NEBL

Summary

NEBL (nebulette, HGNC:16932) is a protein-coding gene on chromosome 10p12.31, encoding Nebulette (O76041). Binds to actin and plays an important role in the assembly of the Z-disk.

This gene encodes a nebulin like protein that is abundantly expressed in cardiac muscle. The encoded protein binds actin and interacts with thin filaments and Z-line associated proteins in striated muscle. This protein may be involved in cardiac myofibril assembly. A shorter isoform of this protein termed LIM nebulette is expressed in non-muscle cells and may function as a component of focal adhesion complexes. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 10529 — RefSeq curated summary.

At a glance

• Gene–disease (curated): dilated cardiomyopathy (Moderate, GenCC) — +1 more curated relationship
• GWAS associations: 26
• Clinical variants (ClinVar): 1,446 total — 1 likely-pathogenic
• Phenotypes (HPO): 3
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_006393

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16932
Approved symbol	NEBL
Name	nebulette
Location	10p12.31
Locus type	gene with protein product
Status	Approved
Aliases	LASP2, LNEBL, bA165O3.1
Ensembl gene	ENSG00000078114
Ensembl biotype	protein_coding
OMIM	605491
Entrez	10529

Gene structure

Transcript identifiers

Ensembl transcripts: 38 — 18 protein_coding, 11 protein_coding_CDS_not_defined, 7 retained_intron, 2 nonsense_mediated_decay

ENST00000377119, ENST00000377122, ENST00000417816, ENST00000434381, ENST00000460652, ENST00000464278, ENST00000473616, ENST00000481592, ENST00000482754, ENST00000485750, ENST00000492325, ENST00000493005, ENST00000498424, ENST00000529198, ENST00000534331, ENST00000649437, ENST00000674540, ENST00000674777, ENST00000675114, ENST00000675700, ENST00000675702, ENST00000675747, ENST00000676018, ENST00000676125, ENST00000863062, ENST00000863063, ENST00000863064, ENST00000863065, ENST00000863066, ENST00000863067, ENST00000863068, ENST00000863069, ENST00000863070, ENST00000963739, ENST00000963740, ENST00000963741, ENST00000963742, ENST00000963743

RefSeq mRNA: 10 — MANE Select: NM_006393 NM_001173484, NM_001377322, NM_001377323, NM_001377324, NM_001377325, NM_001377326, NM_001377327, NM_001377328, NM_006393, NM_213569

CCDS: CCDS7133, CCDS7134

Canonical transcript exons

ENST00000377122 — 28 exons

Exon	Start	End
ENSE00001181266	20808510	20808659
ENSE00001181271	20809806	20809898
ENSE00001181353	20845258	20845368
ENSE00001181355	20850395	20850502
ENSE00001181358	20852545	20852649
ENSE00001181363	20858240	20858344
ENSE00001181368	20859713	20859826
ENSE00001181370	20868664	20868765
ENSE00001181373	20869740	20869841
ENSE00001181379	20888097	20888207
ENSE00001181381	20889845	20889949
ENSE00001181384	20896958	20897029
ENSE00001356059	20787202	20787308
ENSE00001376454	20897125	20897311
ENSE00001724137	20880794	20880904
ENSE00001929333	20779973	20785923
ENSE00003476132	20817600	20817692
ENSE00003500196	20831473	20831583
ENSE00003514832	20826447	20826539
ENSE00003519602	20812769	20812940
ENSE00003524096	20815625	20815717
ENSE00003552999	20828530	20828634
ENSE00003566768	20813939	20814043
ENSE00003571725	20823208	20823300
ENSE00003607379	20840739	20840849
ENSE00003608477	20835513	20835623
ENSE00003618308	20831196	20831306
ENSE00003654874	20819424	20819516

Expression profiles

Bgee: expression breadth ubiquitous, 282 present calls, max score 99.80.

FANTOM5 (CAGE): breadth broad, TPM avg 17.2949 / max 955.1813, expressed in 906 samples.

