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Entry version 221 (02 Jun 2021)
Sequence version 5 (12 Sep 2018)
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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>

<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, PubMed:25339683, PubMed:33163980, PubMed:12563314).

Exists as two enzymatic forms that arise from alternative trafficking of a single protein precursor, one that is targeted to the endolysosomal compartment, whereas the other is released extracellularly (PubMed:21098024, PubMed:9660788, PubMed:20807762).

However, in response to various forms of stress, lysosomal exocytosis may represent a major source of the secretory form (PubMed:20530211, PubMed:12563314, PubMed:20807762, PubMed:9393854, PubMed:22573858).

Curated13 Publications

In the lysosomes, converts sphingomyelin to ceramide (PubMed:20807762, PubMed:21098024).

Plays an important role in the export of cholesterol from the intraendolysosomal membranes (PubMed:25339683).

Also has phospholipase C activities toward 1,2-diacylglycerolphosphocholine and 1,2-diacylglycerolphosphoglycerol (PubMed:25339683).

Modulates stress-induced apoptosis through the production of ceramide (PubMed:8706124).

4 Publications

When secreted, modulates cell signaling with its ability to reorganize the plasma membrane by converting sphingomyelin to ceramide (PubMed:12563314, PubMed:20807762, PubMed:17303575).

Secreted form is increased in response to stress and inflammatory mediators such as IL1B, IFNG or TNF as well as upon infection with bacteria and viruses. Produces the release of ceramide in the outer leaflet of the plasma membrane playing a central role in host defense (PubMed:12563314, PubMed:20807762, PubMed:9393854).

Ceramide reorganizes these rafts into larger signaling platforms that are required to internalize P. aeruginosa, induce apoptosis and regulate the cytokine response in infected cells (PubMed:12563314).

In wounded cells, the lysosomal form is released extracellularly in the presence of Ca2+ and promotes endocytosis and plasma membrane repair (PubMed:20530211).

5 Publications

Lacks residues that bind the cofactor Zn2+ and has no enzyme activity.

Curated1 Publication

Lacks residues that bind the cofactor Zn2+ and has no enzyme activity.

Curated1 Publication

(Microbial infection) Secretion is activated by bacteria such as P. aeruginos, N. gonorrhoeae and others, this activation results in the release of ceramide in the outer leaflet of the plasma membrane which facilitates the infection.

1 Publication2 Publications

(Microbial infection) Secretion is activated by human coronaviruses SARS-CoV and SARS-CoV-2 as well as Zaire ebolavirus, this activation results in the release of ceramide in the outer leaflet of the plasma membrane which facilitates the infection.

2 Publications

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

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

<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+2 PublicationsNote: Binds 2 Zn2+ ions per subunit (PubMed:27349982, PubMed:27725636).4 Publications

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>Activity regulationi

Hydrolysis of liposomal sphingomyelin is stimulated by incorporation of diacylglycerol (DAG), ceramide and free fatty acids into the liposomal membranes (PubMed:25339683). Phosphatidylcholine hydrolysis is inhibited by incorporation of cholesterol, ceramide, DAG, monoacylglycerol and fatty acids (PubMed:25339683). Antidepressants, namely amitriptyline, imipramine, desipramine, fluoxetine, sertraline, escitalopram, and maprotiline inhibit sphingomyelin phosphodiesterase activity (PubMed:33163980, PubMed:22573858).3 Publications
(Microbial infection) The secretory form is activated by P. aeruginosa, this activation results in the release of ceramide in the outer leaflet of the plasma membrane.1 Publication
(Microbial infection) The secretory form is activated by human coronavirus SARS-CoV-2, this activation results in the release of ceramide in the outer leaflet of the plasma membrane.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> 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 bindingi208Zinc 1Combined sources1 Publication1
Metal bindingi210Zinc 1; via tele nitrogenCombined sources1 Publication1
Metal bindingi280Zinc 1Combined sources1 Publication1
Metal bindingi280Zinc 2Combined sources1 Publication1
Metal bindingi320Zinc 2Combined sources1 Publication1
Metal bindingi427Zinc 2; via tele nitrogenCombined sources1 Publication1
Metal bindingi459Zinc 2; via pros nitrogenCombined sources1 Publication1
Metal bindingi461Zinc 1; via tele nitrogenCombined sources1 Publication1

<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

GO - Biological processi

<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 functionGlycosidase, Hydrolase
LigandMetal-binding, Zinc

