MYH7B

Summary

MYH7B (myosin heavy chain 7B, HGNC:15906) is a protein-coding gene on chromosome 20q11.22, encoding Myosin-7B (A7E2Y1). Involved in muscle contraction.

The myosin II molecule is a multi-subunit complex consisting of two heavy chains and four light chains. This gene encodes a heavy chain of myosin II, which is a member of the motor-domain superfamily. The heavy chain includes a globular motor domain, which catalyzes ATP hydrolysis and interacts with actin, and a tail domain in which heptad repeat sequences promote dimerization by interacting to form a rod-like alpha-helical coiled coil. This heavy chain subunit is a slow-twitch myosin. Alternatively spliced transcript variants have been found, but the full-length nature of these variants is not determined.

Source: NCBI Gene 57644 — RefSeq curated summary.

At a glance

• Gene–disease (curated): left ventricular noncompaction (Supportive, GenCC)
• GWAS associations: 19
• Clinical variants (ClinVar): 1,156 total — 3 pathogenic, 9 likely-pathogenic
• Phenotypes (HPO): 33
• Druggable target: yes
• MANE Select transcript: NM_020884

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15906
Approved symbol	MYH7B
Name	myosin heavy chain 7B
Location	20q11.22
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1512, dJ756N5.1, MYH14, MHC14, lncMYH7b
Ensembl gene	ENSG00000078814
Ensembl biotype	protein_coding
OMIM	609928
Entrez	57644

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 9 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000262873, ENST00000433934, ENST00000435272, ENST00000446156, ENST00000453028, ENST00000456649, ENST00000470929, ENST00000481922, ENST00000673749, ENST00000888939, ENST00000971120, ENST00000971121

RefSeq mRNA: 1 — MANE Select: NM_020884 NM_020884

CCDS: CCDS42869

Canonical transcript exons

ENST00000262873 — 45 exons

Exon	Start	End
ENSE00000661510	34987149	34987287
ENSE00000661512	34987765	34987914
ENSE00000661514	34989740	34989919
ENSE00000661515	34990014	34990146
ENSE00000860157	34982459	34982555
ENSE00000860159	34985066	34985129
ENSE00000860163	34993334	34993470
ENSE00000860168	35001245	35001349
ENSE00000860170	35001948	35002085
ENSE00000991756	35001431	35001526
ENSE00001150826	34994146	34994401
ENSE00001150841	34993102	34993225
ENSE00001150844	34991004	34991121
ENSE00001150854	34990234	34990310
ENSE00001150878	34987557	34987675
ENSE00001150886	34986886	34986989
ENSE00001150892	34986100	34986198
ENSE00001318574	34984692	34984715
ENSE00001400402	35002177	35002437
ENSE00001606313	34981033	34981060
ENSE00001610188	34998511	34998629
ENSE00001625537	34988092	34988262
ENSE00001644513	34998295	34998421
ENSE00001656360	34990738	34990825
ENSE00001660540	35000988	35001158
ENSE00001691418	35000768	35000893
ENSE00001697223	34997083	34997173
ENSE00001703767	34995336	34995578
ENSE00001705021	34998719	34998915
ENSE00001708240	34996613	34996758
ENSE00001714826	34999056	34999405
ENSE00001728441	34999791	34999906
ENSE00001729966	34997251	34997640
ENSE00001792993	34999571	34999695
ENSE00001796226	34984854	34984946
ENSE00001796991	35000293	35000689
ENSE00001799312	34996346	34996522
ENSE00003540170	34979661	34979804
ENSE00003611834	34979390	34979496
ENSE00003656203	34980578	34980734
ENSE00003741760	34977632	34977680
ENSE00003897474	34975400	34975499
ENSE00003897506	34958098	34958212
ENSE00003897548	34977934	34978096
ENSE00003929662	34955868	34956007

Expression profiles

Bgee: expression breadth ubiquitous, 195 present calls, max score 99.24.

