MYOM1

Summary

MYOM1 (myomesin 1, HGNC:7613) is a protein-coding gene on chromosome 18p11.31, encoding Myomesin-1 (P52179). Major component of the vertebrate myofibrillar M band.

The giant protein titin, together with its associated proteins, interconnects the major structure of sarcomeres, the M bands and Z discs. The C-terminal end of the titin string extends into the M line, where it binds tightly to M-band constituents of apparent molecular masses of 190 kD (myomesin 1) and 165 kD (myomesin 2). This protein, myomesin 1, like myomesin 2, titin, and other myofibrillar proteins contains structural modules with strong homology to either fibronectin type III (motif I) or immunoglobulin C2 (motif II) domains. Myomesin 1 and myomesin 2 each have a unique N-terminal region followed by 12 modules of motif I or motif II, in the arrangement II-II-I-I-I-I-I-II-II-II-II-II. The two proteins share 50% sequence identity in this repeat-containing region. The head structure formed by these 2 proteins on one end of the titin string extends into the center of the M band. The integrating structure of the sarcomere arises from muscle-specific members of the superfamily of immunoglobulin-like proteins. Alternatively spliced transcript variants encoding different isoforms have been identified.

Source: NCBI Gene 8736 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hypertrophic cardiomyopathy (Limited, GenCC)
• GWAS associations: 3
• Clinical variants (ClinVar): 2,192 total — 1 pathogenic
• Phenotypes (HPO): 2
• MANE Select transcript: NM_003803

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7613
Approved symbol	MYOM1
Name	myomesin 1
Location	18p11.31
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000101605
Ensembl biotype	protein_coding
OMIM	603508
Entrez	8736

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 6 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000261606, ENST00000356443, ENST00000577294, ENST00000581075, ENST00000581804, ENST00000582016, ENST00000941942, ENST00000941943, ENST00000941944, ENST00000941945

RefSeq mRNA: 2 — MANE Select: NM_003803 NM_003803, NM_019856

CCDS: CCDS45823, CCDS45824

Canonical transcript exons

ENST00000356443 — 38 exons

Exon	Start	End
ENSE00001240516	3094170	3094306
ENSE00001240522	3100159	3100203
ENSE00001240526	3100320	3100426
ENSE00001240535	3102474	3102630
ENSE00001240541	3112298	3112412
ENSE00001240549	3116331	3116515
ENSE00001240553	3119869	3119995
ENSE00001240567	3131375	3131496
ENSE00001240573	3134650	3134824
ENSE00001240577	3135547	3135730
ENSE00001240581	3141939	3142063
ENSE00001240585	3149145	3149201
ENSE00001240590	3151694	3151893
ENSE00001240595	3154947	3155088
ENSE00001240598	3164278	3164439
ENSE00001240603	3168817	3168981
ENSE00001240608	3173938	3174000
ENSE00001240615	3174120	3174208
ENSE00001240619	3176042	3176134
ENSE00001240622	3187480	3187637
ENSE00001240625	3188748	3189087
ENSE00001400333	3219803	3219968
ENSE00001403202	3193818	3193958
ENSE00001413714	3129232	3129519
ENSE00001543713	3214934	3215251
ENSE00001592917	3090658	3090802
ENSE00001615622	3066807	3067555
ENSE00001645638	3089174	3089241
ENSE00001692605	3086038	3086151
ENSE00001709505	3089537	3089596
ENSE00001731412	3075454	3075476
ENSE00001738311	3085045	3085132
ENSE00001803821	3075725	3075761
ENSE00003461704	3079179	3079342
ENSE00003484401	3071834	3071889
ENSE00003502967	3126701	3126897
ENSE00003579468	3083789	3083894
ENSE00003600286	3083989	3084027

Expression profiles

Bgee: expression breadth ubiquitous, 215 present calls, max score 99.50.

FANTOM5 (CAGE): breadth broad, TPM avg 8.4256 / max 1723.4838, expressed in 397 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
171001	3.3248	281
171002	2.7495	225
171004	1.8353	124
171005	0.4101	65
171003	0.0884	32
171006	0.0174	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
hindlimb stylopod muscle	UBERON:0004252	99.50	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.42	gold quality
gluteal muscle	UBERON:0002000	99.24	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.24	gold quality
apex of heart	UBERON:0002098	99.23	gold quality
gastrocnemius	UBERON:0001388	99.05	gold quality
triceps brachii	UBERON:0001509	98.89	gold quality
biceps brachii	UBERON:0001507	98.84	gold quality
heart left ventricle	UBERON:0002084	98.83	gold quality
vastus lateralis	UBERON:0001379	98.81	gold quality
skeletal muscle tissue	UBERON:0001134	98.76	gold quality
cardiac ventricle	UBERON:0002082	98.76	gold quality
quadriceps femoris	UBERON:0001377	98.75	gold quality
muscle organ	UBERON:0001630	98.59	gold quality
skeletal muscle organ	UBERON:0014892	98.59	gold quality
right atrium auricular region	UBERON:0006631	98.54	gold quality
muscle of leg	UBERON:0001383	98.52	gold quality
deltoid	UBERON:0001476	98.37	gold quality
diaphragm	UBERON:0001103	98.34	gold quality
cardiac atrium	UBERON:0002081	98.13	gold quality
tibialis anterior	UBERON:0001385	97.91	gold quality
heart right ventricle	UBERON:0002080	97.64	gold quality
heart	UBERON:0000948	97.22	gold quality
left ventricle myocardium	UBERON:0006566	96.94	gold quality
muscle tissue	UBERON:0002385	96.64	gold quality
myocardium	UBERON:0002349	95.85	gold quality
cardiac muscle of right atrium	UBERON:0003379	93.69	gold quality
body of tongue	UBERON:0011876	93.67	gold quality
popliteal artery	UBERON:0002250	92.84	gold quality
tibial artery	UBERON:0007610	92.84	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	11.79
E-ANND-3	yes	6.97
E-CURD-10	no	56.12

