Protein

Prelamin-A/C

Gene

LMNA

Organism

Homo sapiens (Human)

Status

Reviewed-Annotation score: -Experimental evidence at protein levelⁱ

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. 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).12 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 key	Position(s)	DescriptionActions	Length
Siteⁱ	266	Heptad change of phase	1
Siteⁱ	325	StutterBy similarity	1
Siteⁱ	330	Heptad change of phase	1

GO - Molecular functionⁱ

Complete GO annotation on QuickGO ...

GO - Biological processⁱ

Complete GO annotation on QuickGO ...

Enzyme and pathway databases

Reactomeⁱ	R-HSA-1221632 Meiotic synapsis [P02545-2] R-HSA-2980766 Nuclear Envelope Breakdown R-HSA-2995383 Initiation of Nuclear Envelope 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]
SIGNORⁱ	P02545

Reactomeⁱ

R-HSA-1221632 Meiotic synapsis [P02545-2]
R-HSA-2980766 Nuclear Envelope Breakdown
R-HSA-2995383 Initiation of Nuclear Envelope 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]

SIGNORⁱ

P02545

Names & Taxonomyⁱ

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
Gene namesⁱ	Name:LMNA Synonyms:LMN1
Organismⁱ	Homo sapiens (Human)
Taxonomic identifierⁱ	9606 [NCBI]
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
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome 1

Organism-specific databases

EuPathDBⁱ	HostDB:ENSG00000160789.19
Human Gene Nomenclature Database More...HGNCⁱ	HGNC:6636 LMNA
MIMⁱ	150330 gene
neXtProtⁱ	NX_P02545