FANTOM5 promoters (17 alternative TSS)

Promoter ID	TPM avg	Samples expressed
108601	9.6057	803
108587	3.2709	66
108603	1.2420	407
108607	0.7388	179
108600	0.3671	206
108602	0.3274	179
108591	0.3122	49
108599	0.3033	93
108606	0.2142	109
108604	0.1678	104

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
heart right ventricle	UBERON:0002080	99.80	gold quality
myocardium	UBERON:0002349	99.67	gold quality
cranial nerve II	UBERON:0000941	99.64	gold quality
left ventricle myocardium	UBERON:0006566	99.64	gold quality
cardiac muscle of right atrium	UBERON:0003379	99.59	gold quality
apex of heart	UBERON:0002098	99.20	gold quality
renal glomerulus	UBERON:0000074	99.11	gold quality
cardiac atrium	UBERON:0002081	99.04	gold quality
metanephric glomerulus	UBERON:0004736	99.01	gold quality
tongue squamous epithelium	UBERON:0006919	98.98	gold quality
right atrium auricular region	UBERON:0006631	98.95	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.92	gold quality
lateral globus pallidus	UBERON:0002476	98.88	gold quality
middle temporal gyrus	UBERON:0002771	98.82	gold quality
endothelial cell	CL:0000115	98.76	gold quality
medial globus pallidus	UBERON:0002477	98.73	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	98.73	gold quality
cardiac ventricle	UBERON:0002082	98.71	gold quality
heart left ventricle	UBERON:0002084	98.67	gold quality
globus pallidus	UBERON:0001875	98.59	gold quality
paraflocculus	UBERON:0005351	98.59	gold quality
parotid gland	UBERON:0001831	98.58	gold quality
entorhinal cortex	UBERON:0002728	98.36	gold quality
CA1 field of hippocampus	UBERON:0003881	98.23	gold quality
inferior olivary complex	UBERON:0002127	98.09	gold quality
postcentral gyrus	UBERON:0002581	97.94	gold quality
palpebral conjunctiva	UBERON:0001812	97.90	gold quality
superior vestibular nucleus	UBERON:0007227	97.86	gold quality
medulla oblongata	UBERON:0001896	97.79	gold quality
substantia nigra pars reticulata	UBERON:0001966	97.68	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-GEOD-131882	yes	3929.28
E-GEOD-180759	yes	2777.46
E-HCAD-35	yes	96.82
E-CURD-119	yes	34.90
E-HCAD-25	yes	23.28
E-MTAB-10137	yes	4.78
E-GEOD-137537	yes	4.52
E-MTAB-11268	no	3731.87
E-GEOD-83139	no	2.94
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

173 targeting NEBL, 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-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-3162-3P	100.00	65.37	363
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 18)

