphingomyelinase (Asm) deficiency patients in The Netherlands and Belgium: disease spectrum and natural course in attenuated patients."
Hollak C.E., de Sonnaville E.S., Cassiman D., Linthorst G.E., Groener J.E., Morava E., Wevers R.A., Mannens M., Aerts J.M., Meersseman W., Akkerman E., Niezen-Koning K.E., Mulder M.F., Visser G., Wijburg F.A., Lefeber D., Poorthuis B.J.
Mol. Genet. Metab. 107:526-533(2012) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS NPDB HIS-91; PRO-105; PRO-163; CYS-230; SER-373; PRO-551 AND ARG-610 DEL, VARIANTS NPDA ARG-250; SER-465; LEU-477 AND HIS-539. - Ref.42"Identification of seven novel SMPD1 mutations causing Niemann-Pick disease types A and B."
Irun P., Mallen M., Dominguez C., Rodriguez-Sureda V., Alvarez-Sala L.A., Arslan N., Bermejo N., Guerrero C., Perez de Soto I., Villalon L., Giraldo P., Pocovi M.
Clin. Genet. 84:356-361(2013) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS NPDA ARG-228 AND ARG-387, VARIANTS NPDB CYS-230; SER-247; HIS-378; TRP-476; SER-492; PHE-599 AND ARG-610 DEL. - Ref.43"The acid sphingomyelinase sequence variant p.A487V is not associated with decreased levels of enzymatic activity."
Rhein C., Naumann J., Muehle C., Zill P., Adli M., Hegerl U., Hiemke C., Mergl R., Moeller H.J., Reichel M., Kornhuber J.
JIMD Rep. 8:1-6(2013) [PubMed] [Europe PMC] [Abstract]Cited for: CHARACTERIZATION OF VARIANT NPDB ALA-325, CHARACTERIZATION OF VARIANT VAL-487. - Ref.44"Spectrum of SMPD1 mutations in Asian-Indian patients with acid sphingomyelinase (ASM)-deficient Niemann-Pick disease."
Ranganath P., Matta D., Bhavani G.S., Wangnekar S., Jain J.M., Verma I.C., Kabra M., Puri R.D., Danda S., Gupta N., Girisha K.M., Sankar V.H., Patil S.J., Ramadevi A.R., Bhat M., Gowrishankar K., Mandal K., Aggarwal S. , Tamhankar P.M., Tilak P., Phadke S.R., Dalal A.
Am. J. Med. Genet. A 170:2719-2730(2016) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS ALA-36; PHE-510 AND GLY-605, VARIANTS NPDA ARG-216; CYS-230; SER-255; ARG-319; PRO-324; ARG-343; ARG-363; HIS-391; ARG-393; SER-426; ILE-494; HIS-498; ARG-535 AND HIS-602, VARIANTS NPDB PRO-105; PHE-282; ASP-320; CYS-369; SER-465; LEU-520 AND LYS-549. - Ref.45"SMPD1 mutation update: database and comprehensive analysis of published and novel variants."
Zampieri S., Filocamo M., Pianta A., Lualdi S., Gort L., Coll M.J., Sinnott R., Geberhiwot T., Bembi B., Dardis A.
Hum. Mutat. 37:139-147(2016) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS NPDB ILE-258; GLN-476; ASP-577; ARG-598 AND CYS-610, VARIANT NPDA PHE-482 DEL, REVIEW ON VARIANTS. - Ref.46"Alleged detrimental mutations in the SMPD1 gene in patients with Niemann-Pick disease."
Rhein C., Muehle C., Kornhuber J., Reichel M.
Int. J. Mol. Sci. 16:13649-13652(2015) [PubMed] [Europe PMC] [Abstract]Cited for: CHARACTERIZATION OF VARIANT NPDB ALA-325, CHARACTERIZATION OF VARIANTS ALA-36; VAL-487 AND ARG-508, CATALYTIC ACTIVITY.
Ref.12
"Structural and functional analysis of the ASM p.Ala359Asp mutant that causes acid sphingomyelinase deficiency."
Acuna M., Castro-Fernandez V., Latorre M., Castro J., Schuchman E.H., Guixe V., Gonzalez M., Zanlungo S.
Biochem. Biophys. Res. Commun. 479:496-501(2016) [PubMed] [Europe PMC] [Abstract]
Acuna M., Castro-Fernandez V., Latorre M., Castro J., Schuchman E.H., Guixe V., Gonzalez M., Zanlungo S.
Biochem. Biophys. Res. Commun. 479:496-501(2016) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT NPDB ASP-359.
Ref.13
"Epidemiological, clinical and biochemical characterization of the p.(Ala359Asp) SMPD1 variant causing Niemann-Pick disease type B."
Acuna M., Martinez P., Moraga C., He X., Moraga M., Hunter B., Nuernberg P., Gutierrez R.A., Gonzalez M., Schuchman E.H., Santos J.L., Miquel J.F., Mabe P., Zanlungo S.
Eur. J. Hum. Genet. 24:208-213(2016) [PubMed] [Europe PMC] [Abstract]
Acuna M., Martinez P., Moraga C., He X., Moraga M., Hunter B., Nuernberg P., Gutierrez R.A., Gonzalez M., Schuchman E.H., Santos J.L., Miquel J.F., Mabe P., Zanlungo S.
Eur. J. Hum. Genet. 24:208-213(2016) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, VARIANT NPDB ASP-359, CHARACTERIZATION OF VARIANT NPDB ASP-359.
Ref.18
"Niemann-Pick type B disease. Identification of a single codon deletion in the acid sphingomyelinase gene and genotype/phenotype correlations in type A and B patients."
Levran O., Desnick R.J., Schuchman E.H.
J. Clin. Invest. 88:806-810(1991) [PubMed] [Europe PMC] [Abstract]
Levran O., Desnick R.J., Schuchman E.H.
J. Clin. Invest. 88:806-810(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NPDB ARG-610 DEL.
Ref.20
"Identification of a missense mutation (S436R) in the acid sphingomyelinase gene from a Japanese patient with type B Niemann-Pick disease."
Takahashi T., Desnick R.J., Takada G., Schuchman E.H.
Hum. Mutat. 1:70-71(1992) [PubMed] [Europe PMC] [Abstract]
Takahashi T., Desnick R.J., Takada G., Schuchman E.H.
Hum. Mutat. 1:70-71(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NPDB ARG-438.
Ref.21
"Identification and expression of five mutations in the human acid sphingomyelinase gene causing types A and B Niemann-Pick disease. Molecular evidence for genetic heterogeneity in the neuronopathic and non-neuronopathic forms."
Takahashi T., Suchi M., Desnick R.J., Takada G., Schuchman E.H.
