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UniProtKB - P02545 (LMNA_HUMAN)

Entry version 263 (02 Jun 2021)
Sequence version 1 (20 Mar 1987)
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Protein

Prelamin-A/C

Gene

LMNA

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

Lamins are components of the nuclear lamina, a fibrous layer on the nucleoplasmic side of the inner nuclear membrane, which is thought to provide a framework for the nuclear envelope and may also interact with chromatin. Lamin A and C are present in equal amounts in the lamina of mammals. Recruited by DNA repair proteins XRCC4 and IFFO1 to the DNA double-strand breaks (DSBs) to prevent chromosome translocation by immobilizing broken DNA ends (PubMed:31548606).

Plays an important role in nuclear assembly, chromatin organization, nuclear membrane and telomere dynamics. Required for normal development of peripheral nervous system and skeletal muscle and for muscle satellite cell proliferation (PubMed:10080180, PubMed:22431096, PubMed:10814726, PubMed:11799477, PubMed:18551513).

Required for osteoblastogenesis and bone formation (PubMed:12075506, PubMed:15317753, PubMed:18611980).

Also prevents fat infiltration of muscle and bone marrow, helping to maintain the volume and strength of skeletal muscle and bone (PubMed:10587585).

Required for cardiac homeostasis (PubMed:10580070, PubMed:12927431, PubMed:18611980, PubMed:23666920).

13 Publications

Prelamin-A/C can accelerate smooth muscle cell senescence. It acts to disrupt mitosis and induce DNA damage in vascular smooth muscle cells (VSMCs), leading to mitotic failure, genomic instability, and premature senescence.

Miscellaneous

There are three types of lamins in human cells: A, B, and C.
The structural integrity of the lamina is strictly controlled by the cell cycle, as seen by the disintegration and formation of the nuclear envelope in prophase and telophase, respectively.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection describes interesting single amino acid sites on the sequence that are not defined in any other subsection. This subsection can be displayed in different sections ('Function', 'PTM / Processing', 'Pathology and Biotech') according to its content.<p><a href='/help/site' target='_top'>More...</a></p>Sitei266Heptad change of phase1
Sitei325StutterBy similarity1
Sitei330Heptad change of phase1

<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

Complete GO annotation on QuickGO ...

GO - Biological processi

Complete GO annotation on QuickGO ...

Enzyme and pathway databases

Pathway Commons web resource for biological pathway data

More...PathwayCommonsi		P02545

Reactome - a knowledgebase of biological pathways and processes

More...Reactomei		R-HSA-1221632, Meiotic synapsis [P02545-2]
R-HSA-2980766, Nuclear Envelope Breakdown
R-HSA-2995383, Initiation of Nuclear Envelope (NE) Reformation
R-HSA-352238, Breakdown of the nuclear lamina [P02545-1]
R-HSA-381038, XBP1(S) activates chaperone genes
R-HSA-4419969, Depolymerisation of the Nuclear Lamina
R-HSA-6802952, Signaling by BRAF and RAF fusions
R-HSA-8862803, Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models [P02545-1]

SIGNOR Signaling Network Open Resource

More...SIGNORi		P02545

<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:
Prelamin-A/C
Cleaved into the following chain:
Lamin-A/C
Alternative name(s):
70 kDa lamin
Renal carcinoma antigen NY-REN-32
<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:LMNA
Synonyms:LMN1
<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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
<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 1

Organism-specific databases

Human Gene Nomenclature Database

More...HGNCi		HGNC:6636, LMNA

Online Mendelian Inheritance in Man (OMIM)

More...MIMi		150330, gene

neXtProt; the human protein knowledge platform

More...neXtProti		NX_P02545

Eukaryotic Pathogen, Vector and Host Database Resources

More...VEuPathDBi		HostDB:ENSG00000160789.19

<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

<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>Keywords - Cellular componenti