FANTOM5 (CAGE): breadth broad, TPM avg 0.7060 / max 54.1124, expressed in 241 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
184271	0.2516	123
184269	0.1468	63
184276	0.1128	34
184270	0.1119	57
184273	0.0484	20
184272	0.0190	7
184275	0.0154	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	99.24	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.92	gold quality
heart left ventricle	UBERON:0002084	96.33	gold quality
right atrium auricular region	UBERON:0006631	96.33	gold quality
cardiac ventricle	UBERON:0002082	96.11	gold quality
cardiac atrium	UBERON:0002081	94.51	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	93.52	gold quality
heart	UBERON:0000948	91.89	gold quality
body of tongue	UBERON:0011876	90.33	gold quality
biceps brachii	UBERON:0001507	89.44	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	89.04	gold quality
lateral nuclear group of thalamus	UBERON:0002736	88.03	gold quality
sperm	CL:0000019	87.97	gold quality
buccal mucosa cell	CL:0002336	87.80	gold quality
muscle of leg	UBERON:0001383	86.71	gold quality
gastrocnemius	UBERON:0001388	86.50	gold quality
left testis	UBERON:0004533	85.84	gold quality
right testis	UBERON:0004534	85.30	gold quality
muscle organ	UBERON:0001630	84.93	gold quality
heart right ventricle	UBERON:0002080	84.92	gold quality
male germ cell	CL:0000015	84.73	gold quality
left ventricle myocardium	UBERON:0006566	84.60	gold quality
primary visual cortex	UBERON:0002436	84.25	gold quality
right frontal lobe	UBERON:0002810	83.92	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	83.07	gold quality
tongue	UBERON:0001723	82.50	gold quality
testis	UBERON:0000473	82.45	gold quality
skeletal muscle tissue	UBERON:0001134	82.37	gold quality
myocardium	UBERON:0002349	81.72	silver quality
spinal cord	UBERON:0002240	81.63	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-11268	no	1090.40
E-ANND-3	no	3.29
E-MTAB-9801	no	2.55
E-MTAB-5061	no	1.88

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): IKZF4, MEF2A, MYOD1, MYRF

miRNA regulators (miRDB)

16 targeting MYH7B, 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-3119	99.92	71.34	2390
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-3678-3P	99.31	67.10	1432
HSA-MIR-7974	99.24	65.48	1137
HSA-MIR-6770-5P	98.97	66.76	1853
HSA-MIR-4646-3P	98.65	66.98	693
HSA-MIR-6881-3P	98.04	68.24	1777
HSA-MIR-3127-5P	97.52	65.24	786
HSA-MIR-2355-3P	96.84	68.54	909
HSA-MIR-3918	96.13	64.65	1300
HSA-MIR-1237-5P	95.38	62.21	451
HSA-MIR-4488	95.38	62.00	443
HSA-MIR-4697-5P	95.38	61.72	457

Literature-anchored findings (GeneRIF, showing 7)

• MYH7b, the ortholog of slow myosin 2 (SM2) of frogs and birds, is detected as mRNA in heart, slow muscles and extraocular muscles. MYH7b protein is detected only in a subset of fibers, corresponding to slow-tonic fibers, in extraocular muscles. (PMID:19948655)
• Data suggest that transcription and alternative splicing uncouple the level of expression of MYH7b and miR-499 when their coexpression is not required. (PMID:20154144)
• Digenic mutational inheritance of the integrin alpha 7 and the myosin heavy chain 7B genes causes congenital myopathy with left ventricular non-compact cardiomyopathy. [MYH7B] (PMID:23800289)
• The actin-based motor myosin-7b (Myo7b) promotes the accumulation of intermicrovillar adhesion complex (IMAC components at microvillar tips. Myo7b is highly enriched at the tips of microvilli in both kidney and intestinal brush borders, and loss of Myo7b in differentiating intestinal epithelial cells disrupts intermicrovillar adhesion and, thus, brush border assembly. (PMID:27666969)
• Myosin 7b is a regulatory long noncoding RNA (lncMYH7b) in the human heart. (PMID:33895132)
• Functional divergence of the sarcomeric myosin, MYH7b, supports species-specific biological roles. (PMID:36334627)
• Distinct effects of two hearing loss-associated mutations in the sarcomeric myosin MYH7b. (PMID:36963494)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Myh7b	ENSMUSG00000074652
rattus_norvegicus	Myh7b	ENSRNOG00000018997

