NEXN

Summary

NEXN (nexilin F-actin binding protein, HGNC:29557) is a protein-coding gene on chromosome 1p31.1, encoding Nexilin (Q0ZGT2). Involved in regulating cell migration through association with the actin cytoskeleton.

This gene encodes a filamentous actin-binding protein that may function in cell adhesion and migration. Mutations in this gene have been associated with dilated cardiomyopathy, also known as CMD1CC. Alternatively spliced transcript variants have been described.

Source: NCBI Gene 91624 — RefSeq curated summary.

At a glance

• Gene–disease (curated): dilated cardiomyopathy 1CC (Strong, ClinGen) — +3 more curated relationships
• GWAS associations: 4
• Clinical variants (ClinVar): 813 total — 21 pathogenic, 7 likely-pathogenic
• Phenotypes (HPO): 57
• MANE Select transcript: NM_144573

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29557
Approved symbol	NEXN
Name	nexilin F-actin binding protein
Location	1p31.1
Locus type	gene with protein product
Status	Approved
Aliases	nexilin, NELIN
Ensembl gene	ENSG00000162614
Ensembl biotype	protein_coding
OMIM	613121
Entrez	91624

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 11 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000330010, ENST00000334785, ENST00000342754, ENST00000401035, ENST00000440324, ENST00000464998, ENST00000470735, ENST00000480732, ENST00000851033, ENST00000902267, ENST00000902268, ENST00000902269, ENST00000927424, ENST00000951152

RefSeq mRNA: 2 — MANE Select: NM_144573 NM_001172309, NM_144573

CCDS: CCDS41351, CCDS53335

Canonical transcript exons

ENST00000334785 — 13 exons

Exon	Start	End
ENSE00001322751	77925188	77925229
ENSE00001717603	77926716	77926892
ENSE00001736505	77917960	77918038
ENSE00001744111	77926414	77926611
ENSE00001757634	77916055	77916133
ENSE00001798545	77918125	77918273
ENSE00001924258	77888624	77888759
ENSE00003543658	77942023	77942208
ENSE00003593345	77935823	77936044
ENSE00003632010	77933282	77933479
ENSE00003689396	77929316	77929504
ENSE00004283495	77942461	77943895
ENSE00004283497	77917566	77917757

Expression profiles

Bgee: expression breadth ubiquitous, 229 present calls, max score 99.75.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 32.6801 / max 2356.2452, expressed in 1407 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
3618	12.0987	973
3617	6.9863	953
3619	5.3534	844
3616	4.8101	1062
3626	1.3101	432
3628	0.7588	203
3627	0.3928	125
3615	0.3813	224
3624	0.3176	105
3623	0.1808	42

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left ventricle myocardium	UBERON:0006566	99.75	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.72	gold quality
myocardium	UBERON:0002349	99.60	gold quality
cardiac muscle of right atrium	UBERON:0003379	99.58	gold quality
deltoid	UBERON:0001476	99.56	gold quality
biceps brachii	UBERON:0001507	99.50	gold quality
skeletal muscle tissue	UBERON:0001134	99.43	gold quality
vastus lateralis	UBERON:0001379	99.43	gold quality
heart right ventricle	UBERON:0002080	99.42	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.40	gold quality
quadriceps femoris	UBERON:0001377	99.37	gold quality
tibialis anterior	UBERON:0001385	99.34	gold quality
muscle tissue	UBERON:0002385	99.21	gold quality
gastrocnemius	UBERON:0001388	99.02	gold quality
cardiac ventricle	UBERON:0002082	98.87	gold quality
heart left ventricle	UBERON:0002084	98.86	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.82	gold quality
muscle of leg	UBERON:0001383	98.64	gold quality
cardiac atrium	UBERON:0002081	98.63	gold quality
heart	UBERON:0000948	98.57	gold quality
right atrium auricular region	UBERON:0006631	98.57	gold quality
body of tongue	UBERON:0011876	98.54	gold quality
right coronary artery	UBERON:0001625	98.51	gold quality
apex of heart	UBERON:0002098	98.29	gold quality
popliteal artery	UBERON:0002250	98.17	gold quality
aorta	UBERON:0000947	98.16	gold quality
tibial artery	UBERON:0007610	98.16	gold quality
thoracic aorta	UBERON:0001515	98.15	gold quality
ascending aorta	UBERON:0001496	98.12	gold quality
saphenous vein	UBERON:0007318	97.87	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-MTAB-10287	yes	56.41
E-HCAD-1	yes	35.38
E-MTAB-8410	yes	27.19
E-HCAD-10	yes	16.14
E-HCAD-11	yes	11.01
E-GEOD-134144	yes	9.82
E-CURD-46	yes	9.72
E-HCAD-9	yes	6.76
E-MTAB-11268	no	2788.76
E-GEOD-124858	no	1601.59
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

