LMNA

Summary

LMNA (lamin A/C, HGNC:6636) is a protein-coding gene on chromosome 1q22, encoding Prelamin-A/C (P02545). Lamins are intermediate filament proteins that assemble into a filamentous meshwork, and which constitute the major components of the nuclear lamina, a fibrous layer on the nucleoplasmic side of the inner nuclear membrane. It is a selective cancer dependency (DepMap: 11.8% of cell lines) and haploinsufficient (ClinGen: sufficient evidence).

The protein encoded by this gene is part of the nuclear lamina, a two-dimensional matrix of proteins located next to the inner nuclear membrane. The lamin family of proteins make up the matrix and are highly conserved in evolution. During mitosis, the lamina matrix is reversibly disassembled as the lamin proteins are phosphorylated. Lamin proteins are thought to be involved in nuclear stability, chromatin structure and gene expression. Vertebrate lamins consist of two types, A and B. Alternative splicing results in multiple transcript variants. Mutations in this gene lead to several diseases: Emery-Dreifuss muscular dystrophy, familial partial lipodystrophy, limb girdle muscular dystrophy, dilated cardiomyopathy, Charcot-Marie-Tooth disease, and Hutchinson-Gilford progeria syndrome.

Source: NCBI Gene 4000 — RefSeq curated summary.

At a glance

• Gene–disease (curated): dilated cardiomyopathy 1A (Definitive, ClinGen) — +21 more curated relationships
• GWAS associations: 19
• Clinical variants (ClinVar): 2,429 total — 300 pathogenic, 166 likely-pathogenic
• Phenotypes (HPO): 520
• Druggable target: yes — 823 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 11.8% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_170707

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6636
Approved symbol	LMNA
Name	lamin A/C
Location	1q22
Locus type	gene with protein product
Status	Approved
Aliases	HGPS, MADA
Ensembl gene	ENSG00000160789
Ensembl biotype	protein_coding
OMIM	150330
Entrez	4000

Gene structure

Transcript identifiers

Ensembl transcripts: 56 — 25 protein_coding, 12 protein_coding_CDS_not_defined, 10 nonsense_mediated_decay, 9 retained_intron

ENST00000361308, ENST00000368297, ENST00000368298, ENST00000368299, ENST00000368300, ENST00000368301, ENST00000448611, ENST00000459904, ENST00000469565, ENST00000470199, ENST00000470835, ENST00000473598, ENST00000478063, ENST00000495341, ENST00000496738, ENST00000498722, ENST00000502357, ENST00000502751, ENST00000504687, ENST00000506981, ENST00000515459, ENST00000515711, ENST00000515824, ENST00000674518, ENST00000674600, ENST00000674720, ENST00000675431, ENST00000675455, ENST00000675667, ENST00000675874, ENST00000675881, ENST00000675939, ENST00000675989, ENST00000676208, ENST00000676283, ENST00000676385, ENST00000676434, ENST00000677389, ENST00000682650, ENST00000683032, ENST00000683773, ENST00000684195, ENST00000713746, ENST00000713747, ENST00000713748, ENST00000899553, ENST00000899554, ENST00000899555, ENST00000899556, ENST00000899557, ENST00000899558, ENST00000927999, ENST00000968784, ENST00000968785, ENST00000968786, ENST00000968787

RefSeq mRNA: 28 — MANE Select: NM_170707 NM_001257374, NM_001282624, NM_001282625, NM_001282626, NM_001406983, NM_001406984, NM_001406985, NM_001406986, NM_001406987, NM_001406988, NM_001406989, NM_001406990, NM_001406991, NM_001406992, NM_001406993, NM_001406994, NM_001406995, NM_001406996, NM_001406997, NM_001406998, NM_001406999, NM_001407000, NM_001407001, NM_001407002, NM_001407003, NM_005572, NM_170707, NM_170708

CCDS: CCDS1129, CCDS1131, CCDS58038, CCDS72941, CCDS72942

Canonical transcript exons

ENST00000368300 — 12 exons

Exon	Start	End
ENSE00001169671	156114711	156115274
ENSE00001244973	156137654	156137743
ENSE00003469966	156134805	156134975
ENSE00003493697	156135901	156136121
ENSE00003498484	156137113	156137232
ENSE00003507672	156136921	156137028
ENSE00003515933	156135187	156135312
ENSE00003524214	156136214	156136436
ENSE00003563218	156134403	156134528
ENSE00003606184	156138488	156138757
ENSE00003659692	156130617	156130773
ENSE00003849676	156139080	156140081

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.41.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 285.2641 / max 7134.5585, expressed in 1820 samples.

FANTOM5 promoters (17 alternative TSS)

Promoter ID	TPM avg	Samples expressed
5669	242.5956	1814
5673	17.7038	1660
5671	7.0795	1559
5672	6.8844	1473
5670	5.3004	1554
5659	1.0751	338
5658	0.7071	472
5682	0.7010	419
5661	0.6541	231
5678	0.6490	337

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
nipple	UBERON:0002030	99.41	gold quality
mucosa of stomach	UBERON:0001199	99.29	gold quality
skin of abdomen	UBERON:0001416	99.25	gold quality
gall bladder	UBERON:0002110	99.20	gold quality
tendon of biceps brachii	UBERON:0008188	99.20	gold quality
skin of leg	UBERON:0001511	99.19	gold quality
stromal cell of endometrium	CL:0002255	99.14	gold quality
descending thoracic aorta	UBERON:0002345	99.14	gold quality
calcaneal tendon	UBERON:0003701	99.13	gold quality
left uterine tube	UBERON:0001303	99.11	gold quality
ascending aorta	UBERON:0001496	99.11	gold quality
thoracic aorta	UBERON:0001515	99.11	gold quality
vena cava	UBERON:0004087	99.07	gold quality
body of uterus	UBERON:0009853	99.02	gold quality
saphenous vein	UBERON:0007318	99.00	gold quality
aorta	UBERON:0000947	98.99	gold quality
right coronary artery	UBERON:0001625	98.97	gold quality
tibial nerve	UBERON:0001323	98.92	gold quality
popliteal artery	UBERON:0002250	98.92	gold quality
tibial artery	UBERON:0007610	98.92	gold quality
zone of skin	UBERON:0000014	98.89	gold quality
coronary artery	UBERON:0001621	98.85	gold quality
left coronary artery	UBERON:0001626	98.83	gold quality
ectocervix	UBERON:0012249	98.82	gold quality
tendon	UBERON:0000043	98.81	gold quality
pharyngeal mucosa	UBERON:0000355	98.78	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.77	gold quality
mucosa of urinary bladder	UBERON:0001259	98.69	gold quality
trachea	UBERON:0003126	98.68	gold quality
omental fat pad	UBERON:0010414	98.66	gold quality

Single-cell (SCXA)

Detected in 35 experiment(s), a significant marker in 28.

Experiment	Marker?	Max mean expression
E-GEOD-135922	yes	6219.26
E-CURD-126	yes	3239.95
E-GEOD-124472	yes	2555.09
E-CURD-46	yes	1974.97
E-GEOD-106540	yes	1630.69
E-MTAB-7407	yes	1341.11
E-CURD-77	yes	838.99
E-MTAB-6653	yes	785.29
E-CURD-122	yes	73.32
E-HCAD-1	yes	59.56
E-HCAD-10	yes	53.12
E-HCAD-4	yes	45.44
E-HCAD-6	yes	41.13
E-MTAB-6701	yes	40.75
E-CURD-112	yes	40.24

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, MYC, NFAT5, SP1, SP3

miRNA regulators (miRDB)

