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): 2,499 total — 300 pathogenic, 180 likely-pathogenic (top 1% of genes corpus-wide)
• GTEx eGene: eQTL in 9 tissues, sQTL in 29 (q < 0.05)
• Phenotypes (HPO): 520
• ChEMBL bioactivity: 823 clinical-phase molecules tested; no curated mechanism-of-action drug
• Cancer dependency (DepMap): dependent in 11.8% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.41 (moderately constrained)
• MANE Select transcript: NM_170707
• Interaction hub: 4,036 STRING partners (top 1% of genes corpus-wide)

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: 84 — 39 protein_coding, 24 nonsense_mediated_decay, 12 protein_coding_CDS_not_defined, 9 retained_intron

MANE Select: ENST00000368300 · MANE Plus Clinical: ENST00000677389

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3, TSL 2: 9, TSL 3: 1, TSL 4: 5, TSL 5: 5

ENST00000368300, ENST00000677389, ENST00000361308, ENST00000368297, ENST00000368298, ENST00000368299, 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, ENST00000682650, ENST00000683032, ENST00000683773, ENST00000684195, ENST00000713746, ENST00000713747, ENST00000713748, ENST00000899553, ENST00000899554, ENST00000899555, ENST00000899556, ENST00000899557, ENST00000899558, ENST00000927999, ENST00000968784, ENST00000968785, ENST00000968786, ENST00000968787, ENST00001005014, ENST00001005015, ENST00001005016, ENST00001005020, ENST00001005022, ENST00001057275, ENST00001057276, ENST00001057277, ENST00001057279, ENST00001057280, ENST00001057281, ENST00001057283, ENST00001057285, ENST00001057286, ENST00001057287, ENST00001057290, ENST00001057292, ENST00001057293, ENST00001057295, ENST00001057296, ENST00001057299, ENST00001057304, ENST00001117788, ENST00001121866, ENST00001121867, ENST00001121868, ENST00001121869, ENST00001121870

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.

Highest expression (Bgee): nipple, mucosa of stomach, skin of abdomen, gall bladder, tendon of biceps brachii.

Genetic regulation across tissues (GTEx eQTL / sQTL)

LMNA is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 9 tissues and its splicing (sQTL) in 29 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 38 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Esophagus Mucosa	sqtl	3.7e-114	-1.37	1:156137743:C:T
Adipose Visceral Omentum	sqtl	1.6e-71	-1.13	1:156137743:C:T
Colon Sigmoid	sqtl	7.1e-68	-1.26	1:156137743:C:T
Testis	sqtl	3.8e-60	-1.12	1:156137743:C:T
Prostate	sqtl	8.8e-43	-1.37	1:156137743:C:T
Pituitary	sqtl	4.2e-42	-1.25	1:156137743:C:T
Pancreas	sqtl	3.6e-40	-1.28	1:156137743:C:T
Heart Left Ventricle	sqtl	2.4e-31	-1.21	1:156137743:C:T
Stomach	sqtl	6.8e-31	-1.39	1:156137743:C:T
Vagina	sqtl	9.1e-31	-1.41	1:156137743:C:T
Ovary	sqtl	5.4e-27	-1.39	1:156137743:C:T
Heart Atrial Appendage	sqtl	8.6e-25	-1.13	1:156137743:C:T
Artery Coronary	sqtl	1.5e-21	-1.37	1:156137743:C:T
Liver	sqtl	1.7e-18	-1.00	1:156137743:C:T
Brain Cerebellar Hemisphere	sqtl	2.9e-16	-1.02	1:156137743:C:T
Brain Cerebellum	sqtl	2.9e-14	-0.98	1:156137743:C:T
Brain Spinal cord cervical c-1	sqtl	4.8e-13	-0.96	1:156137743:C:T
Whole Blood	eqtl	7.2e-13	+0.38	1:156118465:C:G
Brain Caudate basal ganglia	sqtl	1.2e-12	-0.94	1:156137743:C:T
Brain Putamen basal ganglia	sqtl	1.7e-11	-0.92	1:156137743:C:T

FANTOM5 promoters

showing 10 of 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

showing 100 of 295 tissues 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
sural nerve	UBERON:0015488	98.65	gold quality
endocervix	UBERON:0000458	98.64	gold quality
peritoneum	UBERON:0002358	98.64	gold quality
right ovary	UBERON:0002118	98.62	gold quality
middle frontal gyrus	UBERON:0002702	98.62	gold quality
left adrenal gland	UBERON:0001234	98.61	gold quality
lower esophagus	UBERON:0013473	98.61	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.61	gold quality
esophagus	UBERON:0001043	98.59	gold quality
esophagus mucosa	UBERON:0002469	98.58	gold quality
right atrium auricular region	UBERON:0006631	98.58	gold quality
smooth muscle tissue	UBERON:0001135	98.57	gold quality
right adrenal gland	UBERON:0001233	98.56	gold quality
left adrenal gland cortex	UBERON:0035825	98.56	gold quality
apex of heart	UBERON:0002098	98.52	gold quality
right adrenal gland cortex	UBERON:0035827	98.52	gold quality
urethra	UBERON:0000057	98.50	gold quality
mammalian vulva	UBERON:0000997	98.49	gold quality
uterine cervix	UBERON:0000002	98.48	gold quality
adrenal cortex	UBERON:0001235	98.45	gold quality
gingiva	UBERON:0001828	98.44	gold quality
gingival epithelium	UBERON:0001949	98.43	gold quality
upper lobe of left lung	UBERON:0008952	98.43	gold quality
transverse colon	UBERON:0001157	98.42	gold quality
minor salivary gland	UBERON:0001830	98.42	gold quality
mouth mucosa	UBERON:0003729	98.40	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.39	gold quality
paraflocculus	UBERON:0005351	98.38	gold quality
adipose tissue of abdominal region	UBERON:0007808	98.37	gold quality
cardiac atrium	UBERON:0002081	98.35	gold quality
vagina	UBERON:0000996	98.32	gold quality
upper lobe of lung	UBERON:0008948	98.31	gold quality
left ovary	UBERON:0002119	98.30	gold quality
mucosa of transverse colon	UBERON:0004991	98.29	gold quality
colonic epithelium	UBERON:0000397	98.26	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.26	gold quality
left lobe of thyroid gland	UBERON:0001120	98.20	gold quality
myometrium	UBERON:0001296	98.19	gold quality
cervix squamous epithelium	UBERON:0006922	98.18	gold quality
right lobe of thyroid gland	UBERON:0001119	98.16	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.16	gold quality
adrenal gland	UBERON:0002369	98.15	gold quality
lower esophagus mucosa	UBERON:0035834	98.11	gold quality
body of stomach	UBERON:0001161	98.09	gold quality
thyroid gland	UBERON:0002046	98.09	gold quality
heart left ventricle	UBERON:0002084	98.09	gold quality
subcutaneous adipose tissue	UBERON:0002190	98.09	gold quality
penis	UBERON:0000989	98.08	gold quality
body of tongue	UBERON:0011876	98.08	gold quality
olfactory bulb	UBERON:0002264	98.06	gold quality
layer of synovial tissue	UBERON:0007616	98.01	gold quality
metanephros cortex	UBERON:0010533	98.01	gold quality
cardiac ventricle	UBERON:0002082	97.99	gold quality
saliva-secreting gland	UBERON:0001044	97.97	gold quality
fundus of stomach	UBERON:0001160	97.91	gold quality
stomach	UBERON:0000945	97.90	gold quality
right uterine tube	UBERON:0001302	97.87	gold quality
heart	UBERON:0000948	97.86	gold quality
cervix epithelium	UBERON:0004801	97.85	gold quality
type B pancreatic cell	CL:0000169	97.84	gold quality
synovial joint	UBERON:0002217	97.83	gold quality
periodontal ligament	UBERON:0008266	97.80	gold quality
gastrocnemius	UBERON:0001388	97.72	gold quality
muscle of leg	UBERON:0001383	97.68	gold quality
small intestine Peyer’s patch	UBERON:0003454	97.63	gold quality
right lung	UBERON:0002167	97.62	gold quality
colon	UBERON:0001155	97.61	gold quality
upper arm skin	UBERON:0004263	97.60	gold quality
pericardium	UBERON:0002407	97.59	gold quality
sigmoid colon	UBERON:0001159	97.57	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