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

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-8062	99.88	68.43	995
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-7161-5P	99.68	68.92	1592
HSA-MIR-548U	99.65	67.78	1463
HSA-MIR-5003-5P	99.61	69.13	1624
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-217-5P	99.49	69.93	1419
HSA-MIR-513A-3P	99.39	70.63	3620
HSA-MIR-513C-3P	99.39	70.63	3620
HSA-MIR-6507-3P	99.35	67.32	1059
HSA-MIR-4311	99.31	70.47	3041
HSA-MIR-5690	99.25	67.58	1012
HSA-MIR-4477B	99.23	70.49	1733
HSA-MIR-4426	99.17	66.74	1949

Literature-anchored findings (GeneRIF, showing 13)

• NELIN product is an F-actin associated protein and mediates cell motility (PMID:15823560)
• The findings of thi study on the role of nexilin in maintaining cardiac Z-disk integrity and on the workload dependence to cardiac Z-disk damage in nexilin-linked cardiomyopathy also might have implications for the treatment of NEXN-mutation carriers. (PMID:19881492)
• the mutations in NEXN that we describe here may further expand the knowledge of Z-disc genes in the pathogenesis of HCM. (PMID:20970104)
• Nexilin is a component of the machinery that drives the formation of Listeria monocytogenes comet tails and enteropathogenic Escherichia coli pedestals. (PMID:22381134)
• This is the first study to identify NEXN as a novel coronary artery disease susceptibility gene with both genetic and functional evidence. (PMID:24349201)
• NEXN as a novel gene for ASD and its function to inhibit GATA4 established a critical regulation of an F-actin binding protein on a transcription factor in cardiac development (PMID:24866383)
• NELINinduced phenotypic transformation of human vascular smooth muscle cell was regulated via the RhoA/SRF signaling pathway. (PMID:26458985)
• NEXN targeting by actin-controlled coactivators thus amplifies smooth muscle cell differentiation through the actin cytoskeleton, probably via dense bodies and dense bands. (PMID:30158653)
• Long noncoding RNA NEXN-AS1 mitigates atherosclerosis by regulating the actin-binding protein NEXN. (PMID:30589415)
• In this study, we explored the potential of whole genome sequencing (WGS) and whole transcriptome sequencing (WTS) to find DNA variants in SCD victims with structural normal hearts. We identified 23 candidate variants in regulatory sequences of cardiac genes, including a variant in the promotor region of NEXN, c.-194A>G, that was found to be statistically significantly. (PMID:31392414)
• Childhood onset nexilin dilated cardiomyopathy: A heterozygous and a homozygous case. (PMID:33949776)
• Loss of Nexilin function leads to a recessive lethal fetal cardiomyopathy characterized by cardiomegaly and endocardial fibroelastosis. (PMID:35166435)
• NEXN Gene in Cardiomyopathies and Sudden Cardiac Deaths: Prevalence, Phenotypic Expression, and Prognosis. (PMID:38059363)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	nexn	ENSDARG00000057317
mus_musculus	Nexn	ENSMUSG00000039103
rattus_norvegicus	Nexn	ENSRNOG00000012512
drosophila_melanogaster	Strn-Mlck	FBGN0265045

Paralogs (4): DAPK2 (ENSG00000035664), MYLK (ENSG00000065534), DAPK3 (ENSG00000167657), DAPK1 (ENSG00000196730)

Protein

Protein identifiers

Nexilin — Q0ZGT2 (reviewed: Q0ZGT2)

Alternative names: F-actin-binding protein, Nelin

All UniProt accessions (4): E7ETM8, E7EUA0, H7BXY5, Q0ZGT2

UniProt curated annotations — full annotation on UniProt →

Function. Involved in regulating cell migration through association with the actin cytoskeleton. Has an essential role in the maintenance of Z line and sarcomere integrity.

Subunit / interactions. Interacts with F-actin.

Subcellular location. Cytoplasm. Cytoskeleton. Cell junction. Adherens junction. Myofibril. Sarcomere. Z line.

Tissue specificity. Abundantly expressed in heart and skeletal muscle, and at lower levels in placenta, lung, liver and pancreas. Also expressed in HeLaS3 and MOLT-4 cell lines.