Keywords - Cellular componentⁱ

Intermediate filament, Nucleus

Pathology & Biotechⁱ

Involvement in diseaseⁱ

Emery-Dreifuss muscular dystrophy 2, autosomal dominant (EDMD2)20 Publications

The disease is caused by mutations 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 key	Position(s)	DescriptionActions	Length
Natural variantⁱVAR_039746	25	R → G in EDMD2. 1 PublicationCorresponds to variant dbSNP:rs58327533EnsemblClinVar.	1
Natural variantⁱVAR_039747	25	R → P in EDMD2; mis-localized in the nucleus; causes nuclear deformations and LMNB1 redistribution. 2 PublicationsCorresponds to variant dbSNP:rs61578124EnsemblClinVar.	1
Natural variantⁱVAR_039749	32	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	1
Natural variantⁱVAR_039751	33	E → G in EDMD2. 1 PublicationCorresponds to variant dbSNP:rs267607614EnsemblClinVar.	1
Natural variantⁱVAR_039752	35	L → V in EDMD2. 1 PublicationCorresponds to variant dbSNP:rs56694480EnsemblClinVar.	1
Natural variantⁱVAR_063588	39	N → S in MDCL and EDMD2. 2 PublicationsCorresponds to variant dbSNP:rs57983345EnsemblClinVar.	1
Natural variantⁱVAR_039753	43	A → T in EDMD2. 1 PublicationCorresponds to variant dbSNP:rs60446065EnsemblClinVar.	1
Natural variantⁱVAR_009971	45	Y → C in EDMD2. 2 PublicationsCorresponds to variant dbSNP:rs58436778EnsemblClinVar.	1
Natural variantⁱVAR_009972	50	R → P in EDMD2 and MDCL. 2 PublicationsCorresponds to variant dbSNP:rs60695352EnsemblClinVar.	1
Natural variantⁱVAR_039754	50	R → S in EDMD2. 1 PublicationCorresponds to variant dbSNP:rs59931416EnsemblClinVar.	1
Natural variantⁱVAR_039756	63	I → N in EDMD2. 3 PublicationsCorresponds to variant dbSNP:rs57793737EnsemblClinVar.	1
Natural variantⁱVAR_009974	63	I → 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_039757	65	E → G in EDMD2. 1 Publication	1
Natural variantⁱVAR_009976	112	Missing in EDMD2. 2 Publications	1
Natural variantⁱVAR_017657	133	R → P in EDMD2. 1 PublicationCorresponds to variant dbSNP:rs60864230EnsemblClinVar.	1
Natural variantⁱVAR_039760	140	L → P in EDMD2. 2 PublicationsCorresponds to variant dbSNP:rs60652225EnsemblClinVar.	1
Natural variantⁱVAR_039762	150	T → P in EDMD2. 2 PublicationsCorresponds to variant dbSNP:rs58917027EnsemblClinVar.	1
Natural variantⁱVAR_064962	189	R → P in EDMD2; found also in a patient with limb-girdle muscular dystrophy; sporadic. 1 PublicationCorresponds to variant dbSNP:rs267607643EnsemblClinVar.	1
Natural variantⁱVAR_039763	190	R → 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_064963	190	R → RR in EDMD2. 1 Publication	1
Natural variantⁱVAR_039766	196 – 199	RLQT → S in EDMD2. 1 Publication	4
Natural variantⁱVAR_064964	206	F → L in EDMD2. 1 PublicationCorresponds to variant dbSNP:rs267607629EnsemblClinVar.	1
Natural variantⁱVAR_034708	208	Missing in EDMD2; no obvious effect on nuclear morphology in cultured skin fibroblasts from heterozygous patients; no effect on protein level. 2 Publications	1
Natural variantⁱVAR_039769	222	H → P in EDMD2. 1 PublicationCorresponds to variant dbSNP:rs58034145EnsemblClinVar.	1
Natural variantⁱVAR_009979	222	H → Y in EDMD2. 1 PublicationCorresponds to variant dbSNP:rs28928901EnsemblClinVar.	1
Natural variantⁱVAR_039771	232	G → E in EDMD2. 1 PublicationCorresponds to variant dbSNP:rs57207746EnsemblClinVar.	1
Natural variantⁱVAR_039772	248	L → P in EDMD2. 1 PublicationCorresponds to variant dbSNP:rs58850446EnsemblClinVar.	1
Natural variantⁱVAR_009980	249	R → 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_063589	249	R → W in MDCL and EDMD2; mislocalized in the nucleus; causes nuclear deformations and LMNB1 redistribution. 2 PublicationsCorresponds to variant dbSNP:rs121912496EnsemblClinVar.	1
Natural variantⁱVAR_076563	259	Y → C in EDMD2. 1 Publication	1
Natural variantⁱVAR_009981	261	Missing in EDMD2. 3 Publications	1
Natural variantⁱVAR_039774	267	Y → C in EDMD2. 1 PublicationCorresponds to variant dbSNP:rs57048196EnsemblClinVar.	1
Natural variantⁱVAR_064965	268	S → P in EDMD2. 1 PublicationCorresponds to variant dbSNP:rs267607630EnsemblClinVar.	1
Natural variantⁱVAR_064966	271	L → P in EDMD2. 1 PublicationCorresponds to variant dbSNP:rs267607641EnsemblClinVar.	1
Natural variantⁱVAR_009982	294	Q → P in EDMD2. 2 PublicationsCorresponds to variant dbSNP:rs61616775EnsemblClinVar.	1
Natural variantⁱVAR_064967	295	S → P in EDMD2. 1 PublicationCorresponds to variant dbSNP:rs267607633EnsemblClinVar.	1
Natural variantⁱVAR_064968	303	S → P in EDMD2. 1 PublicationCorresponds to variant dbSNP:rs61527854EnsemblClinVar.	1
Natural variantⁱVAR_009983	336	R → Q in EDMD2. 2 PublicationsCorresponds to variant dbSNP:rs58105277EnsemblClinVar.	1
Natural variantⁱVAR_009984	343	R → Q in EDMD2. 1 PublicationCorresponds to variant dbSNP:rs61177390EnsemblClinVar.	1
Natural variantⁱVAR_064969	355	Missing in EDMD2. 1 Publication	1
Natural variantⁱVAR_009985	358	E → 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_064970	361	E → K in EDMD2. 1 PublicationCorresponds to variant dbSNP:rs267607634EnsemblClinVar.	1
Natural variantⁱVAR_009986	371	M → 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_016205	377	R → 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_039777	377	R → L in EDMD2. 2 PublicationsCorresponds to variant dbSNP:rs61672878EnsemblClinVar.	1
Natural variantⁱVAR_009987	386	R → 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_072818	401	R → 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_039780	446	D → V in EDMD2. 1 PublicationCorresponds to variant dbSNP:rs58541611EnsemblClinVar.	1
Natural variantⁱVAR_064971	449	G → D in EDMD2. 1 PublicationCorresponds to variant dbSNP:rs267607637EnsemblClinVar.	1
Natural variantⁱVAR_009988	453	R → 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_064972	454	L → P in EDMD2. 1 PublicationCorresponds to variant dbSNP:rs267607638EnsemblClinVar.	1
Natural variantⁱVAR_039781	456	N → I in EDMD2; mislocalized in the nucleus; does not alter nuclear size or shape. 2 PublicationsCorresponds to variant dbSNP:rs60992550EnsemblClinVar.	1
Natural variantⁱVAR_039782	456	N → K in EDMD2. 1 PublicationCorresponds to variant dbSNP:rs61235244EnsemblClinVar.	1
Natural variantⁱVAR_064973	461	D → Y in EDMD2. 1 PublicationCorresponds to variant dbSNP:rs267607642EnsemblClinVar.	1
Natural variantⁱVAR_064974	467	W → R in EDMD2. 1 PublicationCorresponds to variant dbSNP:rs267607639EnsemblClinVar.	1
Natural variantⁱVAR_009990	469	I → T in EDMD2. 1 PublicationCorresponds to variant dbSNP:rs57394692EnsemblClinVar.	1
Natural variantⁱVAR_039783	481	Y → H in EDMD2. 1 PublicationCorresponds to variant dbSNP:rs57747780EnsemblClinVar.	1
Natural variantⁱVAR_039784	520	W → 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_009995	527	R → 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_009996	528	T → 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_039785	528	T → R in EDMD2. 2 PublicationsCorresponds to variant dbSNP:rs57629361EnsemblClinVar.	1
Natural variantⁱVAR_009997	530	L → 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_039787	541	R → H in EDMD2. 1 PublicationCorresponds to variant dbSNP:rs61444459EnsemblClinVar.	1
Natural variantⁱVAR_064975	541	R → P in EDMD2; mis-localized in the nucleus; does not alter nuclear size or shape. 1 PublicationCorresponds to variant dbSNP:rs61444459EnsemblClinVar.	1
Natural variantⁱVAR_039788	541	R → 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_064976	602	G → S in EDMD2. 1 PublicationCorresponds to variant dbSNP:rs60662302EnsemblClinVar.	1
Natural variantⁱVAR_039791	624	R → H in EDMD2. 1 PublicationCorresponds to variant dbSNP:rs13768EnsemblClinVar.	1
Natural variantⁱVAR_039792	644	R → 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 mutations affecting the gene represented in this entry.