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Vagina	tissue	169.0	high
Skin 1	tissue	149.7	high
Adipose tissue	tissue	137.6	high
Stomach 1	tissue	126.1	high
Skeletal muscle	tissue	117.8	high
Urinary bladder	tissue	107.3	high
Gallbladder	tissue	87.4	high
Colon	tissue	81.3	high
Pancreas	tissue	76.9	high
Lung	tissue	76.9	high
Esophagus	tissue	75.1	high
Smooth muscle	tissue	73.9	high
Endometrium 1	tissue	73.3	high
Choroid plexus	tissue	71.0
Duodenum	tissue	68.5	high
Small intestine	tissue	66.9	high
Cervix	tissue	63.3	high
Breast	tissue	62.7	high
Appendix	tissue	61.4	high
Pituitary gland	tissue	58.4
Heart muscle	tissue	57.1	high
Bone marrow	tissue	54.6	high
Salivary gland	tissue	53.3	high
Ovary	tissue	52.4	high
Adrenal gland	tissue	51.7	high
Spinal cord	tissue	51.2
Placenta	tissue	49.8	high
Liver	tissue	48.4	high
Prostate	tissue	42.3	high
Seminal vesicle	tissue	40.4	high
Spleen	tissue	38.8	low
Locus coeruleus	tissue	37.1
Fallopian tube	tissue	36.2	high
Rectum	tissue	36.0	high
Corpus callosum	tissue	33.9
Nucleus accumbens	tissue	31.0
Thyroid gland	tissue	30.8	high
Superior colliculi	tissue	30.4
Kidney	tissue	29.8	high
Hippocampus	tissue	29.6	high
Medulla oblongata	tissue	28.3
Midbrain	tissue	26.9
Substantia nigra	tissue	26.7
Frontal cortex	tissue	26.0
Postcentral gyrus	tissue	23.2
Tongue	tissue	22.3
Thalamus	tissue	22.0
Tonsil	tissue	21.4	high
Pons	tissue	21.3
Parathyroid gland	tissue	20.5	high
Testis	tissue	18.7	high
Cerebellum	tissue	17.3	high
Lymph node	tissue	17.0	high
Hypothalamus	tissue	16.8
Periaqueductal gray	tissue	15.8
Cerebral cortex	tissue	15.0	high
Somatosensory cortex	tissue	15.0
Motor cortex	tissue	14.8
Thymus	tissue	14.3
Hippocampal formation	tissue	14.2

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Blood vessel (282.8), Angular gyrus (white matter) (88.8), Temporal white matter (74.7), Parieto-temporal junction (white matter) (71.0), Anterior thalamic nucleus, ventral (70.2).

Regulation

Is transcription factor: no

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

miRNA regulators (miRDB)

Targeting LMNA by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 96 miRNAs:

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

gnomAD constraint: pLI 1, LOEUF 0.412, missense Z 3.1 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000368300 splits into 4 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
1:156,114,919–156,135,909	254 / 421.9	0.60	no
1:156,135,910–156,135,973	38 / 32.5	1.17	no
1:156,135,974–156,136,228	33 / 75.3	0.44	no
1:156,136,229–156,139,103	327 / 387.6	0.84	no
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.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): SNU-201 (-2.284), SW579 (-2.262), MPP 89 (-1.692), IGR-39 (-1.546), 170-MG-BA (-1.393), HCC1395 (-1.363), SNU-1105 (-1.21), WM793 (-1.123), Onda 8 (-1.1), SNU-423 (-1.096), D-502MG (-1.094), CAL-78 (-1.055), Mero-95 (-1.045), YH-13 (-1.029), Becker (-1.025).

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), KRT9 (ENSG00000171403), KRT20 (ENSG00000171431), KRT27 (ENSG00000171446), KRT2 (ENSG00000172867), KRT28 (ENSG00000173908), DES (ENSG00000175084), LMNB2 (ENSG00000176619), SYNM (ENSG00000182253), KRT76 (ENSG00000185069), KRT6B (ENSG00000185479), KRT79 (ENSG00000185640), KRT73 (ENSG00000186049), KRT5 (ENSG00000186081), KRT26 (ENSG00000186393), KRT10 (ENSG00000186395), KRT3 (ENSG00000186442), KRT16 (ENSG00000186832), KRT14 (ENSG00000186847), KRT12 (ENSG00000187242), KRT77 (ENSG00000189182)

+8 more (showing top 60).

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:96794) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 260 distinct phenotype terms.

Mouse phenotype (MP)	Records
premature death	16
postnatal growth retardation	11
decreased body weight	10
abnormal cell nucleus morphology	10
decreased subcutaneous adipose tissue amount	6
weight loss	5
abnormal gait	5
dilated cardiomyopathy	5
premature aging	5
decreased heart rate	5
decreased bone mineral density	4
decreased body size	4
dilated heart left ventricle	4
cardiac fibrosis	4
rib fractures	4
postnatal lethality, complete penetrance	4
kyphosis	3
abnormal myocardial fiber morphology	3
dystrophic muscle	3
prolonged PR interval	3
decreased circulating glucose level	3
abnormal nuclear lamina morphology	3
decreased skeletal muscle fiber size	3
cardiac muscle degeneration	3
decreased grip strength	3

+235 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos taurus	O77788	96.7%	Diamond
Sus scrofa	Q3ZD69	96.1%	Diamond
Helix pomatia	P16275	95.3%	Diamond
Macaca fascicularis	Q4R899	89.8%	Diamond
Gallus gallus	P16053	86.3%	Diamond
Lymnaea stagnalis	Q6QUW1	73.9%	Diamond
Xenopus laevis	P21910	71.1%	Diamond
Hypsibius exemplaris	A0A125S9M6	65.8%	Diamond
Drosophila melanogaster	P08928	54.2%	Diamond
Caenorhabditis elegans	Q21443	40.5%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
RAB25	protein-coding	57111
SEMA4A	protein-coding	64218
MEX3A	protein-coding	92312
LAMTOR2	protein-coding	28956
PMF1-BGLAP	protein-coding	100527963
PMF1	protein-coding	11243
SLC25A44	protein-coding	9673
UBQLN4	protein-coding	56893