J. Biol. Chem. 267:12552-12558(1992) [PubMed] [Europe PMC] [Abstract]
Takahashi T., Suchi M., Desnick R.J., Takada G., Schuchman E.H.
J. Biol. Chem. 267:12552-12558(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NPDA ILE-384, VARIANTS NPDB ARG-244 AND SER-385.
Ref.22
"A family with visceral course of Niemann-Pick disease, macular halo syndrome and low sphingomyelin degradation rate."
Sperl W., Bart G., Vanier M.T., Christomanou H., Baldissera I., Steichensdorf E., Paschke E.
J. Inherit. Metab. Dis. 17:93-103(1994) [PubMed] [Europe PMC] [Abstract]
Sperl W., Bart G., Vanier M.T., Christomanou H., Baldissera I., Steichensdorf E., Paschke E.
J. Inherit. Metab. Dis. 17:93-103(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NPDB GLY-393.
Ref.25
"Identification of three novel mutations in the acid sphingomyelinase gene of Japanese patients with Niemann-Pick disease type A and B."
Ida H., Rennert O.M., Maekawa K., Eto Y.
Hum. Mutat. 7:65-67(1996) [PubMed] [Europe PMC] [Abstract]
Ida H., Rennert O.M., Maekawa K., Eto Y.
Hum. Mutat. 7:65-67(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NPDB GLN-248.
Ref.27
"The demographics and distribution of type B Niemann-Pick disease: novel mutations lead to new genotype/phenotype correlations."
Simonaro C.M., Desnick R.J., McGovern M.M., Wasserstein M.P., Schuchman E.H.
Am. J. Hum. Genet. 71:1413-1419(2002) [PubMed] [Europe PMC] [Abstract]
Simonaro C.M., Desnick R.J., McGovern M.M., Wasserstein M.P., Schuchman E.H.
Am. J. Hum. Genet. 71:1413-1419(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPDB VAL-51; TRP-94; PRO-139; ARG-159; PRO-198; CYS-202; MET-227; CYS-230; ASP-234; SER-247; ARG-250; HIS-291; ALA-325; ARG-332; ASP-359; HIS-378; LEU-378; PRO-381; VAL-415; TYR-423; ARG-433; PRO-434; CYS-437; VAL-454; ASP-458; TRP-476; LEU-477; LEU-482; ASN-490; SER-496; CYS-498; GLN-516; VAL-517; ARG-535; PRO-551; ASN-578; HIS-602 AND PRO-602, VARIANT VAL-487.
Ref.28
"Seven novel Acid sphingomyelinase gene mutations in Niemann-Pick type A and B patients."
Sikora J., Pavluu-Pereira H., Elleder M., Roelofs H., Wevers R.A.
Ann. Hum. Genet. 67:63-70(2003) [PubMed] [Europe PMC] [Abstract]
Sikora J., Pavluu-Pereira H., Elleder M., Roelofs H., Wevers R.A.
Ann. Hum. Genet. 67:63-70(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPDA ARG-250; TYR-321; SER-465; LEU-477 AND HIS-539, VARIANTS NPDB SER-373 AND ARG-610 DEL.
Ref.30
"Acid sphingomyelinase: identification of nine novel mutations among Italian Niemann Pick type B patients and characterization of in vivo functional in-frame start codon."
Pittis M.G., Ricci V., Guerci V.I., Marcais C., Ciana G., Dardis A., Gerin F., Stroppiano M., Vanier M.T., Filocamo M., Bembi B.
Hum. Mutat. 24:186-187(2004) [PubMed] [Europe PMC] [Abstract]
Pittis M.G., Ricci V., Guerci V.I., Marcais C., Ciana G., Dardis A., Gerin F., Stroppiano M., Vanier M.T., Filocamo M., Bembi B.
Hum. Mutat. 24:186-187(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPDB PRO-105; PRO-227; CYS-246; THR-283; LYS-294 AND ILE-384.
Ref.31
"Functional in vitro characterization of 14 SMPD1 mutations identified in Italian patients affected by Niemann Pick type B disease."
Dardis A., Zampieri S., Filocamo M., Burlina A., Bembi B., Pittis M.G.
Hum. Mutat. 26:164-164(2005) [PubMed] [Europe PMC] [Abstract]
Dardis A., Zampieri S., Filocamo M., Burlina A., Bembi B., Pittis M.G.
Hum. Mutat. 26:164-164(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPDB ALA-132 AND TYR-565, CHARACTERIZATION OF VARIANTS NPDB PRO-105; ALA-132; PRO-227; CYS-246; THR-283; TYR-565; HIS-602 AND PRO-602.
Ref.33
"Clinical findings in Niemann-Pick disease type B."
Muessig K., Harzer K., Mayrhofer H., Kraegeloh-Mann I., Haering H.-U., Machicao F.
Intern. Med. J. 36:135-136(2006) [PubMed] [Europe PMC] [Abstract]
Muessig K., Harzer K., Mayrhofer H., Kraegeloh-Mann I., Haering H.-U., Machicao F.
Intern. Med. J. 36:135-136(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPDB ARG-168 AND ASN-178, VARIANT GLY-507.
Ref.34
"Characterization of common SMPD1 mutations causing types A and B Niemann-Pick disease and generation of mutation-specific mouse models."
Jones I., He X., Katouzian F., Darroch P.I., Schuchman E.H.
Mol. Genet. Metab. 95:152-162(2008) [PubMed] [Europe PMC] [Abstract]
Jones I., He X., Katouzian F., Darroch P.I., Schuchman E.H.
Mol. Genet. Metab. 95:152-162(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANTS NPDA PRO-304 AND LEU-498, CHARACTERIZATION OF VARIANTS NPDB TYR-423 AND ARG-610 DEL, FUNCTION, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY.
Ref.35
"A novel missense mutation of the SMPD1 gene in a Taiwanese patient with type B Niemann-Pick disease."
Lan M.Y., Lin S.J., Chen Y.F., Peng C.H., Liu Y.F.
Ann. Hematol. 88:695-697(2009) [PubMed] [Europe PMC] [Abstract]
Lan M.Y., Lin S.J., Chen Y.F., Peng C.H., Liu Y.F.
Ann. Hematol. 88:695-697(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPDB ARG-332 AND ASP-453.
Ref.36
"Identification and characterization of SMPD1 mutations causing Niemann-Pick types A and B in Spanish patients."
Rodriguez-Pascau L., Gort L., Schuchman E.H., Vilageliu L., Grinberg D., Chabas A.
Hum. Mutat. 30:1117-1122(2009) [PubMed] [Europe PMC] [Abstract]
Rodriguez-Pascau L., Gort L., Schuchman E.H., Vilageliu L., Grinberg D., Chabas A.