Disease relevance. Cardiomyopathy, dilated, 1CC (CMD1CC) [MIM:613122] An autosomal dominant form of dilated cardiomyopathy, 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. Cardiomyopathy, dilated, 2M (CMD2M) [MIM:621261] A form of dilated cardiomyopathy, a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. CMD2M is an autosomal recessive, severe form characterized by fetal or perinatal death or by severe symptoms in infants. The disease is caused by variants affecting the gene represented in this entry. Cardiomyopathy, familial hypertrophic, 20 (CMH20) [MIM:613876] A hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (4)

UniProt ID	Names	Canonical?
Q0ZGT2-1	1	yes
Q0ZGT2-2	2
Q0ZGT2-3	3
Q0ZGT2-4	4

RefSeq proteins (2): NP_001165780, NP_653174* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013098	Ig_I-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily

Pfam: PF07679

UniProt features (36 total): sequence variant 9, modified residue 8, region of interest 6, sequence conflict 6, splice variant 4, chain 1, domain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q0ZGT2-F1	70.78	0.20

Functional residue map

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

Post-translational modifications (8): 241, 357, 365, 370, 564, 569, 16, 80

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 236 (showing top): GOBP_NEURON_RECOGNITION, GOBP_NEUROGENESIS, CHANDRAN_METASTASIS_DN, SENESE_HDAC1_AND_HDAC2_TARGETS_DN, GOBP_CELL_CELL_ADHESION, PICCALUGA_ANGIOIMMUNOBLASTIC_LYMPHOMA_UP, TCF4_Q5, TGCTGAY_UNKNOWN, TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_10D_UP, GFI1_01, GOMF_ACTIN_BINDING, GOCC_NEURON_PROJECTION, GOMF_STRUCTURAL_CONSTITUENT_OF_MUSCLE, GOBP_CELL_PROJECTION_ORGANIZATION, YANAGIHARA_ESX1_TARGETS

GO Biological Process (5): homophilic cell-cell adhesion (GO:0007156), axon guidance (GO:0007411), regulation of cell migration (GO:0030334), regulation of cytoskeleton organization (GO:0051493), dendrite self-avoidance (GO:0070593)

GO Molecular Function (5): structural constituent of muscle (GO:0008307), actin filament binding (GO:0051015), cell-cell adhesion mediator activity (GO:0098632), actin binding (GO:0003779), protein binding (GO:0005515)

GO Cellular Component (9): plasma membrane (GO:0005886), adherens junction (GO:0005912), focal adhesion (GO:0005925), actin cytoskeleton (GO:0015629), Z disc (GO:0030018), axon (GO:0030424), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), anchoring junction (GO:0070161)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell-cell adhesion	2
cellular anatomical structure	2
axonogenesis	1
neuron projection guidance	1
cell migration	1
regulation of cell motility	1
cytoskeleton organization	1
regulation of organelle organization	1
neuron recognition	1
structural molecule activity	1
actin binding	1
protein-containing complex binding	1
cell adhesion mediator activity	1
cytoskeletal protein binding	1
binding	1
membrane	1
cell periphery	1
cell-cell junction	1
cell-substrate junction	1
cytoskeleton	1
I band	1
neuron projection	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
cell junction	1

Protein interactions and networks

STRING

1020 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NEXN	HCLS1	P14317	815
NEXN	CTTN	Q14247	798
NEXN	PPP1R9A	Q9ULJ8	781
NEXN	RBM20	Q5T481	767
NEXN	PPP1R9B	Q96SB3	758
NEXN	VCL	P18206	751
NEXN	CSRP3	P50461	714
NEXN	TCAP	O15273	697
NEXN	ABCC9	O60706	696
NEXN	LDB3	O75112	689
NEXN	ACTN2	P35609	668
NEXN	TMPO	P08918	657
NEXN	EYA4	O95677	655
NEXN	MYH7	P12883	648
NEXN	DBN1	Q16643	645

IntAct

52 interactions, top by confidence:

A	B	Type	Score
BCL7A	ARID1A	psi-mi:“MI:0914”(association)	0.640
NEXN	GADD45GIP1	psi-mi:“MI:0915”(physical association)	0.400
CECR2	NEXN	psi-mi:“MI:0915”(physical association)	0.400
Tubgcp3		psi-mi:“MI:0915”(physical association)	0.400
Cdk1		psi-mi:“MI:0915”(physical association)	0.400
Trim69		psi-mi:“MI:0915”(physical association)	0.400
NELL1	NEXN	psi-mi:“MI:0915”(physical association)	0.400
PCNA	NEXN	psi-mi:“MI:0915”(physical association)	0.370
NEXN	HMGB1	psi-mi:“MI:0915”(physical association)	0.370
HMGB2	NEXN	psi-mi:“MI:0915”(physical association)	0.370
NEXN		psi-mi:“MI:0915”(physical association)	0.370
NEXN	HSPB1	psi-mi:“MI:0915”(physical association)	0.370
MYO1C	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
BCAR1	MYO1C	psi-mi:“MI:0914”(association)	0.350
OCRL	MYO1C	psi-mi:“MI:0914”(association)	0.350
CUL1	LGALS8	psi-mi:“MI:0914”(association)	0.350
NEXN	MYO1B	psi-mi:“MI:0914”(association)	0.350
DISC1	NUDT21	psi-mi:“MI:0914”(association)	0.350
slrP	DHX15	psi-mi:“MI:0914”(association)	0.350
CTBP1	TAF15	psi-mi:“MI:0914”(association)	0.350
DAPK1	MYO1C	psi-mi:“MI:0914”(association)	0.350
GRB2	MYO1C	psi-mi:“MI:0914”(association)	0.350
CALD1		psi-mi:“MI:0914”(association)	0.350
CAPZB	ENAH	psi-mi:“MI:0914”(association)	0.350
CTTN		psi-mi:“MI:0914”(association)	0.350
MTMR10	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
NXT1	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
SLC39A3	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
EMCN	PLEKHG3	psi-mi:“MI:0914”(association)	0.350

BioGRID (128): NEXN (Two-hybrid), NEXN (Affinity Capture-MS), NEXN (Affinity Capture-MS), NEXN (Affinity Capture-MS), NEXN (Affinity Capture-MS), NEXN (Affinity Capture-MS), NEXN (Affinity Capture-MS), NEXN (Affinity Capture-MS), NEXN (Affinity Capture-MS), NEXN (Affinity Capture-MS), NEXN (Affinity Capture-MS), NEXN (Affinity Capture-MS), NEXN (Affinity Capture-MS), NEXN (Affinity Capture-MS), NEXN (Affinity Capture-MS)

ESM2 similar proteins: A0A1C3NSL9, A1C9W6, A3LYI0, A4R227, A5DXA0, A9ZLL8, C0HK92, G5EG14, J7M799, M9MRD1, O62203, P0CO16, P0CO17, P0CP34, P0CP35, P0CU47, P34433, P34531, P34554, P46504, Q09237, Q09501, Q0UG82, Q0WQ57, Q0ZGT2, Q18221, Q1DUF9, Q2KN97, Q2KN98, Q2KN99, Q2KNA0, Q2KNA1, Q4IL82, Q4KME6, Q4PGL2, Q5A2K0, Q60JJ0, Q60M48, Q69YQ0, Q6CBW0

Diamond homologs: A2AAJ9, A2AJ76, A2ASS6, A8DYP0, D3YXG0, D3ZEY0, E9Q8Q6, G4SLH0, G5EBF1, O01761, O35136, P0C5E3, P11799, P17948, P31836, P35969, P53767, Q05793, Q0ZGT2, Q15746, Q15772, Q23551, Q3UH53, Q5DTJ9, Q5GIT4, Q5MD89, Q5VST9, Q62407, Q63638, Q696W0, Q6PDN3, Q6ZP82, Q7TPW1, Q86TC9, Q8AV58, Q8NDA2, Q8QHL3, Q8WX93, Q8WZ42, Q924C5

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 60 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.

GO biological processes:

GO term	Partners	Fold	FDR
actin filament organization	6	14.0×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	21
Likely pathogenic	7
Uncertain significance	480
Likely benign	197
Benign	21

Top pathogenic / likely-pathogenic (28)