Protein

Protein identifiers

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

All UniProt accessions (14): A0A384MQX1, A0A6Q8PF59, A0A6Q8PF80, A0A6Q8PFF5, A0A6Q8PFJ0, A0A6Q8PFM1, A0A6Q8PGH0, P02545, 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 (322 total): sequence variant 140, modified residue 76, mutagenesis site 28, cross-link 20, region of interest 13, strand 12, splice variant 9, helix 6, 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 by resolution:

PDB	Title	Method	Resolution (Å)
7WZZ	Crystal structure of peptide KAGQVVTIW in complex with HLA-B5801	X-RAY DIFFRACTION	1.3
7X1B	Crystal structure of peptide KAGQVVTI in complex with HLA-B5801	X-RAY DIFFRACTION	1.4
1IFR	Structure of Lamin A/C Globular Domain	X-RAY DIFFRACTION	1.4
3GEF	Crystal structure of the R482W mutant of lamin A/C	X-RAY DIFFRACTION	1.5
8I33	Coil 1a of lamin A (residue 25-65)	X-RAY DIFFRACTION	1.62
7Z21	BAF A12T bound to the lamin A/C Ig-fold domain	X-RAY DIFFRACTION	1.63
7CRG	Beta-strand-mediated dimeric formation of the extended Ig-like domains of human lamin A/C	X-RAY DIFFRACTION	1.8
7X5D	Crystal Structure of the K316C mutant of Human Lamin A/C Coil 2 (residues 244-340)	X-RAY DIFFRACTION	1.82
6YF5	Lamin A 17-70 coil1A dimer stabilized by C-terminal capping	X-RAY DIFFRACTION	1.83
6GHD	Structural analysis of the ternary complex between lamin A/C, BAF and emerin identifies …	X-RAY DIFFRACTION	2.1
7YVD	The crystal structure of the progerin C-terminal peptide and the Ig-like domain of lamin …	X-RAY DIFFRACTION	2.1
1X8Y	Human lamin coil 2B	X-RAY DIFFRACTION	2.2
6RPR	LEM domain of Emerin mutant T43I in complex with BAF dimer and the Igfold of the lamin A/C	X-RAY DIFFRACTION	2.26
2XV5	Human lamin A coil 2B fragment	X-RAY DIFFRACTION	2.4
9UL6	Crystal structure of Lamin A/C Ig-like domain mutant - R435C	X-RAY DIFFRACTION	2.5
6SNZ	Crystal structure of lamin A coil1b tetramer	X-RAY DIFFRACTION	2.6
6YSH	Lamin A 1-70 coil1A dimer stabilized by C-terminal capping	X-RAY DIFFRACTION	2.83
6YJD	Lamin A coil2 dimer stabilized by N-terminal capping	X-RAY DIFFRACTION	2.9
3V5B	Structure of Coil 2b of human lamin	X-RAY DIFFRACTION	3
3V4Q	Structure of R335W mutant of human Lamin	X-RAY DIFFRACTION	3.06
6JLB	Crystal structure of lamin A/C fragment and assembly mechanisms of intermediate filaments	X-RAY DIFFRACTION	3.21
3V4W	Structure of E347K mutant of Lamin	X-RAY DIFFRACTION	3.7
7D9N	Crystal structure of a non-canonic progeria mutation S143F at lamin A/C and its …	X-RAY DIFFRACTION	3.7
2YPT	Crystal structure of the human nuclear membrane zinc metalloprotease ZMPSTE24 mutant …	X-RAY DIFFRACTION	3.8
9J8M	Cryo-EM structure of BAF-Lamin A/C IgF-nucleosome complex (High mobility complex)	ELECTRON MICROSCOPY	3.82
9J8O	Cryo-EM structure of BAF-Lamin A/C IgF-H1-nucleosome complex	ELECTRON MICROSCOPY	4.05
9J8N	Cryo-EM structure of BAF-Lamin A/C IgF-nucleosome complex (Low mobility complex)	ELECTRON MICROSCOPY	7.14
1IVT	NMR structures of the C-terminal globular domain of human lamin A/C	SOLUTION NMR

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Predicted intracellular proteins, Plasma proteins, Cancer-related genes, Candidate cancer biomarkers, Disease related genes, Human disease related genes, Congenital disorders of metabolism, Congenital disorders of lipid/glycolipid metabolism, Other congenital disorders of metabolism, Congenital malformations, Congenital malformations of skin, Other congenital malformations, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nuclear speckles

Antibody reliability (HPA): IH supported · IF supported

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)

Position	Role
266	heptad change of phase
325	stutter
330	heptad change of phase
646–647	cleavage; by endoprotease

Post-translational modifications (97)

Type	Positions
Cysteine methyl ester	661
S-farnesyl cysteine	661
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo2)	32, 97, 171, 201, 208, 219, 233, 260, 270, 311, 366, 378, 417, 420, 450, 470, 486, 597
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo)	201
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo1)	597
N-acetylmethionine	1
Phosphothreonine	3, 10, 19, 416, 496, 505, 510, 548
Phosphoserine	5, 12, 18, 22, 51, 66, 71, 107, 212, 277, 282, 301, 307, 390, 392, 395, 398, 403, 404, 406, 407, 414, 423, 426, 429, 431, 458, 463, 533, 546, 568, 571, 612, 613, 616, 619, 628, 632, 636, 652
N6-acetyllysine	32, 78, 97, 108, 114, 123, 135, 144, 155, 171, 180, 201, 208, 233, 260, 265, 270, 311, 316, 341, 417, 450, 457, 486
N6-succinyllysine	32, 171

Glycosylation sites (2)

Type	Positions
O-linked (glcnac) serine	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 during mitosis; when …
22	mimics phosphorylation; increased localization to the nucleoplasm during interphase. causes redistribution between the nucleus and the …
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; associated with …
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 during mitosis; when …
392	mimics phosphorylation; increased localization to the nucleoplasm during interphase. causes redistribution between the nucleus and the …
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 with d-22 and d-392.
644	does not affect tail cleavage.
647	completely inhibits tail cleavage.