96 targeting LMNA, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 11.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Some lamin A mutants causing disease can be aberrantly localized, partially disrupt the endogenous lamina and alter emerin localization, whereas others localize normally in transfected cells. (PMID:11792809)
• Certain dilated cardiomyopathy- and Emery-Dreyfuss muscular dystrophy-associated LMNA mutations result in misassembly of A-type lamins and give rise to a variety of nuclear structure abnormalities which may contribute to disease progression. (PMID:11792810)
• A population of cultured skin fibroblasts from lipodystrophic patients with heterozygous R482Q/W mutations in the lamin A/C gene present dysmorphic nuclei or a disorganization of the nuclear lamina, or both. (PMID:11792811)
• Lamin A-binding is mediated by the central region of emerin, residues 70-178, outside the LEM-domain. (PMID:11792821)
• homozygous defects in LMNA, encoding lamin A/C nuclear-envelope proteins, cause autosomal recessive axonal neuropathy in human (Charcot-Marie-Tooth disorder type 2) and mouse (PMID:11799477)
• LMNA gene mutations account for 33% of the dilated cardiomyopathies with atrioventricular block, all familial autosomal dominant. (PMID:11897440)
• genes known to be responsible for Emery-Dreifuss muscular dystrophy (PMID:11973618)
• Novel missense mutations in two families with the Dunnigan variety of familial partial lipodystrophy, cardiac conduction system defects, and cardiomyopathy suggest a multisystem dystrophy syndrome due to LMNA mutations. (PMID:12015247)
• 1H, 13C and 15N resonance assignments of the C-terminal domain (PMID:12018485)
• LMNA mutation is associated with autosomal dominant Emery-Dreifuss mucular dystrophy amd limb-girdle muscular dystrophy (PMID:12032588)
• solution structure of the human lamin A/C C-terminal globular domain which contains specific mutations causing four different heritable diseases (PMID:12057196)
• mutation causes mandibuloacral dysplasia (PMID:12075506)
• regions of PKC-alpha that are crucial for binding to lamin A, and vice versa (PMID:12112001)
• Absence of mutations in exon 8 of the gene in combination antiretroviral therapy-associated partial lipodystrophy. (PMID:12138353)
• Mutations in the lamin A/C gene found associated with lipodystrophy, cardiac abnormalities, and muscular dystrophy. (PMID:12196663)
• In this study, we identify a novel interaction between lamin A/C and hsMOK2 by using the yeast two-hybrid system (PMID:12409453)
• The autosomal recessive axonal Charcot-Marie-Tooth type 2 due to mutation (c.892C>T-p.R298C) in a gene encoding Lamin A/C nuclear envelope proteins and the first gene in which a mutation leads to autosomal recessive Charcot-Marie-Tooth type 2. (PMID:12467734)
• LMNA missense mutations in nondiabetic carriers with Dunnigan-type familial partial lipodystrophy (FPLD) are associated with elevated levels of serum C-reactive protein and free fatty acid, particularly in women. (PMID:12524233)
• Mutations in LMNA cause a severe and progressive dilated cardiomyopathy in a relevant proportion of patients. (PMID:12628721)
• French family affected with a new phenotype composed of autosomal dominant severe dilated cardiomyopathy & a specific quadriceps muscle myopathy;identified missense mutation in the lamin A/C gene that cosegregated with the disease (PMID:12673789)
• Hutchinson-Gilford progeria appears to represent a novel laminopathy, caused by a single heterozygous splicing mutation in the LMNA gene, leading to a major loss of Lamin A expression, intimately associated to nuclear alterations (PMID:12702809)
• point mutations in Hutchinson-Gilford progeria syndrome (PMID:12714972)
• The carboxyl-terminal region common to lamins A and C contains a DNA binding domain. (PMID:12718522)
• Results suggest that nuclear aggregate formation is in part due to overexpression of lamin A, but that there are also mutant-specific effects. (PMID:12729796)
• LMNA mutation was studied in Hutchinson-Gilford progeria. It does not occur in Wiedemann-Rautenstrauch progeroid syndrome. (PMID:12768443)
• the lamin a-emerin complex might have a role in muscular dystrophy and cardiomyopathy (PMID:12783988)
• In this study, we excluded mutations within the complete coding region and the promoter of LMNA and the CRABP II gene in HIV-1 infected patients (PMID:12844477)
• A specific phenotype characterized by early atrial fibrillation is associated with LMNA mutation. (PMID:12920062)
• REVIEW: The recent explosion in the number of identified mutations within the LMNA gene, which encodes two protein products lamins A and C, has allowed the identification of an allelic series of disorders, all caused by mutations within this one gene (PMID:13129702)
• Nuclear lamin A/C aggregates and a reduced incorporation of bromouridine were noted in fibroblasts from a familial partial lipodystrophy patient carrying an R482L lamin A/C mutation, demonstrating RNA transcription interference (PMID:14597414)
• data demonstrate that lamin C and lamin A interact in vivo directly with nesprin-1alpha and with emerin and that lamin A or C is sufficient for the correct anchorage of emerin and nesprin-1alpha at the nuclear envelope in human cells (PMID:14644157)
• A new LMNA mutation (1621C>T, R541C) was found in two members of a French family with a history of ventricular rhythm disturbances and an uncommon form of systolic left ventricle dysfunction. (PMID:14675861)
• LMNA represents the first gene implicated in both recessive and dominant forms of Charcot-Marie-Tooth disease (PMID:14985400)
• identified the epitope recognized by a new panel of mAbs against lamin A/C as a sequence of 9 amino acids that contain a complete beta-strand of the Ig-like globular domain; the major site of lipodystrophy missense mutation, R482 is present in the epitope (PMID:15026149)
• Review. Naturally occurring mutations in LMNA have been shown to be responsible for distinct diseases called laminopathies, including dilated cardiomyopathy with or without conduction defect and with or without variable skeletal muscle involvement. (PMID:15080529)
• The H566H polymorphism was associated with metabolic syndrome and also higher mean fasting triglyceride and lower mean HDL-cholesterol concentrations in the Old Order Amish. (PMID:15205219)
• Review. Laminopathies are genetic diseases that encompass a wide spectrum of phenotypes with diverse tissue pathologies and result mainly from mutations in the LMNA gene encoding nuclear lamin A/C. (PMID:15205220)
• the distinctive ensemble of heterotypic lamin interactions in a particular cell type affects the stability of the lamin polymer (PMID:15284226)
• a novel mutation associated with familial partial lipodystrophy (PMID:15298354)
• Heterozygous splicing mutation in the LMNA gene, leading to the complete or partial loss of exon 11 in mRNAs encoding Lamin A in restrictive dermopathy was found. (PMID:15317753)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	lmna	ENSDARG00000013415
mus_musculus	Lmna	ENSMUSG00000028063
rattus_norvegicus	Lmna	ENSRNOG00000019638

Paralogs (68): KRT33A (ENSG00000006059), VIM (ENSG00000026025), KRT31 (ENSG00000094796), NEFM (ENSG00000104722), KRT23 (ENSG00000108244), KRT37 (ENSG00000108417), KRT32 (ENSG00000108759), KRT18 (ENSG00000111057), LMNB1 (ENSG00000113368), KRT36 (ENSG00000126337), KRT17 (ENSG00000128422), GFAP (ENSG00000131095), KRT34 (ENSG00000131737), KRT33B (ENSG00000131738), NES (ENSG00000132688), PRPH (ENSG00000135406), KRT85 (ENSG00000135443), KRT7 (ENSG00000135480), KRT71 (ENSG00000139648), INA (ENSG00000148798), LMNTD1 (ENSG00000152936), KRT84 (ENSG00000161849), KRT82 (ENSG00000161850), KRT80 (ENSG00000167767), KRT1 (ENSG00000167768), KRT24 (ENSG00000167916), KRT8 (ENSG00000170421), KRT78 (ENSG00000170423), KRT86 (ENSG00000170442), KRT75 (ENSG00000170454), KRT6C (ENSG00000170465), KRT4 (ENSG00000170477), KRT74 (ENSG00000170484), KRT72 (ENSG00000170486), KRT83 (ENSG00000170523), BFSP2 (ENSG00000170819), KRT19 (ENSG00000171345), KRT15 (ENSG00000171346), KRT38 (ENSG00000171360), KRT13 (ENSG00000171401)

Protein

Protein identifiers

Prelamin-A/C — P02545 (reviewed: P02545)

All UniProt accessions (14): P02545, A0A384MQX1, A0A6Q8PF59, A0A6Q8PF80, A0A6Q8PFF5, A0A6Q8PFJ0, A0A6Q8PFM1, A0A6Q8PGH0, A0A6Q8PHQ9, A0A804HL68, D6RB20, H0YAB0, Q3BDU5, Q5TCI8

UniProt curated annotations — full annotation on UniProt →

Function. Lamins are intermediate filament proteins that assemble into a filamentous meshwork, and which constitute the major components of the nuclear lamina, a fibrous layer on the nucleoplasmic side of the inner nuclear membrane. Lamins provide a framework for the nuclear envelope, bridging the nuclear envelope and chromatin, thereby playing an important role in nuclear assembly, chromatin organization, nuclear membrane and telomere dynamics. Lamin A and C also regulate matrix stiffness by conferring nuclear mechanical properties. 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. Lamin A and C are present in equal amounts in the lamina of mammals. Also involved in DNA repair: recruited by DNA repair proteins XRCC4 and IFFO1 to the DNA double-strand breaks (DSBs) to prevent chromosome translocation by immobilizing broken DNA ends. Required for normal development of peripheral nervous system and skeletal muscle and for muscle satellite cell proliferation. Required for osteoblastogenesis and bone formation. Also prevents fat infiltration of muscle and bone marrow, helping to maintain the volume and strength of skeletal muscle and bone. Required for cardiac homeostasis. 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.

Subunit / interactions. Homodimer of lamin A and lamin C. Lamin dimers then assemble into dimeric head-to-tail polymers. Ultimately, two head-to-tail polymers assemble laterally into a protofilament with a uniformly shaped rod of 3.5 nm in diameter. Interacts with lamin-associated polypeptides IA, IB and TMPO-alpha, RB1 and with emerin. Interacts with SREBF1, SREBF2, SUN2 and TMEM43. Interacts with TMEM201. Proteolytically processed isoform A interacts with NARF. Interacts with SUN1. Interacts with MLIP. Interacts with DMPK; may regulate nuclear envelope stability. Interacts with SUV39H1; the interaction increases stability of SUV39H1. Interacts with SYNE2. Interacts with ITSN1 isoform 2. Interacts with IFFO1; enables the formation of an interior nucleoskeleton that is recruited to DNA double-strand breaks. Interacts with EMD. Interacts (via C-terminus) with LEMD2 (via N-terminus) (in vitro).