Enzyme and pathway databases

BRENDA Comprehensive Enzyme Information System

More...
BRENDAi
3.1.4.12, 2681

Pathway Commons web resource for biological pathway data

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PathwayCommonsi
P17405

Reactome - a knowledgebase of biological pathways and processes

More...
Reactomei
R-HSA-1660662, Glycosphingolipid metabolism

SIGNOR Signaling Network Open Resource

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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%5Fand%5Ftaxonomy%5Fsection">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 phosphodiesteraseCurated (EC:3.1.4.126 Publications)
Alternative name(s):
Acid sphingomyelinase2 Publications
Short name:
aSMase
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">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:SMPD1Imported
Synonyms:ASM1 Publication
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">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>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">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 identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">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
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes%5Fmanual">proteome</a> can consist of several components.<br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 11

Organism-specific databases

Human Gene Nomenclature Database

More...
HGNCi
HGNC:11120, SMPD1

Online Mendelian Inheritance in Man (OMIM)

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MIMi
607608, gene

neXtProt; the human protein knowledge platform

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neXtProti
NX_P17405

Eukaryotic Pathogen, Vector and Host Database Resources

More...
VEuPathDBi
HostDB:ENSG00000166311.9

<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

Keywords - Cellular componenti

Lipid droplet, 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)19 Publications
The disease is caused by variants 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.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
<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_060872105L → P in NPDA and NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains very low enzyme activity. 5 PublicationsCorresponds to variant dbSNP:rs751269562EnsemblClinVar.1
Natural variantiVAR_060877186P → L in NPDA; reduces enzyme activity; intermediate form with clinical features of both Niemann-Pick disease types A and B. 1 PublicationCorresponds to variant dbSNP:rs1057517195EnsemblClinVar.1
Natural variantiVAR_068435211W → R in NPDA; results in less than 0.5% of wild-type activity. 1 Publication1
Natural variantiVAR_077311216L → R in NPDA. 1 Publication1
Natural variantiVAR_075324228C → R in NPDA. 1 PublicationCorresponds to variant dbSNP:rs1564923612EnsemblClinVar.1
Natural variantiVAR_060882230R → C in NPDB and NPDA; some patients have a NPDA/NPDB intermediate phenotype. 5 PublicationsCorresponds to variants dbSNP:rs989639224 and dbSNP:rs1057516483EnsemblClinVarEnsembl.1
Natural variantiVAR_060883230R → H in NPDA; intermediate form with clinical features of both Niemann-Pick disease types A and B. 1 PublicationCorresponds to variant dbSNP:rs141387770EnsemblClinVar.1
Natural variantiVAR_060885243A → V in NPDA; intermediate form with clinical features of both Niemann-Pick disease types A and B. 1 PublicationCorresponds to variant dbSNP:rs1291958011Ensembl.1
Natural variantiVAR_075325247G → D in NPDA; severe decrease in activity; the mutant is highly unstable. 1 PublicationCorresponds to variant dbSNP:rs1590739350EnsemblClinVar.1
Natural variantiVAR_060887247G → S in NPDA and NPDB. 4 PublicationsCorresponds to variant dbSNP:rs587779408EnsemblClinVar.1
Natural variantiVAR_060888248E → K in NPDA. 1 PublicationCorresponds to variant dbSNP:rs200763423EnsemblClinVar.1
Natural variantiVAR_015287250S → R in NPDA and NPDB; also found in patients with an intermediate form. 4 PublicationsCorresponds to variant dbSNP:rs750779804EnsemblClinVar.1