Paralogs (44): MYH13 (ENSG00000006788), MYO16 (ENSG00000041515), MYO9A (ENSG00000066933), MYO3B (ENSG00000071909), MYO15A (ENSG00000091536), MYH7 (ENSG00000092054), MYO3A (ENSG00000095777), MYO9B (ENSG00000099331), MYH9 (ENSG00000100345), MYH14 (ENSG00000105357), MYH1 (ENSG00000109061), MYH3 (ENSG00000109063), MYH2 (ENSG00000125414), MYO1B (ENSG00000128641), MYO5C (ENSG00000128833), CGNL1 (ENSG00000128849), MYH8 (ENSG00000133020), MYH10 (ENSG00000133026), MYH11 (ENSG00000133392), MYO18B (ENSG00000133454), CCDC102A (ENSG00000135736), MYO1G (ENSG00000136286), MYO7A (ENSG00000137474), MYO1F (ENSG00000142347), CGN (ENSG00000143375), TMF1 (ENSG00000144747), MYH15 (ENSG00000144821), MYO10 (ENSG00000145555), CCDC102B (ENSG00000150636), MYO1E (ENSG00000157483), CCDC158 (ENSG00000163749), MYO1A (ENSG00000166866), MYO5B (ENSG00000167306), MYO7B (ENSG00000169994), MYO1H (ENSG00000174527), MYO1D (ENSG00000176658), MYO18A (ENSG00000196535), MYO6 (ENSG00000196586), MYO5A (ENSG00000197535), MYH6 (ENSG00000197616)

Protein

Protein identifiers

Myosin-7B — A7E2Y1 (reviewed: A7E2Y1)

Alternative names: Antigen MLAA-21, Myosin cardiac muscle beta chain, Myosin heavy chain 7B, cardiac muscle beta isoform, Slow A MYH14

All UniProt accessions (6): A7E2Y1, Q5JW45, Q5JW46, Q5JW47, Q5JW48, Q5JW49

UniProt curated annotations — full annotation on UniProt →

Function. Involved in muscle contraction.

Subunit / interactions. Muscle myosin is a hexameric protein that consists of 2 heavy chain subunits (MHC), 2 alkali light chain subunits (MLC) and 2 regulatory light chain subunits (MLC-2).

Subcellular location. Membrane.

Tissue specificity. Expressed in heart, skeletal muscle, testis, and all specific brain regions examined. Slightly lower expression was detected in ovary and kidney, and intermediate expression was detected in lung, pancreas, spleen and liver.

Miscellaneous. Expression does not vary in normal patients compared to patients with acute monocytic leukemia. The cardiac alpha isoform is a ‘fast’ ATPase myosin, while the beta isoform is a ‘slow’ ATPase. Alternative downstream initiation is supported by sequence conservation.

Similarity. Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family.

Isoforms (4)

UniProt ID	Names	Canonical?
A7E2Y1-1	1	yes
A7E2Y1-2	2
A7E2Y1-3	3
A7E2Y1-4	4

RefSeq proteins (1): NP_065935* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001609	Myosin_head_motor_dom-like	Domain
IPR002928	Myosin_tail	Domain
IPR004009	SH3_Myosin	Domain
IPR008989	Myosin_S1_N	Homologous_superfamily
IPR014751	XRCC4-like_C	Homologous_superfamily
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR036961	Kinesin_motor_dom_sf	Homologous_superfamily

Pfam: PF00063, PF01576, PF02736

UniProt features (27 total): sequence variant 8, sequence conflict 5, splice variant 4, domain 3, region of interest 3, chain 1, coiled-coil region 1, compositionally biased region 1, binding site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A7E2Y1-F1	73.79	0.09

Functional residue map

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

Ligand- & substrate-binding residues (1): 219–226

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 294 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, GOBP_MITOTIC_CYTOKINESIS, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_BEHAVIOR, GOBP_REGULATION_OF_CALCIUM_MEDIATED_SIGNALING, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, CCAWYNNGAAR_UNKNOWN, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_SENSORY_PERCEPTION_OF_MECHANICAL_STIMULUS, NIKOLSKY_BREAST_CANCER_20Q11_AMPLICON, KEGG_TIGHT_JUNCTION, GOBP_MULTICELLULAR_ORGANISMAL_MOVEMENT, GOBP_SKELETAL_MUSCLE_CONTRACTION, RODRIGUES_NTN1_TARGETS_DN, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS

GO Biological Process (4): regulation of cytosolic calcium ion concentration (GO:0051480), regulation of cardiac muscle cell contraction (GO:0086004), regulation of CAMKK-AMPK signaling cascade (GO:1905289), regulation of calcium-mediated signaling (GO:0050848)

GO Molecular Function (7): microfilament motor activity (GO:0000146), ATP binding (GO:0005524), actin filament binding (GO:0051015), nucleotide binding (GO:0000166), cytoskeletal motor activity (GO:0003774), actin binding (GO:0003779), protein binding (GO:0005515)