Subcellular location. Nucleus lamina. Nucleus envelope. Nucleus. Nucleoplasm. Nucleus matrix Nucleus speckle.

Tissue specificity. In the arteries, prelamin-A/C accumulation is not observed in young healthy vessels but is prevalent in medial vascular smooth muscle cells (VSMCs) from aged individuals and in atherosclerotic lesions, where it often colocalizes with senescent and degenerate VSMCs. Prelamin-A/C expression increases with age and disease. In normal aging, the accumulation of prelamin-A/C is caused in part by the down-regulation of ZMPSTE24/FACE1 in response to oxidative stress.

Post-translational modifications. Proteolytic cleavage of the C-terminal of 18 residues of prelamin-A/C results in the production of lamin-A/C. The prelamin-A/C maturation pathway includes farnesylation of CAAX motif by protein farnesyltransferase (FNTA and FNTB), removal of the last three amino acids (-AAX) by RCE1/FACE2 and/or ZMPSTE24, methylation of the C-terminal cysteine by ICMT and endoproteolytic removal of the last 15 C-terminal amino acids by ZMPSTE24. Proteolytic cleavage requires prior farnesylation and methylation, and absence of these blocks cleavage. Farnesylation of prelamin-A/C facilitates nuclear envelope targeting. Phosphorylation plays a key role in lamin organization, subcellular localization and nuclear envelope disintegration. Phosphorylation by CDK1 at Ser-22 and Ser-392 at the onset of mitosis drives lamin disassembly and nuclear envelope breakdown. Phosphorylation at Ser-22 and Ser-392 during interphase promotes localization to the nucleoplasm and regulates lamina assembly. Phosphorylation at Ser-22, Ser-392 and Ser-628 during interphase causes redistribution between the nucleus and the cytoplasm. Phosphorylation at Ser-22 by CDK1 regulates matrix stiffness. Phosphorylation status of Ser-22 determines its localization between double-strand break (DSB) sites and the nuclear matrix. Phosphorylated by ATR at Ser-282 in response to DNA damage, leading to lamin disassembly and nuclear envelope rupture. Phosphorylation also regulates stability in micronuclei arising from genome instability: phosphorylation at Ser-395 by ATR in response to genome instability and double-stranded DNA breaks primes LMNA for subsequent phosphorylation at Ser-392 by CDK1 and micronuclei envelope rupture. The rupture of micronuclear envelope triggers the cGAS-STING pathway thereby activating the type I interferon response and innate immunity. Acetylation by KAT8 is required for nuclear architecture. Sumoylation is necessary for the localization to the nuclear envelope.

Disease relevance. Emery-Dreifuss muscular dystrophy 2, autosomal dominant (EDMD2) [MIM:181350] A 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. The disease is caused by variants affecting the gene represented in this entry. Emery-Dreifuss muscular dystrophy 3, autosomal recessive (EDMD3) [MIM:616516] A 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. The disease is caused by variants affecting the gene represented in this entry. Cardiomyopathy, dilated, 1A (CMD1A) [MIM:115200] A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. The disease is caused by variants affecting the gene represented in this entry. Lipodystrophy, familial partial, 2 (FPLD2) [MIM:151660] An autosomal dominant 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. The disease is caused by variants affecting the gene represented in this entry. Charcot-Marie-Tooth disease, axonal, type 2B1 (CMT2B1) [MIM:605588] A 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. Hutchinson-Gilford progeria syndrome (HGPS) [MIM:176670] Rare genetic disorder characterized by features reminiscent of marked premature aging. 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. Cardiomyopathy, dilated, with hypergonadotropic hypogonadism (CMDHH) [MIM:212112] A disorder characterized by the association of genital anomalies, hypergonadotropic hypogonadism and dilated cardiomyopathy. Patients can present other variable clinical manifestations including intellectual disability, 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. The disease is caused by variants affecting the gene represented in this entry. Mandibuloacral dysplasia with type A lipodystrophy (MADA) [MIM:248370] A form of mandibuloacral dysplasia, a rare progeroid disorder with clinical and genetic heterogeneity, characterized by growth retardation, craniofacial dysmorphic features due to distal bone resorption, musculoskeletal and skin abnormalities associated with lipodystrophy. MADA is an autosomal recessive disease characterized by mandibular and clavicular hypoplasia, acroosteolysis, delayed closure of the cranial suture, progeroid appearance, partial alopecia, soft tissue calcinosis, joint contractures, and partial lipodystrophy with loss of subcutaneous fat from the extremities. Adipose tissue in the face, neck and trunk is normal or increased. The disease is caused by variants affecting the gene represented in this entry. Restrictive dermopathy 2 (RSDM2) [MIM:619793] An autosomal dominant form of restrictive dermopathy, a genodermatosis mainly characterized by intrauterine growth retardation, tight and rigid skin with erosions, prominent superficial vasculature and epidermal hyperkeratosis, facial dysmorphism, sparse/absent eyelashes and eyebrows, mineralization defects of the skull, thin dysplastic clavicles, pulmonary hypoplasia, multiple joint contractures and an early neonatal lethal course. Liveborn children usually die within the first week of life. The disease is caused by variants affecting the gene represented in this entry. Heart-hand syndrome Slovenian type (HHS-Slovenian) [MIM:610140] Heart-hand syndrome (HHS) is a clinically and genetically heterogeneous disorder characterized by the co-occurrence of a congenital cardiac disease and limb malformations. The disease is caused by variants affecting the gene represented in this entry. Muscular dystrophy congenital LMNA-related (MDCL) [MIM:613205] A form of congenital muscular dystrophy. Patients present at birth, or within the first few months of life, with hypotonia, muscle weakness and often with joint contractures. The disease is caused by variants affecting the gene represented in this entry. Defects in LMNA may cause a late-onset cardiocutaneous progeria syndrome characterized by cutaneous manifestations of aging appearing in the third decade of life, cardiac valve calcification and dysfunction, prominent atherosclerosis, and cardiomyopathy, leading to death on average in the fourth decade.

Miscellaneous. Disease-associated isoform. Polymorphism at codon 608 results in activation of a cryptic splice donor site within exon 11, resulting in a truncated protein product that lacks the site for endoproteolytic cleavage.

Similarity. Belongs to the intermediate filament family.

Isoforms (6)

UniProt ID	Names	Canonical?
P02545-1	A, Lamin-A	yes
P02545-2	C, Lamin-C
P02545-3	ADelta10, Lamin ADelta10
P02545-4	4
P02545-5	5
P02545-6	6, Progerin

RefSeq proteins (28): NP_001244303, NP_001269553, NP_001269554, NP_001269555, NP_001393912, NP_001393913, NP_001393914, NP_001393915, NP_001393916, NP_001393917, NP_001393918, NP_001393919, NP_001393920, NP_001393921, NP_001393922, NP_001393923, NP_001393924, NP_001393925, NP_001393926, NP_001393927, NP_001393928, NP_001393929, NP_001393930, NP_001393931, NP_001393932, NP_005563, NP_733821, NP_733822 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001322	Lamin_tail_dom	Domain
IPR018039	IF_conserved	Conserved_site
IPR036415	Lamin_tail_dom_sf	Homologous_superfamily
IPR039008	IF_rod_dom	Domain

Pfam: PF00038, PF00932

UniProt features (321 total): sequence variant 140, modified residue 76, mutagenesis site 28, cross-link 20, region of interest 13, strand 12, splice variant 9, helix 5, site 4, chain 2, glycosylation site 2, propeptide 2, sequence conflict 2, domain 2, lipid moiety-binding region 1, short sequence motif 1, compositionally biased region 1, turn 1

Structure

Experimental structures (PDB)

28 structures.