• our data demonstrate the importance of this cardiac-specific nebulin isoform in myofibril organization and function. Our data demonstrate that nebulette plays a significant role in the structure and stability of the cardiac Z-line. (PMID:11822876)
• LIM-nebulette, Lasp-1, and zyxin may play an important role in the organization of focal adhesions (PMID:15004028)
• filamin-C, a known component of striated muscle Z-lines, interacts with nebulette modules (PMID:17987659)
• the importance of the nebulette-TPM interactions in the maintenance and stability of the thin filaments. (PMID:18823973)
• Different mutations in nebulette transgene trigger a pathological cascade leading to endocardial fibroelastosis and dilated cardiomyopathy in mutant embryonic mouse hearts. (PMID:20951326)
• Report oncogenic potential of MLL-NEBL and NEBL-MLL fusion genes in acute myeloid leukemia. (PMID:23340173)
• Data indicate that lasp-2 interacts with the focal adhesion proteins vinculin and paxillin. (PMID:23389630)
• We identify the SH3 domains of nebulin and nebulette as novel ligands of proline-rich regions of Xin and XIRP2 (PMID:23985323)
• predisposition to multibacillary leprosy in Vietnam is associated with CUBN and NEBL common variants in the chromosome 10p13 linkage region (PMID:24563210)
• LASP2 may play a significant role in suppressing CRC progression and provided a novel biomarker for CRC therapy (PMID:28606091)
• The levels of phosphorylated FAK (Tyr397 and Tyr925) were increased after overexpressing Lasp2 and were downregulated by transfecting Lasp2-siRNA. (PMID:28667800)
• Survival analysis suggested that overexpressed NEBL in patients with colorectal cancer was associated with a positive prognosis for overall survival. (PMID:29257257)
• Upregulation of LASP2 inhibits pancreatic cancer cell migration and invasion through suppressing TGF-beta-induced EMT. (PMID:30945341)
• Knockdown of LASP2 inhibits the proliferation, migration, and invasion of cervical cancer cells. (PMID:31026088)
• LASP2 is downregulated in human liver cancer and contributes to hepatoblastoma cell malignant phenotypes through MAPK/ERK pathway. (PMID:32325347)
• LASP2 inhibits trophoblast cell migration and invasion in preeclampsia through inactivation of the Wnt/beta-catenin signaling pathway. (PMID:32635793)
• LASP2 functions as a potential prognostic factor and therapeutic target in nasopharyngeal carcinoma. (PMID:33015783)
• Downregulation of NEBL promotes migration and invasion of clear cell renal cell carcinoma by inducing epithelial-mesenchymal transition. (PMID:38215565)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Nebl	ENSMUSG00000053702
rattus_norvegicus	Nebl	ENSRNOG00000049452
drosophila_melanogaster	Hil	FBGN0050147
caenorhabditis_elegans		WBGENE00003089

Paralogs (4): LASP1 (ENSG00000002834), KY (ENSG00000174611), NEB (ENSG00000183091), NRAP (ENSG00000197893)

Protein

Protein identifiers

Nebulette — O76041 (reviewed: O76041)

Alternative names: Actin-binding Z-disk protein

All UniProt accessions (5): O76041, A0A0U1RQY0, A0A0U1RRI4, A0A0U1RRK0, A0A6Q8PF21

UniProt curated annotations — full annotation on UniProt →

Function. Binds to actin and plays an important role in the assembly of the Z-disk. May functionally link sarcomeric actin to the desmin intermediate filaments in the heart muscle sarcomeres. May play a role in the assembly of focal adhesions.

Subunit / interactions. Interacts (via nebulin repeats 1-5) with DESM (via rod region). Interacts (via SH3 domain) with XIRP2. Interacts with ZYX/Zyxin.

Subcellular location. Cytoplasm.

Tissue specificity. Abundantly expressed in cardiac muscle, but not in skeletal or smooth muscle. Localized to Z-lines in cardiac cells and to dense bodies in nonmuscle cells. Isoform 2 is expressed in non-muscle cells such as in fibroblasts.

Miscellaneous. Expressed in non-muscle cells. May be transcribed from an upstream promoter active in non-muscle cells.

Isoforms (2)

UniProt ID	Names	Canonical?
O76041-1	1	yes
O76041-2	2, LIM-nebulette, LNEBL

RefSeq proteins (10): NP_001166955, NP_001364251, NP_001364252, NP_001364253, NP_001364254, NP_001364255, NP_001364256, NP_001364257, NP_006384, NP_998734 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000900	Nebulin_repeat	Repeat
IPR001452	SH3_domain	Domain
IPR035631	Nebulette_SH3	Domain
IPR036028	SH3-like_dom_sf	Homologous_superfamily
IPR055297	NEBU/NEBL	Family

Pfam: PF00880, PF14604

UniProt features (55 total): repeat 23, sequence conflict 9, sequence variant 6, strand 5, splice variant 3, region of interest 2, modified residue 2, chain 1, domain 1, compositionally biased region 1, turn 1, helix 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
4F14	X-RAY DIFFRACTION	1.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O76041-F1	62.00	0.02