Intermediate filament, Nucleus

<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

Emery-Dreifuss muscular dystrophy 2, autosomal dominant (EDMD2)20 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA form of Emery-Dreifuss muscular dystrophy, a degenerative myopathy characterized by weakness and atrophy of muscle without involvement of the nervous system, early contractures of the elbows, Achilles tendons and spine, and cardiomyopathy associated with cardiac conduction defects.
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_03974625R → G in EDMD2. 1 PublicationCorresponds to variant dbSNP:rs58327533EnsemblClinVar.1
Natural variantiVAR_03974725R → P in EDMD2; mis-localized in the nucleus; causes nuclear deformations and LMNB1 redistribution. 2 PublicationsCorresponds to variant dbSNP:rs61578124EnsemblClinVar.1
Natural variantiVAR_03974932Missing in EDMD2; abnormal nuclear localization in a honeycomb expression pattern in about 11% of cultured skin fibroblasts from heterozygous patients; no effect on protein level. 3 Publications1
Natural variantiVAR_03975133E → G in EDMD2. 1 PublicationCorresponds to variant dbSNP:rs267607614EnsemblClinVar.1
Natural variantiVAR_03975235L → V in EDMD2. 1 PublicationCorresponds to variant dbSNP:rs56694480EnsemblClinVar.1
Natural variantiVAR_06358839N → S in MDCL and EDMD2. 2 PublicationsCorresponds to variant dbSNP:rs57983345EnsemblClinVar.1
Natural variantiVAR_03975343A → T in EDMD2. 1 PublicationCorresponds to variant dbSNP:rs60446065EnsemblClinVar.1
Natural variantiVAR_00997145Y → C in EDMD2. 2 PublicationsCorresponds to variant dbSNP:rs58436778EnsemblClinVar.1
Natural variantiVAR_00997250R → P in EDMD2 and MDCL. 2 PublicationsCorresponds to variant dbSNP:rs60695352EnsemblClinVar.1
Natural variantiVAR_03975450R → S in EDMD2. 1 PublicationCorresponds to variant dbSNP:rs59931416EnsemblClinVar.1
Natural variantiVAR_03975663I → N in EDMD2. 3 PublicationsCorresponds to variant dbSNP:rs57793737EnsemblClinVar.1
Natural variantiVAR_00997463I → S in EDMD2; no effect on protein level; no obvious effect on nuclear morphology in cultured skin fibroblasts from heterozygous patients. 2 PublicationsCorresponds to variant dbSNP:rs57793737EnsemblClinVar.1
Natural variantiVAR_03975765E → G in EDMD2. 1 Publication1
Natural variantiVAR_009976112Missing in EDMD2. 2 Publications1
Natural variantiVAR_017657133R → P in EDMD2. 1 PublicationCorresponds to variant dbSNP:rs60864230EnsemblClinVar.1
Natural variantiVAR_039760140L → P in EDMD2. 2 PublicationsCorresponds to variant dbSNP:rs60652225EnsemblClinVar.1
Natural variantiVAR_039762150T → P in EDMD2. 2 PublicationsCorresponds to variant dbSNP:rs58917027EnsemblClinVar.1
Natural variantiVAR_064962189R → P in EDMD2; found also in a patient with limb-girdle muscular dystrophy; sporadic. 1 PublicationCorresponds to variant dbSNP:rs267607643Ensembl.1
Natural variantiVAR_039763190R → Q in EDMD2 and CMD1A; aberrant localization with decreased nuclear rim staining and increased formation of intranuclear foci. 2 PublicationsCorresponds to variant dbSNP:rs267607571EnsemblClinVar.1
Natural variantiVAR_064963190R → RR in EDMD2. 1 Publication1
Natural variantiVAR_039766196 – 199RLQT → S in EDMD2. 1 Publication4
Natural variantiVAR_064964206F → L in EDMD2. 1 PublicationCorresponds to variant dbSNP:rs267607629EnsemblClinVar.1
Natural variantiVAR_034708208Missing in EDMD2; no obvious effect on nuclear morphology in cultured skin fibroblasts from heterozygous patients; no effect on protein level. 2 Publications1
Natural variantiVAR_039769222H → P in EDMD2. 1 PublicationCorresponds to variant dbSNP:rs58034145EnsemblClinVar.1