PDB	Method	Resolution (Å)
7WZZ	X-RAY DIFFRACTION	1.3
7X1B	X-RAY DIFFRACTION	1.4
1IFR	X-RAY DIFFRACTION	1.4
3GEF	X-RAY DIFFRACTION	1.5
8I33	X-RAY DIFFRACTION	1.62
7Z21	X-RAY DIFFRACTION	1.63
7CRG	X-RAY DIFFRACTION	1.8
7X5D	X-RAY DIFFRACTION	1.82
6YF5	X-RAY DIFFRACTION	1.83
6GHD	X-RAY DIFFRACTION	2.1
7YVD	X-RAY DIFFRACTION	2.1
1X8Y	X-RAY DIFFRACTION	2.2
6RPR	X-RAY DIFFRACTION	2.26
2XV5	X-RAY DIFFRACTION	2.4
9UL6	X-RAY DIFFRACTION	2.5
6SNZ	X-RAY DIFFRACTION	2.6
6YSH	X-RAY DIFFRACTION	2.83
6YJD	X-RAY DIFFRACTION	2.9
3V5B	X-RAY DIFFRACTION	3
3V4Q	X-RAY DIFFRACTION	3.06
6JLB	X-RAY DIFFRACTION	3.21
3V4W	X-RAY DIFFRACTION	3.7
7D9N	X-RAY DIFFRACTION	3.7
2YPT	X-RAY DIFFRACTION	3.8
9J8M	ELECTRON MICROSCOPY	3.82
9J8O	ELECTRON MICROSCOPY	4.05
9J8N	ELECTRON MICROSCOPY	7.14
1IVT	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P02545-F1	77.55	0.60

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (4): 266 (heptad change of phase); 325 (stutter); 330 (heptad change of phase); 646–647 (cleavage; by endoprotease)

Post-translational modifications (97): 661, 661, 32, 97, 171, 201, 201, 208, 219, 233, 260, 270, 311, 366, 378, 417, 420, 450, 470, 486 …

Glycosylation sites (2): 625, 628

Mutagenesis-validated functional residues (28):

Position	Phenotype
20–23	mitotic arrest; when associated with missing 391-p–p-393.
22	impaired disassembly of the nuclear envelope during mitosis. strongly decreased disassembly of the nuclear envelope duri
22	mimics phosphorylation; increased localization to the nucleoplasm during interphase. causes redistribution between the n
28	impaired lamin assembly.
32	impaired lamin assembly.
41	impaired lamin assembly.
201	decreased sumoylation; aberrant localization with decreased nuclear rim staining and formation of intranuclear foci; ass
282	impaired phosphorylation by atr in response to dna damage, leading to decreased nuclear envelope rupture.
373	impaired lamin assembly.
375	impaired lamin assembly.
377	impaired lamin assembly.
381	impaired lamin assembly.
384	impaired lamin assembly.
386	loss of interaction with iffo1.
386	impaired lamin assembly.
390	decreased localization to the nucleoplasm during interphase.
391–393	mitotic arrest; when associated with missing 20-p–p-23.
392	impaired disassembly of the nuclear envelope during mitosis. strongly decreased disassembly of the nuclear envelope duri
392	mimics phosphorylation; increased localization to the nucleoplasm during interphase. causes redistribution between the n
395	impaired phosphorylation by atr in response to genome instability leading ro decreased phosphorylation by cdk1.
395	mimics phosphorylation; disassembly of the micronuclear envelope in response to genome instability.
404–407	mimics phosphorylation; increased localization to the nucleoplasm during interphase.
628	mimics phosphorylation; causes redistribution between the nucleus and the cytoplasm during interphase; when associated w
644	does not affect tail cleavage.
647	completely inhibits tail cleavage.

Function

Pathways and Gene Ontology

Reactome pathways

15 pathways

ID	Pathway
R-HSA-381038	XBP1(S) activates chaperone genes
R-HSA-6802952	Signaling by BRAF and RAF1 fusions
R-HSA-1221632	Meiotic synapsis
R-HSA-2980766	Nuclear Envelope Breakdown
R-HSA-2995383	Initiation of Nuclear Envelope (NE) Reformation
R-HSA-352238	Breakdown of the nuclear lamina
R-HSA-4419969	Depolymerization of the Nuclear Lamina
R-HSA-8862803	Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer’s disease models
R-HSA-1643685	Disease
R-HSA-2262752	Cellular responses to stress
R-HSA-381070	IRE1alpha activates chaperones
R-HSA-381119	Unfolded Protein Response (UPR)
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers
R-HSA-6802957	Oncogenic MAPK signaling
R-HSA-8953897	Cellular responses to stimuli

MSigDB gene sets: 1351 (showing top): GOBP_CHROMOSOME_ORGANIZATION, AP1_01, REACTOME_UNFOLDED_PROTEIN_RESPONSE_UPR, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, REACTOME_MEIOTIC_SYNAPSIS, GOBP_CHROMOSOME_LOCALIZATION, GOZGIT_ESR1_TARGETS_DN, MAZ_Q6, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOBP_VENTRICULAR_CARDIAC_MUSCLE_CELL_DIFFERENTIATION, GOBP_TELOMERE_ORGANIZATION, GOBP_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE

GO Biological Process (26): double-strand break repair via nonhomologous end joining (GO:0006303), protein import into nucleus (GO:0006606), nuclear envelope organization (GO:0006998), nuclear migration (GO:0007097), muscle organ development (GO:0007517), intracellular protein localization (GO:0008104), negative regulation of cell population proliferation (GO:0008285), positive regulation of gene expression (GO:0010628), regulation of cell migration (GO:0030334), establishment or maintenance of microtubule cytoskeleton polarity (GO:0030951), heterochromatin formation (GO:0031507), regulation of protein stability (GO:0031647), regulation of telomere maintenance (GO:0032204), protein localization to nucleus (GO:0034504), nuclear pore localization (GO:0051664), ventricular cardiac muscle cell development (GO:0055015), cellular response to hypoxia (GO:0071456), negative regulation of mesenchymal cell proliferation (GO:0072201), negative regulation of release of cytochrome c from mitochondria (GO:0090201), cellular senescence (GO:0090398), protein localization to nuclear envelope (GO:0090435), regulation of protein localization to nucleus (GO:1900180), negative regulation of cardiac muscle hypertrophy in response to stress (GO:1903243), DNA double-strand break attachment to nuclear envelope (GO:1990683), negative regulation of extrinsic apoptotic signaling pathway (GO:2001237), nucleus organization (GO:0006997)

GO Molecular Function (5): structural molecule activity (GO:0005198), structural constituent of cytoskeleton (GO:0005200), identical protein binding (GO:0042802), structural constituent of nuclear lamina (GO:0160123), protein binding (GO:0005515)

GO Cellular Component (13): nucleus (GO:0005634), nuclear envelope (GO:0005635), lamin filament (GO:0005638), nuclear lamina (GO:0005652), nucleoplasm (GO:0005654), cytosol (GO:0005829), intermediate filament (GO:0005882), nuclear matrix (GO:0016363), nuclear speck (GO:0016607), nuclear membrane (GO:0031965), site of double-strand break (GO:0035861), perinuclear region of cytoplasm (GO:0048471), nuclear lumen (GO:0031981)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
IRE1alpha activates chaperones	1
Oncogenic MAPK signaling	1
Meiosis	1
Mitotic Prophase	1
Nuclear Envelope (NE) Reassembly	1
Apoptotic cleavage of cellular proteins	1
Nuclear Envelope Breakdown	1
Neurodegenerative Diseases	1
Cellular responses to stimuli	1
Unfolded Protein Response (UPR)	1
Cellular responses to stress	1
Disease	1
Diseases of signal transduction by growth factor receptors and second messengers	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
nucleus	3
nucleus organization	2
cellular response to stress	2
structural molecule activity	2
nuclear envelope	2
nuclear lumen	2
cytoplasm	2
double-strand break repair	1
intracellular protein transport	1
protein localization to nucleus	1
import into nucleus	1
establishment of protein localization to organelle	1
endomembrane system organization	1
membrane organization	1
intracellular transport	1
nucleus localization	1
establishment of organelle localization	1
animal organ development	1
muscle structure development	1
macromolecule localization	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
cell migration	1
regulation of cell motility	1
microtubule cytoskeleton organization	1
establishment or maintenance of cytoskeleton polarity	1
cellular component assembly	1
heterochromatin boundary formation	1
negative regulation of gene expression, epigenetic	1
heterochromatin organization	1
regulation of biological quality	1
telomere maintenance	1
regulation of chromosome organization	1
regulation of DNA metabolic process	1
protein localization to organelle	1

Protein interactions and networks

STRING

4858 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LMNA	EMD	P50402	997
LMNA	SUN2	Q9UH99	982
LMNA	SUN1	O94901	978
LMNA	SYNE1	Q8NF91	970
LMNA	SYNE2	Q8WXH0	966
LMNA	ZMPSTE24	O75844	928
LMNA	BANF1	O75531	847
LMNA	TMPO	P08918	838
LMNA	SGCD	Q92629	815
LMNA	BANF2	Q9H503	811
LMNA	BSCL2	Q96G97	803
LMNA	TMEM43	Q9BTV4	801
LMNA	SREBF1	P36956	790
LMNA	ZNF239	Q16600	788
LMNA	PKP2	Q99959	754

IntAct

496 interactions, top by confidence:

A	B	Type	Score
LMNA	LMNB1	psi-mi:“MI:2364”(proximity)	0.930
LMNA	LMNB1	psi-mi:“MI:0915”(physical association)	0.930
LMNA	LMNB2	psi-mi:“MI:0915”(physical association)	0.850
EMD	LMNA	psi-mi:“MI:0407”(direct interaction)	0.800
LMNA	EMD	psi-mi:“MI:0403”(colocalization)	0.800
DUSP13B	LMNA	psi-mi:“MI:0915”(physical association)	0.780
LMNA	DUSP13B	psi-mi:“MI:0915”(physical association)	0.780
SUN2	LMNA	psi-mi:“MI:0914”(association)	0.720
SUN2	LMNA	psi-mi:“MI:0915”(physical association)	0.720
CFTR	XPO1	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
LMNA	SNW1	psi-mi:“MI:0915”(physical association)	0.670
TMPO	LMNA	psi-mi:“MI:0407”(direct interaction)	0.630
LMNA		psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-7	LMNA	psi-mi:“MI:0915”(physical association)	0.560
	LMNA	psi-mi:“MI:0915”(physical association)	0.560
LMNA	KRTAP10-7	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (1819): LMNA (Affinity Capture-MS), LMNA (Affinity Capture-MS), LMNA (Affinity Capture-MS), LMNA (Two-hybrid), DUSP13 (Two-hybrid), KRTAP10-7 (Two-hybrid), KRTAP10-3 (Two-hybrid), LMNA (Affinity Capture-RNA), LMNA (Affinity Capture-RNA), LMNA (Affinity Capture-RNA), LMNA (Affinity Capture-RNA), LMNA (Affinity Capture-MS), LMNA (Affinity Capture-MS), LMNA (Affinity Capture-MS), LMNA (Affinity Capture-MS)

ESM2 similar proteins: A0A125S9M4, A0A125S9M5, A0A125S9M6, A0A8C0N8E3, O62654, P02540, P02541, P02542, P02543, P02544, P02545, P08552, P08670, P09654, P10999, P11048, P14732, P16275, P17661, P20152, P21910, P22488, P23239, P23729, P24789, P24790, P31000, P31001, P31393, P35617, P48616, P48670, P48673, P48674, P48675, P48676, P48678, P48679, P84198, Q03427

Diamond homologs: A0A125S9M6, A0JND2, A4FUZ0, A5A6M8, A6NCN2, A7YWK3, O43790, P02542, P02545, P02547, P02548, P04104, P04260, P04261, P04262, P04263, P07196, P07744, P08551, P08928, P09010, P10999, P12035, P12036, P13647, P13648, P15241, P16884, P19013, P19246, P19527, P21619, P21910, P25691, P35908, P48671, P48672, P48678, P48679, P78385

SIGNOR signaling

12 interactions.

A	Effect	B	Mechanism
CDK1	up-regulates	LMNA	phosphorylation
“Caspase 6 complex”	down-regulates	LMNA	cleavage
LMNA	“up-regulates activity”	SUN2	relocalization
SRC	“up-regulates activity”	LMNA	phosphorylation
CASP6	down-regulates	LMNA	cleavage
LMNA	down-regulates	Adipogenesis
PRKCA	“up-regulates activity”	LMNA	phosphorylation
PRKCA	unknown	LMNA	phosphorylation
LMNA	up-regulates	Membrane_blebbing

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 163 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Depolymerization of the Nuclear Lamina	5	35.6×	6e-05
Initiation of Nuclear Envelope (NE) Reformation	5	28.1×	2e-04
Nuclear Envelope Breakdown	5	21.4×	4e-04
Meiosis	6	16.0×	3e-04
Meiotic synapsis	9	11.9×	4e-05
Reproduction	6	10.7×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
heterochromatin formation	7	12.5×	5e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

2429 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	300
Likely pathogenic	166
Uncertain significance	882
Likely benign	550
Benign	55

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
100690	NM_170707.4(LMNA):c.1620G>A (p.Met540Ile)	Pathogenic
1010089	NM_170707.4(LMNA):c.239_256del (p.Ala80_Leu85del)	Pathogenic
1068933	NM_170707.4(LMNA):c.1253del (p.Lys418fs)	Pathogenic
1069289	NM_170707.4(LMNA):c.481G>T (p.Glu161Ter)	Pathogenic
1069324	NM_170707.4(LMNA):c.1150G>A (p.Glu384Lys)	Pathogenic
1069623	NM_170707.4(LMNA):c.526del (p.Ala175_Leu176insTer)	Pathogenic
1069958	NM_170707.4(LMNA):c.1232del (p.Gly411fs)	Pathogenic
1070600	NM_170707.4(LMNA):c.298_299del (p.Ala100fs)	Pathogenic
1071831	NM_170707.4(LMNA):c.792_793insGCCGGGCGCGGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCCGATGCGGGCGGATCACGAGGTCAGGAGATCGAGACCATCCCGGCTAAAACGGTGAAACCCCGTCTCTACNNNNNNNNNNAAAAAAAAAAAAAAAAAAAAAAGAAGGAGCTGGAG (p.Lys265delinsAlaGlyArgGlyGlySerArgLeuTer)	Pathogenic
1071868	NC_000001.10:g.(?156083461)(156110880_?)del	Pathogenic
1071869	NC_000001.10:g.(?156084700)(156108907_?)del	Pathogenic
1071935	NM_170707.4(LMNA):c.275T>C (p.Leu92Pro)	Pathogenic
1072048	NM_170707.4(LMNA):c.1526del (p.Pro509fs)	Pathogenic
1072148	NM_170707.4(LMNA):c.186dup (p.Ile63fs)	Pathogenic
1072780	NM_170707.4(LMNA):c.1377dup (p.Glu460Ter)	Pathogenic
1073872	NM_170707.4(LMNA):c.1321del (p.Ala441fs)	Pathogenic
1076432	NM_170707.4(LMNA):c.1248del (p.Lys418fs)	Pathogenic
1076448	NM_170707.4(LMNA):c.1414C>T (p.Gln472Ter)	Pathogenic
1076704	NM_170707.4(LMNA):c.1A>T (p.Met1Leu)	Pathogenic
1187608	NM_170707.4(LMNA):c.433G>T (p.Glu145Ter)	Pathogenic
1323240	NM_170707.4(LMNA):c.65del (p.Ser22fs)	Pathogenic
1338321	NM_170707.4(LMNA):c.810+2T>C	Pathogenic
1347909	NC_000001.10:g.(?156105693)(156106165_?)del	Pathogenic
1357086	NM_170707.4(LMNA):c.280T>C (p.Ser94Pro)	Pathogenic
1358953	NM_170707.4(LMNA):c.283_284delinsTG (p.Val95Ter)	Pathogenic
1364147	NM_170707.4(LMNA):c.422T>C (p.Leu141Pro)	Pathogenic
1383718	NM_170707.4(LMNA):c.1232dup (p.Gly412fs)	Pathogenic
1412639	NM_170707.4(LMNA):c.203A>T (p.Glu68Val)	Pathogenic
1434231	NM_170707.4(LMNA):c.623_626dup (p.Asn209fs)	Pathogenic
1434909	NM_170707.4(LMNA):c.334G>T (p.Glu112Ter)	Pathogenic

SpliceAI

1360 predictions. Top by Δscore:

Variant	Effect	Δscore
1:156115252:GAGTT:G	donor_gain	1.0000
1:156115270:GCGCG:G	donor_gain	1.0000
1:156115272:GCG:G	donor_gain	1.0000
1:156115273:CGGTG:C	donor_loss	1.0000
1:156115274:GGTG:G	donor_loss	1.0000
1:156115275:G:T	donor_loss	1.0000
1:156115276:T:A	donor_loss	1.0000
1:156130615:A:AG	acceptor_gain	1.0000
1:156130615:A:AT	acceptor_loss	1.0000
1:156130616:G:GA	acceptor_gain	1.0000
1:156130616:GC:G	acceptor_gain	1.0000
1:156130616:GCA:G	acceptor_gain	1.0000
1:156130616:GCAA:G	acceptor_gain	1.0000
1:156130616:GCAAT:G	acceptor_gain	1.0000
1:156130770:CAAG:C	donor_loss	1.0000
1:156130774:GTG:G	donor_loss	1.0000
1:156134390:T:A	acceptor_gain	1.0000
1:156134398:CACA:C	acceptor_loss	1.0000
1:156134400:C:G	acceptor_gain	1.0000
1:156134401:A:AG	acceptor_gain	1.0000
1:156134401:AGCTT:A	acceptor_gain	1.0000
1:156134402:G:GA	acceptor_gain	1.0000
1:156134402:GC:G	acceptor_gain	1.0000
1:156134402:GCT:G	acceptor_gain	1.0000
1:156134402:GCTT:G	acceptor_gain	1.0000
1:156134402:GCTTG:G	acceptor_gain	1.0000
1:156134524:G:GG	donor_gain	1.0000
1:156134524:GTGAG:G	donor_loss	1.0000
1:156134526:GAGGT:G	donor_loss	1.0000
1:156134527:AGGTG:A	donor_loss	1.0000