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 (2): 795, 96

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 241 (showing top): KOBAYASHI_EGFR_SIGNALING_24HR_UP, GOBP_MUSCLE_TISSUE_DEVELOPMENT, HNF3ALPHA_Q6, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, JAEGER_METASTASIS_DN, GCANCTGNY_MYOD_Q6, TTTGTAG_MIR520D, GOZGIT_ESR1_TARGETS_DN, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOBP_CARDIAC_MYOFIBRIL_ASSEMBLY, LHX3_01, CACCAGC_MIR138, CHX10_01, RODWELL_AGING_KIDNEY_NO_BLOOD_DN, MODULE_66

GO Biological Process (1): cardiac muscle thin filament assembly (GO:0071691)

GO Molecular Function (7): tropomyosin binding (GO:0005523), cytoskeletal protein binding (GO:0008092), structural constituent of muscle (GO:0008307), filamin binding (GO:0031005), actin filament binding (GO:0051015), actin binding (GO:0003779), protein binding (GO:0005515)

GO Cellular Component (5): stress fiber (GO:0001725), Z disc (GO:0030018), I band (GO:0031674), extracellular exosome (GO:0070062), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoskeletal protein binding	3
cellular anatomical structure	3
actin filament organization	1
cardiac myofibril assembly	1
protein binding	1
structural molecule activity	1
actin binding	1
protein-containing complex binding	1
binding	1
actomyosin	1
contractile actin filament bundle	1
I band	1
sarcomere	1
extracellular vesicle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1104 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NEBL	MYPN	Q86TC9	939
NEBL	TTN	Q8WZ42	858
NEBL	HAND2	P61296	797
NEBL	ACTN2	P35609	772
NEBL	ANKRD1	Q15327	686
NEBL	XIRP2	A4UGR9	631
NEBL	VCL	P18206	564
NEBL	FLNC	Q14315	562
NEBL	KLHL41	O60662	557
NEBL	CSRP3	P50461	554
NEBL	LPP	Q93052	546
NEBL	VASP	P50552	535
NEBL	PXN	P49023	528
NEBL	TMOD1	P28289	523
NEBL	GATA4	P43694	523

IntAct

190 interactions, top by confidence:

A	B	Type	Score
NEBL	TRAF2	psi-mi:“MI:0915”(physical association)	0.780
MAD1L1	NEBL	psi-mi:“MI:0915”(physical association)	0.780
TRAF2	NEBL	psi-mi:“MI:0915”(physical association)	0.780
NEBL	MAD1L1	psi-mi:“MI:0915”(physical association)	0.780
GOLGA2	NEBL	psi-mi:“MI:0915”(physical association)	0.670
TRAF1	NEBL	psi-mi:“MI:0915”(physical association)	0.670
NEBL	GOLGA2	psi-mi:“MI:0915”(physical association)	0.670
XIRP2	NEBL	psi-mi:“MI:0915”(physical association)	0.670
NEBL	XIRP2	psi-mi:“MI:0407”(direct interaction)	0.670
XIRP2	NEBL	psi-mi:“MI:0407”(direct interaction)	0.670
NEBL	XIRP1	psi-mi:“MI:0915”(physical association)	0.600
XIRP1	NEBL	psi-mi:“MI:0407”(direct interaction)	0.600
NEBL	XIRP1	psi-mi:“MI:0407”(direct interaction)	0.600
NEBL		psi-mi:“MI:0915”(physical association)	0.560
NEBL	HOMER3	psi-mi:“MI:0915”(physical association)	0.560
NEBL	TRIM27	psi-mi:“MI:0915”(physical association)	0.560
NEBL	FLJ13057	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (90): NEBL (Two-hybrid), NEBL (Two-hybrid), NEBL (Two-hybrid), NEBL (Two-hybrid), NEBL (Two-hybrid), NEBL (Two-hybrid), NEBL (Two-hybrid), NEBL (Two-hybrid), NEBL (Two-hybrid), GMCL1 (Two-hybrid), CCDC136 (Two-hybrid), LZTS2 (Two-hybrid), MIPOL1 (Two-hybrid), FAM9B (Two-hybrid), NUTM1 (Two-hybrid)