Variant ID	HGVS	Classification
1382020	NM_144573.4(NEXN):c.1233_1234insGCCGGGCCCGGTGGCTCACGCCTGTAATCCCAGCACATTGGGAGGCCGAGACTGGAGGATCACGAGTTCAGGAGATCGATACCATACANNNNNNNNNNAAAAAAAAAAAAAAAAAAAAAAGAATTTGAACAACTG (p.Arg412delinsAlaGlyProGlyGlySerArgLeuTer)	Pathogenic
1993576	NM_144573.4(NEXN):c.1170del (p.Lys390fs)	Pathogenic
2103973	NM_144573.4(NEXN):c.717dup (p.Glu240fs)	Pathogenic
2118680	NM_144573.4(NEXN):c.676del (p.Ser226fs)	Pathogenic
2123226	NM_144573.4(NEXN):c.1501A>T (p.Arg501Ter)	Pathogenic
2132590	NM_144573.4(NEXN):c.1084A>T (p.Lys362Ter)	Pathogenic
2936967	NM_144573.4(NEXN):c.298G>T (p.Gly100Ter)	Pathogenic
2947595	NM_144573.4(NEXN):c.1536dup (p.Met513fs)	Pathogenic
2949465	NM_144573.4(NEXN):c.813_814insGG (p.Lys272fs)	Pathogenic
2953278	NM_144573.4(NEXN):c.798del (p.Glu267fs)	Pathogenic
3751520	NM_144573.4(NEXN):c.518_519del (p.Val173fs)	Pathogenic
4056074	NEXN, 3-BP DEL, 1582GAA	Pathogenic
4056076	NEXN, 1-BP DEL, NT1302	Pathogenic
4056077	NM_144573.4(NEXN):c.1156dup (p.Met386fs)	Pathogenic
4056078	NEXN, 6-BP DEL, NT1579	Pathogenic
4056079	NEXN, IVS8, G-A, -1	Pathogenic
4056080	NEXN, ARG391TER	Pathogenic
4056081	NEXN, ARG392TER	Pathogenic
4787364	NM_144573.4(NEXN):c.1015del (p.Glu339fs)	Pathogenic
4787433	NM_144573.4(NEXN):c.718del (p.Glu240fs)	Pathogenic
538107	NM_144573.4(NEXN):c.1348dup (p.Ser450fs)	Pathogenic
1461682	NM_144573.4(NEXN):c.1251+1del	Likely pathogenic
201935	NM_144573.4(NEXN):c.1935C>G (p.Phe645Leu)	Likely pathogenic
2156496	NM_144573.4(NEXN):c.688-1G>A	Likely pathogenic
2929334	NM_144573.4(NEXN):c.865-9_892del	Likely pathogenic
3748873	NM_144573.4(NEXN):c.687+2T>C	Likely pathogenic
4687953	NM_144573.4(NEXN):c.794_797del (p.Gln265fs)	Likely pathogenic
4813078	NM_144573.4(NEXN):c.226G>T (p.Glu76Ter)	Likely pathogenic

SpliceAI

1815 predictions. Top by Δscore:

Variant	Effect	Δscore
1:77888755:GCAGG:G	donor_gain	1.0000
1:77888758:GG:G	donor_gain	1.0000
1:77888759:GG:G	donor_gain	1.0000
1:77888760:G:GG	donor_gain	1.0000
1:77917559:A:AG	acceptor_gain	1.0000
1:77917755:G:GT	donor_gain	1.0000
1:77918034:AACAG:A	donor_loss	1.0000
1:77918039:GT:G	donor_loss	1.0000
1:77918040:T:A	donor_loss	1.0000
1:77918114:T:G	acceptor_gain	1.0000
1:77918121:TTAG:T	acceptor_loss	1.0000
1:77918220:GA:G	donor_gain	1.0000
1:77918272:AG:A	donor_loss	1.0000
1:77918273:GG:G	donor_loss	1.0000
1:77918274:GT:G	donor_loss	1.0000
1:77926585:G:GT	donor_gain	1.0000
1:77926585:G:T	donor_gain	1.0000
1:77926586:A:T	donor_gain	1.0000
1:77926607:T:G	donor_gain	1.0000
1:77926889:AATGG:A	donor_loss	1.0000
1:77926892:GGT:G	donor_loss	1.0000
1:77926893:G:GC	donor_loss	1.0000
1:77926894:T:A	donor_loss	1.0000
1:77929311:GTTA:G	acceptor_loss	1.0000
1:77929312:TTA:T	acceptor_loss	1.0000
1:77929315:G:GA	acceptor_loss	1.0000
1:77933475:GAGAG:G	donor_gain	1.0000
1:77933477:GAG:G	donor_gain	1.0000
1:77933477:GAGGT:G	donor_loss	1.0000
1:77933478:AGGTA:A	donor_loss	1.0000