Natural variantiVAR_060889253D → E in NPDA; strongly reduces enzyme activity; intermediate form with clinical features of both Niemann-Pick disease types A and B. 1 Publication1
Natural variantiVAR_068436253D → H in NPDA; results in loss of activity. 1 PublicationCorresponds to variant dbSNP:rs398123479EnsemblClinVar.1
Natural variantiVAR_077312255P → S in NPDA. 1 Publication1
Natural variantiVAR_060890280D → A in NPDA; strongly reduces enzyme activity; intermediate form with clinical features of both Niemann-Pick disease types A and B. 1 Publication1
Natural variantiVAR_060893294Q → K in NPDA; strongly reduces enzyme activity; intermediate form with clinical features of both Niemann-Pick disease types A and B. 3 PublicationsCorresponds to variant dbSNP:rs120074128EnsemblClinVar.1
Natural variantiVAR_005060304L → P in NPDA; in 23% of NPDA Ashkenazi Jewish patients; abolishes enzyme activity. 2 PublicationsCorresponds to variant dbSNP:rs120074124EnsemblClinVar.1
Natural variantiVAR_060895315Y → H in NPDA. 1 Publication1
Natural variantiVAR_077314319G → R in NPDA. 1 PublicationCorresponds to variant dbSNP:rs757934797EnsemblClinVar.1
Natural variantiVAR_015288321H → Y in NPDA. 2 Publications1
Natural variantiVAR_077316324T → P in NPDA; unknown pathological significance. 1 Publication1
Natural variantiVAR_060898343L → P in NPDA; strongly reduces enzyme activity; intermediate form with clinical features of both Niemann-Pick disease types A and B. 2 Publications1
Natural variantiVAR_077317343L → R in NPDA. 1 Publication1
Natural variantiVAR_077318363L → R in NPDA; unknown pathological significance. 1 Publication1
Natural variantiVAR_060900369Y → C in NPDA. 2 PublicationsCorresponds to variant dbSNP:rs372287825EnsemblClinVar.1
Natural variantiVAR_005061384M → I in NPDA and NPDB. 2 PublicationsCorresponds to variant dbSNP:rs120074121EnsemblClinVar.1
Natural variantiVAR_075327387C → R in NPDA. 1 Publication1
Natural variantiVAR_077319391N → H in NPDA. 1 Publication1
Natural variantiVAR_005063391N → T in NPDA. 1 Publication1
Natural variantiVAR_060904392Missing in NPDA. 1 Publication1
Natural variantiVAR_077320393W → R in NPDA; intermediate form. 1 Publication1
Natural variantiVAR_060906423H → R in NPDA. 1 PublicationCorresponds to variant dbSNP:rs767492080Ensembl.1
Natural variantiVAR_077321426G → S in NPDA. 1 PublicationCorresponds to variant dbSNP:rs1554935136EnsemblClinVar.1
Natural variantiVAR_011388448Y → C in NPDA. 1 PublicationCorresponds to variant dbSNP:rs747143343EnsemblClinVar.1
Natural variantiVAR_060910452L → P in NPDA. 1 Publication1
Natural variantiVAR_015291465F → S in NPDA. 2 PublicationsCorresponds to variant dbSNP:rs1319643225Ensembl.1
Natural variantiVAR_060913469Y → S in NPDA. 1 PublicationCorresponds to variant dbSNP:rs267607074EnsemblClinVar.1
Natural variantiVAR_015292477P → L in NPDA and NPDB. 4 PublicationsCorresponds to variant dbSNP:rs753508874EnsemblClinVar.1
Natural variantiVAR_075329482Missing in NPDA; unknown pathological significance. 1 Publication1
Natural variantiVAR_060916484A → E in NPDA. 1 PublicationCorresponds to variant dbSNP:rs267607075EnsemblClinVar.1
Natural variantiVAR_077322494N → I in NPDA; intermediate form. 1 Publication1
Natural variantiVAR_060922498R → H in NPDA. 2 PublicationsCorresponds to variant dbSNP:rs120074117EnsemblClinVar.1
Natural variantiVAR_005066498R → L in NPDA; in 32% of NPDA Ashkenazi Jewish patients; nearly abolishes enzyme activity. 4 PublicationsCorresponds to variant dbSNP:rs120074117EnsemblClinVar.1
Natural variantiVAR_060926519Y → C in NPDA. 1 PublicationCorresponds to variant dbSNP:rs371837210EnsemblClinVar.1
Natural variantiVAR_060927535W → R in NPDB and NPDA; also in patients with an intermediate form. 3 PublicationsCorresponds to variant dbSNP:rs1554935555EnsemblClinVar.1
Natural variantiVAR_015293539Y → H in NPDA. 2 Publications1
Natural variantiVAR_075331572F → L in NPDA; results in decreased activity; decreased stability. 1 Publication1
Natural variantiVAR_005067579G → S in NPDA; impairs enzyme activity; also in patients with an intermediate form. 2 PublicationsCorresponds to variant dbSNP:rs120074119EnsemblClinVar.1