Hum. Mutat. 30:1117-1122(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPDA SER-247; CYS-369; PHE-392 DEL; ARG-423; SER-469; GLU-484 AND THR-594 DEL, VARIANTS NPDB CYS-230; HIS-378; TRP-476; ALA-488 AND ARG-610 DEL.
Ref.37
"Identification and characterization of eight novel SMPD1 mutations causing types A and B Niemann-Pick disease."
Desnick J.P., Kim J., He X., Wasserstein M.P., Simonaro C.M., Schuchman E.H.
Mol. Med. 16:316-321(2010) [PubMed] [Europe PMC] [Abstract]
Desnick J.P., Kim J., He X., Wasserstein M.P., Simonaro C.M., Schuchman E.H.
Mol. Med. 16:316-321(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPDA ARG-211 AND HIS-253, VARIANTS NPDB MET-314; ARG-427 AND HIS-525, CHARACTERIZATION OF VARIANTS NPDA ARG-211 AND HIS-253, CHARACTERIZATION OF VARIANTS NPDB MET-314; ARG-427 AND HIS-525.
Ref.38
"PAS-positive macrophages--not always infection."
Meersseman W., Verschueren P., Tousseyn T., De Vos R., Cassiman D.
Lancet 377:1890-1890(2011) [PubMed] [Europe PMC] [Abstract]
Meersseman W., Verschueren P., Tousseyn T., De Vos R., Cassiman D.
Lancet 377:1890-1890(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NPDB PRO-163.
Ref.41
"Acid sphingomyelinase (Asm) deficiency patients in The Netherlands and Belgium: disease spectrum and natural course in attenuated patients."
Hollak C.E., de Sonnaville E.S., Cassiman D., Linthorst G.E., Groener J.E., Morava E., Wevers R.A., Mannens M., Aerts J.M., Meersseman W., Akkerman E., Niezen-Koning K.E., Mulder M.F., Visser G., Wijburg F.A., Lefeber D., Poorthuis B.J.
Mol. Genet. Metab. 107:526-533(2012) [PubMed] [Europe PMC] [Abstract]
Hollak C.E., de Sonnaville E.S., Cassiman D., Linthorst G.E., Groener J.E., Morava E., Wevers R.A., Mannens M., Aerts J.M., Meersseman W., Akkerman E., Niezen-Koning K.E., Mulder M.F., Visser G., Wijburg F.A., Lefeber D., Poorthuis B.J.
Mol. Genet. Metab. 107:526-533(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPDB HIS-91; PRO-105; PRO-163; CYS-230; SER-373; PRO-551 AND ARG-610 DEL, VARIANTS NPDA ARG-250; SER-465; LEU-477 AND HIS-539.
Ref.42
"Identification of seven novel SMPD1 mutations causing Niemann-Pick disease types A and B."
Irun P., Mallen M., Dominguez C., Rodriguez-Sureda V., Alvarez-Sala L.A., Arslan N., Bermejo N., Guerrero C., Perez de Soto I., Villalon L., Giraldo P., Pocovi M.
Clin. Genet. 84:356-361(2013) [PubMed] [Europe PMC] [Abstract]
Irun P., Mallen M., Dominguez C., Rodriguez-Sureda V., Alvarez-Sala L.A., Arslan N., Bermejo N., Guerrero C., Perez de Soto I., Villalon L., Giraldo P., Pocovi M.
Clin. Genet. 84:356-361(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPDA ARG-228 AND ARG-387, VARIANTS NPDB CYS-230; SER-247; HIS-378; TRP-476; SER-492; PHE-599 AND ARG-610 DEL.
Ref.43
"The acid sphingomyelinase sequence variant p.A487V is not associated with decreased levels of enzymatic activity."
Rhein C., Naumann J., Muehle C., Zill P., Adli M., Hegerl U., Hiemke C., Mergl R., Moeller H.J., Reichel M., Kornhuber J.
JIMD Rep. 8:1-6(2013) [PubMed] [Europe PMC] [Abstract]
Rhein C., Naumann J., Muehle C., Zill P., Adli M., Hegerl U., Hiemke C., Mergl R., Moeller H.J., Reichel M., Kornhuber J.
JIMD Rep. 8:1-6(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT NPDB ALA-325, CHARACTERIZATION OF VARIANT VAL-487.
Ref.44
"Spectrum of SMPD1 mutations in Asian-Indian patients with acid sphingomyelinase (ASM)-deficient Niemann-Pick disease."
Ranganath P., Matta D., Bhavani G.S., Wangnekar S., Jain J.M., Verma I.C., Kabra M., Puri R.D., Danda S., Gupta N., Girisha K.M., Sankar V.H., Patil S.J., Ramadevi A.R., Bhat M., Gowrishankar K., Mandal K., Aggarwal S. , Tamhankar P.M., Tilak P., Phadke S.R., Dalal A.
Am. J. Med. Genet. A 170:2719-2730(2016) [PubMed] [Europe PMC] [Abstract]
Ranganath P., Matta D., Bhavani G.S., Wangnekar S., Jain J.M., Verma I.C., Kabra M., Puri R.D., Danda S., Gupta N., Girisha K.M., Sankar V.H., Patil S.J., Ramadevi A.R., Bhat M., Gowrishankar K., Mandal K., Aggarwal S. , Tamhankar P.M., Tilak P., Phadke S.R., Dalal A.
Am. J. Med. Genet. A 170:2719-2730(2016) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ALA-36; PHE-510 AND GLY-605, VARIANTS NPDA ARG-216; CYS-230; SER-255; ARG-319; PRO-324; ARG-343; ARG-363; HIS-391; ARG-393; SER-426; ILE-494; HIS-498; ARG-535 AND HIS-602, VARIANTS NPDB PRO-105; PHE-282; ASP-320; CYS-369; SER-465; LEU-520 AND LYS-549.
Ref.45
"SMPD1 mutation update: database and comprehensive analysis of published and novel variants."
Zampieri S., Filocamo M., Pianta A., Lualdi S., Gort L., Coll M.J., Sinnott R., Geberhiwot T., Bembi B., Dardis A.
Hum. Mutat. 37:139-147(2016) [PubMed] [Europe PMC] [Abstract]
Zampieri S., Filocamo M., Pianta A., Lualdi S., Gort L., Coll M.J., Sinnott R., Geberhiwot T., Bembi B., Dardis A.
Hum. Mutat. 37:139-147(2016) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPDB ILE-258; GLN-476; ASP-577; ARG-598 AND CYS-610, VARIANT NPDA PHE-482 DEL, REVIEW ON VARIANTS.