GO Cellular Component (7): cytoplasm (GO:0005737), membrane (GO:0016020), myosin II complex (GO:0016460), myosin filament (GO:0032982), cardiac myofibril (GO:0097512), myosin complex (GO:0016459), myofibril (GO:0030016)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
myosin complex	2
intracellular calcium ion homeostasis	1
regulation of cardiac muscle contraction	1
cardiac muscle cell contraction	1
regulation of actin filament-based movement	1
regulation of calcium-mediated signaling	1
CAMKK-AMPK signaling cascade	1
calcium-mediated signaling	1
regulation of intracellular signal transduction	1
cytoskeletal motor activity	1
polypeptide conformation or assembly isomerase activity	1
ATP-dependent activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
actin binding	1
protein-containing complex binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
molecular_function	1
cytoskeletal protein binding	1
binding	1
intracellular anatomical structure	1
supramolecular fiber	1
myofibril	1
actin cytoskeleton	1
protein-containing complex	1
contractile muscle fiber	1

Protein interactions and networks

STRING

1660 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MYH7B	PURB	Q96QR8	872
MYH7B	SOX6	P35712	852
MYH7B	MED13	Q9UHV7	829
MYH7B	PIGU	Q9H490	797
MYH7B	MYLK3	Q32MK0	760
MYH7B	MYL2	P10916	713
MYH7B	TNNI1	P19237	655
MYH7B	PCDH11X	Q9BZA7	654
MYH7B	NPPB	P16860	646
MYH7B	MYL7	Q01449	627
MYH7B	NPPA	P01160	551
MYH7B	TCAP	O15273	539
MYH7B	TRPC4AP	Q8TEL6	533
MYH7B	MYL10	Q9BUA6	531
MYH7B	TPM3	P06753	512

IntAct

33 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
SMYD1	MYH7B	psi-mi:“MI:0915”(physical association)	0.510
MYH7B	SMYD1	psi-mi:“MI:0915”(physical association)	0.510
ESR2	FBLL1	psi-mi:“MI:0914”(association)	0.460
HLCS	MYH7B	psi-mi:“MI:0915”(physical association)	0.400
TNS2	MYH7B	psi-mi:“MI:0915”(physical association)	0.370
MYH7B	SRRM1	psi-mi:“MI:0914”(association)	0.350
LRRCC1		psi-mi:“MI:0914”(association)	0.350
	MTMR11	psi-mi:“MI:0914”(association)	0.350
CFTR	MYH7B	psi-mi:“MI:0914”(association)	0.350
MAPT	SEPTIN8	psi-mi:“MI:0914”(association)	0.350
TMEM183A	MYH7B	psi-mi:“MI:0914”(association)	0.350
LRRCC1	MYH7B	psi-mi:“MI:0914”(association)	0.350
KRT39	MYH7B	psi-mi:“MI:0914”(association)	0.350
MYH7B	HSPA8	psi-mi:“MI:0914”(association)	0.350
CHTOP	MYH7B	psi-mi:“MI:0914”(association)	0.350
C5orf24	MYH7B	psi-mi:“MI:0914”(association)	0.350
AP4B1	MYH7B	psi-mi:“MI:0914”(association)	0.350
MYH7B	TCP1	psi-mi:“MI:0914”(association)	0.350
FBXL14	MYH7B	psi-mi:“MI:0914”(association)	0.350
MAGEB3	MYH7B	psi-mi:“MI:0914”(association)	0.350
MFGE8	MYH7B	psi-mi:“MI:0914”(association)	0.350
MRPS23	MYH7B	psi-mi:“MI:0914”(association)	0.350
RAB27B	MYH7B	psi-mi:“MI:0914”(association)	0.350

BioGRID (77): ACO2 (Co-fractionation), ACTN4 (Co-fractionation), ALDOA (Co-fractionation), ALDOC (Co-fractionation), CKB (Co-fractionation), GPD1L (Co-fractionation), MYH7B (Co-fractionation), TPM1 (Co-fractionation), TPM3 (Co-fractionation), TPM4 (Co-fractionation), MYH7B (Two-hybrid), CACNA2D1 (Affinity Capture-MS), KPNA4 (Affinity Capture-MS), RBBP5 (Affinity Capture-MS), SEC62 (Affinity Capture-MS)