Natural variantiVAR_009979222H → Y in EDMD2. 1 PublicationCorresponds to variant dbSNP:rs28928901EnsemblClinVar.1
Natural variantiVAR_039771232G → E in EDMD2. 1 PublicationCorresponds to variant dbSNP:rs57207746EnsemblClinVar.1
Natural variantiVAR_039772248L → P in EDMD2. 1 PublicationCorresponds to variant dbSNP:rs58850446EnsemblClinVar.1
Natural variantiVAR_009980249R → Q in EDMD2; no obvious effect on nuclear morphology in cultured skin fibroblasts from heterozygous patients; no effect on protein level. 9 PublicationsCorresponds to variant dbSNP:rs59332535EnsemblClinVar.1
Natural variantiVAR_063589249R → W in MDCL and EDMD2; mislocalized in the nucleus; causes nuclear deformations and LMNB1 redistribution. 2 PublicationsCorresponds to variant dbSNP:rs121912496EnsemblClinVar.1
Natural variantiVAR_076563259Y → C in EDMD2. 1 Publication1
Natural variantiVAR_009981261Missing in EDMD2. 3 Publications1
Natural variantiVAR_039774267Y → C in EDMD2. 1 PublicationCorresponds to variant dbSNP:rs57048196EnsemblClinVar.1
Natural variantiVAR_064965268S → P in EDMD2. 1 PublicationCorresponds to variant dbSNP:rs267607630EnsemblClinVar.1
Natural variantiVAR_064966271L → P in EDMD2. 1 PublicationCorresponds to variant dbSNP:rs267607641EnsemblClinVar.1
Natural variantiVAR_009982294Q → P in EDMD2. 2 PublicationsCorresponds to variant dbSNP:rs61616775EnsemblClinVar.1
Natural variantiVAR_064967295S → P in EDMD2. 1 PublicationCorresponds to variant dbSNP:rs267607633EnsemblClinVar.1
Natural variantiVAR_064968303S → P in EDMD2. 1 PublicationCorresponds to variant dbSNP:rs61527854EnsemblClinVar.1
Natural variantiVAR_009983336R → Q in EDMD2. 2 PublicationsCorresponds to variant dbSNP:rs58105277EnsemblClinVar.1
Natural variantiVAR_009984343R → Q in EDMD2. 1 PublicationCorresponds to variant dbSNP:rs61177390EnsemblClinVar.1
Natural variantiVAR_064969355Missing in EDMD2. 1 Publication1
Natural variantiVAR_009985358E → K in EDMD2 and MDCL; aberrant localization with decreased nuclear rim staining and formation of intranuclear foci when transfected in C2C12 myoblasts; no obvious effect on nuclear morphology in cultured skin fibroblasts from heterozygous patients; distribution of endogenous LMNA, LMNB1 and LMNB2 are altered in cells expressing this mutant; interacts with itself and with wild-type LMNA and LMNB1; no effect on protein level. 6 PublicationsCorresponds to variant dbSNP:rs60458016EnsemblClinVar.1
Natural variantiVAR_064970361E → K in EDMD2. 1 PublicationCorresponds to variant dbSNP:rs267607634EnsemblClinVar.1
Natural variantiVAR_009986371M → K in EDMD2; dramatically aberrant localization with decreased nuclear rim staining and formation of intranuclear foci; distribution of endogenous LMNA, LMNB1 and LMNB2 are altered in cells expressing this mutant; causes an increased loss of endogenous EMD from the nuclear envelope; interacts with itself and with wild-type LMNA and LMNB1; no decrease in the stability compared with wild-type. 2 PublicationsCorresponds to variant dbSNP:rs59653062EnsemblClinVar.1
Natural variantiVAR_016205377R → H in EDMD2; no obvious effect on nuclear morphology in cultured skin fibroblasts from heterozygous patients; no effect on protein level. 6 PublicationsCorresponds to variant dbSNP:rs61672878EnsemblClinVar.1
Natural variantiVAR_039777377R → L in EDMD2. 2 PublicationsCorresponds to variant dbSNP:rs61672878EnsemblClinVar.1