Related information in OMIM

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Natural variantⁱVAR_076562	24	T → S in EDMD3. 1 Publication		1
Natural variantⁱVAR_067697	225	R → Q in EDMD3. 1 PublicationCorresponds to variant dbSNP:rs199474724EnsemblClinVar.		1

Cardiomyopathy, dilated 1A (CMD1A)17 Publications

The disease is caused by mutations 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 key	Position(s)	DescriptionActions	Length
Natural variantⁱVAR_034706	60	R → 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_009975	85	L → 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_039758	89	R → 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_067257	92	L → F in CMD1A. 1 PublicationCorresponds to variant dbSNP:rs267607560EnsemblClinVar.	1
Natural variantⁱVAR_039759	97	K → E in CMD1A. 1 PublicationCorresponds to variant dbSNP:rs59065411EnsemblClinVar.	1
Natural variantⁱVAR_070174	101	R → 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_039761	143	S → P in CMD1A. 1 PublicationCorresponds to variant dbSNP:rs61661343EnsemblClinVar.	1
Natural variantⁱVAR_017660	161	E → K in CMD1A. 2 PublicationsCorresponds to variant dbSNP:rs28933093EnsemblClinVar.	1
Natural variantⁱVAR_070176	166	R → 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_039763	190	R → 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_039764	190	R → W in CMD1A. 3 PublicationsCorresponds to variant dbSNP:rs59026483EnsemblClinVar.	1
Natural variantⁱVAR_039765	192	D → 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_009977	195	N → 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_009978	203	E → 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_039767	203	E → 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_070177	210	I → 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_039768	215	L → P in CMD1A; aberrant localization with decreased nuclear rim staining and formation of intranuclear foci. 2 PublicationsCorresponds to variant dbSNP:rs61295588EnsemblClinVar.	1
Natural variantⁱVAR_039775	317	E → K in CMD1A. 2 PublicationsCorresponds to variant dbSNP:rs56816490EnsemblClinVar.	1
Natural variantⁱVAR_070179	318	A → T in CMD1A; no effect on nuclear morphology and lamin A localization. 1 PublicationCorresponds to variant dbSNP:rs267607574EnsemblClinVar.	1
Natural variantⁱVAR_039776	349	R → L in CMD1A. 1 PublicationCorresponds to variant dbSNP:rs58789393EnsemblClinVar.	1
Natural variantⁱVAR_070180	388	R → H in CMD1A; no effect on nuclear morphology but restricts lamin A to the cytoplasm. 1 PublicationCorresponds to variant dbSNP:rs267607576EnsemblClinVar.	1
Natural variantⁱVAR_039778	399	R → C in FPLD2 and CMD1A; no effect on nuclear morphology and lamin A localization. 2 PublicationsCorresponds to variant dbSNP:rs58672172EnsemblClinVar.	1
Natural variantⁱVAR_039779	435	R → C in CMD1A. 1 PublicationCorresponds to variant dbSNP:rs150840924EnsemblClinVar.	1
Natural variantⁱVAR_070182	471	R → H in CMD1A; no effect on nuclear morphology and lamin A localization. 1 PublicationCorresponds to variant dbSNP:rs267607578EnsemblClinVar.	1
Natural variantⁱVAR_067258	523	G → R in CMD1A. 1 PublicationCorresponds to variant dbSNP:rs201583907EnsemblClinVar.	1
Natural variantⁱVAR_039786	541	R → 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_039788	541	R → 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_039789	573	S → 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 mutations 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 key	Position(s)	DescriptionActions	Length
Natural variantⁱVAR_039748	28	R → W in FPLD2. 1 PublicationCorresponds to variant dbSNP:rs59914820EnsemblClinVar.	1
Natural variantⁱVAR_034706	60	R → 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_039755	62	R → G in FPLD2. 1 PublicationCorresponds to variant dbSNP:rs56793579EnsemblClinVar.	1
Natural variantⁱVAR_016913	133	R → L in FPLD2. 1 PublicationCorresponds to variant dbSNP:rs60864230EnsemblClinVar.	1
Natural variantⁱVAR_039770	230	D → N in FPLD2. 1 PublicationCorresponds to variant dbSNP:rs61214927EnsemblClinVar.	1
Natural variantⁱVAR_039778	399	R → C in FPLD2 and CMD1A; no effect on nuclear morphology and lamin A localization. 2 PublicationsCorresponds to variant dbSNP:rs58672172EnsemblClinVar.	1
Natural variantⁱVAR_070181	439	R → 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_009989	465	G → D in FPLD2. 1 PublicationCorresponds to variant dbSNP:rs61282106EnsemblClinVar.	1
Natural variantⁱVAR_009991	482	R → 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_009992	482	R → 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_009993	482	R → 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_009994	486	K → 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_071968	515	K → E in FPLD2. 1 Publication	1
Natural variantⁱVAR_009995	527	R → 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_009998	582	R → H in FPLD2. 1 PublicationCorresponds to variant dbSNP:rs57830985EnsemblClinVar.	1