AlphaMissense

4308 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:156115014:G:C	K32N	1.000
1:156115014:G:T	K32N	1.000
1:156115022:T:C	L35P	1.000
1:156115031:T:A	L38H	1.000
1:156115031:T:C	L38P	1.000
1:156115033:A:G	N39D	1.000
1:156115035:T:A	N39K	1.000
1:156115035:T:G	N39K	1.000
1:156115039:C:A	R41S	1.000
1:156115040:G:C	R41P	1.000
1:156115043:T:C	L42S	1.000
1:156115051:T:C	Y45H	1.000
1:156115055:T:A	I46N	1.000
1:156115055:T:G	I46S	1.000
1:156115067:G:C	R50P	1.000
1:156115073:T:C	L52P	1.000
1:156115094:T:C	L59P	1.000
1:156115172:T:C	L85P	1.000
1:156115180:G:C	A88P	1.000
1:156115183:C:A	R89S	1.000
1:156115184:G:C	R89P	1.000
1:156115193:T:C	L92P	1.000
1:156115214:G:C	R99P	1.000
1:156115223:T:C	L102P	1.000
1:156115229:T:C	L104P	1.000
1:156130703:T:C	L148P	1.000
1:156134437:T:C	L183P	1.000
1:156134452:T:C	L188P	1.000
1:156134458:G:C	R190P	1.000
1:156134472:A:G	N195D	1.000

dbSNP variants (sampled 300 via entrez): RS1000064140 (1:156095615 T>C), RS1000109884 (1:156081652 C>T), RS1000233283 (1:156115889 G>A), RS1000259993 (1:156135413 T>C), RS1000372765 (1:156095918 A>G), RS1000414053 (1:156107805 T>C), RS1000425996 (1:156128075 G>A), RS1000428024 (1:156082177 C>T), RS1000507847 (1:156101135 A>G), RS1000521041 (1:156101377 A>G), RS1000623199 (1:156122930 C>A), RS1000623358 (1:156100987 T>A), RS1000668572 (1:156116702 T>A,C), RS1000679005 (1:156108241 C>G,T), RS1000776343 (1:156116217 C>G)

Disease associations

OMIM: gene MIM:150330 | disease phenotypes: MIM:248370, MIM:115200, MIM:151660, MIM:176670, MIM:212112, MIM:605588, MIM:610140, MIM:613205, MIM:616516, MIM:159001, MIM:181350, MIM:619793, MIM:275210, MIM:118220, MIM:310300, MIM:613426, MIM:192600, MIM:182960, MIM:616689, MIM:609040, MIM:125850, MIM:606391, MIM:604169, MIM:115195, MIM:601494, MIM:600996, MIM:604772, MIM:610549, MIM:194200, MIM:162500, MIM:158810, MIM:253601

GenCC curated gene-disease

Disease	Classification	Inheritance
dilated cardiomyopathy 1A	Definitive	Autosomal dominant
Hutchinson-Gilford progeria syndrome	Definitive	Autosomal dominant
Emery-Dreifuss muscular dystrophy 2, autosomal dominant	Definitive	Semidominant
familial partial lipodystrophy, Dunnigan type	Definitive	Autosomal dominant
restrictive dermopathy 2	Definitive	Autosomal recessive
Charcot-Marie-Tooth disease type 2B1	Strong	Autosomal dominant
heart-hand syndrome, Slovenian type	Strong	Autosomal dominant
atrioventricular block	Strong	Autosomal dominant
mandibuloacral dysplasia with type A lipodystrophy	Strong	Autosomal recessive
Emery-Dreifuss muscular dystrophy 3, autosomal recessive	Strong	Autosomal recessive
atrial fibrillation	Moderate	Autosomal dominant
familial isolated dilated cardiomyopathy	Supportive	Autosomal dominant
congenital muscular dystrophy due to LMNA mutation	Supportive	Autosomal dominant
lethal restrictive dermopathy	Supportive	Autosomal dominant
dilated cardiomyopathy-hypergonadotropic hypogonadism syndrome	Supportive	Autosomal recessive
autosomal semi-dominant severe lipodystrophic laminopathy	Supportive	Semidominant
LMNA-related cardiocutaneous progeria syndrome	Supportive	Autosomal dominant
atypical Werner syndrome	Supportive	Autosomal dominant
autosomal dominant Emery-Dreifuss muscular dystrophy	Supportive	Autosomal dominant
autosomal recessive Emery-Dreifuss muscular dystrophy	Supportive	Autosomal recessive
arrhythmogenic right ventricular cardiomyopathy	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (3)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
dilated cardiomyopathy 1A	Definitive	AD
lipodystrophy	Definitive	SD
arrhythmogenic right ventricular cardiomyopathy	Limited	AD

Mondo (63): Charcot-Marie-Tooth disease type 2 (MONDO:0018993), cardiomyopathy (MONDO:0004994), mandibuloacral dysplasia with type A lipodystrophy (MONDO:0009557), dilated cardiomyopathy (MONDO:0005021), dilated cardiomyopathy 1A (MONDO:0007269), familial partial lipodystrophy, Dunnigan type (MONDO:0007906), Hutchinson-Gilford progeria syndrome (MONDO:0008310), dilated cardiomyopathy-hypergonadotropic hypogonadism syndrome (MONDO:0008915), Charcot-Marie-Tooth disease type 2B1 (MONDO:0011569), heart-hand syndrome, Slovenian type (MONDO:0012417), congenital muscular dystrophy due to LMNA mutation (MONDO:0013178), Emery-Dreifuss muscular dystrophy 3, autosomal recessive (MONDO:0014676), Emery-Dreifuss muscular dystrophy 2, autosomal dominant (MONDO:0021569), restrictive dermopathy 2 (MONDO:0030781), muscular dystrophy (MONDO:0020121)

Orphanet (43): Autosomal dominant Charcot-Marie-Tooth disease type 2 (Orphanet:64746), Rare cardiomyopathy (Orphanet:167848), Mandibuloacral dysplasia (Orphanet:2457), Mandibuloacral dysplasia with type A lipodystrophy (Orphanet:90153), Dilated cardiomyopathy (Orphanet:217604), Congenital muscular dystrophy due to LMNA mutation (Orphanet:157973), Heart-hand syndrome, Slovenian type (Orphanet:168796), Dilated cardiomyopathy-hypergonadotropic hypogonadism syndrome (Orphanet:2229), Familial partial lipodystrophy, Dunnigan type (Orphanet:2348), Emery-Dreifuss muscular dystrophy (Orphanet:261), Autosomal dominant limb-girdle muscular dystrophy type 1B (Orphanet:264), Familial dilated cardiomyopathy with conduction defect due to LMNA mutation (Orphanet:300751), Hutchinson-Gilford progeria syndrome (Orphanet:740), Autosomal recessive Emery-Dreifuss muscular dystrophy (Orphanet:98855), Charcot-Marie-Tooth disease type 2B1 (Orphanet:98856)

HPO phenotypes

520 total (30 of 520 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000035	Abnormal testis morphology
HP:0000047	Hypospadias
HP:0000050	Hypoplastic male external genitalia
HP:0000073	Ureteral duplication
HP:0000134	Female hypogonadism
HP:0000135	Hypogonadism
HP:0000144	Decreased fertility
HP:0000147	Polycystic ovaries
HP:0000160	Narrow mouth
HP:0000164	Abnormality of the dentition
HP:0000176	Submucous cleft hard palate
HP:0000200	Short lingual frenulum
HP:0000218	High palate
HP:0000233	Thin vermilion border
HP:0000239	Large fontanelles
HP:0000270	Delayed cranial suture closure
HP:0000272	Malar flattening
HP:0000275	Narrow face
HP:0000278	Retrognathia
HP:0000287	Increased facial adipose tissue
HP:0000293	Full cheeks
HP:0000308	Microretrognathia
HP:0000311	Round face
HP:0000316	Hypertelorism
HP:0000320	Bird-like facies
HP:0000331	Short chin
HP:0000347	Micrognathia
HP:0000365	Hearing impairment

GWAS associations

19 associations (top):

Study	Trait	p-value
GCST004749_53	Lung cancer in ever smokers	7.000000e-06
GCST007088_3	Ischemic heart disease in rheumatoid arthritis	5.000000e-07
GCST007239_3	Ovarian cancer	2.000000e-06
GCST008362_92	Birth weight	8.000000e-12
GCST008972_109	Urate levels	3.000000e-08
GCST010696_19	Cortical thickness (min-P)	2.000000e-10
GCST010697_10	Cortical surface area (min-P)	3.000000e-10
GCST010698_59	Subcortical volume (min-P)	9.000000e-10
GCST010699_20	Brain morphology (min-P)	7.000000e-10
GCST010700_5	Cortical thickness (MOSTest)	8.000000e-17
GCST010701_66	Cortical surface area (MOSTest)	1.000000e-09
GCST010702_43	Subcortical volume (MOSTest)	3.000000e-10
GCST010703_253	Brain morphology (MOSTest)	4.000000e-14
GCST012489_121	Heel bone mineral density x serum urate levels interaction	4.000000e-10
GCST90000025_771	Appendicular lean mass	1.000000e-12
GCST90002393_156	Monocyte count	3.000000e-14
GCST90002398_493	Neutrophil count	6.000000e-10
GCST90002407_1	White blood cell count	8.000000e-12
GCST90020026_629	Hip index	1.000000e-08

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0001425	ischemic cardiomyopathy
EFO:0004344	birth weight
EFO:0004531	urate measurement
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness
EFO:0009270	heel bone mineral density
EFO:0004980	appendicular lean mass
EFO:0005091	monocyte count
EFO:0004833	neutrophil count
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (39)