Natural variantiVAR_009987386R → K in EDMD2; dramatically aberrant localization with decreased nuclear rim staining and formation of intranuclear foci; distribution of endogenous LMNA, LMNB1 and LMNB2 are altered in cells expressing this mutant; causes an increased loss of endogenous EMD from the nuclear envelope; interacts with itself and with wild-type LMNA and LMNB1; no decrease in the stability compared with wild-type. 4 PublicationsCorresponds to variant dbSNP:rs267607545EnsemblClinVar.1
Natural variantiVAR_072818401R → C in EDMD2; abnormal nuclear localization in a honeycomb expression pattern in about 22% of cultured skin fibroblasts from heterozygous patients; enhances the interaction with SYNE2; no effect on nuclear localization; no effect on protein level. 3 PublicationsCorresponds to variant dbSNP:rs61094188EnsemblClinVar.1
Natural variantiVAR_039780446D → V in EDMD2. 1 PublicationCorresponds to variant dbSNP:rs58541611EnsemblClinVar.1
Natural variantiVAR_064971449G → D in EDMD2. 1 PublicationCorresponds to variant dbSNP:rs267607637EnsemblClinVar.1
Natural variantiVAR_009988453R → W in EDMD2; abnormal nuclear localization; forms nuclear foci in about 8% of cultured skin fibroblasts from heterozygous patients; interacts with itself and with wild-type LMNA and LMNB1; no effect on protein level. 8 PublicationsCorresponds to variant dbSNP:rs58932704EnsemblClinVar.1
Natural variantiVAR_064972454L → P in EDMD2. 1 PublicationCorresponds to variant dbSNP:rs267607638EnsemblClinVar.1
Natural variantiVAR_039781456N → I in EDMD2; mislocalized in the nucleus; does not alter nuclear size or shape. 2 PublicationsCorresponds to variant dbSNP:rs60992550EnsemblClinVar.1
Natural variantiVAR_039782456N → K in EDMD2. 1 PublicationCorresponds to variant dbSNP:rs61235244EnsemblClinVar.1
Natural variantiVAR_064973461D → Y in EDMD2. 1 PublicationCorresponds to variant dbSNP:rs267607642EnsemblClinVar.1
Natural variantiVAR_064974467W → R in EDMD2. 1 PublicationCorresponds to variant dbSNP:rs267607639EnsemblClinVar.1
Natural variantiVAR_009990469I → T in EDMD2. 1 PublicationCorresponds to variant dbSNP:rs57394692EnsemblClinVar.1
Natural variantiVAR_039783481Y → H in EDMD2. 1 PublicationCorresponds to variant dbSNP:rs57747780EnsemblClinVar.1
Natural variantiVAR_039784520W → S in EDMD2; interacts with itself and with wild-type LMNA and LMNB1; no decrease in the stability compared with wild-type. 2 PublicationsCorresponds to variant dbSNP:rs58362413EnsemblClinVar.1
Natural variantiVAR_009995527R → P in EDMD2 and FPLD2; interacts with itself and with wild-type LMNA and LMNB1; reduced binding to SUN1; abnormal nuclear localization; forms nuclear foci in about 13% of cultured skin fibroblasts from heterozygous patients; no effect on protein level. 11 PublicationsCorresponds to variant dbSNP:rs57520892EnsemblClinVar.1
Natural variantiVAR_009996528T → K in EDMD2; interacts with itself and with wild-type LMNA and LMNB1; no decrease in the stability compared with wild-type. 4 PublicationsCorresponds to variant dbSNP:rs57629361EnsemblClinVar.1
Natural variantiVAR_039785528T → R in EDMD2. 2 PublicationsCorresponds to variant dbSNP:rs57629361EnsemblClinVar.1
Natural variantiVAR_009997530L → P in EDMD2; interacts with itself and with wild-type LMNA and LMNB1; reduced binding to SUN1; no decrease in the stability compared with wild-type. 3 PublicationsCorresponds to variant dbSNP:rs60934003EnsemblClinVar.1
Natural variantiVAR_039787541R → H in EDMD2. 1 PublicationCorresponds to variant dbSNP:rs61444459EnsemblClinVar.1
Natural variantiVAR_064975541R → P in EDMD2; mis-localized in the nucleus; does not alter nuclear size or shape. 1 PublicationCorresponds to variant dbSNP:rs61444459EnsemblClinVar.1