ESM2 similar proteins: A2AQP0, A5PF48, A7E2Y1, F1PT61, F4IUG9, F4JM19, O08638, P02563, P02564, P02566, P02567, P08799, P10568, P11055, P12844, P12845, P12847, P12883, P13533, P13539, P13540, P13541, P24733, P35749, P49824, P79293, P97479, Q02566, Q076A3, Q076A4, Q076A5, Q13402, Q23979, Q29P71, Q29RW1, Q60LV4, Q8MJU9, Q8MJV0, Q8N1T3, Q90339

Diamond homologs: A2AQP0, A7E2Y1, F1PT61, F4I507, F4I5Q6, F4IVR7, G3UW82, K7U9N8, O08638, O14157, O94477, P02563, P02564, P02565, P02566, P02567, P04461, P05659, P05661, P08799, P08964, P10587, P11055, P12844, P12845, P12847, P12882, P12883, P13533, P13535, P13538, P13539, P13540, P13541, P13542, P14105, P19524, P21271, P24733, P32492

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

1156 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	9
Uncertain significance	714
Likely benign	325
Benign	66

Top pathogenic / likely-pathogenic (12)

Variant ID	HGVS	Classification
638682	NM_020884.7(MYH7B):c.611_615dup (p.Lys206fs)	Pathogenic
638683	NM_020884.7(MYH7B):c.624+1G>A	Pathogenic
638684	NM_020884.7(MYH7B):c.4931_4932del (p.Thr1644fs)	Pathogenic
2576998	NM_020884.7(MYH7B):c.2700+2T>A	Likely pathogenic
3251994	NM_020884.7(MYH7B):c.2812G>T (p.Glu938Ter)	Likely pathogenic
3775822	NM_020884.7(MYH7B):c.882_883del (p.Gly295fs)	Likely pathogenic
3776213	NM_020884.7(MYH7B):c.2176del (p.Arg726fs)	Likely pathogenic
599537	NM_020884.7(MYH7B):c.2986G>A (p.Val996Met)	Likely pathogenic
638678	NM_020884.7(MYH7B):c.1837T>C (p.Phe613Leu)	Likely pathogenic
638679	NM_020884.7(MYH7B):c.2719G>C (p.Asp907His)	Likely pathogenic
638680	NM_020884.7(MYH7B):c.4415G>A (p.Arg1472Gln)	Likely pathogenic
638681	NM_020884.7(MYH7B):c.5335G>C (p.Glu1779Gln)	Likely pathogenic

SpliceAI

12041 predictions. Top by Δscore:

Variant	Effect	Δscore
19:50203668:GCCG:G	donor_gain	1.0000
19:50203669:CCGG:C	donor_loss	1.0000
19:50203670:CGG:C	donor_loss	1.0000
19:50203672:G:GG	donor_gain	1.0000
19:50203672:GTGA:G	donor_loss	1.0000
19:50210359:GCA:G	acceptor_loss	1.0000
19:50210360:CAG:C	acceptor_loss	1.0000
19:50210362:GA:G	acceptor_gain	1.0000
19:50210362:GACC:G	acceptor_gain	1.0000
19:50210771:G:GG	donor_gain	1.0000
19:50217612:CA:C	acceptor_loss	1.0000
19:50217613:A:AG	acceptor_gain	1.0000
19:50217614:G:GC	acceptor_gain	1.0000
19:50217614:GAC:G	acceptor_gain	1.0000
19:50217614:GACGT:G	acceptor_gain	1.0000
19:50217767:GCAGG:G	donor_gain	1.0000
19:50217770:GG:G	donor_gain	1.0000
19:50217771:GG:G	donor_gain	1.0000
19:50217772:G:GG	donor_gain	1.0000
19:50217773:T:G	donor_loss	1.0000
19:50223233:T:TA	acceptor_gain	1.0000
19:50223237:A:AG	acceptor_gain	1.0000
19:50223238:T:G	acceptor_gain	1.0000
19:50223243:A:AG	acceptor_gain	1.0000
19:50223243:ACAGT:A	acceptor_gain	1.0000
19:50223244:C:G	acceptor_gain	1.0000
19:50223245:A:AC	acceptor_loss	1.0000
19:50223245:A:AG	acceptor_gain	1.0000
19:50223245:AGT:A	acceptor_gain	1.0000
19:50223245:AGTG:A	acceptor_gain	1.0000