AlphaMissense

4504 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:77942644:T:A	W615R	1.000
1:77942644:T:C	W615R	1.000
1:77942717:T:C	L639P	1.000
1:77942807:T:C	L669P	1.000
1:77942546:C:A	P582Q	0.999
1:77942552:T:C	F584S	0.999
1:77942603:T:C	F601S	0.999
1:77942609:T:A	V603D	0.999
1:77942645:G:C	W615S	0.999
1:77942646:G:C	W615C	0.999
1:77942646:G:T	W615C	0.999
1:77942755:T:C	Y652H	0.999
1:77942755:T:G	Y652D	0.999
1:77942756:A:C	Y652S	0.999
1:77942761:T:C	C654R	0.999
1:77942763:T:G	C654W	0.999
1:77942794:A:C	S665R	0.999
1:77942796:T:A	S665R	0.999
1:77942796:T:G	S665R	0.999
1:77942802:T:G	C667W	0.999
1:77942546:C:G	P582R	0.998
1:77942564:T:A	L588H	0.998
1:77942717:T:A	L639H	0.998
1:77942755:T:A	Y652N	0.998
1:77942762:G:A	C654Y	0.998
1:77942767:G:C	A656P	0.998
1:77942768:C:A	A656E	0.998
1:77942775:C:A	N658K	0.998
1:77942775:C:G	N658K	0.998
1:77942800:T:C	C667R	0.998

dbSNP variants (sampled 300 via entrez): RS1000082959 (1:77924349 G>A), RS1000138289 (1:77914368 G>C), RS1000154245 (1:77924649 T>C), RS1000155179 (1:77913335 A>G), RS1000179159 (1:77939232 A>G), RS1000207986 (1:77893546 G>T), RS1000220696 (1:77927897 G>A), RS1000230062 (1:77943346 T>C), RS1000297354 (1:77910403 T>A,C), RS1000406628 (1:77903145 T>G), RS1000459303 (1:77944372 C>T), RS1000500047 (1:77894505 A>G), RS1000507498 (1:77914585 A>C,G), RS1000582238 (1:77943117 G>C), RS1000611660 (1:77939528 C>T)

Disease associations

OMIM: gene MIM:613121 | disease phenotypes: MIM:613122, MIM:613876, MIM:192600, MIM:115200, MIM:621261, MIM:115195, MIM:613426, MIM:609040

GenCC curated gene-disease

Disease	Classification	Inheritance
dilated cardiomyopathy 1CC	Strong	Semidominant
familial isolated dilated cardiomyopathy	Supportive	Autosomal dominant
hypertrophic cardiomyopathy	Limited	Autosomal dominant
hypertrophic cardiomyopathy 20	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
hypertrophic cardiomyopathy	Limited	AD
dilated cardiomyopathy 1CC	Strong	AD

Mondo (16): dilated cardiomyopathy 1CC (MONDO:0013147), hypertrophic cardiomyopathy 20 (MONDO:0013477), heart failure (MONDO:0005252), cardiomyopathy (MONDO:0004994), dilated cardiomyopathy (MONDO:0005021), familial hypertrophic cardiomyopathy (MONDO:0024573), dilated cardiomyopathy 1A (MONDO:0007269), familial dilated cardiomyopathy (MONDO:0016333), hypertrophic cardiomyopathy 1 (MONDO:0008647), hypertrophic cardiomyopathy (MONDO:0005045), cardiomyopathy, dilated, 2M (MONDO:0979243), long QT syndrome (MONDO:0002442), hypertrophic cardiomyopathy 2 (MONDO:0007266), dilated cardiomyopathy 1S (MONDO:0013262), arrhythmogenic right ventricular dysplasia 9 (MONDO:0012180)

Orphanet (9): Familial isolated dilated cardiomyopathy (Orphanet:154), Rare cardiomyopathy (Orphanet:167848), Dilated cardiomyopathy (Orphanet:217604), Rare familial disorder with hypertrophic cardiomyopathy (Orphanet:99739), Familial dilated cardiomyopathy with conduction defect due to LMNA mutation (Orphanet:300751), Familial dilated cardiomyopathy (Orphanet:217607), Rare hypertrophic cardiomyopathy (Orphanet:217569), Left ventricular noncompaction (Orphanet:54260), NON RARE IN EUROPE: Familial isolated hypertrophic cardiomyopathy (Orphanet:155)