Descriptor	Name	Tree numbers
D019571	Arrhythmogenic Right Ventricular Dysplasia	C14.240.400.145; C14.280.238.028; C14.280.400.145; C16.131.240.400.145
D001281	Atrial Fibrillation	C14.280.067.198; C23.550.073.198
D054537	Atrioventricular Block	C14.280.067.558.230; C14.280.123.500.230; C23.550.073.425.062
D009202	Cardiomyopathies	C14.280.238
D002311	Cardiomyopathy, Dilated	C14.280.195.160; C14.280.238.070; C16.320.488.750
D002312	Cardiomyopathy, Hypertrophic	C14.280.238.100; C14.280.484.048.750.070.160
D024741	Cardiomyopathy, Hypertrophic, Familial	C14.280.238.100.500; C14.280.484.048.750.070.160.500; C16.320.160
D002607	Charcot-Marie-Tooth Disease	C10.500.300.200; C10.574.500.495.200; C10.668.829.800.300.200; C16.131.666.300.200; C16.320.400.375.200
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D000083083	Laminopathies	C16.320.488
D008060	Lipodystrophy	C17.800.849.391; C18.452.584.625; C18.452.880.391
D052496	Lipodystrophy, Familial Partial	C16.320.488.813; C17.800.849.391.700; C18.452.584.563.798; C18.452.584.625.700; C18.452.880.391.700
D008133	Long QT Syndrome	C14.280.067.565; C14.280.123.625; C16.131.240.400.715; C23.550.073.547
D008659	Metabolic Diseases	C18.452
D009136	Muscular Dystrophies	C05.651.534.500; C10.668.491.175.500; C16.320.577
D049288	Muscular Dystrophies, Limb-Girdle	C05.651.534.500.280; C10.668.491.175.500.149; C16.320.577.280
D020389	Muscular Dystrophy, Emery-Dreifuss	C05.651.534.500.350; C10.668.491.175.500.350; C16.320.322.625; C16.320.577.350
D009205	Myocarditis	C14.280.238.625
D009468	Neuromuscular Diseases	C10.668
D011115	Polyneuropathies	C10.668.829.800
D012804	Sick Sinus Syndrome	C14.280.067.093.249; C14.280.067.558.536; C14.280.123.500.536; C23.550.073.093.249; C23.550.073.425.440
D017180	Tachycardia, Ventricular	C14.280.067.845.940; C14.280.123.875.940; C23.550.073.845.940
D014927	Wolff-Parkinson-White Syndrome	C14.280.067.780.977; C14.280.123.750.977; C16.131.240.400.980
C563409	Arrhythmogenic Right Ventricular Dysplasia, Familial, 2 (supp.)
C563808	Arrhythmogenic Right Ventricular Dysplasia, Familial, 9 (supp.)
C563306	Cardiomyopathy, Dilated, 1D (supp.)
C563538	Cardiomyopathy, Dilated, 1s (supp.)
C566171	Cardiomyopathy, Familial Hypertrophic, 2 (supp.)
C537990	Charcot-Marie-Tooth disease, Type 2B1 (supp.)
C562710	Diabetes Mellitus, Insulin-Resistant, with Acanthosis Nigricans (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1293235 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

823 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,023,123 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1008	BEPRIDIL	4	11,776
CHEMBL101	PHENYLBUTAZONE	4	59,455
CHEMBL1010	CEFOTAXIME SODIUM	4	4,928
CHEMBL1018	DIENESTROL	4	5,607
CHEMBL1024	IFOSFAMIDE	4	139,212
CHEMBL103	PROGESTERONE	4	162,141
CHEMBL104	CLOTRIMAZOLE	4	56,325
CHEMBL1043	DAPSONE	4	64,779
CHEMBL1046	AMINOCAPROIC ACID	4	95,343
CHEMBL106	FLUCONAZOLE	4	58,942
CHEMBL107	COLCHICINE	4	93,932
CHEMBL1070	NABUMETONE	4	55,063
CHEMBL1071	OXAPROZIN	4	51,044
CHEMBL1072	BUMETANIDE	4	22,087
CHEMBL1073	GLIPIZIDE	4	42,268
CHEMBL1077	BROMFENAC	4	12,495
CHEMBL1077896	ROPIVACAINE	4	17,078
CHEMBL1079	TIZANIDINE	4	12,099
CHEMBL1079604	METAXALONE	4	5,021
CHEMBL108	CARBAMAZEPINE	4	53,528
CHEMBL1082607	SALMETEROL XINAFOATE	4
CHEMBL1083993	AMIODARONE HYDROCHLORIDE	4
CHEMBL108545	METHYL SALICYLATE	4
CHEMBL1086	DIBUCAINE	4
CHEMBL1089	PHENELZINE	4
CHEMBL1091	HYDROCORTISONE ACETATE	4
CHEMBL1095292	BRETYLIUM TOSYLATE	4
CHEMBL11	IMIPRAMINE	4
CHEMBL1103	FURAZOLIDONE	4
CHEMBL1108	DROPERIDOL	4

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

6100 potent at pChembl≥5 of 6100 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.00	Potency	1	nM	CHEMBL299683
9.00	Potency	1	nM	DIMENHYDRINATE
9.00	Potency	1	nM	CHEMBL34730
9.00	Potency	1	nM	CHEMBL1354897
9.00	Potency	1	nM	CHEMBL3208546
9.00	Potency	1	nM	LISINOPRIL
9.00	Potency	1	nM	AZELASTINE HYDROCHLORIDE
9.00	Potency	1	nM	CHEMBL1525482
9.00	Potency	1	nM	BETA-CCM
9.00	Potency	1	nM	CHEMBL1414201
8.96	Potency	1.1	nM	VINCRISTINE
8.96	Potency	1.1	nM	PYRILAMINE
8.96	Potency	1.1	nM	XYLAZINE HYDROCHLORIDE
8.96	Potency	1.1	nM	NEBOGLAMINE
8.96	Potency	1.1	nM	CHEMBL1559809
8.89	Potency	1.3	nM	CHEMBL1609179
8.89	Potency	1.3	nM	3-AMINOBENZAMIDE
8.89	Potency	1.3	nM	CHEMBL1477366
8.85	Potency	1.4	nM	CHEMBL1255748
8.85	Potency	1.4	nM	CARBON TETRACHLORIDE
8.85	Potency	1.4	nM	CHEMBL1393947
8.85	Potency	1.4	nM	CHEMBL1309943
8.80	Potency	1.6	nM	CHEMBL1603820
8.80	Potency	1.6	nM	CHEMBL1357195
8.80	Potency	1.6	nM	ESATENOLOL
8.74	Potency	1.8	nM	NIMODIPINE
8.74	Potency	1.8	nM	CHEMBL1512321
8.74	Potency	1.8	nM	CHEMBL1336122
8.74	Potency	1.8	nM	MODAFINIL
8.74	Potency	1.8	nM	PACLITAXEL
8.74	Potency	1.8	nM	ETHACRIDINE
8.74	Potency	1.8	nM	CHEMBL1317208
8.74	Potency	1.8	nM	CHEMBL1401685
8.74	Potency	1.8	nM	SULFADIMETHOXINE
8.74	Potency	1.8	nM	CHEMBL1362780
8.74	Potency	1.8	nM	7-CHLOROKYNURENIC ACID
8.70	Potency	2	nM	ETHAVERINE
8.70	Potency	2	nM	EBSELEN
8.70	Potency	2	nM	CHEMBL1594626
8.70	Potency	2	nM	CHEMBL1526957
8.70	Potency	2	nM	CHEMBL1438136
8.70	Potency	2	nM	CHEMBL1425133
8.70	Potency	2	nM	CHEMBL1427364
8.70	Potency	2	nM	KETOTIFEN
8.70	Potency	2	nM	CHEMBL280563
8.70	Potency	2	nM	CHEMBL51533
8.70	Potency	2	nM	CHEMBL1372997
8.70	Potency	2	nM	(-)-ROLIPRAM
8.70	Potency	2	nM	VENLAFAXINE
8.70	Potency	2	nM	METHIMAZOLE

PubChem BioAssay actives

4 with measured affinity, of 12 total; 3 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2179180: Binding affinity against LMNA (unknown origin) assessed as apparent dissociation constant incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	kd	0.5480	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148607: Binding affinity to human LMNA incubated for 45 mins by Kinobead based pull down assay	kd	2.3977	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148607: Binding affinity to human LMNA incubated for 45 mins by Kinobead based pull down assay	kd	5.4119	uM