AlphaMissense

12936 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:34979773:T:C	L146P	0.999
20:34980610:C:A	N167K	0.999
20:34980610:C:G	N167K	0.999
20:34981054:T:C	L216P	0.999
20:34982460:G:A	G219R	0.999
20:34982460:G:C	G219R	0.999
20:34982461:G:A	G219E	0.999
20:34982461:G:T	G219V	0.999
20:34982476:G:A	G224D	0.999
20:34982489:C:A	N228K	0.999
20:34982489:C:G	N228K	0.999
20:34982515:C:A	A237D	0.999
20:34984906:G:A	G276D	0.999
20:34984944:T:C	F289L	0.999
20:34984946:T:A	F289L	0.999
20:34984946:T:G	F289L	0.999
20:34985079:G:C	R294P	0.999
20:34987888:G:C	D506H	0.999
20:34987889:A:C	D506A	0.999
20:34987889:A:T	D506V	0.999
20:34987897:G:T	G509W	0.999
20:34987900:T:C	F510L	0.999
20:34987902:T:A	F510L	0.999
20:34987902:T:G	F510L	0.999
20:34990035:T:A	W639R	0.999
20:34990035:T:C	W639R	0.999
20:34990745:T:C	L704P	0.999
20:34990797:C:G	C721W	0.999
20:34991037:T:C	L742P	0.999
20:34991048:G:T	G746W	0.999

dbSNP variants (sampled 300 via entrez): RS1000057354 (20:34997119 G>A), RS1000073857 (20:34957544 C>T), RS1000122977 (20:34992123 C>A,T), RS1000164843 (20:34974324 C>T), RS1000240943 (20:34970556 TG>T,TGG), RS1000254987 (20:34988215 A>G), RS1000318200 (20:34986765 C>T), RS1000362717 (20:34957270 G>C), RS1000502922 (20:34981794 G>A,C,T), RS1000523139 (20:34991871 G>A), RS1000538429 (20:34975355 C>T), RS1000545235 (20:34956455 C>T), RS1000623160 (20:34977360 G>A), RS1000640367 (20:34956709 G>A), RS1000668533 (20:34969066 G>A)

Disease associations

OMIM: gene MIM:609928 | disease phenotypes: MIM:192600, MIM:604169

GenCC curated gene-disease

Disease	Classification	Inheritance
left ventricular noncompaction	Supportive	Autosomal dominant

Mondo (3): hypertrophic cardiomyopathy (MONDO:0005045), hypertrophic cardiomyopathy 1 (MONDO:0008647), left ventricular noncompaction (MONDO:0018901)

Orphanet (2): Rare hypertrophic cardiomyopathy (Orphanet:217569), Left ventricular noncompaction (Orphanet:54260)

HPO phenotypes

33 total (30 of 33 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000365	Hearing impairment
HP:0000408	Progressive sensorineural hearing impairment
HP:0000762	Decreased nerve conduction velocity
HP:0001250	Seizure
HP:0001265	Hyporeflexia
HP:0001284	Areflexia
HP:0001337	Tremor
HP:0001369	Arthritis
HP:0001605	Vocal cord paralysis
HP:0001609	Hoarse voice
HP:0001760	Abnormal foot morphology
HP:0002015	Dysphagia
HP:0002460	Distal muscle weakness
HP:0002936	Distal sensory impairment
HP:0003198	Myopathy
HP:0003458	EMG: myopathic abnormalities
HP:0003557	Increased variability in muscle fiber diameter
HP:0003621	Juvenile onset
HP:0003676	Progressive
HP:0003693	Distal amyotrophy
HP:0003701	Proximal muscle weakness
HP:0006844	Absent patellar reflexes
HP:0007340	Lower limb muscle weakness
HP:0008180	Mildly elevated creatine kinase
HP:0008619	Bilateral sensorineural hearing impairment
HP:0009063	Progressive distal muscle weakness
HP:0009830	Peripheral neuropathy
HP:0010219	Structural foot deformity
HP:0011808	Decreased patellar reflex

GWAS associations

19 associations (top):