Ref.46
"Alleged detrimental mutations in the SMPD1 gene in patients with Niemann-Pick disease."
Rhein C., Muehle C., Kornhuber J., Reichel M.
Int. J. Mol. Sci. 16:13649-13652(2015) [PubMed] [Europe PMC] [Abstract]
Rhein C., Muehle C., Kornhuber J., Reichel M.
Int. J. Mol. Sci. 16:13649-13652(2015) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT NPDB ALA-325, CHARACTERIZATION OF VARIANTS ALA-36; VAL-487 AND ARG-508, CATALYTIC ACTIVITY.
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA late-onset lysosomal storage disorder caused by failure to hydrolyze sphingomyelin to ceramide. It results in the accumulation of sphingomyelin and other metabolically related lipids in reticuloendothelial and other cell types throughout the body, leading to cell death. Clinical signs involve only visceral organs. The most constant sign is hepatosplenomegaly which can be associated with pulmonary symptoms. Patients remain free of neurologic manifestations. However, a phenotypic continuum exists between type A (basic neurovisceral) and type B (purely visceral) forms of Niemann-Pick disease, and the intermediate types encompass a cluster of variants combining clinical features of both types A and B. In Niemann-Pick disease type B, onset of the first symptoms occurs in early childhood and patients can survive into adulthood.
See also OMIM:607616| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_060870 | 51 | D → V in NPDB; unknown pathological significance. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_075322 | 91 | C → H in NPDB; requires 2 nucleotide substitutions. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060871 | 94 | C → W in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060873 | 132 | V → A in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains 13% residual enzyme activity. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060874 | 139 | L → P in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_011387 | 159 | C → R in NPDB. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_075323 | 163 | L → P in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060875 | 168 | G → R in NPDB; also in patients with an intermediate form. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060876 | 178 | I → N in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060878 | 198 | A → P in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060879 | 202 | R → C in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060880 | 227 | L → M in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060881 | 227 | L → P in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains no enzyme activity. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060884 | 234 | G → D in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_005058 | 244 | G → R in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060886 | 246 | W → C in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains no enzyme activity. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_005059 | 248 | E → Q in NPDB; 30% residual activity. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_075326 | 258 | T → I in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_077313 | 282 | P → F in NPDB; requires 2 nucleotide substitutions. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060891 | 283 | A → T in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains no enzyme activity. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060892 | 291 | R → H in NPDB; also in patients with an intermediate form; unknown pathological significance. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_068437 | 314 | V → M in NPDB; results in 20% of wild-type activity. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_077315 | 320 | N → D in NPDB; unknown pathological significance. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060896 | 325 | P → A in NPDB; results in 1-4% of wild type activity. 3 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060897 | 332 | P → R in NPDB. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060899 | 359 | A → D in NPDB; sphingomyelinase activity is decreased to 4% of wild-type activity; no effect on protein abundance; no effect on protein localization to lysosome; no effect on protein localization to extracellular space. 3 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_015289 | 373 | P → S in NPDB. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060901 | 378 | R → H in NPDB; reduces enzyme activity; some patients have a NPDA/NPDB intermediate phenotype. 4 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060902 | 378 | R → L in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060903 | 381 | S → P in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_005062 | 385 | N → S in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_005064 | 393 | W → G in NPDB; low sphingomyelin degradation rates. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060905 | 415 | A → V in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_015290 | 423 | H → Y in NPDB; abolishes enzyme activity. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_068438 | 427 | H → R in NPDB; results in loss of activity; the patient also carries mutation H-228 that has sufficient activity to account for the Niemann-Pick disease type B phenotype. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060907 | 433 | C → R in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060908 | 434 | L → P in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060909 | 437 | W → C in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_005065 | 438 | S → R in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_068439 | 453 | A → D in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060911 | 454 | A → V in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060912 | 458 | G → D in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_075328 | 476 | R → Q in NPDB; unknown pathological significance. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060914 | 476 | R → W in NPDB; some patients have a NPDA/NPDB intermediate phenotype. 4 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060915 | 482 | F → L in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060918 | 488 | T → A in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060919 | 490 | Y → N in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_075330 | 492 | G → S in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060920 | 496 | G → S in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060921 | 498 | R → C in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060924 | 516 | H → Q in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060925 | 517 | E → V in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_077324 | 520 | I → L in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_068440 | 522 | N → S in NPDB. 1 Publication Manual assertion based on experiment ini | 1 | |
| Natural variantiVAR_068441 | 525 | Q → H in NPDB; results in 64% of wild-type activity. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_077325 | 549 | N → K in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060928 | 551 | L → P in NPDB. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060929 | 565 | D → Y in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains 6.8% residual enzyme activity. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_075332 | 577 | H → D in NPDB; unknown pathological significance. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060930 | 578 | K → N in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_075333 | 598 | Q → R in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_075334 | 599 | L → F in NPDB; unknown pathological significance. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060933 | 602 | R → P in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains very low enzyme activity. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_075335 | 610 | R → C in NPDB; unknown pathological significance. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_005068 | 610 | Missing in NPDB; nearly abolishes enzyme activity; some patients have a NPDA/NPDB intermediate phenotype. 6 Publications Manual assertion based on experiment ini