Function

Pathways and Gene Ontology

Reactome pathways

6 curated (TAS) of 15; 5 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

15 pathways:

ID	Pathway	Evidence
R-HSA-6802952	Signaling by BRAF and RAF1 fusions ⚕	curated
R-HSA-352238	Breakdown of the nuclear lamina	curated
R-HSA-4419969	Depolymerization of the Nuclear Lamina	curated
R-HSA-2995383	Initiation of Nuclear Envelope (NE) Reformation	curated
R-HSA-2980766	Nuclear Envelope Breakdown	curated
R-HSA-381038	XBP1(S) activates chaperone genes	curated
R-HSA-8862803	Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer’s disease models ⚕	electronic
R-HSA-1643685	Disease ⚕	—
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	—
R-HSA-2262752	Cellular responses to stress	—
R-HSA-381070	IRE1alpha activates chaperones	—
R-HSA-1221632	Meiotic synapsis	electronic
R-HSA-381119	Unfolded Protein Response (UPR)	—

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 (17): double-strand break repair via nonhomologous end joining (GO:0006303), 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), regulation of cell migration (GO:0030334), establishment or maintenance of microtubule cytoskeleton polarity (GO:0030951), heterochromatin formation (GO:0031507), regulation of telomere maintenance (GO:0032204), protein localization to nucleus (GO:0034504), nuclear pore localization (GO:0051664), cellular response to hypoxia (GO:0071456), cellular senescence (GO:0090398), protein localization to nuclear envelope (GO:0090435), negative regulation of cardiac muscle hypertrophy in response to stress (GO:1903243), DNA double-strand break attachment to nuclear envelope (GO:1990683)

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

13 top-level categories:

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

60 GO namespaces:

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
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
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
telomere maintenance	1
regulation of chromosome organization	1
regulation of DNA metabolic process	1
protein localization to organelle	1
protein-containing complex localization	1
localization within membrane	1
response to hypoxia	1
cellular response to decreased oxygen levels	1
cellular process	1
protein localization to nucleus	1
negative regulation of cardiac muscle hypertrophy	1
negative regulation of cardiac muscle adaptation	1
cardiac muscle hypertrophy in response to stress	1
regulation of cardiac muscle hypertrophy in response to stress	1
chromosome attachment to the nuclear envelope	1
molecular_function	1
cytoskeleton	1
cytoskeleton organization	1
protein binding	1
binding	1
intracellular membrane-bounded organelle	1
endomembrane system	1
organelle envelope	1
nuclear lamina	1
intermediate filament	1
nuclear periphery	1
intermediate filament cytoskeleton	1
polymeric cytoskeletal fiber	1
nuclear ribonucleoprotein granule	1
organelle membrane	1
site of DNA damage	1
intracellular organelle lumen	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 21 of 35 annotations. The rest are phylogenetic / computational / electronic (IEA).

21 experimentally-supported GO terms:

GO term	NS	Evidence
DNA double-strand break attachment to nuclear envelope	BP	direct assay
cellular response to hypoxia	BP	expression pattern
cellular senescence	BP	direct assay
double-strand break repair via nonhomologous end joining	BP	mutant phenotype
intracellular protein localization	BP	mutant phenotype
muscle organ development	BP	mutant phenotype
negative regulation of cell population proliferation	BP	mutant phenotype
nuclear envelope organization	BP	direct assay
regulation of telomere maintenance	BP	mutant phenotype
nuclear envelope	CC	direct assay
nuclear lamina	CC	direct assay
nuclear matrix	CC	direct assay
nuclear membrane	CC	direct assay
nuclear speck	CC	direct assay
nucleoplasm	CC	direct assay
nucleus	CC	direct assay
perinuclear region of cytoplasm	CC	direct assay
site of double-strand break	CC	direct assay
identical protein binding	MF	physical interaction
structural constituent of cytoskeleton	MF	direct assay
structural constituent of nuclear lamina	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 4,036 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LMNA	EMD	P50402	954
LMNA	SYNE2	Q8WXH0	916
LMNA	ZMPSTE24	O75844	913
LMNA	SUN1	O94901	878
LMNA	SYNE1	Q8NF91	876
LMNA	SUN2	Q9UH99	872
LMNA	BSCL2	Q96G97	797
LMNA	PRKAG2	Q9UGJ0	744
LMNA	TMPO	P08918	738
LMNA	TTN	Q8WZ42	716
LMNA	RBM20	Q5T481	715
LMNA	MYH7	P12883	712
LMNA	TMEM43	Q9BTV4	701
LMNA	WRN	Q14191	697
LMNA	AGPAT2	O15120	695

IntAct

Human interaction partners of LMNA in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 124 partners by confidence:

Partner	Interaction type	MIscore	Records
LMNB1	proximity	0.930	16
LMNB2	physical association	0.850	3
EMD	direct interaction	0.800	3
DUSP13B	physical association	0.780	7
SUN2	association	0.720	3
NUP155	association	0.670	4
SNW1	physical association	0.670	3
TMPO	direct interaction	0.630	1
H2AX	proximity	0.600	2
IFFO1	association	0.580	5
ABLIM2	physical association	0.560	3
ASB9	physical association	0.560	3
ATL1	physical association	0.560	3
BAG6	physical association	0.560	3
BAHD1	physical association	0.560	3
BRPF3	physical association	0.560	3
CDCA7L	physical association	0.560	3
CIMAP1D	physical association	0.560	3
FAM161A	physical association	0.560	3
FAM221B	physical association	0.560	3
FAM3B	physical association	0.560	3
FAM9A	physical association	0.560	3
GMCL2	physical association	0.560	3
IK	physical association	0.560	3
IL16	physical association	0.560	3
INKA1	physical association	0.560	3
IQUB	physical association	0.560	3
KLF6	physical association	0.560	3
KRTAP10-7	physical association	0.560	3
NEBL	physical association	0.560	3

BioGRID (1,820 interactions; top human partners by supporting records in a sample of 600 records): SMURF2 (Affinity Capture-Western; 5 records), TMPO (Proximity Label-MS; 5 records), LMNB1 (Two-hybrid; 4 records), RNF123 (Affinity Capture-MS; 4 records), EGFR (Affinity Capture-MS; 3 records), KPNA6 (Affinity Capture-MS; 3 records), LMNB2 (Affinity Capture-MS; 3 records), MATR3 (Affinity Capture-MS; 3 records), AHCTF1 (Proximity Label-MS; 2 records), AKTIP (Affinity Capture-MS; 2 records), CA5A (Affinity Capture-Western; 2 records), CDC5L (Affinity Capture-MS; 2 records), DUSP13 (Two-hybrid; 2 records), EMD (Proximity Label-MS; 2 records), FUS (Affinity Capture-MS; 2 records)

SIGNOR signaling

showing 9 of 12 signaling 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

Protein complexes (CORUM) (4)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

4 complexes by size:

Complex	Subunits	Members
Emerin complex 24	15	H3C1, LMNB1, MCM2, MCM4, RB1, RBL2, BANF2, H1-1, MCM6, SAP130, EMD, LMNA, C1QBP, HNRNPU, NMI
★ CTCF-PARP1-HIS-KPNA-LMNA-TOP complex	9	TOP2A, NPM1, CTCF, H2AC18, H2AZ1, KPNA1, KPNA3, LMNA, PARP1
Emerin architectural complex	6	ACTB, EMD, LMNA, LMNB1, NMI, SPTAN1
NF-YA-LaminA complex	2	LMNA, NFYA