Natural variantiVAR_039788541R → S in EDMD2 and CMD1A; modest and non-specific nuclear membrane alterations; the phenotype is entirely reversed by coexpression of the S-541 mutation and wild-type lamin-C. 2 PublicationsCorresponds to variant dbSNP:rs56984562EnsemblClinVar.1
Natural variantiVAR_064976602G → S in EDMD2. 1 PublicationCorresponds to variant dbSNP:rs60662302EnsemblClinVar.1
Natural variantiVAR_039791624R → H in EDMD2. 1 PublicationCorresponds to variant dbSNP:rs13768EnsemblClinVar.1
Natural variantiVAR_039792644R → C in HGPS and EDMD2; partially inhibits tail cleavage. 3 PublicationsCorresponds to variant dbSNP:rs142000963EnsemblClinVar.1
Emery-Dreifuss muscular dystrophy 3, autosomal recessive (EDMD3)2 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA form of Emery-Dreifuss muscular dystrophy, a degenerative myopathy characterized by weakness and atrophy of muscle without involvement of the nervous system, early contractures of the elbows, Achilles tendons and spine, and cardiomyopathy associated with cardiac conduction defects.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07656224T → S in EDMD3. 1 Publication1
Natural variantiVAR_067697225R → Q in EDMD3. 1 PublicationCorresponds to variant dbSNP:rs199474724EnsemblClinVar.1
Cardiomyopathy, dilated 1A (CMD1A)17 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03470660R → G in CMD1A and FPLD2; interacts with itself and with wild-type LMNA and LMNB1; no decrease in the stability compared with wild-type. 3 PublicationsCorresponds to variant dbSNP:rs28928900EnsemblClinVar.1
Natural variantiVAR_00997585L → R in CMD1A; interacts with itself and with wild-type LMNA and LMNB1; no decrease in the stability compared with wild-type. 2 PublicationsCorresponds to variant dbSNP:rs28933090EnsemblClinVar.1
Natural variantiVAR_03975889R → L in CMD1A; dramatically aberrant localization with almost no nuclear rim staining and formation of intranuclear foci. 2 PublicationsCorresponds to variant dbSNP:rs59040894EnsemblClinVar.1
Natural variantiVAR_06725792L → F in CMD1A. 1 PublicationCorresponds to variant dbSNP:rs267607560EnsemblClinVar.1
Natural variantiVAR_03975997K → E in CMD1A. 1 PublicationCorresponds to variant dbSNP:rs59065411EnsemblClinVar.1
Natural variantiVAR_070174101R → P in CMD1A; dramatically aberrant localization with almost no nuclear rim staining and formation of intranuclear foci. 1 PublicationCorresponds to variant dbSNP:rs267607568EnsemblClinVar.1
Natural variantiVAR_039761143S → P in CMD1A. 1 PublicationCorresponds to variant dbSNP:rs61661343EnsemblClinVar.1
Natural variantiVAR_017660161E → K in CMD1A. 2 PublicationsCorresponds to variant dbSNP:rs28933093EnsemblClinVar.1
Natural variantiVAR_070176166R → P in CMD1A; dramatically aberrant localization with almost no nuclear rim staining and formation of intranuclear foci. 1 PublicationCorresponds to variant dbSNP:rs267607570EnsemblClinVar.1
Natural variantiVAR_039763190R → Q in EDMD2 and CMD1A; aberrant localization with decreased nuclear rim staining and increased formation of intranuclear foci. 2 PublicationsCorresponds to variant dbSNP:rs267607571EnsemblClinVar.1
Natural variantiVAR_039764190R → W in CMD1A. 3 PublicationsCorresponds to variant dbSNP:rs59026483EnsemblClinVar.1
Natural variantiVAR_039765192D → G in CMD1A; dramatically increases the size of intranuclear speckles and reduces their number; this phenotype is only partially reversed by coexpression of the G-192 mutation and wild-type lamin-C; precludes insertion of lamin-C into the nuclear envelope when co-transfected with the G-192 LMNA; G-192 lamin-C expression totally disrupts the SUMO1 pattern. 1 PublicationCorresponds to variant dbSNP:rs57045855EnsemblClinVar.1
