<p>An evidence describes the source of an annotation, e.g. an experiment that has been published in the scientific literature, an orthologous protein, a record from another database, etc.</p>
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<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>
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<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
<p>Manually curated information for which there is published experimental evidence.</p>
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Manual assertion based on experiment ini
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 key
Position(s)
DescriptionActions
Graphical view
Length
<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>Sitei
<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
identical protein binding Source: IntAct
<p>Inferred from Physical Interaction</p>
<p>Covers physical interactions between the gene product of interest and another molecule (or ion, or complex).</p>
<p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#ipi">GO evidence code guide</a></p>
Inferred from physical interactioni
structural molecule activity Source: UniProtKB
<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%2Dgo%2Devidence%2Dcodes#tas">GO evidence code guide</a></p>
Traceable author statementi
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND C).
"Structural organization of the human gene encoding nuclear lamin A and nuclear lamin C." Lin F., Worman H.J. J Biol Chem 268:16321-16326(1993) [PubMed] [Europe PMC] [Abstract]
cellular protein localization Source: CAFA
<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%2Dgo%2Devidence%2Dcodes#imp">GO evidence code guide</a></p>
Inferred from mutant phenotypei
cellular response to hypoxia Source: UniProtKB
<p>Inferred from Expression Pattern</p>
<p>Covers cases where the annotation is inferred from the timing or location of expression of a gene.</p>
<p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#iep">GO evidence code guide</a></p>
Inferred from expression patterni
DNA double-strand break attachment to nuclear envelope 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%2Dgo%2Devidence%2Dcodes#ida">GO evidence code guide</a></p>
Inferred from direct assayi
<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
<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
<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>Organismi
<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 identifieri
<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 lineagei
<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
<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
Cited for: SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS EDMD2 LYS-32 DEL; SER-63; GLN-249; LYS-358; CYS-401; TRP-453 AND PRO-527, CHARACTERIZATION OF VARIANTS EDMD2 LYS-208 DEL AND HIS-377, CHARACTERIZATION OF VARIANT FPLD2 LEU-482, CHARACTERIZATION OF VARIANT CMD1A CYS-541.
Cited for: FUNCTION, INTERACTION WITH IFFO1, SUBCELLULAR LOCATION, MUTAGENESIS OF SER-22; GLU-358 AND ARG-386, REGION.
Note:Farnesylation of prelamin-A/C facilitates nuclear envelope targeting and subsequent cleavage by ZMPSTE24/FACE1 to remove the farnesyl group produces mature lamin-A/C, which can then be inserted into the nuclear lamina. EMD is required for proper localization of non-farnesylated prelamin-A/C.
"Structural organization of the human gene encoding nuclear lamin A and nuclear lamin C." Lin F., Worman H.J. J Biol Chem 268:16321-16326(1993) [PubMed] [Europe PMC] [Abstract]
"Structural organization of the human gene encoding nuclear lamin A and nuclear lamin C." Lin F., Worman H.J. J Biol Chem 268:16321-16326(1993) [PubMed] [Europe PMC] [Abstract]
nuclear matrix Source: UniProtKBInferred from direct assayi
<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
<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
Cited for: SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS EDMD2 LYS-32 DEL; SER-63; GLN-249; LYS-358; CYS-401; TRP-453 AND PRO-527, CHARACTERIZATION OF VARIANTS EDMD2 LYS-208 DEL AND HIS-377, CHARACTERIZATION OF VARIANT FPLD2 LEU-482, CHARACTERIZATION OF VARIANT CMD1A CYS-541.
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.
<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_039746
Missing 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 Publications
Cited for: SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS EDMD2 LYS-32 DEL; SER-63; GLN-249; LYS-358; CYS-401; TRP-453 AND PRO-527, CHARACTERIZATION OF VARIANTS EDMD2 LYS-208 DEL AND HIS-377, CHARACTERIZATION OF VARIANT FPLD2 LEU-482, CHARACTERIZATION OF VARIANT CMD1A CYS-541.
I → Sin EDMD2; no effect on protein level; no obvious effect on nuclear morphology in cultured skin fibroblasts from heterozygous patients.2 Publications
Cited for: SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS EDMD2 LYS-32 DEL; SER-63; GLN-249; LYS-358; CYS-401; TRP-453 AND PRO-527, CHARACTERIZATION OF VARIANTS EDMD2 LYS-208 DEL AND HIS-377, CHARACTERIZATION OF VARIANT FPLD2 LEU-482, CHARACTERIZATION OF VARIANT CMD1A CYS-541.
Missing in EDMD2; no obvious effect on nuclear morphology in cultured skin fibroblasts from heterozygous patients; no effect on protein level.2 Publications
Cited for: SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS EDMD2 LYS-32 DEL; SER-63; GLN-249; LYS-358; CYS-401; TRP-453 AND PRO-527, CHARACTERIZATION OF VARIANTS EDMD2 LYS-208 DEL AND HIS-377, CHARACTERIZATION OF VARIANT FPLD2 LEU-482, CHARACTERIZATION OF VARIANT CMD1A CYS-541.
R → Qin EDMD2; no obvious effect on nuclear morphology in cultured skin fibroblasts from heterozygous patients; no effect on protein level.9 Publications
Cited for: SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS EDMD2 LYS-32 DEL; SER-63; GLN-249; LYS-358; CYS-401; TRP-453 AND PRO-527, CHARACTERIZATION OF VARIANTS EDMD2 LYS-208 DEL AND HIS-377, CHARACTERIZATION OF VARIANT FPLD2 LEU-482, CHARACTERIZATION OF VARIANT CMD1A CYS-541.