CTD chemical–gene interactions

141 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Particulate Matter	increases abundance, affects cotreatment, increases expression, increases methylation, affects expression (+1 more)	6
sodium arsenite	decreases expression, increases abundance, increases expression, affects expression, affects cotreatment	5
Benzo(a)pyrene	decreases expression, increases expression, increases methylation, affects cotreatment	4
Resveratrol	decreases acetylation, increases cleavage, increases reaction, affects binding, increases activity	3
Air Pollutants	affects cotreatment, decreases expression, increases abundance, increases oxidation, increases expression	3
Arsenic	increases abundance, affects methylation, affects cotreatment, decreases expression	3
Quercetin	decreases expression, decreases phosphorylation	3
Valproic Acid	affects expression, decreases expression, increases expression	3
bisphenol A	increases expression, affects cotreatment, decreases expression	2
methacrylaldehyde	affects cotreatment, decreases expression, increases oxidation, increases abundance	2
mercuric bromide	increases expression, affects cotreatment	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	2
bisphenol S	increases expression, affects cotreatment, decreases expression	2
Zoledronic Acid	decreases expression, decreases farnesylation	2
Acrolein	increases abundance, affects cotreatment, decreases expression, increases oxidation	2
Vehicle Emissions	affects expression, increases abundance, increases expression	2
Dinitrochlorobenzene	affects binding, increases metabolic processing	2
Doxorubicin	increases cleavage, affects phosphorylation, affects response to substance	2
Mustard Gas	affects reaction, increases cleavage, increases reaction, increases phosphorylation	2
Nickel	increases expression	2
Ozone	affects cotreatment, decreases expression, increases oxidation, increases abundance	2
Phenylmercuric Acetate	increases expression, affects cotreatment	2
Smoke	increases abundance, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Cyclosporine	increases expression	2
Cadmium Chloride	increases cleavage, increases expression	2
Ritonavir	increases expression, increases farnesylation	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1

ChEMBL screening assays

12 unique, capped per target: 9 binding, 3 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1614073	Functional	PUBCHEM_BIOASSAY: Confirmation Concentration-Response Assay for Modulators of Lamin A Splicing. (Class of assay: confirmatory) [Related pubchem assays: 1487 ]	PubChem BioAssay data set
CHEMBL5338463	Binding	Binding affinity to LMNA (unknown origin) assessed as fold change in protein upregulation at 200 uM preincubated for 2 hrs followed by pronase addition and measured after 30 mins by coomassie blue staining based SDS-PAGE gel analysis	Structurally Diverse Alkaloids with Anti-Renal-Fibrosis Activity from the Centipede Scolopendra subspinipes mutilans. — J Nat Prod

Cellosaurus cell lines

192 cell lines: 70 transformed cell line, 51 finite cell line, 44 induced pluripotent stem cell, 16 cancer cell line, 6 telomerase immortalized cell line, 5 factor-dependent cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_0Q88	AG10587	Transformed cell line	Male
CVCL_0Q91	AG10579	Transformed cell line	Male
CVCL_0Q95	AG10677	Finite cell line	Male
CVCL_0Q96	AG10801	Transformed cell line	Female
CVCL_0Q97	AG11513	Finite cell line	Female
CVCL_1D62	HeLa Kyoto EGFP-LaminA/H2B-mCherry	Cancer cell line	Female
CVCL_1Y86	HGADFN003	Finite cell line	Male
CVCL_1Y87	HGADFN122	Finite cell line	Female
CVCL_1Y88	HGADFN127	Finite cell line	Female
CVCL_1Y89	HGADFN143	Finite cell line	Male

Clinical trials (associated diseases)

600 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00032591	PHASE4	COMPLETED	The Home INR Study
NCT00127712	PHASE4	COMPLETED	Prevention of Atrial Fibrillation Following Noncardiac Thoracic Surgery
NCT00157781	PHASE4	COMPLETED	LEAF - Low Energy In Atrial Fibrillation
NCT00170313	PHASE4	TERMINATED	CORE: Study to Evaluate the Conducted AF-Response-Algorithm in Patients Suffering From Heart Failure and Atrial Fibrillation
NCT00189319	PHASE4	COMPLETED	To Evaluate the Impact of Oral Flecainide on Quality of Life in Patients With Paroxysmal Atrial Fibrillation
NCT00196144	PHASE4	COMPLETED	FFS - Far Field Sensing Test Study in Cardiac Dual Chamber Pacemakers
NCT00196157	PHASE4	UNKNOWN	Line Versus Spot Ablation in Persistent Atrial Fibrillation
NCT00196183	PHASE4	COMPLETED	Trigger- vs. Substrate-Ablation for Paroxysmal Atrial Fibrillation
NCT00196209	PHASE4	UNKNOWN	Cardioversion vs. Catheter Ablation for Persistent Atrial Fibrillation
NCT00227344	PHASE4	TERMINATED	CACAF2 Study: Catheter Ablation for Cure of Atrial Fibrillation
NCT00232219	PHASE4	COMPLETED	Use of Fish Oils to Reduce Recurrence of Atrial Fibrillation Following DC Cardioversion
NCT00232232	PHASE4	COMPLETED	Use of Fish Oils to Prevent Atrial Mechanical Stunning and Atrial Remodeling Due to Atrial Arrhythmia
NCT00232245	PHASE4	COMPLETED	Use of Fish Oils to Reduce the Frequency and Duration of Episodes of Atrial Fibrillation in Patients With Paroxysmal Atrial Fibrillation.
NCT00239226	PHASE4	COMPLETED	Electrophysiologically Guided PAcing Site Selection Study
NCT00247780	PHASE4	COMPLETED	Cavotricuspid Isthmusblock and Circumferential Pulmonary Vein Isolation in Patients With Atrial Fibrillation
NCT00256152	PHASE4	COMPLETED	Asymptomatic Atrial Fibrillation and Stroke Evaluation in Pacemaker Patients and the Atrial Fibrillation Reduction Atrial Pacing Trial
NCT00262119	PHASE4	COMPLETED	MINERVA: MINimizE Right Ventricular Pacing to Prevent Atrial Fibrillation and Heart Failure
NCT00287209	PHASE4	COMPLETED	Reduction of Atrial Fibrillation Study in Patients Undergoing Coronary Artery Bypass Grafting. (RASCABG 1 Study)
NCT00289042	PHASE4	COMPLETED	Assessment of Cardioversion Using Transesophageal Echocardiography II (ACUTE II)
NCT00313443	PHASE4	COMPLETED	Concentrations of Amiodarone in Fat Tissue During Chronic Treatment
NCT00340314	PHASE4	COMPLETED	A Trial of Circumferential Pulmonary Vein Ablation (CPVA) Versus Antiarrhythmic Drug Therapy in for Paroxysmal Atrial Fibrillation (AF)
NCT00343499	PHASE4	TERMINATED	The Use of DIOVAN to Reduce Post-Cardioversion Recurrence of Atrial Fibrillation Trial (the DRAFT Trial)
NCT00408473	PHASE4	TERMINATED	Comparative Study of Flecainide CR and Placebo in the Early Treatment of Atrial Fibrillation.
NCT00420017	PHASE4	COMPLETED	Prevention of Atrial Fibrillation Following Esophagectomy
NCT00438113	PHASE4	COMPLETED	Atrial Substrate Modification With Aggressive Blood Pressure Lowering to Prevent AF
NCT00446966	PHASE4	COMPLETED	Fish Oil for Reduction of Atrial Fibrillation After Cardiac Surgery
NCT00449410	PHASE4	COMPLETED	Silent Cerebrovascular Lesion and Cognitive Decline Prevention by Cholesterol Lowering in Elderly AF Patients
NCT00466973	PHASE4	WITHDRAWN	Atrial Fibrillation Ablation Device Comparison Study
NCT00511173	PHASE4	COMPLETED	Comparison of Warfarin Dosing Using Decision Model Versus Pharmacogenetic Algorithm
NCT00512915	PHASE4	COMPLETED	Avoid FFS - Use of the Atrial Pacemaker Lead 1699 With Very Short Tip Ring Spacing to Avoid Far Field Sensing
NCT00552084	PHASE4	COMPLETED	Evaluating the Effectiveness of Fish Oil Supplements at Reducing the Recurrence of Atrial Fibrillation
NCT00559988	PHASE4	TERMINATED	Combined Use of BIOTRONIK Home Monitoring and Predefined Anticoagulation to Reduce Stroke Risk
NCT00579098	PHASE4	COMPLETED	The Use of Statins Following a Left Atrial Catheter Ablation Procedure to Prevent Atrial Fibrillation
NCT00586287	PHASE4	COMPLETED	Study to Find Out the Appropriate Initial Dose of the Anticoagulant Drug Phenprocoumon
NCT00597077	PHASE4	COMPLETED	Atrial Fibrillation and Congestive Heart Failure Trial
NCT00603317	PHASE4	COMPLETED	Pharmacodynamic Drug Interaction Between Warfarin and Amoxicillin-clavulanic Acid
NCT00605748	PHASE4	UNKNOWN	Pulmonary Vein (PV) -Isolation: Arrhythmogenic Vein(s) Versus All Veins
NCT00643188	PHASE4	COMPLETED	Catheter Ablation vs. Standard Conventional Treatment in Patients With LV Dysfunction and AF
NCT00678340	PHASE4	COMPLETED	Randomized Trial of Two Ablation Catheters in Paroxysmal Atrial Fibrillation
NCT00680927	PHASE4	COMPLETED	Reveal® XT Performance Trial (XPECT)