Natural variantiVAR_009977195N → K in CMD1A; dramatically aberrant localization with decreased nuclear rim staining and formation of intranuclear foci; distribution of endogenous LMNA, LMNB1 and LMNB2 are altered in cells expressing this mutant; causes an increased loss of endogenous EMD from the nuclear envelope; interacts with itself and with wild-type LMNA and LMNB1; no decrease in the stability compared with wild-type. 2 PublicationsCorresponds to variant dbSNP:rs28933091EnsemblClinVar.1
Natural variantiVAR_009978203E → G in CMD1A; interacts with itself and with wild-type LMNA and LMNB1; no decrease in the stability compared with wild-type; decreased sumoylation; aberrant localization with decreased nuclear rim staining and formation of intranuclear foci; associated with increased cell death. 3 PublicationsCorresponds to variant dbSNP:rs28933092EnsemblClinVar.1
Natural variantiVAR_039767203E → K in CMD1A; decreased sumoylation; aberrant localization with decreased nuclear rim staining and formation of intranuclear foci; associated with increased cell death. 3 PublicationsCorresponds to variant dbSNP:rs61195471EnsemblClinVar.1
Natural variantiVAR_070177210I → S in CMD1A; dramatically aberrant localization with almost no nuclear rim staining and increased formation of intranuclear foci. 1 PublicationCorresponds to variant dbSNP:rs267607572EnsemblClinVar.1
Natural variantiVAR_039768215L → P in CMD1A; aberrant localization with decreased nuclear rim staining and formation of intranuclear foci. 2 PublicationsCorresponds to variant dbSNP:rs61295588EnsemblClinVar.1
Natural variantiVAR_039775317E → K in CMD1A. 2 PublicationsCorresponds to variant dbSNP:rs56816490EnsemblClinVar.1
Natural variantiVAR_070179318A → T in CMD1A; no effect on nuclear morphology and lamin A localization. 1 PublicationCorresponds to variant dbSNP:rs267607574EnsemblClinVar.1
Natural variantiVAR_039776349R → L in CMD1A. 1 PublicationCorresponds to variant dbSNP:rs58789393EnsemblClinVar.1
Natural variantiVAR_070180388R → H in CMD1A; no effect on nuclear morphology but restricts lamin A to the cytoplasm. 1 PublicationCorresponds to variant dbSNP:rs267607576EnsemblClinVar.1
Natural variantiVAR_039778399R → C in FPLD2 and CMD1A; no effect on nuclear morphology and lamin A localization. 2 PublicationsCorresponds to variant dbSNP:rs58672172EnsemblClinVar.1
Natural variantiVAR_039779435R → C in CMD1A. 1 PublicationCorresponds to variant dbSNP:rs150840924EnsemblClinVar.1
Natural variantiVAR_070182471R → H in CMD1A; no effect on nuclear morphology and lamin A localization. 1 PublicationCorresponds to variant dbSNP:rs267607578EnsemblClinVar.1
Natural variantiVAR_067258523G → R in CMD1A; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs201583907EnsemblClinVar.1
Natural variantiVAR_039786541R → C in CMD1A; grossly abnormal nuclear shape with the nuclear envelope producing prominent lobules in about 10% of cultured skin fibroblasts from heterozygous patients. 3 PublicationsCorresponds to variant dbSNP:rs56984562EnsemblClinVar.1
Natural variantiVAR_039788541R → S in EDMD2 and CMD1A; modest and non-specific nuclear membrane alterations; the phenotype is entirely reversed by coexpression of the S-541 mutation and wild-type lamin-C. 2 PublicationsCorresponds to variant dbSNP:rs56984562EnsemblClinVar.1
Natural variantiVAR_039789573S → L in CMD1A, FPLD2 and MADA. 3 PublicationsCorresponds to variant dbSNP:rs60890628EnsemblClinVar.1