HPO phenotypes

57 total (30 of 57 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000407	Sensorineural hearing impairment
HP:0000969	Edema
HP:0001263	Global developmental delay
HP:0001511	Intrauterine growth retardation
HP:0001541	Ascites
HP:0001558	Decreased fetal movement
HP:0001561	Polyhydramnios
HP:0001635	Congestive heart failure
HP:0001639	Hypertrophic cardiomyopathy
HP:0001640	Cardiomegaly
HP:0001644	Dilated cardiomyopathy
HP:0001649	Tachycardia
HP:0001653	Mitral regurgitation
HP:0001706	Endocardial fibroelastosis
HP:0001712	Left ventricular hypertrophy
HP:0001727	Thromboembolic stroke
HP:0001789	Hydrops fetalis
HP:0001790	Nonimmune hydrops fetalis
HP:0001791	Fetal ascites
HP:0002202	Pleural effusion
HP:0002875	Exertional dyspnea
HP:0003198	Myopathy
HP:0003457	EMG abnormality
HP:0003581	Adult onset
HP:0003584	Late onset
HP:0003593	Infantile onset
HP:0003596	Middle age onset
HP:0003621	Juvenile onset

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST004747_15	Lung cancer in never smokers	4.000000e-06
GCST007430_16	Peak expiratory flow	1.000000e-06
GCST007431_108	Lung function (FEV1/FVC)	6.000000e-15
GCST007432_32	FEV1	9.000000e-07

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0009718	peak expiratory flow
EFO:0004713	FEV/FVC ratio
EFO:0004314	forced expiratory volume

MeSH disease descriptors (11)