| 1 |
Keywords - Diseasei
Disease mutation, Neurodegeneration, Niemann-Pick diseaseOrganism-specific databases
DisGeNET More...DisGeNETi | 6609 |
GeneReviews a resource of expert-authored, peer-reviewed disease descriptions. More...GeneReviewsi | SMPD1 |
MalaCards human disease database More...MalaCardsi | SMPD1 |
| MIMi | 257200 phenotype 607616 phenotype |
Orphanet; a database dedicated to information on rare diseases and orphan drugs More...Orphaneti | 77292 Niemann-Pick disease type A 77293 Niemann-Pick disease type B |
The Pharmacogenetics and Pharmacogenomics Knowledge Base More...PharmGKBi | PA35969 |
Chemistry databases
ChEMBL database of bioactive drug-like small molecules More...ChEMBLi | CHEMBL2760 |
Drug and drug target database More...DrugBanki | DB00381 Amlodipine DB00477 Chlorpromazine DB01151 Desipramine |
Polymorphism and mutation databases
BioMuta curated single-nucleotide variation and disease association database More...BioMutai | SMPD1 |
Domain mapping of disease mutations (DMDM) More...DMDMi | 224471897 |
<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi
Molecule processing
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| <p>This subsection of the ‘PTM / Processing’ section denotes the presence of an N-terminal signal peptide.<p><a href='/help/signal' target='_top'>More...</a></p>Signal peptidei | 1 – 46 | Add BLAST | 46 | |
| <p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_0000002323 | 47 – 631 | Sphingomyelin phosphodiesteraseAdd BLAST | 585 |
Amino acid modifications
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| <p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM / Processing</a> section specifies the position and type of each covalently attached glycan group (mono-, di-, or polysaccharide).<p><a href='/help/carbohyd' target='_top'>More...</a></p>Glycosylationi | 88 | N-linked (GlcNAc...) asparaginePROSITE-ProRule annotation <p>Manual validated information which has been generated by the UniProtKB automatic annotation system.</p> <p><a href="/manual/evidences#ECO:0000255">More...</a></p> Manual assertion according to rulesi Combined sourcesManual assertion inferred from combination of experimental and computational evidencei 2 PublicationsManual assertion based on experiment ini
| 1 | |
| <p>This subsection of the PTM / Processing":/help/ptm_processing_section section describes the positions of cysteine residues participating in disulfide bonds.<p><a href='/help/disulfid' target='_top'>More...</a></p>Disulfide bondi | 91 ↔ 167 | PROSITE-ProRule annotation Manual assertion according to rulesi Combined sourcesManual assertion inferred from combination of experimental and computational evidencei 1 PublicationManual assertion based on experiment ini
| ||
| Disulfide bondi | 94 ↔ 159 | PROSITE-ProRule annotation Manual assertion according to rulesi Combined sourcesManual assertion inferred from combination of experimental and computational evidencei 1 PublicationManual assertion based on experiment ini
| ||
| Disulfide bondi | 122 ↔ 133 | PROSITE-ProRule annotation Manual assertion according to rulesi Combined sourcesManual assertion inferred from combination of experimental and computational evidencei 2 PublicationsManual assertion based on experiment ini
| ||
| Glycosylationi | 177 | N-linked (GlcNAc...) asparaginePROSITE-ProRule annotation Manual assertion according to rulesi Combined sourcesManual assertion inferred from combination of experimental and computational evidencei 2 PublicationsManual assertion based on experiment ini
| 1 | |
| Disulfide bondi | 223 ↔ 228 | PROSITE-ProRule annotation Manual assertion according to rulesi Combined sourcesManual assertion inferred from combination of experimental and computational evidencei 2 PublicationsManual assertion based on experiment ini
| ||
| Disulfide bondi | 229 ↔ 252 | PROSITE-ProRule annotation Manual assertion according to rulesi Combined sourcesManual assertion inferred from combination of experimental and computational evidencei 2 PublicationsManual assertion based on experiment ini
| ||
| Glycosylationi | 337 | N-linked (GlcNAc...) asparaginePROSITE-ProRule annotation Manual assertion according to rulesi Combined sourcesManual assertion inferred from combination of experimental and computational evidencei 2 PublicationsManual assertion based on experiment ini
| 1 | |
| Disulfide bondi | 387 ↔ 433 | PROSITE-ProRule annotation Manual assertion according to rulesi Combined sourcesManual assertion inferred from combination of experimental and computational evidencei 2 PublicationsManual assertion based on experiment ini
| ||
| Glycosylationi | 397 | N-linked (GlcNAc...) asparaginePROSITE-ProRule annotation Manual assertion according to rulesi Combined sourcesManual assertion inferred from combination of experimental and computational evidencei 2 PublicationsManual assertion based on experiment ini
| 1 | |
| Glycosylationi | 505 | N-linked (GlcNAc...) asparagineCombined sources Manual assertion inferred from combination of experimental and computational evidencei 1 PublicationManual assertion based on experiment ini
| 1 | |
| Glycosylationi | 522 | N-linked (GlcNAc...) asparaginePROSITE-ProRule annotation Manual assertion according to rulesi Combined sourcesManual assertion inferred from combination of experimental and computational evidencei 2 PublicationsManual assertion based on experiment ini
| 1 | |
| Disulfide bondi | 586 ↔ 590 | PROSITE-ProRule annotation Manual assertion according to rulesi Combined sourcesManual assertion inferred from combination of experimental and computational evidencei 2 PublicationsManual assertion based on experiment ini
| ||
| Disulfide bondi | 596 ↔ 609 | PROSITE-ProRule annotation Manual assertion according to rulesi Combined sourcesManual assertion inferred from combination of experimental and computational evidencei 2 PublicationsManual assertion based on experiment ini
|
Keywords - PTMi
Disulfide bond, GlycoproteinProteomic databases
MaxQB - The MaxQuant DataBase More...MaxQBi | P17405 |
PaxDb, a database of protein abundance averages across all three domains of life More...PaxDbi | P17405 |
PeptideAtlas More...PeptideAtlasi | P17405 |
PRoteomics IDEntifications database More...PRIDEi | P17405 |
ProteomicsDB human proteome resource More...ProteomicsDBi | 53470 53471 [P17405-2] 53472 [P17405-3] |
PTM databases
iPTMnet integrated resource for PTMs in systems biology context More...iPTMneti | P17405 |
Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat. More...PhosphoSitePlusi | P17405 |
<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni
Gene expression databases
Bgee dataBase for Gene Expression Evolution More...Bgeei | ENSG00000166311 Expressed in 212 organ(s), highest expression level in right lobe of liver |
CleanEx database of gene expression profiles More...CleanExi | HS_SMPD1 |
ExpressionAtlas, Differential and Baseline Expression More...ExpressionAtlasi | P17405 baseline and differential |
Genevisible search portal to normalized and curated expression data from Genevestigator More...Genevisiblei | P17405 HS |
<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni
<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei
Monomer.1 Publication
Manual assertion based on experiment ini
- Ref.14"Structure of human acid sphingomyelinase reveals the role of the saposin domain in activating substrate hydrolysis."
Xiong Z.J., Huang J., Poda G., Pomes R., Prive G.G.
J. Mol. Biol. 428:3026-3042(2016) [PubMed] [Europe PMC] [Abstract]Cited for: X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 47-629 OF MUTANT SER-631 IN COMPLEX WITH ZINC, CATALYTIC ACTIVITY, GLYCOSYLATION AT ASN-88; ASN-177; ASN-337; ASN-397; ASN-505 AND ASN-522, DISULFIDE BONDS, SUBUNIT.