ESM2 similar proteins: A0A1C3NSL9, A6ZM93, A9ZLL8, B3LLS9, B5VPF9, C0HK92, C0HK94, C5DGV3, C5DX05, C7GL88, C8ZEN7, E7LYB2, H2KYS8, J7M3T1, J7M799, J7MDG6, M9MRD1, O17389, O45168, O76041, P07197, P08553, P0CP34, P0CP35, P0CU43, P0CU44, P0CU45, P0CU46, P0CU47, P0CU48, P0CU50, P12839, P14448, P16053, Q05050, Q09231, Q09501, Q18879, Q4WUL0, Q4X212

Diamond homologs: A0JNB0, A1Y2K1, A4IF63, A5D7F8, A5D8S5, A7A261, B0BNA1, B1V8A0, D2GXS7, D3ZQG6, F1RDG9, F7H9X2, G3X8Y1, O08641, O35179, O35180, O35964, O43125, O70277, O75382, O76041, P06241, P09769, P13406, P19706, P27446, P32793, P39688, P43603, P62484, P62993, P62994, Q02977, Q05876, Q08012, Q0CJU8, Q0U6X7, Q13588, Q1E878, Q28E95

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

1446 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	794
Likely benign	456
Benign	96

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
689490	NM_006393.3(NEBL):c.1253del (p.Asn418fs)	Likely pathogenic

SpliceAI

8880 predictions. Top by Δscore:

Variant	Effect	Δscore
10:20785919:GTCCT:G	acceptor_gain	1.0000
10:20785920:TCCT:T	acceptor_gain	1.0000
10:20785921:CCTC:C	acceptor_gain	1.0000
10:20785922:CT:C	acceptor_gain	1.0000
10:20785924:C:CC	acceptor_gain	1.0000
10:20787195:CACTT:C	donor_loss	1.0000
10:20787196:ACTTA:A	donor_loss	1.0000
10:20787197:CTTAC:C	donor_loss	1.0000
10:20787198:TTACT:T	donor_loss	1.0000
10:20787199:TA:T	donor_loss	1.0000
10:20787200:A:AC	donor_gain	1.0000
10:20787200:ACTAG:A	donor_loss	1.0000
10:20787201:C:CT	donor_gain	1.0000
10:20787201:CTAG:C	donor_gain	1.0000
10:20787201:CTAGA:C	donor_gain	1.0000
10:20787307:TG:T	acceptor_gain	1.0000
10:20787307:TGC:T	acceptor_loss	1.0000
10:20787308:GCTG:G	acceptor_loss	1.0000
10:20787309:C:CC	acceptor_gain	1.0000
10:20787309:C:CG	acceptor_loss	1.0000
10:20787313:A:C	acceptor_gain	1.0000
10:20787316:T:C	acceptor_gain	1.0000
10:20787316:T:TC	acceptor_gain	1.0000
10:20787322:A:C	acceptor_gain	1.0000
10:20812936:TTTAC:T	acceptor_gain	1.0000
10:20812937:TTAC:T	acceptor_gain	1.0000
10:20812938:TAC:T	acceptor_gain	1.0000
10:20812939:AC:A	acceptor_gain	1.0000
10:20812940:CC:C	acceptor_gain	1.0000
10:20812941:C:CC	acceptor_gain	1.0000

AlphaMissense

6837 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:20785811:C:T	G994D	0.999
10:20785812:C:G	G994R	0.999
10:20785821:A:G	W991R	0.999
10:20785821:A:T	W991R	0.999
10:20785856:T:C	D979G	0.999
10:20785868:A:G	F975S	0.999
10:20785778:A:G	L1005P	0.998
10:20785819:C:A	W991C	0.998
10:20785819:C:G	W991C	0.998
10:20785850:A:T	I981N	0.998
10:20785856:T:A	D979V	0.998
10:20785856:T:G	D979A	0.998
10:20785857:C:G	D979H	0.998
10:20785867:A:C	F975L	0.998
10:20785867:A:T	F975L	0.998
10:20785869:A:G	F975L	0.998
10:20785910:G:T	A961D	0.998
10:20785913:C:G	R960P	0.998
10:20785778:A:T	L1005H	0.997
10:20785784:C:T	G1003E	0.997
10:20785850:A:C	I981S	0.997
10:20785868:A:C	F975C	0.997
10:20785811:C:A	G994V	0.996
10:20785917:A:C	Y959D	0.996
10:20785820:C:G	W991S	0.994
10:20785841:A:T	V984E	0.994
10:20785859:C:A	G978V	0.994
10:20785905:A:C	Y963D	0.994
10:20785776:G:T	P1006T	0.993
10:20785785:C:G	G1003R	0.993