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 124 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
Meiosis	7	24.7×	3e-06
Meiotic synapsis	10	17.4×	1e-07
Reproduction	7	16.4×	4e-05
DNA Damage/Telomere Stress Induced Senescence	6	12.1×	9e-04
Condensation of Prophase Chromosomes	5	9.7×	8e-03
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks	5	9.0×	9e-03
Cell Cycle	10	4.5×	5e-03

GO biological processes:

GO term	Partners	Fold	FDR
heterochromatin formation	6	13.4×	9e-04

Disease & clinical

Genetic variants

Variant evidence for LMNA: 2,499 ClinVar records (480 pathogenic / likely pathogenic); 19 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

2,499 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	300
Likely pathogenic	180
Uncertain significance	900
Likely benign	569
Benign	49

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 480 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
66908	NM_170707.4(LMNA):c.568C>T (p.Arg190Trp)	Pathogenic	criteria provided, multiple submitters, no conflicts	18
14495	NM_170707.4(LMNA):c.1130G>A (p.Arg377His)	Pathogenic	criteria provided, multiple submitters, no conflicts	14
14525	NM_170707.4(LMNA):c.1072G>A (p.Glu358Lys)	Pathogenic	criteria provided, multiple submitters, no conflicts	14
48096	NM_170707.4(LMNA):c.961C>T (p.Arg321Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	14
14500	NM_170707.4(LMNA):c.1824C>T (p.Gly608=)	Pathogenic	criteria provided, multiple submitters, no conflicts	13
14481	NM_170707.4(LMNA):c.1580G>C (p.Arg527Pro)	Pathogenic	criteria provided, multiple submitters, no conflicts	10
66791	NM_170707.4(LMNA):c.116A>G (p.Asn39Ser)	Pathogenic	criteria provided, multiple submitters, no conflicts	9
14483	NM_170707.4(LMNA):c.585C>G (p.Asn195Lys)	Pathogenic	criteria provided, multiple submitters, no conflicts	7
66853	NM_170707.4(LMNA):c.1608+1G>A	Pathogenic	criteria provided, multiple submitters, no conflicts	7
66955	NM_170707.4(LMNA):c.908_909del (p.Ser303fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	7
48041	NM_170707.4(LMNA):c.1526dup (p.Thr510fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	6
48075	NM_170707.4(LMNA):c.700C>T (p.Gln234Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	6
66811	NM_170707.4(LMNA):c.1366A>G (p.Asn456Asp)	Pathogenic	criteria provided, multiple submitters, no conflicts	6
66817	NM_170707.4(LMNA):c.1380+1G>A	Pathogenic	criteria provided, multiple submitters, no conflicts	6
66882	NM_170707.4(LMNA):c.244G>A (p.Glu82Lys)	Pathogenic	criteria provided, multiple submitters, no conflicts	6

Per-variant reference — Sugi Variant

Explore LMNA’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 37 predictions of 724):

Position(s)	Effect	Δscore	Sites
1:156115275–156115276	donor_loss	1.0000	5
1:156130615–156130616	acceptor_loss	1.0000	6
1:156130774–156130775	donor_loss	1.0000	5
1:156134390	acceptor_gain	1.0000
1:156134400	acceptor_gain	1.0000
1:156134401–156134402	acceptor_loss	1.0000	6
1:156134529–156134530	donor_loss	1.0000	5
1:156134780	acceptor_gain	1.0000
1:156134795–156134796	acceptor_gain	1.0000	2
1:156134803–156134804	acceptor_loss	1.0000	5

AlphaMissense

2,292 missense substitutions predicted likely pathogenic (of 4,308 scored), across 541 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M187	9	0.919	0.989
M371	9	0.885	0.991
N39	8	0.999	1.000
N195	8	0.999	1.000
D93	8	0.997	0.999
D370	8	0.997	0.999
N456	8	0.997	1.000
F206	8	0.996	1.000
N56	8	0.991	0.999
F483	8	0.981	1.000
D364	8	0.980	0.996
D40	8	0.979	0.997
D192	8	0.976	0.992
D461	8	0.967	0.997
D87	8	0.938	0.977
D230	8	0.938	0.979
H506	8	0.903	0.995
H252	8	0.895	0.998
D446	8	0.893	0.984
D47	8	0.872	0.987

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Disease associations

OMIM: gene MIM:150330 | disease phenotypes: MIM:248370, MIM:115200, MIM:151660, MIM:176670, MIM:605588, MIM:613205, MIM:616516, MIM:159001, MIM:181350, MIM:212112, MIM:610140, MIM:619793, MIM:118220, MIM:310300, MIM:182960, MIM:192600, MIM:609040, MIM:604169, MIM:601494, MIM:158810, MIM:613426, MIM:253601

GenCC curated gene-disease

21 curated gene-disease records:

Disease	Classification	Inheritance	Records
dilated cardiomyopathy 1A	Definitive	Autosomal dominant	3
Hutchinson-Gilford progeria syndrome	Definitive	Autosomal dominant	4
Emery-Dreifuss muscular dystrophy 2, autosomal dominant	Definitive	Semidominant	3
familial partial lipodystrophy, Dunnigan type	Definitive	Autosomal dominant	4
restrictive dermopathy 2	Definitive	Autosomal recessive	2
Charcot-Marie-Tooth disease type 2B1	Strong	Autosomal dominant	5
heart-hand syndrome, Slovenian type	Strong	Autosomal dominant	4
atrioventricular block	Strong	Autosomal dominant
mandibuloacral dysplasia with type A lipodystrophy	Strong	Autosomal recessive	2
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	2

ClinGen Gene-Disease Validity

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

3 validity classifications:

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

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (28 panels, 22 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

28 panels:

Panel	Rating
Arrhythmogenic right ventricular cardiomyopathy	green
Congenital muscular dystrophy	green
Congenital myopathy	green
DDG2P	green
Diabetes with additional phenotypes suggestive of a monogenic aetiology	green
Dilated Cardiomyopathy and conduction defects	green
Dilated and arrhythmogenic cardiomyopathy	green
Familial diabetes	green
Fetal anomalies	green
Hereditary neuropathy	green
Hereditary neuropathy or pain disorder	green
Insulin resistance (including lipodystrophy)	green
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies	green
Monogenic diabetes	green
Other rare neuromuscular disorders	green
Paediatric or syndromic cardiomyopathy	green
Pigmentary skin disorders	green
Progressive cardiac conduction disease	green
Severe insulin resistance and lipodystrophy syndromes	green
Skeletal dysplasia	green
Sudden unexplained death or survivors of a cardiac event	green
Unexplained death in infancy and sudden unexplained death in childhood	green
Clefting	amber
Hypotonic infant	amber
Intellectual disability	amber
Leukodystrophy, childhood onset	amber
Paediatric disorders	amber
Primary ovarian insufficiency	amber