<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi
| With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| CASP7 | P55210 | 6 | EBI-7095800,EBI-523958 |
Protein-protein interaction databases
The Biological General Repository for Interaction Datasets (BioGrid) More...BioGridi | 112493, 14 interactors |
Protein interaction database and analysis system More...IntActi | P17405, 7 interactors |
Molecular INTeraction database More...MINTi | P17405 |
STRING: functional protein association networks More...STRINGi | 9606.ENSP00000340409 |
Chemistry databases
BindingDB database of measured binding affinities More...BindingDBi | P17405 |
<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more detailsHide details| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| <p>This subsection of the ‘Structure’ section is used to indicate the positions of experimentally determined helical regions within the protein sequence.<p><a href='/help/helix' target='_top'>More...</a></p>Helixi | 87 – 89 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 3 | |
| Helixi | 90 – 105 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 16 | |
| Helixi | 108 – 124 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 17 | |
| Helixi | 130 – 150 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 21 | |
| <p>This subsection of the ‘Structure’ section is used to indicate the positions of experimentally determined hydrogen-bonded turns within the protein sequence. These elements correspond to the DSSP secondary structure code ‘T’.<p><a href='/help/turn' target='_top'>More...</a></p>Turni | 151 – 153 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 3 | |
| Helixi | 161 – 163 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 3 | |
| Turni | 165 – 167 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 3 | |
| <p>This subsection of the ‘Structure’ section is used to indicate the positions of experimentally determined beta strands within the protein sequence.<p><a href='/help/strand' target='_top'>More...</a></p>Beta strandi | 200 – 206 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 7 | |
| Beta strandi | 224 – 227 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 4 | |
| Beta strandi | 249 – 251 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 3 | |
| Helixi | 256 – 264 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 9 | |
| Helixi | 267 – 269 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 3 | |
| Beta strandi | 273 – 277 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 5 | |
| Helixi | 291 – 309 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 19 | |
| Beta strandi | 314 – 316 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 3 | |
| Beta strandi | 322 – 325 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 4 | |
| Beta strandi | 336 – 340 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 5 | |
| Helixi | 341 – 350 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 10 | |
| Turni | 352 – 354 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 3 | |
| Helixi | 357 – 366 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 10 | |
| Beta strandi | 369 – 374 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 6 | |
| Beta strandi | 377 – 381 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 5 | |
| Helixi | 384 – 387 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 4 | |
| Helixi | 392 – 395 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 4 | |
| Helixi | 401 – 403 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 3 | |
| Helixi | 404 – 418 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 15 | |
| Beta strandi | 421 – 425 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 5 | |
| Helixi | 430 – 432 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 3 | |
| Helixi | 435 – 447 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 13 | |
| Turni | 448 – 451 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 4 | |
| Beta strandi | 452 – 457 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 6 | |
| Beta strandi | 464 – 469 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 6 | |
| Turni | 471 – 473 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 3 | |
| Beta strandi | 476 – 483 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 8 | |
| Turni | 490 – 492 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 3 | |
| Beta strandi | 496 – 503 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 8 | |
| Beta strandi | 513 – 520 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 8 | |
| Helixi | 523 – 526 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 4 | |
| Beta strandi | 536 – 540 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 5 | |
| Helixi | 541 – 545 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 5 | |
| Helixi | 552 – 563 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 12 | |
| Helixi | 566 – 576 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 11 | |
| Turni | 577 – 579 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 3 | |
| Helixi | 588 – 599 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 12 | |
| Beta strandi | 602 – 604 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 3 | |
| Helixi | 606 – 609 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 4 | |
| Turni | 610 – 612 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 3 |
3D structure databases
Protein Model Portal of the PSI-Nature Structural Biology Knowledgebase More...ProteinModelPortali | P17405 |
SWISS-MODEL Repository - a database of annotated 3D protein structure models More...SMRi | P17405 |
Database of comparative protein structure models More...ModBasei | Search... |
MobiDB: a database of protein disorder and mobility annotations More...MobiDBi | Search... |
<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi
Domains and Repeats
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| <p>This subsection of the <a href="http://www.uniprot.org/help/family_and_domains_section">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini | 87 – 171 | Saposin B-typePROSITE-ProRule annotation Manual assertion according to rulesi Add BLAST | 85 |
<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi
Belongs to the acid sphingomyelinase family.Curated
Keywords - Domaini
SignalPhylogenomic databases
evolutionary genealogy of genes: Non-supervised Orthologous Groups More...eggNOGi | KOG3770 Eukaryota ENOG410YYPB LUCA |
The HOVERGEN Database of Homologous Vertebrate Genes More...HOVERGENi | HBG004288 |
InParanoid: Eukaryotic Ortholog Groups More...InParanoidi | P17405 |
KEGG Orthology (KO) More...KOi | K12350 |
Database of Orthologous Groups More...OrthoDBi | EOG091G03M6 |
Database for complete collections of gene phylogenies More...PhylomeDBi | P17405 |
TreeFam database of animal gene trees More...TreeFami | TF313674 |
Family and domain databases
Gene3D Structural and Functional Annotation of Protein Families More...Gene3Di | 3.60.21.10, 1 hit |
Integrated resource of protein families, domains and functional sites More...InterProi | View protein in InterPro IPR004843 Calcineurin-like_PHP_ApaH IPR029052 Metallo-depent_PP-like IPR011001 Saposin-like IPR008139 SaposinB_dom IPR011160 Sphingomy_PDE |
Pfam protein domain database More...Pfami | View protein in Pfam PF00149 Metallophos, 1 hit |
PIRSF; a whole-protein classification database More...PIRSFi | PIRSF000948 Sphingomy_PDE, 1 hit |
Simple Modular Architecture Research Tool; a protein domain database More...SMARTi | View protein in SMART SM00741 SapB, 1 hit |
Superfamily database of structural and functional annotation More...SUPFAMi | SSF47862 SSF47862, 1 hit |
PROSITE; a protein domain and family database More...PROSITEi | View protein in PROSITE PS50015 SAP_B, 1 hit |
<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>.<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (4+)i
<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.
<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.