Natural variantiVAR_060931594Missing in NPDA. 1 Publication1
Natural variantiVAR_060932602R → H in NPDB and NPDA; expresses protein level comparable to wild-type SMPD1 expressing cells; retains about 10% residual enzyme activity; loss of location to lysosome. 4 PublicationsCorresponds to variant dbSNP:rs370129081EnsemblClinVar.1
Niemann-Pick disease B (NPDB)25 Publications
The disease is caused by variants 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.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06087051D → V in NPDB; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs748589919Ensembl.1
Natural variantiVAR_07532291C → H in NPDB; requires 2 nucleotide substitutions. 1 Publication1
Natural variantiVAR_06087194C → W in NPDB. 1 Publication1
Natural variantiVAR_060872105L → P in NPDA and NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains very low enzyme activity. 5 PublicationsCorresponds to variant dbSNP:rs751269562EnsemblClinVar.1
Natural variantiVAR_060873132V → A in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains 13% residual enzyme activity. 1 Publication1
Natural variantiVAR_060874139L → P in NPDB. 1 PublicationCorresponds to variant dbSNP:rs797044797EnsemblClinVar.1
Natural variantiVAR_011387159C → R in NPDB. 2 PublicationsCorresponds to variant dbSNP:rs727504166EnsemblClinVar.1
Natural variantiVAR_075323163L → P in NPDB. 1 PublicationCorresponds to variant dbSNP:rs780134410EnsemblClinVar.1
Natural variantiVAR_060875168G → R in NPDB; also in patients with an intermediate form. 2 Publications1
Natural variantiVAR_060876178I → N in NPDB. 1 PublicationCorresponds to variant dbSNP:rs749780769EnsemblClinVar.1
Natural variantiVAR_060878198A → P in NPDB. 1 PublicationCorresponds to variant dbSNP:rs797044798EnsemblClinVar.1
Natural variantiVAR_060879202R → C in NPDB. 1 PublicationCorresponds to variant dbSNP:rs749595299EnsemblClinVar.1
Natural variantiVAR_060880227L → M in NPDB. 1 Publication1
Natural variantiVAR_060881227L → P in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains no enzyme activity. 2 PublicationsCorresponds to variant dbSNP:rs764317969EnsemblClinVar.1
Natural variantiVAR_060882230R → C in NPDB and NPDA; some patients have a NPDA/NPDB intermediate phenotype. 5 PublicationsCorresponds to variants dbSNP:rs989639224 and dbSNP:rs1057516483EnsemblClinVarEnsembl.1
Natural variantiVAR_060884234G → D in NPDB. 1 Publication1
Natural variantiVAR_005058244G → R in NPDB. 1 PublicationCorresponds to variant dbSNP:rs120074122EnsemblClinVar.1
Natural variantiVAR_060886246W → C in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains no enzyme activity. 2 Publications1
Natural variantiVAR_060887247G → S in NPDA and NPDB. 4 PublicationsCorresponds to variant dbSNP:rs587779408EnsemblClinVar.1
Natural variantiVAR_005059248E → Q in NPDB; 30% residual activity. 1 PublicationCorresponds to variant dbSNP:rs200763423EnsemblClinVar.1
Natural variantiVAR_015287250S → R in NPDA and NPDB; also found in patients with an intermediate form. 4 PublicationsCorresponds to variant dbSNP:rs750779804EnsemblClinVar.1
Natural variantiVAR_075326258T → I in NPDB. 1 Publication1
Natural variantiVAR_077313282P → F in NPDB; requires 2 nucleotide substitutions. 1 Publication1
Natural variantiVAR_060891283A → T in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains no enzyme activity. 2 PublicationsCorresponds to variant dbSNP:rs752148586EnsemblClinVar.1
Natural variantiVAR_060892291R → H in NPDB; also in patients with an intermediate form; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs1803161EnsemblClinVar.1
Natural variantiVAR_068437314V → M in NPDB; results in 20% of wild-type activity. 1 PublicationCorresponds to variant dbSNP:rs1228068212EnsemblClinVar.1
Natural variantiVAR_077315320N → D in NPDB; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs779927660EnsemblClinVar.1
Natural variantiVAR_060896325P → A in NPDB; results in 1-4% of wild type activity. 3 PublicationsCorresponds to variant dbSNP:rs761308217EnsemblClinVar.1
Natural variantiVAR_060897332P → R in NPDB. 2 PublicationsCorresponds to variant dbSNP:rs202081954EnsemblClinVar.1