dbSNP variants (sampled 300 via entrez): RS1000009408 (10:21212044 T>A,C), RS1000010178 (10:20921472 C>T), RS1000012316 (10:21062023 G>A), RS1000018465 (10:20942757 C>A), RS1000023910 (10:21153722 G>C), RS1000024384 (10:20924713 G>A,C), RS1000025784 (10:20822962 TG>T), RS1000025943 (10:20805300 C>A,T), RS1000031304 (10:21191108 A>G), RS1000038184 (10:21272653 G>C), RS1000043024 (10:21033497 T>C), RS1000046273 (10:20799250 G>T), RS1000047413 (10:21073644 A>T), RS1000048779 (10:21012411 G>A), RS1000062087 (10:21165734 C>A,G,T)

Disease associations

OMIM: gene MIM:605491 | disease phenotypes: MIM:115195, MIM:192600, MIM:194200

GenCC curated gene-disease

Disease	Classification	Inheritance
dilated cardiomyopathy	Moderate	Autosomal dominant
hypertrophic cardiomyopathy	Moderate	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
dilated cardiomyopathy	Limited	AD

Mondo (9): dilated cardiomyopathy (MONDO:0005021), hypertrophic cardiomyopathy 2 (MONDO:0007266), hypertrophic cardiomyopathy (MONDO:0005045), long QT syndrome (MONDO:0002442), distal monosomy 10p (MONDO:0011055), familial hypertrophic cardiomyopathy (MONDO:0024573), cardiomyopathy (MONDO:0004994), Wolff-Parkinson-White syndrome (MONDO:0008685), cardiac arrest (MONDO:0000745)

Orphanet (7): Dilated cardiomyopathy (Orphanet:217604), Rare hypertrophic cardiomyopathy (Orphanet:217569), Distal deletion 10p syndrome (Orphanet:1580), Rare familial disorder with hypertrophic cardiomyopathy (Orphanet:99739), Rare cardiomyopathy (Orphanet:167848), NON RARE IN EUROPE: Familial isolated hypertrophic cardiomyopathy (Orphanet:155), NON RARE IN EUROPE: Wolff-Parkinson-White syndrome (Orphanet:907)

HPO phenotypes

3 total (3 of 3 shown, HPO-id order):

HPO	Term
HP:0001644	Dilated cardiomyopathy
HP:0001639	Hypertrophic cardiomyopathy
HP:0001716	Wolff-Parkinson-White syndrome

GWAS associations

26 associations (top):