Charcot-Marie-Tooth disease 2B1 (CMT2B1)1 Publication

The disease is caused by mutations 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 key	Position(s)	DescriptionActions	Graphical view	Length
Natural variantⁱVAR_017661	298	R → C in CMT2B1. 1 PublicationCorresponds to variant dbSNP:rs59885338EnsemblClinVar.		1

Hutchinson-Gilford progeria syndrome (HGPS)10 Publications

The disease is caused by mutations 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 key	Position(s)	DescriptionActions	Length
Natural variantⁱVAR_070175	138	E → K in HGPS; might be associated with early and severe strokes. 1 PublicationCorresponds to variant dbSNP:rs267607649EnsemblClinVar.	1
Natural variantⁱVAR_017658	140	L → R in HGPS; phenotype originally designated as atypical Werner syndrome. 1 PublicationCorresponds to variant dbSNP:rs60652225EnsemblClinVar.	1
Natural variantⁱVAR_034707	143	S → F in HGPS. 1 PublicationCorresponds to variant dbSNP:rs58912633EnsemblClinVar.	1
Natural variantⁱVAR_017659	145	E → K in HGPS; atypical. 1 PublicationCorresponds to variant dbSNP:rs60310264EnsemblClinVar.	1
Natural variantⁱVAR_070178	300	D → 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_017662	471	R → C in HGPS. 1 PublicationCorresponds to variant dbSNP:rs28928902EnsemblClinVar.	1
Natural variantⁱVAR_017663	527	R → C in HGPS. 1 PublicationCorresponds to variant dbSNP:rs57318642EnsemblClinVar.	1
Natural variantⁱVAR_034710	542	K → N in HGPS. 1 PublicationCorresponds to variant dbSNP:rs56673169EnsemblClinVar.	1
Natural variantⁱVAR_017664	608	G → S in HGPS; reduced binding to SUN1; may affect splicing by activating a cryptic splice donor site. 3 Publications

UniProtKB - P02545 (LMNA_HUMAN)

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Prelamin-A/C

LMNA

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Nucleus

Nucleus

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Pathology & Biotechⁱ

Involvement in diseaseⁱ

Emery-Dreifuss muscular dystrophy 2, autosomal dominant (EDMD2)20 Publications

Emery-Dreifuss muscular dystrophy 3, autosomal recessive (EDMD3)2 Publications

Cardiomyopathy, dilated 1A (CMD1A)17 Publications

Lipodystrophy, familial partial, 2 (FPLD2)11 Publications

Charcot-Marie-Tooth disease 2B1 (CMT2B1)1 Publication

Hutchinson-Gilford progeria syndrome (HGPS)10 Publications

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UniProtKB - P02545 (LMNA_HUMAN)

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Prelamin-A/C

LMNA

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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

Miscellaneous

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Enzyme and pathway databases

<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

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<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

Nucleus

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Cytoskeleton

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<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

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Functionⁱ

GO - Molecular functionⁱ

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Subcellular locationⁱ

Pathology & Biotechⁱ