This entry describes 4 <p>This subsection of the ‘Sequence’ section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basketAdded to basketThis entry has 4 described isoforms and 5 potential isoforms that are <p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>computationally mapped.iShow all
Isoform 1 (identifier: P17405-1) [UniParc]FASTAAdd to basketAdded to basket
Also known as: ASM-1
This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
« Hide
10 20 30 40 50
MPRYGASLRQ SCPRSGREQG QDGTAGAPGL LWMGLVLALA LALALALALS
60 70 80 90 100
DSRVLWAPAE AHPLSPQGHP ARLHRIVPRL RDVFGWGNLT CPICKGLFTA
110 120 130 140 150
INLGLKKEPN VARVGSVAIK LCNLLKIAPP AVCQSIVHLF EDDMVEVWRR
160 170 180 190 200
SVLSPSEACG LLLGSTCGHW DIFSSWNISL PTVPKPPPKP PSPPAPGAPV
210 220 230 240 250
SRILFLTDLH WDHDYLEGTD PDCADPLCCR RGSGLPPASR PGAGYWGEYS
260 270 280 290 300
KCDLPLRTLE SLLSGLGPAG PFDMVYWTGD IPAHDVWHQT RQDQLRALTT
310 320 330 340 350
VTALVRKFLG PVPVYPAVGN HESTPVNSFP PPFIEGNHSS RWLYEAMAKA
360 370 380 390 400
WEPWLPAEAL RTLRIGGFYA LSPYPGLRLI SLNMNFCSRE NFWLLINSTD
410 420 430 440 450
PAGQLQWLVG ELQAAEDRGD KVHIIGHIPP GHCLKSWSWN YYRIVARYEN
460 470 480 490 500
TLAAQFFGHT HVDEFEVFYD EETLSRPLAV AFLAPSATTY IGLNPGYRVY
510 520 530 540 550
QIDGNYSGSS HVVLDHETYI LNLTQANIPG AIPHWQLLYR ARETYGLPNT
560 570 580 590 600
LPTAWHNLVY RMRGDMQLFQ TFWFLYHKGH PPSEPCGTPC RLATLCAQLS
610 620 630
ARADSPALCR HLMPDGSLPE AQSLWPRPLF C
Note: Most abundant (90%).
Show »Length:631
Mass (Da):69,936
Last modified:September 12, 2018 - v5
<p>The checksum is a form of redundancy check that is calculated
from the sequence. It is useful for tracking sequence updates.</p>
<p>It should be noted that while, in theory, two different sequences could
have the same checksum value, the likelihood that this would happen
is extremely low.</p>
<p>However UniProtKB may contain entries with identical sequences in case
of multiple genes (paralogs).</p>
<p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64)
using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1.
The algorithm is described in the ISO 3309 standard.
</p>
<p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br />
<strong>Cyclic redundancy and other checksums</strong><br />
<a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p>
Checksum:iF229709F6A9B0E9E
Isoform 2 (identifier: P17405-2) [UniParc]FASTAAdd to basketAdded to basket
Also known as: ASM-2
The sequence of this isoform differs from the canonical sequence as follows:
365-376: IGGFYALSPYPG → YLSSVETQEGKR
377-420: Missing.
« Hide
10 20 30 40 50
MPRYGASLRQ SCPRSGREQG QDGTAGAPGL LWMGLVLALA LALALALALS
60 70 80 90 100
DSRVLWAPAE AHPLSPQGHP ARLHRIVPRL RDVFGWGNLT CPICKGLFTA
110 120 130 140 150
INLGLKKEPN VARVGSVAIK LCNLLKIAPP AVCQSIVHLF EDDMVEVWRR
160 170 180 190 200
SVLSPSEACG LLLGSTCGHW DIFSSWNISL PTVPKPPPKP PSPPAPGAPV
210 220 230 240 250
SRILFLTDLH WDHDYLEGTD PDCADPLCCR RGSGLPPASR PGAGYWGEYS
260 270 280 290 300
KCDLPLRTLE SLLSGLGPAG PFDMVYWTGD IPAHDVWHQT RQDQLRALTT
310 320 330 340 350
VTALVRKFLG PVPVYPAVGN HESTPVNSFP PPFIEGNHSS RWLYEAMAKA
360 370 380 390 400
WEPWLPAEAL RTLRYLSSVE TQEGKRKVHI IGHIPPGHCL KSWSWNYYRI
410 420 430 440 450
VARYENTLAA QFFGHTHVDE FEVFYDEETL SRPLAVAFLA PSATTYIGLN
460 470 480 490 500
PGYRVYQIDG NYSGSSHVVL DHETYILNLT QANIPGAIPH WQLLYRARET
510 520 530 540 550
YGLPNTLPTA WHNLVYRMRG DMQLFQTFWF LYHKGHPPSE PCGTPCRLAT
560 570 580
LCAQLSARAD SPALCRHLMP DGSLPEAQSL WPRPLFC
Note: Intermediate abundance (10%).
Show »Isoform 3 (identifier: P17405-3) [UniParc]FASTAAdd to basketAdded to basket
Also known as: ASM-3
The sequence of this isoform differs from the canonical sequence as follows:
365-420: Missing.
« Hide
10 20 30 40 50
MPRYGASLRQ SCPRSGREQG QDGTAGAPGL LWMGLVLALA LALALALALS
60 70 80 90 100
DSRVLWAPAE AHPLSPQGHP ARLHRIVPRL RDVFGWGNLT CPICKGLFTA
110 120 130 140 150
INLGLKKEPN VARVGSVAIK LCNLLKIAPP AVCQSIVHLF EDDMVEVWRR
160 170 180 190 200
SVLSPSEACG LLLGSTCGHW DIFSSWNISL PTVPKPPPKP PSPPAPGAPV
210 220 230 240 250
SRILFLTDLH WDHDYLEGTD PDCADPLCCR RGSGLPPASR PGAGYWGEYS
260 270 280 290 300
KCDLPLRTLE SLLSGLGPAG PFDMVYWTGD IPAHDVWHQT RQDQLRALTT
310 320 330 340 350
VTALVRKFLG PVPVYPAVGN HESTPVNSFP PPFIEGNHSS RWLYEAMAKA
360 370 380 390 400
WEPWLPAEAL RTLRKVHIIG HIPPGHCLKS WSWNYYRIVA RYENTLAAQF
410 420 430 440 450
FGHTHVDEFE VFYDEETLSR PLAVAFLAPS ATTYIGLNPG YRVYQIDGNY
460 470 480 490 500
SGSSHVVLDH ETYILNLTQA NIPGAIPHWQ LLYRARETYG LPNTLPTAWH
510 520 530 540 550
NLVYRMRGDM QLFQTFWFLY HKGHPPSEPC GTPCRLATLC AQLSARADSP
560 570
ALCRHLMPDG SLPEAQSLWP RPLFC
Note: Low abundance (<1%).
Show »Isoform 4 (identifier: P17405-4) [UniParc]FASTAAdd to basketAdded to basket
The sequence of this isoform differs from the canonical sequence as follows:
106-106: Missing.