Lipodystrophy, familial partial, 2 (FPLD2)11 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA disorder characterized by the loss of subcutaneous adipose tissue in the lower parts of the body (limbs, buttocks, trunk). It is accompanied by an accumulation of adipose tissue in the face and neck causing a double chin, fat neck, or cushingoid appearance. Adipose tissue may also accumulate in the axillae, back, labia majora, and intraabdominal region. Affected patients are insulin-resistant and may develop glucose intolerance and diabetes mellitus after age 20 years, hypertriglyceridemia, and low levels of high density lipoprotein cholesterol.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03974828R → W in FPLD2. 1 PublicationCorresponds to variant dbSNP:rs59914820EnsemblClinVar.1
Natural variantiVAR_03470660R → G in CMD1A and FPLD2; interacts with itself and with wild-type LMNA and LMNB1; no decrease in the stability compared with wild-type. 3 PublicationsCorresponds to variant dbSNP:rs28928900EnsemblClinVar.1
Natural variantiVAR_03975562R → G in FPLD2. 1 PublicationCorresponds to variant dbSNP:rs56793579EnsemblClinVar.1
Natural variantiVAR_016913133R → L in FPLD2. 1 PublicationCorresponds to variant dbSNP:rs60864230EnsemblClinVar.1
Natural variantiVAR_039770230D → N in FPLD2. 1 PublicationCorresponds to variant dbSNP:rs61214927EnsemblClinVar.1
Natural variantiVAR_039778399R → C in FPLD2 and CMD1A; no effect on nuclear morphology and lamin A localization. 2 PublicationsCorresponds to variant dbSNP:rs58672172EnsemblClinVar.1
Natural variantiVAR_070181439R → C in FPLD2; increase in nuclear blebbing and formation of honeycomb-like structures in the nuclei with no accumulation of prelamin A in skin fibroblasts; causes oligomerization of the C-terminal globular domain of lamins A and C under no-reducing conditions and increases binding affinity for DNA; increases sensitivity to oxidative stress; no significant differences in stability and structure compared with the wild-type. 1 PublicationCorresponds to variant dbSNP:rs62636506EnsemblClinVar.1
Natural variantiVAR_009989465G → D in FPLD2. 1 PublicationCorresponds to variant dbSNP:rs61282106EnsemblClinVar.1
Natural variantiVAR_009991482R → L in FPLD2; abnormal nuclear localization in a honeycomb expression pattern in about 10% of cultured skin fibroblasts from heterozygous patients; no effect on protein level. 2 PublicationsCorresponds to variant dbSNP:rs11575937EnsemblClinVar.1
Natural variantiVAR_009992482R → Q in FPLD2; interacts with itself and with wild-type LMNA and LMNB1; no decrease in the stability compared with wild-type. 3 PublicationsCorresponds to variant dbSNP:rs11575937EnsemblClinVar.1
Natural variantiVAR_009993482R → W in FPLD2; interacts with itself and with wild-type LMNA and LMNB1; no decrease in the stability compared with wild-type; decreases binding affinity for DNA; increases sensitivity to oxidative stress. 4 PublicationsCorresponds to variant dbSNP:rs57920071EnsemblClinVar.1
Natural variantiVAR_009994486K → N in FPLD2; interacts with itself and with wild-type LMNA and LMNB1; no decrease in the stability compared with wild-type. 1 PublicationCorresponds to variant dbSNP:rs59981161EnsemblClinVar.1
Natural variantiVAR_071968515K → E in FPLD2. 1 Publication1
Natural variantiVAR_009995527R → P in EDMD2 and FPLD2; interacts with itself and with wild-type LMNA and LMNB1; reduced binding to SUN1; abnormal nuclear localization; forms nuclear foci in about 13% of cultured skin fibroblasts from heterozygous patients; no effect on protein level. 11 PublicationsCorresponds to variant dbSNP:rs57520892EnsemblClinVar.1
Natural variantiVAR_009998582R → H in FPLD2. 1 PublicationCorresponds to variant dbSNP:rs57830985EnsemblClinVar.1
Charcot-Marie-Tooth disease 2B1 (CMT2B1)1 Publication