Descriptor	Name	Tree numbers
D009202	Cardiomyopathies	C14.280.238
D002311	Cardiomyopathy, Dilated	C14.280.195.160; C14.280.238.070; C16.320.488.750
D002312	Cardiomyopathy, Hypertrophic	C14.280.238.100; C14.280.484.048.750.070.160
D024741	Cardiomyopathy, Hypertrophic, Familial	C14.280.238.100.500; C14.280.484.048.750.070.160.500; C16.320.160
D006333	Heart Failure	C14.280.434
D008133	Long QT Syndrome	C14.280.067.565; C14.280.123.625; C16.131.240.400.715; C23.550.073.547
C563808	Arrhythmogenic Right Ventricular Dysplasia, Familial, 9 (supp.)
C567733	Cardiomyopathy, Dilated, 1CC (supp.)
C563538	Cardiomyopathy, Dilated, 1s (supp.)
C566171	Cardiomyopathy, Familial Hypertrophic, 2 (supp.)
C536231	familial dilated cardiomyopathy (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression	4
sodium arsenite	increases expression, decreases expression, affects cotreatment, increases abundance	4
(+)-JQ1 compound	decreases expression	3
Valproic Acid	affects expression, decreases expression	3
Air Pollutants	decreases expression, increases abundance	2
Calcitriol	decreases expression, increases expression	2
Doxorubicin	affects expression, decreases expression	2
Estradiol	affects cotreatment, decreases expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Particulate Matter	decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
shuanghuang shengbai	increases expression	1
triphenyl phosphate	affects expression	1
glycidyl methacrylate	increases expression	1
testosterone undecanoate	affects cotreatment, decreases expression	1
1,6-hexamethylene diisocyanate	affects expression	1
trimellitic anhydride	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
ammonium hexachloroplatinate	affects expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
nickel sulfate	decreases expression	1
coumarin	affects phosphorylation	1
resorcinol	decreases expression	1
triadimefon	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00879060	PHASE4	COMPLETED	Clinical and Therapeutic Implications of Fibrosis in Hypertrophic Cardiomyopathy
NCT01721967	PHASE4	COMPLETED	Ranolazine for the Treatment of Chest Pain in HCM Patients
NCT02948998	PHASE4	UNKNOWN	Evaluating the Effect of Spironolactone on Hypertrophic Cardiomyopathy
NCT03249272	PHASE4	TERMINATED	Microvascular Dysfunction in Nonischemic Cardiomyopathy: Insights From CMR Assessment of Coronary Flow Reserve
NCT04133532	PHASE4	COMPLETED	Effect of Metoprolol in Post Alcohol Septal Ablation Patients With Hypertrophic Cardiomyopathy
NCT06401343	PHASE4	RECRUITING	Use of SGLT2i in noHCM With HFpEF
NCT07103655	PHASE4	NOT_YET_RECRUITING	The Therapeutic Value of Mavacamten in Hypertrophic Cardiomyopathy With Mid-to-Apical Left Ventricular Obstruction
NCT07600177	PHASE4	RECRUITING	Mavacamten to Aficamten Transition in Patients With Obstructive Hypertrophic Cardiomyopathy
NCT00083772	PHASE4	TERMINATED	Use of Nesiritide in the Management of Acute Diastolic Heart Failure
NCT00146848	PHASE4	COMPLETED	PEGASUS CRT Study: Atrial Support Study in Cardiac Resynchronization Therapy
NCT00154115	PHASE4	COMPLETED	Levosimendan in High Risk Heart Valve Surgery
NCT00170313	PHASE4	TERMINATED	CORE: Study to Evaluate the Conducted AF-Response-Algorithm in Patients Suffering From Heart Failure and Atrial Fibrillation
NCT00180596	PHASE4	COMPLETED	PACMAN - PAcing for CardioMyopathies, a EuropeAN Study
NCT00187200	PHASE4	COMPLETED	Response of Cardiac Resynchronization Therapy Optimization With Ventricle to Ventricle Timing in Heart Failure Patients
NCT00206232	PHASE4	COMPLETED	Novel Treatment for Diastolic Heart Failure in Women
NCT00206856	PHASE4	TERMINATED	Rapid Assessment of Bedside BNP In Treatment of Heart Failure (RABBIT)
NCT00219388	PHASE4	COMPLETED	Efficacy and Safety of Treatment With Simdax® Versus Dobutrex® in Decompensated Heart Failure Patients.
NCT00288587	PHASE4	COMPLETED	Extracorporeal Ultrafiltration (UF) vs. Usual and Customary Care for Patients With Severe Heart Failure (HF)
NCT00305526	PHASE4	TERMINATED	REBEAT Resynchronisation and Beta-Blocker European Trial
NCT00324766	PHASE4	COMPLETED	Levosimendan in Acute Heart Failure Following Acute Myocardial Infarction.
NCT00347087	PHASE4	COMPLETED	Effect of Irbesartan on Insulin Sensitivity in Chronic Heart Failure
NCT00371085	PHASE4	COMPLETED	Congestive Heart Failure Outreach Program
NCT00384566	PHASE4	WITHDRAWN	A Comparison of the Effect of Carvedilol and Metoprolol on Airways Tone in Patients With Heart Failure
NCT00391846	PHASE4	COMPLETED	Evaluation of Heart Failure Treatment Guided by N-terminal Pro B-type Natriuretic Peptide (NTproBNP) vs Clinical Symptoms and Signs Alone
NCT00400582	PHASE4	COMPLETED	A Pharmacogenomic Study of Candesartan in Heart Failure
NCT00402376	PHASE4	TERMINATED	Evaluation of Myocardial Improvement in Patients Supported by Ventricular Assist Device Under Optimal Pharmacological Therapy
NCT00418119	PHASE4	UNKNOWN	Erythropoietin Treatment in Patients With Systolic Left Ventricular Dysfunction, Mild Anemia and Normal Renal Function
NCT00422318	PHASE4	COMPLETED	Treatment of Hyperuricemia in Patients With Heart Failure
NCT00477789	PHASE4	COMPLETED	Effects of Allopurinol on Diastolic Function in Chronic Heart Failure Patients
NCT00480077	PHASE4	TERMINATED	Diagnostic Outcome Trial in Heart Failure (DOT-HF Trial)
NCT00489177	PHASE4	COMPLETED	Optimal Programming to Improve Mechanical Indices, Symptoms and Exercise in Cardiac Resynchronization Therapy.
NCT00491907	PHASE4	TERMINATED	Effect of Folic Acid on Endothelial and Baroreceptor Function in Patients With Heart Failure
NCT00497900	PHASE4	COMPLETED	The Effect of Calcium and Vitamin D in Patients With Heart Failure
NCT00498472	PHASE4	COMPLETED	NT-proBNP in the Optimization of Treatment After Recent Acute Heart Failure Trial
NCT00512759	PHASE4	COMPLETED	Goal-directed Afterload Reduction in Acute Congestive Cardiac Decompensation Study
NCT00517426	PHASE4	COMPLETED	Effects of Acetazolamide and CO2 Inhalation on Exercise-induced Periodic Breathing in Heart Failure
NCT00517725	PHASE4	COMPLETED	Nebivolol Versus Bisoprolol Versus Carvedilol in Heart Failure
NCT00527059	PHASE4	UNKNOWN	Renal Effects of Levosimendan in Patients Admitted With Acute Decompensated Heart Failure
NCT00551499	PHASE4	COMPLETED	Cardiac Resynchronisation Therapy in Combination With Overdrive Pacing in the Treatment of Central Sleep Apnea in CHF
NCT00552851	PHASE4	UNKNOWN	Changes of Left Ventricular Mass and Cardiac Function in Patients With Active Acromegaly During Treatment With the Growth Hormone Receptor Antagonist Pegvisomant