« Hide
Show »10 20 30 40 50
MPRYGASLRQ SCPRSGREQG QDGTAGAPGL LWMGLVLALA LALALALALS
60 70 80 90 100
DSRVLWAPAE AHPLSPQGHP ARLHRIVPRL RDVFGWGNLT CPICKGLFTA
110 120 130 140 150
INLGLKEPNV ARVGSVAIKL CNLLKIAPPA VCQSIVHLFE DDMVEVWRRS
160 170 180 190 200
VLSPSEACGL LLGSTCGHWD IFSSWNISLP TVPKPPPKPP SPPAPGAPVS
210 220 230 240 250
RILFLTDLHW DHDYLEGTDP DCADPLCCRR GSGLPPASRP GAGYWGEYSK
260 270 280 290 300
CDLPLRTLES LLSGLGPAGP FDMVYWTGDI PAHDVWHQTR QDQLRALTTV
310 320 330 340 350
TALVRKFLGP VPVYPAVGNH ESTPVNSFPP PFIEGNHSSR WLYEAMAKAW
360 370 380 390 400
EPWLPAEALR TLRIGGFYAL SPYPGLRLIS LNMNFCSREN FWLLINSTDP
410 420 430 440 450
AGQLQWLVGE LQAAEDRGDK VHIIGHIPPG HCLKSWSWNY YRIVARYENT
460 470 480 490 500
LAAQFFGHTH VDEFEVFYDE ETLSRPLAVA FLAPSATTYI GLNPGYRVYQ
510 520 530 540 550
IDGNYSGSSH VVLDHETYIL NLTQANIPGA IPHWQLLYRA RETYGLPNTL
560 570 580 590 600
PTAWHNLVYR MRGDMQLFQT FWFLYHKGHP PSEPCGTPCR LATLCAQLSA
610 620 630
RADSPALCRH LMPDGSLPEA QSLWPRPLFC
Computationally mapped potential isoform sequencesi
There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket| Entry | Entry name | Protein names | Gene names | Length | Annotation | ||
|---|---|---|---|---|---|---|---|
| E9PQT3 | E9PQT3_HUMAN | Sphingomyelin phosphodiesterase Sphingomyelin phosphodiesterase | SMPD1 | 402 | Annotation score: Annotation score:1 out of 5 <p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p> | ||
| G3V1E1 | G3V1E1_HUMAN | Sphingomyelin phosphodiesterase 1, ... Sphingomyelin phosphodiesterase 1, acid lysosomal (Acid sphingomyelinase), isoform CRA_d | SMPD1 hCG_24080 | 366 | Annotation score: Annotation score:1 out of 5 <p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p> | ||
| E9PPK6 | E9PPK6_HUMAN | Sphingomyelin phosphodiesterase Sphingomyelin phosphodiesterase | SMPD1 | 171 | Annotation score: Annotation score:1 out of 5 <p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p> | ||
| H0YEP5 | H0YEP5_HUMAN | Sphingomyelin phosphodiesterase Sphingomyelin phosphodiesterase | SMPD1 | 317 | Annotation score: Annotation score:1 out of 5 <p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p> | ||
| E9PL59 | E9PL59_HUMAN | Sphingomyelin phosphodiesterase Sphingomyelin phosphodiesterase | SMPD1 | 52 | Annotation score: Annotation score:1 out of 5 <p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p> |
Experimental Info
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| <p>This subsection of the ‘Sequence’ section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti | 270 | G → D in BAF85077 (PubMed:14702039).Curated | 1 |
<p>This subsection of the ‘Sequence’ section provides information on polymorphic variants. If the variant is associated with a disease state, the description of the latter can be found in the <a href="http://www.uniprot.org/manual/involvement_in_disease">'Involvement in disease'</a> subsection.<p><a href='/help/polymorphism' target='_top'>More...</a></p>Polymorphismi
A common polymorphism arises from a variable number of hexanucleotide repeat sequence within the signal peptide region.
Natural variant
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_080641 | 36 – 39 | Missing 2 Publications Manual assertion based on experiment ini
| 4 | |
| Natural variantiVAR_038191 | 36 | V → A Polymorphism; does not affect enzymatic activity. 3 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_080642 | 48 – 49 | Missing 4 Publications Manual assertion based on experiment ini
| 2 | |
| Natural variantiVAR_060870 | 51 | D → V in NPDB; unknown pathological significance. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_075322 | 91 | C → H in NPDB; requires 2 nucleotide substitutions. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060871 | 94 | C → W in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060872 | 105 | L → P in NPDA and NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains very low enzyme activity. 5 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060873 | 132 | V → A in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains 13% residual enzyme activity. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060874 | 139 | L → P in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_011387 | 159 | C → R in NPDB. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_075323 | 163 | L → P in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060875 | 168 | G → R in NPDB; also in patients with an intermediate form. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060876 | 178 | I → N in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060877 | 186 | P → L in NPDA; reduces enzyme activity; intermediate form with clinical features of both Niemann-Pick disease types A and B. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060878 | 198 | A → P in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060879 | 202 | R → C in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_068435 | 211 | W → R in NPDA; results in less than 0.5% of wild-type activity. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_077311 | 216 | L → R in NPDA. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060880 | 227 | L → M in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060881 | 227 | L → P in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains no enzyme activity. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_075324 | 228 | C → R in NPDA. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060882 | 230 | R → C in NPDB and NPDA; some patients have a NPDA/NPDB intermediate phenotype. 5 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060883 | 230 | R → H in NPDA; intermediate form with clinical features of both Niemann-Pick disease types A and B. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060884 | 234 | G → D in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060885 | 243 | A → V in NPDA; intermediate form with clinical features of both Niemann-Pick disease types A and B. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_005058 | 244 | G → R in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060886 | 246 | W → C in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains no enzyme activity. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_075325 | 247 | G → D in NPDA; severe decrease in activity; the mutant is highly unstable. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060887 | 247 | G → S in NPDA and NPDB. 4 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060888 | 248 | E → K in NPDA. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_005059 | 248 | E → Q in NPDB; 30% residual activity. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_015287 | 250 | S → R in NPDA and NPDB; also found in patients with an intermediate form. 4 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060889 | 253 | D → E in NPDA; strongly reduces enzyme activity; intermediate form with clinical features of both Niemann-Pick disease types A and B. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_068436 | 253 | D → H in NPDA; results in loss of activity. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_077312 | 255 | P → S in NPDA. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_075326 | 258 | T → I in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060890 | 280 | D → A in NPDA; strongly reduces enzyme activity; intermediate form with clinical features of both Niemann-Pick disease types A and B. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_077313 | 282 | P → F in NPDB; requires 2 nucleotide substitutions. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060891 | 283 | A → T in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains no enzyme activity. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060892 | 291 | R → H in NPDB; also in patients with an intermediate form; unknown pathological significance. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060893 | 294 | Q → K in NPDA; strongly reduces enzyme activity; intermediate form with clinical features of both Niemann-Pick disease types A and B. 3 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060894 | 296 | R → Q1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_005060 | 304 | L → P in NPDA; in 23% of NPDA Ashkenazi Jewish patients; abolishes enzyme activity. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_068437 | 314 | V → M in NPDB; results in 20% of wild-type activity. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060895 |