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA recessive axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_017661298R → C in CMT2B1. 1 PublicationCorresponds to variant dbSNP:rs59885338EnsemblClinVar.1
Hutchinson-Gilford progeria syndrome (HGPS)10 Publications
The disease is caused by variants affecting the gene represented in this entry. HGPS is caused by the toxic accumulation of a truncated form of lamin-A/C. This mutant protein, called progerin (isoform 6), acts to deregulate mitosis and DNA damage signaling, leading to premature cell death and senescence. The mutant form is mainly generated by a silent or missense mutation at codon 608 of prelamin A that causes activation of a cryptic splice donor site, resulting in production of isoform 6 with a deletion of 50 amino acids near the C terminus. Progerin lacks the conserved ZMPSTE24/FACE1 cleavage site and therefore remains permanently farnesylated. Thus, although it can enter the nucleus and associate with the nuclear envelope, it cannot incorporate normally into the nuclear lamina (PubMed:12714972).1 Publication
Disease descriptionRare genetic disorder characterized by features reminiscent of marked premature aging.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_070175138E → K in HGPS; might be associated with early and severe strokes. 1 PublicationCorresponds to variant dbSNP:rs267607649EnsemblClinVar.1
Natural variantiVAR_017658140L → R in HGPS; phenotype originally designated as atypical Werner syndrome. 1 PublicationCorresponds to variant dbSNP:rs60652225EnsemblClinVar.1
Natural variantiVAR_034707143S → F in HGPS. 1 PublicationCorresponds to variant dbSNP:rs58912633EnsemblClinVar.1
Natural variantiVAR_017659145E → K in HGPS; atypical. 1 PublicationCorresponds to variant dbSNP:rs60310264EnsemblClinVar.1
Natural variantiVAR_070178300D → G in HGPS; atypical form with late onset; abnormal nuclear morphology with single or multple blebs, lobulation and occasional ringed or donut shaped nuclei. 1 PublicationCorresponds to variant dbSNP:rs79907212EnsemblClinVar.1
Natural variantiVAR_017662471R → C in HGPS. 1 PublicationCorresponds to variant dbSNP:rs28928902EnsemblClinVar.1
Natural variantiVAR_017663527R → C in HGPS. 1 PublicationCorresponds to variant dbSNP:rs57318642EnsemblClinVar.1
Natural variantiVAR_034710542K → N in HGPS. 1 PublicationCorresponds to variant dbSNP:rs56673169EnsemblClinVar.1
Natural variantiVAR_017664608G → S in HGPS; reduced binding to SUN1; may affect splicing by activating a cryptic splice donor site. 3 PublicationsCorresponds to variant dbSNP:rs61064130EnsemblClinVar.1
Natural variantiVAR_039792644R → C in HGPS and EDMD2; partially inhibits tail cleavage. 3 PublicationsCorresponds to variant dbSNP:rs142000963EnsemblClinVar.1
Cardiomyopathy, dilated, with hypergonadotropic hypogonadism (CMDHH)3 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA disorder characterized by the association of genital anomalies, hypergonadotropic hypogonadism and dilated cardiomyopathy. Patients can present other variable clinical manifestations including mental retardation, skeletal anomalies, scleroderma-like skin, graying and thinning of hair, osteoporosis. Dilated cardiomyopathy is characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01765657A → P in CMDHH; phenotype originally designated as atypical Werner syndrome. 1 PublicationCorresponds to variant dbSNP:rs28928903EnsemblClinVar.1
Natural variantiVAR_06405559L → R in CMDHH. 2 PublicationsCorresponds to variant dbSNP:rs58922911EnsemblClinVar.1
Mandibuloacral dysplasia with type A lipodystrophy (MADA)3 Publications