Study	Trait	p-value
GCST001941_14	Ovarian cancer	2.000000e-08
GCST001941_15	Ovarian cancer	1.000000e-07
GCST002431_1	Response to radiotherapy in cancer (late toxicity)	6.000000e-06
GCST002431_5	Response to radiotherapy in cancer (late toxicity)	8.000000e-06
GCST002830_36	Urate levels in lean individuals	4.000000e-07
GCST002940_2	Sporadic pituitary adenoma	2.000000e-10
GCST003560_1	Coronary artery aneurysm in Kawasaki disease	7.000000e-09
GCST003992_45	Photic sneeze reflex	6.000000e-13
GCST004262_2	Liver injury in combined anti-retroviral and anti-tuberculosis drug-treated HIV with tuberculosis	1.000000e-06
GCST004373_8	Atrial fibrillation	2.000000e-14
GCST006606_9	Response to TNF inhibitor in rheumatoid arthritis (change in swollen 28-joint count)	6.000000e-08
GCST006979_563	Heel bone mineral density	7.000000e-15
GCST007096_86	Pulse pressure	2.000000e-08
GCST008151_49	Waist circumference	5.000000e-06
GCST008160_44	Waist circumference	5.000000e-06
GCST008367_11	Plasma anti-thyroglobulin and anti-thyroid peroxidase levels (bivariate analysis)	4.000000e-06
GCST008368_16	Plasma anti-thyroid peroxidase levels	4.000000e-06
GCST009391_2071	Metabolite levels	9.000000e-06
GCST009439_23	Age-related cognitive decline (language) (slope of z-scores)	1.000000e-06
GCST009444_4	Age-related cognitive decline (global cognition) (slope of z-scores)	7.000000e-08
GCST009723_1	Vertical cup-disc ratio (adjusted for vertical disc diameter)	2.000000e-10
GCST009724_20	Vertical cup-disc ratio (multi-trait analysis)	9.000000e-12
GCST010002_283	Refractive error	5.000000e-09
GCST011122_65	Walking pace	4.000000e-08
GCST012322_39	Triglyceride levels x SSRI defined daily dose interaction in schizophrenia or bipolar disorder	5.000000e-09
GCST90000514_13	Gastroesophageal reflux disease	1.000000e-09

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement
EFO:0007887	autosomal dominant compelling helio-ophthalmic outburst syndrome
EFO:0004653	response to TNF antagonist
EFO:0005413	joint damage measurement
EFO:0009270	heel bone mineral density
EFO:0005763	pulse pressure measurement
EFO:0010346	cholesteryl ester 18:3 measurement
EFO:0007710	cognitive decline measurement
EFO:0006939	cup-to-disc ratio measurement
EFO:0004530	triglyceride measurement
EFO:0005658	response to selective serotonin reuptake inhibitor

MeSH disease descriptors (9)