E → Kin 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 Publications
Cited for: SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS EDMD2 LYS-32 DEL; SER-63; GLN-249; LYS-358; CYS-401; TRP-453 AND PRO-527, CHARACTERIZATION OF VARIANTS EDMD2 LYS-208 DEL AND HIS-377, CHARACTERIZATION OF VARIANT FPLD2 LEU-482, CHARACTERIZATION OF VARIANT CMD1A CYS-541.
M → Kin 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 Publications
R → Hin EDMD2; no obvious effect on nuclear morphology in cultured skin fibroblasts from heterozygous patients; no effect on protein level.6 Publications
Cited for: SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS EDMD2 LYS-32 DEL; SER-63; GLN-249; LYS-358; CYS-401; TRP-453 AND PRO-527, CHARACTERIZATION OF VARIANTS EDMD2 LYS-208 DEL AND HIS-377, CHARACTERIZATION OF VARIANT FPLD2 LEU-482, CHARACTERIZATION OF VARIANT CMD1A CYS-541.
R → Kin 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 Publications
R → Cin 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 Publications
Cited for: SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS EDMD2 LYS-32 DEL; SER-63; GLN-249; LYS-358; CYS-401; TRP-453 AND PRO-527, CHARACTERIZATION OF VARIANTS EDMD2 LYS-208 DEL AND HIS-377, CHARACTERIZATION OF VARIANT FPLD2 LEU-482, CHARACTERIZATION OF VARIANT CMD1A CYS-541.
R → Win 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 Publications
Cited for: SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS EDMD2 LYS-32 DEL; SER-63; GLN-249; LYS-358; CYS-401; TRP-453 AND PRO-527, CHARACTERIZATION OF VARIANTS EDMD2 LYS-208 DEL AND HIS-377, CHARACTERIZATION OF VARIANT FPLD2 LEU-482, CHARACTERIZATION OF VARIANT CMD1A CYS-541.
R → Pin 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 Publications
Cited for: SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS EDMD2 LYS-32 DEL; SER-63; GLN-249; LYS-358; CYS-401; TRP-453 AND PRO-527, CHARACTERIZATION OF VARIANTS EDMD2 LYS-208 DEL AND HIS-377, CHARACTERIZATION OF VARIANT FPLD2 LEU-482, CHARACTERIZATION OF VARIANT CMD1A CYS-541.
L → Pin 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 Publications
R → Sin 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 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.
Cited for: SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS EDMD2 LYS-32 DEL; SER-63; GLN-249; LYS-358; CYS-401; TRP-453 AND PRO-527, CHARACTERIZATION OF VARIANTS EDMD2 LYS-208 DEL AND HIS-377, CHARACTERIZATION OF VARIANT FPLD2 LEU-482, CHARACTERIZATION OF VARIANT CMD1A CYS-541.
Cited for: VARIANTS CMD1A PHE-92; LYS-161; LYS-317 AND ARG-523.
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.
D → Gin 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 Publication
N → Kin 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 Publications
E → Gin 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 Publications
E → Kin CMD1A; decreased sumoylation; aberrant localization with decreased nuclear rim staining and formation of intranuclear foci; associated with increased cell death.3 Publications
R → Cin CMD1A; grossly abnormal nuclear shape with the nuclear envelope producing prominent lobules in about 10% of cultured skin fibroblasts from heterozygous patients.3 Publications
Cited for: SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS EDMD2 LYS-32 DEL; SER-63; GLN-249; LYS-358; CYS-401; TRP-453 AND PRO-527, CHARACTERIZATION OF VARIANTS EDMD2 LYS-208 DEL AND HIS-377, CHARACTERIZATION OF VARIANT FPLD2 LEU-482, CHARACTERIZATION OF VARIANT CMD1A CYS-541.
R → Sin 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 Publications
Cited for: SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS EDMD2 LYS-32 DEL; SER-63; GLN-249; LYS-358; CYS-401; TRP-453 AND PRO-527, CHARACTERIZATION OF VARIANTS EDMD2 LYS-208 DEL AND HIS-377, CHARACTERIZATION OF VARIANT FPLD2 LEU-482, CHARACTERIZATION OF VARIANT CMD1A CYS-541.
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.
R → Cin 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 Publication
R → Lin 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 Publications
Cited for: SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS EDMD2 LYS-32 DEL; SER-63; GLN-249; LYS-358; CYS-401; TRP-453 AND PRO-527, CHARACTERIZATION OF VARIANTS EDMD2 LYS-208 DEL AND HIS-377, CHARACTERIZATION OF VARIANT FPLD2 LEU-482, CHARACTERIZATION OF VARIANT CMD1A CYS-541.
R → Win 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 Publications
R → Pin 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 Publications
Cited for: SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS EDMD2 LYS-32 DEL; SER-63; GLN-249; LYS-358; CYS-401; TRP-453 AND PRO-527, CHARACTERIZATION OF VARIANTS EDMD2 LYS-208 DEL AND HIS-377, CHARACTERIZATION OF VARIANT FPLD2 LEU-482, CHARACTERIZATION OF VARIANT CMD1A CYS-541.
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.
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
D → Gin HGPS; atypical form with late onset; abnormal nuclear morphology with single or multple blebs, lobulation and occasional ringed or donut shaped nuclei.1 Publication
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.