Mondo (46): mandibuloacral dysplasia with type A lipodystrophy (MONDO:0009557), Charcot-Marie-Tooth disease type 2 (MONDO:0018993), dilated cardiomyopathy 1A (MONDO:0007269), familial partial lipodystrophy, Dunnigan type (MONDO:0007906), Hutchinson-Gilford progeria syndrome (MONDO:0008310), Charcot-Marie-Tooth disease type 2B1 (MONDO:0011569), 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), dilated cardiomyopathy-hypergonadotropic hypogonadism syndrome (MONDO:0008915), heart-hand syndrome, Slovenian type (MONDO:0012417), cardiomyopathy (MONDO:0004994), restrictive dermopathy 2 (MONDO:0030781), muscular dystrophy (MONDO:0020121), dilated cardiomyopathy (MONDO:0005021), Charcot-Marie-Tooth disease (MONDO:0015626), familial partial lipodystrophy (MONDO:0020088), long QT syndrome (MONDO:0002442), Emery-Dreifuss muscular dystrophy (MONDO:0016830), laminopathy (MONDO:0021106), neuronopathy, distal hereditary motor, autosomal dominant (MONDO:0015362), hypertrophic cardiomyopathy 1 (MONDO:0008647), arrhythmogenic right ventricular dysplasia 9 (MONDO:0012180), sick sinus syndrome (MONDO:0001823), familial dilated cardiomyopathy (MONDO:0016333), congenital muscular dystrophy (MONDO:0019950), mandibuloacral dysplasia (MONDO:0016584), arrhythmogenic right ventricular cardiomyopathy (MONDO:0016587), left ventricular noncompaction (MONDO:0018901), dilated cardiomyopathy 1D (MONDO:0011095), limb-girdle muscular dystrophy (MONDO:0016971), neuromuscular disease (MONDO:0019056), monogenic diabetes (MONDO:0015967), Bethlem myopathy 1A (MONDO:0024530), lipodystrophy (MONDO:0006573), dilated cardiomyopathy 1S (MONDO:0013262), autosomal recessive limb-girdle muscular dystrophy type 2B (MONDO:0009676), atrial fibrillation (MONDO:0004981), atrioventricular block (MONDO:0000465), (MONDO:0015470), (MONDO:0010143), autosomal semi-dominant severe lipodystrophic laminopathy (MONDO:0017230), LMNA-related cardiocutaneous progeria syndrome (MONDO:0018203), atypical Werner syndrome (MONDO:0019321), autosomal dominant Emery-Dreifuss muscular dystrophy (MONDO:0020336), (MONDO:0008406)

Orphanet (30): Mandibuloacral dysplasia (Orphanet:2457), Mandibuloacral dysplasia with type A lipodystrophy (Orphanet:90153), Autosomal dominant Charcot-Marie-Tooth disease type 2 (Orphanet:64746), Congenital muscular dystrophy due to LMNA mutation (Orphanet:157973), 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), Heart-hand syndrome, Slovenian type (Orphanet:168796), Dilated cardiomyopathy-hypergonadotropic hypogonadism syndrome (Orphanet:2229), Rare cardiomyopathy (Orphanet:167848), Muscular dystrophy (Orphanet:98473), Dilated cardiomyopathy (Orphanet:217604), Charcot-Marie-Tooth disease/Hereditary motor and sensory neuropathy (Orphanet:166), Familial partial lipodystrophy (Orphanet:98306), Laminopathy (Orphanet:98301), Autosomal dominant distal hereditary motor neuropathy (Orphanet:140465), Familial dilated cardiomyopathy (Orphanet:217607), Congenital muscular dystrophy (Orphanet:97242), Inherited arrhythmogenic cardiomyopathy (Orphanet:247), Left ventricular noncompaction (Orphanet:54260), Familial isolated dilated cardiomyopathy (Orphanet:154), Limb-girdle muscular dystrophy (Orphanet:263), Neuromuscular disease (Orphanet:68381), Rare genetic diabetes mellitus (Orphanet:183625), Bethlem muscular dystrophy (Orphanet:610), Dysferlin-related limb-girdle muscular dystrophy R2 (Orphanet:268)

HPO phenotypes

showing 60 of 520 phenotypes (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
HP:0000369	Low-set ears
HP:0000405	Conductive hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000418	Narrow nasal ridge
HP:0000431	Wide nasal bridge
HP:0000436	Abnormal nasal tip morphology
HP:0000444	Convex nasal ridge
HP:0000453	Choanal atresia
HP:0000460	Narrow nose
HP:0000465	Webbed neck
HP:0000467	Neck muscle weakness
HP:0000468	Increased adipose tissue around the neck
HP:0000494	Downslanted palpebral fissures
HP:0000506	Telecanthus
HP:0000508	Ptosis
HP:0000518	Cataract
HP:0000519	Developmental cataract
HP:0000520	Proptosis
HP:0000534	Abnormal eyebrow morphology
HP:0000546	Retinal degeneration
HP:0000561	Absent eyelashes
HP:0000586	Shallow orbits
HP:0000621	Entropion
HP:0000668	Hypodontia
HP:0000678	Dental crowding
HP:0000684	Delayed eruption of teeth
HP:0000685	Hypoplasia of teeth
HP:0000695	Natal tooth
HP:0000765	Abnormal thorax morphology
HP:0000767	Pectus excavatum

GWAS associations

19 associations:

Study	Trait	p-value
GCST010700_5	Cortical thickness (MOSTest)	8e-17
GCST90002393_345	Monocyte count	3e-14
GCST010703_205	Brain morphology (MOSTest)	4e-14
GCST90000025_211	Appendicular lean mass	1e-12
GCST008362_150	Birth weight	8e-12
GCST90002407_219	White blood cell count	8e-12
GCST010696_10	Cortical thickness (min-P)	2e-10
GCST010697_21	Cortical surface area (min-P)	3e-10
GCST010702_25	Subcortical volume (MOSTest)	3e-10
GCST012489_146	Heel bone mineral density x serum urate levels interaction	4e-10
GCST90002398_443	Neutrophil count	6e-10
GCST010699_50	Brain morphology (min-P)	7e-10
GCST010698_84	Subcortical volume (min-P)	9e-10
GCST010701_97	Cortical surface area (MOSTest)	1e-9
GCST90020026_13	Hip index	1e-8
GCST008972_2	Urate levels	3e-8
GCST007088_3	Ischemic heart disease in rheumatoid arthritis	5e-7
GCST007239_3	Ovarian cancer	2e-6
GCST004749_78	Lung cancer in ever smokers	7e-6

EFO canonical traits (from GWAS)

10 canonical traits:

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

26 disease descriptors:

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
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
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
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
D009468	Neuromuscular Diseases	C10.668
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
C563808	Arrhythmogenic Right Ventricular Dysplasia, Familial, 9 *(supp.)*
C563306	Cardiomyopathy, Dilated, 1D *(supp.)*
C563538	Cardiomyopathy, Dilated, 1s *(supp.)*
C537990	Charcot-Marie-Tooth disease, Type 2B1 *(supp.)*
C567633	Emery-Dreifuss Muscular Dystrophy, Atypical, Autosomal Recessive *(supp.)*
C535852	Heart-hand syndrome, Slovenian type *(supp.)*
C535898	Limb-girdle muscular dystrophy, type 1B *(supp.)*
C535899	Limb-girdle muscular dystrophy, type 2B *(supp.)*
C535705	Mandibuloacral dysplasia with type A lipodystrophy *(supp.)*
C567708	Muscular Dystrophy, Congenital, Lmna-Related *(supp.)*
C536231	familial dilated cardiomyopathy *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1293235 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 842,699 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

showing 60 of 823 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL1330792	ACETARSONE	4	2,078
CHEMBL1589	ACETOHEXAMIDE	4	18,443
CHEMBL1265	ADAPALENE	4	12,307
CHEMBL1483	ALBENDAZOLE	4	19,210
CHEMBL1467	ALLOPURINOL	4	85,872
CHEMBL1505	ALMOTRIPTAN	4	7,500
CHEMBL661	ALPRAZOLAM	4	131,051
CHEMBL1455	ALTRETAMINE	4	103,108
CHEMBL660	AMANTADINE	4	70,248
CHEMBL1569	AMANTADINE HYDROCHLORIDE	4	11,279
CHEMBL177	AMIKACIN	4	50,927
CHEMBL945	AMILORIDE	4	64,123
CHEMBL1046	AMINOCAPROIC ACID	4	96,126
CHEMBL1370561	AMINOPHYLLINE	4	30,987
CHEMBL288470	AMINOPYRINE	4	8,309
CHEMBL1083993	AMIODARONE HYDROCHLORIDE	4	3,298
CHEMBL243712	AMISULPRIDE	4	10,675
CHEMBL1200964	AMITRIPTYLINE HYDROCHLORIDE	4	9,435
CHEMBL1113	AMOXAPINE	4	20,303
CHEMBL267345	AMPHOTERICIN B	4	87,420
CHEMBL116	AMPRENAVIR	4
CHEMBL1305	ANTAZOLINE	4
CHEMBL53	APOMORPHINE	4
CHEMBL3187985	APOMORPHINE HYDROCHLORIDE	4
CHEMBL5483015	ARSENIC TRIOXIDE	4
CHEMBL566534	ARTEMETHER	4
CHEMBL296419	ASTEMIZOLE	4
CHEMBL24	ATENOLOL	4
CHEMBL1200522	AVOBENZONE	4
CHEMBL1489	AZACITIDINE	4
CHEMBL515914	AZARIBINE	4
CHEMBL1542	AZATHIOPRINE	4
CHEMBL1238	AZELAIC ACID	4
CHEMBL1200809	AZELASTINE HYDROCHLORIDE	4
CHEMBL529	AZITHROMYCIN	4
CHEMBL701	BACLOFEN	4
CHEMBL444	BARBITAL	4
CHEMBL1684	BENDROFLUMETHIAZIDE	4
CHEMBL297302	BENPERIDOL	4
CHEMBL388590	BENZBROMARONE	4
CHEMBL232201	BENZIODARONE	4
CHEMBL1200370	BENZOYL PEROXIDE	4
CHEMBL1008	BEPRIDIL	4
CHEMBL1293	BETA CAROTENE	4
CHEMBL1691	BETAXOLOL HYDROCHLORIDE	4
CHEMBL1201323	BETAZOLE	4
CHEMBL1768	BETHANECHOL CHLORIDE	4
CHEMBL857	BIOTIN	4
CHEMBL942	BISACODYL	4
CHEMBL1592101	BISMUTH SUBGALLATE	4
CHEMBL1120	BISMUTH SUBSALICYLATE	4
CHEMBL1472989	BISOPROLOL FUMARATE	4
CHEMBL290106	BITHIONOL	4
CHEMBL1095292	BRETYLIUM TOSYLATE	4
CHEMBL207538	BREXANOLONE	4
CHEMBL844	BRIMONIDINE	4
CHEMBL1077	BROMFENAC	4
CHEMBL1319139	BROMHEXINE HYDROCHLORIDE	4
CHEMBL493	BROMOCRIPTINE	4
CHEMBL1200503	BROMOCRIPTINE MESYLATE	4

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 1 human assays (3 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM

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	affects expression, decreases expression, increases abundance, affects cotreatment, increases expression (+1 more)	6
sodium arsenite	decreases expression, increases abundance, increases expression, affects expression, affects cotreatment	5
Benzo(a)pyrene	increases methylation, affects cotreatment, decreases expression, increases expression	4
Resveratrol	increases reaction, affects binding, increases activity, decreases acetylation, increases cleavage	3
Air Pollutants	decreases expression, increases abundance, increases oxidation, increases expression, affects cotreatment	3
Arsenic	affects methylation, affects cotreatment, decreases expression, increases abundance	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	affects cotreatment, decreases expression, increases oxidation, increases abundance	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	increases cleavage, increases reaction, increases phosphorylation, affects reaction	2
Nickel	increases expression	2
Ozone	increases oxidation, increases abundance, affects cotreatment, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	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)

Via MONDO — disease-level, not drug-specific.

showing 60 of 600 trials:

NCT	Phase	Status	Title
NCT00032591	Phase 4	COMPLETED	The Home INR Study
NCT00127712	Phase 4	COMPLETED	Prevention of Atrial Fibrillation Following Noncardiac Thoracic Surgery
NCT00157781	Phase 4	COMPLETED	LEAF - Low Energy In Atrial Fibrillation
NCT00170313	Phase 4	TERMINATED	CORE: Study to Evaluate the Conducted AF-Response-Algorithm in Patients Suffering From Heart Failure and Atrial Fibrillation
NCT00189319	Phase 4	COMPLETED	To Evaluate the Impact of Oral Flecainide on Quality of Life in Patients With Paroxysmal Atrial Fibrillation
NCT00196144	Phase 4	COMPLETED	FFS - Far Field Sensing Test Study in Cardiac Dual Chamber Pacemakers
NCT00196157	Phase 4	UNKNOWN	Line Versus Spot Ablation in Persistent Atrial Fibrillation
NCT00196183	Phase 4	COMPLETED	Trigger- vs. Substrate-Ablation for Paroxysmal Atrial Fibrillation
NCT00196209	Phase 4	UNKNOWN	Cardioversion vs. Catheter Ablation for Persistent Atrial Fibrillation
NCT00227344	Phase 4	TERMINATED	CACAF2 Study: Catheter Ablation for Cure of Atrial Fibrillation
NCT00232219	Phase 4	COMPLETED	Use of Fish Oils to Reduce Recurrence of Atrial Fibrillation Following DC Cardioversion
NCT00232232	Phase 4	COMPLETED	Use of Fish Oils to Prevent Atrial Mechanical Stunning and Atrial Remodeling Due to Atrial Arrhythmia
NCT00232245	Phase 4	COMPLETED	Use of Fish Oils to Reduce the Frequency and Duration of Episodes of Atrial Fibrillation in Patients With Paroxysmal Atrial Fibrillation.
NCT00239226	Phase 4	COMPLETED	Electrophysiologically Guided PAcing Site Selection Study
NCT00247780	Phase 4	COMPLETED	Cavotricuspid Isthmusblock and Circumferential Pulmonary Vein Isolation in Patients With Atrial Fibrillation
NCT00256152	Phase 4	COMPLETED	Asymptomatic Atrial Fibrillation and Stroke Evaluation in Pacemaker Patients and the Atrial Fibrillation Reduction Atrial Pacing Trial
NCT00262119	Phase 4	COMPLETED	MINERVA: MINimizE Right Ventricular Pacing to Prevent Atrial Fibrillation and Heart Failure
NCT00287209	Phase 4	COMPLETED	Reduction of Atrial Fibrillation Study in Patients Undergoing Coronary Artery Bypass Grafting. (RASCABG 1 Study)
NCT00289042	Phase 4	COMPLETED	Assessment of Cardioversion Using Transesophageal Echocardiography II (ACUTE II)
NCT00313443	Phase 4	COMPLETED	Concentrations of Amiodarone in Fat Tissue During Chronic Treatment
NCT00340314	Phase 4	COMPLETED	A Trial of Circumferential Pulmonary Vein Ablation (CPVA) Versus Antiarrhythmic Drug Therapy in for Paroxysmal Atrial Fibrillation (AF)
NCT00343499	Phase 4	TERMINATED	The Use of DIOVAN to Reduce Post-Cardioversion Recurrence of Atrial Fibrillation Trial (the DRAFT Trial)
NCT00408473	Phase 4	TERMINATED	Comparative Study of Flecainide CR and Placebo in the Early Treatment of Atrial Fibrillation.
NCT00420017	Phase 4	COMPLETED	Prevention of Atrial Fibrillation Following Esophagectomy
NCT00438113	Phase 4	COMPLETED	Atrial Substrate Modification With Aggressive Blood Pressure Lowering to Prevent AF
NCT00446966	Phase 4	COMPLETED	Fish Oil for Reduction of Atrial Fibrillation After Cardiac Surgery
NCT00449410	Phase 4	COMPLETED	Silent Cerebrovascular Lesion and Cognitive Decline Prevention by Cholesterol Lowering in Elderly AF Patients
NCT00466973	Phase 4	WITHDRAWN	Atrial Fibrillation Ablation Device Comparison Study
NCT00511173	Phase 4	COMPLETED	Comparison of Warfarin Dosing Using Decision Model Versus Pharmacogenetic Algorithm
NCT00512915	Phase 4	COMPLETED	Avoid FFS - Use of the Atrial Pacemaker Lead 1699 With Very Short Tip Ring Spacing to Avoid Far Field Sensing
NCT00552084	Phase 4	COMPLETED	Evaluating the Effectiveness of Fish Oil Supplements at Reducing the Recurrence of Atrial Fibrillation
NCT00559988	Phase 4	TERMINATED	Combined Use of BIOTRONIK Home Monitoring and Predefined Anticoagulation to Reduce Stroke Risk
NCT00579098	Phase 4	COMPLETED	The Use of Statins Following a Left Atrial Catheter Ablation Procedure to Prevent Atrial Fibrillation
NCT00586287	Phase 4	COMPLETED	Study to Find Out the Appropriate Initial Dose of the Anticoagulant Drug Phenprocoumon
NCT00597077	Phase 4	COMPLETED	Atrial Fibrillation and Congestive Heart Failure Trial
NCT00603317	Phase 4	COMPLETED	Pharmacodynamic Drug Interaction Between Warfarin and Amoxicillin-clavulanic Acid
NCT00605748	Phase 4	UNKNOWN	Pulmonary Vein (PV) -Isolation: Arrhythmogenic Vein(s) Versus All Veins
NCT00643188	Phase 4	COMPLETED	Catheter Ablation vs. Standard Conventional Treatment in Patients With LV Dysfunction and AF
NCT00678340	Phase 4	COMPLETED	Randomized Trial of Two Ablation Catheters in Paroxysmal Atrial Fibrillation
NCT00680927	Phase 4	COMPLETED	Reveal® XT Performance Trial (XPECT)
NCT00702117	Phase 4	COMPLETED	Ajmaline Utilization in the Diagnosis and Treatment of Cardiac Arrhythmias
NCT00724581	Phase 4	UNKNOWN	Amiodarone Prophylaxis for Atrial Fibrillation in Patients Undergoing Surgery for Lung Cancer
NCT00765089	Phase 4	COMPLETED	Bipolar Radiofrequency Ablation -Role in Prevention of Postoperative Atrial Fibrillation
NCT00769938	Phase 4	COMPLETED	WOEST ( What is the Optimal antiplatElet & Anticoagulant Therapy in Patients With Oral Anticoagulation and Coronary StenTing)
NCT00774566	Phase 4	COMPLETED	PV-Isolation With the Cryoballoon Versus RF:a Randomized Controlled Prospective Non-inferiority Trial (FreezeAF)
NCT00776633	Phase 4	UNKNOWN	Triple Therapy in Patients on Oral Anticoagulation After Drug Eluting Stent Implantation
NCT00783900	Phase 4	COMPLETED	Intravenous Administration of Metoprolol Versus Biatrial Pacing in the Prevention of Atrial Fibrillation After Cardiac Surgery
NCT00784316	Phase 4	COMPLETED	Intravenous Metoprolol Versus Intravenous Amiodarone in the Prevention of Atrial Fibrillation After Cardiac Surgery
NCT00787800	Phase 4	COMPLETED	The Use of Dual Chamber ICD With Special Programmed Features to Lower the Risk of Inappropriate Shock
NCT00789139	Phase 4	COMPLETED	Recurrence of Arrhythmias After Pulmonary Veins Isolation Detected by ICM
NCT00791089	Phase 4	TERMINATED	Effects of Fish Oil on Post Ablation Arrhythmias
NCT00807586	Phase 4	COMPLETED	Corticosteroid Pulse After Ablation
NCT00834925	Phase 4	UNKNOWN	Low Dose of Diltiazem for Rate Control of Atrial Fibrillation
NCT00839566	Phase 4	TERMINATED	PAF-HEFT (Permanent Atrial Fibrillation in Heart Failure Trial)
NCT00848445	Phase 4	COMPLETED	Atrial Fibrillation: Canadian Atrial Fibrillation Evaluation (CAFE) Study -
NCT00861237	Phase 4	TERMINATED	Homeopathy for Prevention of Atrial Fibrillation After Aortocoronary Bypass Surgery
NCT00863213	Phase 4	COMPLETED	Study of Ablation Versus antiaRrhythmic Drugs in Persistent Atrial Fibrillation
NCT00926783	Phase 4	COMPLETED	Selective Complex Fractionated Atrial Electrograms (CFAE) Targeting for Atrial Fibrillation
NCT00959205	Phase 4	UNKNOWN	The Efficacy and Safety of CARTO 3D Mapping System Versus Conventional Method in AF and VT
NCT00969735	Phase 4	COMPLETED	Cryoenergy Or Radiofrequency for Pulmonary Vein Isolation

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for LMNA across ~30M SureChEMBL compounds — explore on Sugi Predict.