Study	Trait	p-value
GCST001365_5	Anticoagulant levels	1.000000e-06
GCST001573_2	Prothrombin time	5.000000e-13
GCST003419_1	Congenital left-sided heart lesions	1.000000e-08
GCST003871_13	QRS complex (Cornell)	5.000000e-11
GCST004142_11	Melanoma	2.000000e-18
GCST005956_31	Waist-to-hip ratio adjusted for BMI	8.000000e-08
GCST005958_16	Waist-to-hip ratio adjusted for BMI (age >50)	6.000000e-06
GCST005962_40	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	3.000000e-08
GCST007103_28	QRS duration	1.000000e-09
GCST007104_28	QRS duration	2.000000e-11
GCST007876_125	Estimated glomerular filtration rate	7.000000e-18
GCST007877_23	Creatinine levels	9.000000e-09
GCST008103_149	Bipolar disorder	3.000000e-06
GCST008362_40	Birth weight	9.000000e-10
GCST008363_131	Offspring birth weight	7.000000e-09
GCST010142_10	Fish- and plant-related diet	8.000000e-12
GCST90011899_86	Aspartate aminotransferase levels	8.000000e-15
GCST90013663_7	Alanine aminotransferase levels	3.000000e-12
GCST90013664_33	Aspartate aminotransferase levels	3.000000e-11

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0004633	protein C measurement
EFO:0008390	prothrombin time measurement
EFO:0005054	QRS complex
EFO:0007742	QRS amplitude
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0004344	birth weight
EFO:0005939	parental genotype effect measurement
EFO:0008111	diet measurement
EFO:0004736	aspartate aminotransferase measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D002312	Cardiomyopathy, Hypertrophic	C14.280.238.100; C14.280.484.048.750.070.160

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3831286 (PROTEIN COMPLEX)

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs3746444	MIR499A, MYH7B		0.00	0

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	2
aristolochic acid I	increases expression	1
bisphenol A	increases expression	1
beta-lapachone	decreases expression	1
calfactant	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Arsenic	affects methylation	1
Diuron	decreases expression	1
Doxorubicin	decreases expression	1
Rotenone	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Triclosan	decreases expression	1
Valproic Acid	increases methylation	1
8-Bromo Cyclic Adenosine Monophosphate	decreases expression	1
Nanotubes, Carbon	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

231 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
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.
NCT00001631	PHASE2	COMPLETED	Study of Blood Flow in Heart Muscle
NCT00001894	PHASE2	COMPLETED	A Comparison of Two Treatments: Pacemaker and Percutaneous Transluminal Septal Ablation for Hypertrophic Cardiomyopathy
NCT00001960	PHASE2	COMPLETED	Studying the Effectiveness of Pacemaker Therapy in Children Who Have Thickened Heart Muscle
NCT00011076	PHASE2	COMPLETED	Pirfenidone to Treat Hypertrophic Cardiomyopathy
NCT00035386	PHASE2	COMPLETED	Alcohol Septal Ablation in Obstructive Hypertrophic Cardiomyopathy: A Pilot Study
NCT00430833	PHASE2	UNKNOWN	CHANCE - Candesartan in Hypertrophic Cardiomyopathy
NCT00500552	PHASE2	COMPLETED	Perhexiline Therapy in Patients With Hypertrophic Cardiomyopathy
NCT01150461	PHASE2	COMPLETED	Effect of Losartan in Patients With Nonobstructive Hypertrophic Cardiomyopathy
NCT01230918	PHASE2	TERMINATED	Study to Develop a Non-invasive Marker for Monitoring Myocardial Fibrosis
NCT01447654	PHASE2	COMPLETED	Inhibition of the Renin Angiotensin System With Losartan in Patients With Hypertrophic Cardiomyopathy
NCT01696370	PHASE2	UNKNOWN	Trimetazidine Therapy in Hypertrophic Cardiomyopathy
NCT01912534	PHASE2	COMPLETED	Valsartan for Attenuating Disease Evolution In Early Sarcomeric HCM
NCT02590809	PHASE2	COMPLETED	Hypertrophic Cardiomyopathy Symptom Release by BX1514M
NCT03496168	PHASE2	COMPLETED	Extension Study of Mavacamten (MYK-461) in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy Previously Enrolled in PIONEER
NCT03532802	PHASE2	COMPLETED	The Effect of Metoprolol in Patients With Hypertrophic Obstructive Cardiomyopathy.
NCT03832660	PHASE2	COMPLETED	Sacubitril/Valsartan vs Lifestyle in Hypertrophic Cardiomyopathy
NCT04219826	PHASE2	COMPLETED	Dose-finding Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of CK-3773274 in Adults With Hypertrophic Cardiomyopathy
NCT04426578	PHASE2	UNKNOWN	Role of Perhexiline in Hypertrophic Cardiomyopathy