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
D006323	Heart Arrest	C14.280.383
D008133	Long QT Syndrome	C14.280.067.565; C14.280.123.625; C16.131.240.400.715; C23.550.073.547
D014927	Wolff-Parkinson-White Syndrome	C14.280.067.780.977; C14.280.123.750.977; C16.131.240.400.980
C566171	Cardiomyopathy, Familial Hypertrophic, 2 (supp.)
C563337	Digeorge Syndrome-Velocardiofacial Syndrome Complex 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases expression	7
Acetaminophen	increases expression, decreases expression, affects cotreatment	3
Tobacco Smoke Pollution	decreases expression, increases methylation, affects expression	3
Vorinostat	affects cotreatment, increases expression	2
Nickel	decreases expression	2
Cyclosporine	increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
aristolochic acid I	decreases expression	1
bufotalin	decreases expression	1
methylmercuric chloride	decreases expression	1
methylselenic acid	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression	1
sulforaphane	decreases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	increases expression	1
butyraldehyde	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
bicalutamide	increases expression	1
2-palmitoylglycerol	increases expression	1
entinostat	increases expression	1
monomethylarsonous 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
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	decreases methylation	1
jinfukang	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation, decreases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00374465	PHASE4	UNKNOWN	Therapy With Verapamil or Carvedilol in Chronic Heart Failure
NCT01293903	PHASE4	COMPLETED	Study of Qiliqiangxin Capsule to Treat Dilated Cardiomyopathy
NCT01557140	PHASE4	COMPLETED	A Randomized Trial of Carvedilol in Chronic Chagas Cardiomyopathy
NCT01917149	PHASE4	COMPLETED	Supramaximal Titrated Inhibition of RAAS in Dilated Cardiomyopathy
NCT02115581	PHASE4	COMPLETED	Coenzyme Q10 Supplementation in Children With Idiopathic Dilated Cardiomyopathy
NCT06236022	PHASE4	RECRUITING	The Effects of Sirolimus in Patients With Dilated Cardiomyopathy Infected With Kaposi Sarcoma-associated Virus
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
NCT00333827	PHASE3	COMPLETED	Cell Therapy In Dilated Cardiomyopathy
NCT00505154	PHASE3	COMPLETED	Effect of Rosuvastatin on Left Ventricular Remodeling
NCT01223703	PHASE3	COMPLETED	PUFAs and Left Ventricular Function in Heart Failure
NCT01583114	PHASE3	TERMINATED	PREclinical Mutation CARriers From Families With DIlated Cardiomyopathy and ACE Inhibitors
NCT01914081	PHASE3	UNKNOWN	Resveratrol: A Potential Anti- Remodeling Agent in Heart Failure, From Bench to Bedside
NCT02989181	PHASE3	UNKNOWN	Continues Positive Airway Pressure Treatment for Patients With Dilated Cardiomyopathy and Obstructive Sleep Apnea
NCT03439514	PHASE3	TERMINATED	A Study of ARRY-371797 (PF-07265803) in Patients With Symptomatic Dilated Cardiomyopathy Due to a Lamin A/C Gene Mutation
NCT05237323	PHASE3	COMPLETED	Micophenolate Mofetil Versus Azathioprine in Myocarditis
NCT05849766	PHASE3	COMPLETED	Effect of Dapagliflozin on Cardiac Structure, Function and Secondary Mitral Regurgitation in Patients with Left Ventricle Dysfunction
NCT06250257	PHASE3	RECRUITING	Bromocriptine in Dilated Cardiomyopathy Among Women of Reproductive Age
NCT00317967	PHASE3	COMPLETED	Study to Determine if Atorvastatin Reduces Size and Stiffness of Muscle in the Left Ventricle of the Heart
NCT00698074	PHASE3	UNKNOWN	Diastolic Ventricular Interaction and the Effects of Biventricular Pacing in Hypertrophic Cardiomyopathy
NCT00821353	PHASE3	COMPLETED	Antiarrhythmic Therapy Versus Catheter Ablation for Atrial Fibrillation in Hypertrophic Cardiomyopathy
NCT02431221	PHASE3	WITHDRAWN	Efficacy, Safety, and Tolerability of Perhexiline in Subjects With Hypertrophic Cardiomyopathy and Heart Failure
NCT03470545	PHASE3	COMPLETED	Clinical Study to Evaluate Mavacamten (MYK-461) in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy
NCT05174416	PHASE3	COMPLETED	A Study to Evaluate the Efficacy and Safety of Mavacamten in Chinese Adults With Symptomatic Obstructive HCM
NCT05182658	PHASE3	ACTIVE_NOT_RECRUITING	Empagliflozin in Hypertrophic Cardiomyopathy
NCT05186818	PHASE3	COMPLETED	Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic oHCM
NCT05767346	PHASE3	COMPLETED	Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Metoprolol Succinate in Adults With Symptomatic oHCM
NCT06116968	PHASE3	COMPLETED	An Open-Label Study of Aficamten for Chinese Patients With Symptomatic oHCM
NCT06873828	PHASE3	NOT_YET_RECRUITING	Evaluation of the Efficacy and Safety of Wearable ECG (AT-Patch) in Patients With Hypertrophic Cardiomyopathy Requiring 48-Hour Holter MonitoringEvaluation of the Efficacy and Safety of Wearable ECG (AT-Patch) in Patients With Hypertrophic Cardiomyopathy Requiring 48-Hour Holter Monitoring
NCT07021976	PHASE3	RECRUITING	A Phase III Trial of HRS-1893 in Patients With Obstructive Hypertrophic Cardiomyopathy
NCT07023341	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Learn More About How Well Aficamten Works in Japanese Participants With Symptomatic Obstructive Hypertrophic Cardiomyopathy
NCT07202897	PHASE3	NOT_YET_RECRUITING	LA-HCM Study : Rivaroxaban for Antithrombotic Prevention in Hypertrophic Cardiomyopathy Patients With Abnormal Left Atrial Strain.
NCT00629018	PHASE2	COMPLETED	Safety and Efficacy Study of Stem Cell Transplantation to Treat Dilated Cardiomyopathy
NCT00629096	PHASE2	COMPLETED	Intracoronary Infusion of Autologous Bone Marrow Cells for Treatment of Idiopathic Dilated Cardiomyopathy