Natural variantiVAR_060899359A → 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 PublicationsCorresponds to variant dbSNP:rs797044800EnsemblClinVar.1
Natural variantiVAR_015289373P → S in NPDB. 2 PublicationsCorresponds to variant dbSNP:rs1342372980EnsemblClinVar.1
Natural variantiVAR_060901378R → H in NPDB; reduces enzyme activity; some patients have a NPDA/NPDB intermediate phenotype. 4 PublicationsCorresponds to variant dbSNP:rs559088058EnsemblClinVar.1
Natural variantiVAR_060902378R → L in NPDB. 1 Publication1
Natural variantiVAR_060903381S → P in NPDB. 1 Publication1
Natural variantiVAR_005061384M → I in NPDA and NPDB. 2 PublicationsCorresponds to variant dbSNP:rs120074121EnsemblClinVar.1
Natural variantiVAR_005062385N → S in NPDB. 1 PublicationCorresponds to variant dbSNP:rs120074123EnsemblClinVar.1
Natural variantiVAR_005064393W → G in NPDB; low sphingomyelin degradation rates. 1 PublicationCorresponds to variant dbSNP:rs120074125EnsemblClinVar.1
Natural variantiVAR_060905415A → V in NPDB. 1 PublicationCorresponds to variant dbSNP:rs1451199796Ensembl.1
Natural variantiVAR_015290423H → Y in NPDB; abolishes enzyme activity. 2 PublicationsCorresponds to variant dbSNP:rs120074126EnsemblClinVar.1
Natural variantiVAR_068438427H → 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 PublicationCorresponds to variant dbSNP:rs794727629EnsemblClinVar.1
Natural variantiVAR_060907433C → R in NPDB. 1 PublicationCorresponds to variant dbSNP:rs779528546EnsemblClinVar.1
Natural variantiVAR_060908434L → P in NPDB. 1 Publication1
Natural variantiVAR_060909437W → C in NPDB. 1 Publication1
Natural variantiVAR_005065438S → R in NPDB. 1 PublicationCorresponds to variant dbSNP:rs267607073EnsemblClinVar.1
Natural variantiVAR_068439453A → D in NPDB. 1 Publication1
Natural variantiVAR_060911454A → V in NPDB. 1 PublicationCorresponds to variant dbSNP:rs1402734026EnsemblClinVar.1
Natural variantiVAR_060912458G → D in NPDB. 1 Publication1
Natural variantiVAR_075328476R → Q in NPDB; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs763566905EnsemblClinVar.1
Natural variantiVAR_060914476R → W in NPDB; some patients have a NPDA/NPDB intermediate phenotype. 4 PublicationsCorresponds to variant dbSNP:rs182812968EnsemblClinVar.1
Natural variantiVAR_015292477P → L in NPDA and NPDB. 4 PublicationsCorresponds to variant dbSNP:rs753508874EnsemblClinVar.1
Natural variantiVAR_060915482F → L in NPDB. 1 Publication1
Natural variantiVAR_060918488T → A in NPDB. 1 Publication1
Natural variantiVAR_060919490Y → N in NPDB. 1 PublicationCorresponds to variant dbSNP:rs398123477EnsemblClinVar.1
Natural variantiVAR_075330492G → S in NPDB. 1 PublicationCorresponds to variant dbSNP:rs144873307EnsemblClinVar.1
Natural variantiVAR_060920496G → S in NPDB. 1 PublicationCorresponds to variant dbSNP:rs1554935371EnsemblClinVar.1
Natural variantiVAR_060921498R → C in NPDB. 1 PublicationCorresponds to variant dbSNP:rs769904764EnsemblClinVar.1
Natural variantiVAR_060924516H → Q in NPDB. 1 Publication1
Natural variantiVAR_060925517E → V in NPDB. 1 PublicationCorresponds to variant dbSNP:rs142787001EnsemblClinVar.1
Natural variantiVAR_077324520I → L in NPDB. 1 Publication1
Natural variantiVAR_068440522N → S in NPDB. 1 Publication1
Natural variantiVAR_068441525Q → H in NPDB; results in 64% of wild-type activity. 1 Publication1
Natural variantiVAR_060927535W → R in NPDB and NPDA; also in patients with an intermediate form. 3 PublicationsCorresponds to variant dbSNP:rs1554935555EnsemblClinVar.1
Natural variantiVAR_077325549N → K in NPDB. 1 Publication1
Natural variantiVAR_060928551L → P in NPDB. 2 Publications1
Natural variantiVAR_060929565D → Y in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains 6.8% residual enzyme activity. 1 Publication1
Natural variantiVAR_075332577H → D in NPDB; unknown pathological significance. 1 Publication1
Natural variantiVAR_060930578K → N in NPDB. 1 PublicationCorresponds to variant dbSNP:rs747342458EnsemblClinVar.1
Natural variantiVAR_075333598Q → R in NPDB. 1 PublicationCorresponds to variant dbSNP:rs1554935731