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
IGF1	Activation

Upstream regulators (CollecTRI, top): MEF2C

miRNA regulators (miRDB)

28 targeting MYOM1, 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-4789-3P	99.99	70.75	2484
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-5004-5P	99.68	66.63	1294
HSA-MIR-452-5P	99.65	69.63	1762
HSA-MIR-4676-3P	99.65	69.31	1733
HSA-MIR-892C-3P	99.65	69.38	1745
HSA-MIR-3685	99.62	68.83	1621
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-548G-3P	99.48	68.67	2159
HSA-MIR-4279	99.19	66.70	2437
HSA-MIR-384	98.71	67.34	1229
HSA-MIR-6826-3P	98.19	66.32	1153
HSA-MIR-6870-3P	98.08	65.10	692
HSA-MIR-3674	97.01	68.86	1171
HSA-MIR-4790-3P	96.63	67.08	806
HSA-MIR-376A-2-5P	96.43	68.06	715
HSA-MIR-3935	96.33	66.79	797

Literature-anchored findings (GeneRIF, showing 9)

• Results identify muscle-type creatine kinase as a binding partner of a central portion of myomesin and the closely related M-protein. (PMID:12972258)
• visco-elastic properties of myomesin might be crucial for the stability of the sarcomere (PMID:15890201)
• EH-myomesin levels were up-regulated at least 10 times in dilated cardiomyopathy patients compared to controls. (PMID:21069531)
• This missense mutation caused significant changes of biochemical and biophysical properties of myomesin fragments indicating a role in the pathogenesis of hypertrophic cardiomyopathy . (PMID:21256114)
• Our results suggest that the downregulation of MBNL proteins should lead to the abnormal splicing of MYOM1 exon 17a in DM1 muscle. (PMID:21794030)
• myomesin could act as a highly elastic ribbon to maintain the overall structural organization of the sarcomeric M-band. (PMID:22347812)
• individual subfragments of titin and myomesin composed of Fn type III and Ig-like domains can activate expression of two IGF-1 splice forms in cultured myoblasts (PMID:25152160)
• Crystal structure of the obscurin(-like-1):myomesin complex reveals a trans-complementation mechanism whereby an incomplete immunoglobulin-like domain assimilates an isoform-specific myomesin interdomain sequence. (PMID:27989621)
• Knockout of MYOM1 in human cardiomyocytes leads to myocardial atrophy via impairing calcium homeostasis. (PMID:33452765)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	myom1a	ENSDARG00000061249
danio_rerio	myom1b	ENSDARG00000104836
mus_musculus	Myom1	ENSMUSG00000024049
rattus_norvegicus	Myom1	ENSRNOG00000057701
drosophila_melanogaster	mtgo	FBGN0259735
caenorhabditis_elegans		WBGENE00007944

Paralogs (11): MYOM2 (ENSG00000036448), FNDC3B (ENSG00000075420), MYBPC2 (ENSG00000086967), FNDC3A (ENSG00000102531), OBSL1 (ENSG00000124006), MYBPH (ENSG00000133055), MYBPC3 (ENSG00000134571), MYOM3 (ENSG00000142661), IGSF22 (ENSG00000179057), MYBPC1 (ENSG00000196091), MYBPHL (ENSG00000221986)

Protein

Protein identifiers

Myomesin-1 — P52179 (reviewed: P52179)

Alternative names: 190 kDa connectin-associated protein, 190 kDa titin-associated protein, Myomesin family member 1

All UniProt accessions (2): P52179, J3KRK2

UniProt curated annotations — full annotation on UniProt →

Function. Major component of the vertebrate myofibrillar M band. Binds myosin, titin, and light meromyosin. This binding is dose dependent.

Subunit / interactions. Homodimer. Interacts with TTN/titin. Interacts with PNKD.

Subcellular location. Cytoplasm. Myofibril. Sarcomere. M line.

Isoforms (2)

UniProt ID	Names	Canonical?
P52179-1	1	yes
P52179-2	2

RefSeq proteins (2): NP_003794, NP_062830 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR003961	FN3_dom	Domain
IPR007110	Ig-like_dom	Domain
IPR013098	Ig_I-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036116	FN3_sf	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR050964	Striated_Muscle_Regulatory	Family

Pfam: PF00041, PF07679

UniProt features (122 total): strand 52, sequence conflict 14, helix 11, domain 10, sequence variant 8, compositionally biased region 7, repeat 6, region of interest 4, modified residue 4, turn 3, chain 1, disulfide bond 1, splice variant 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
6T3O	X-RAY DIFFRACTION	1.8
3RBS	X-RAY DIFFRACTION	1.85
5FM8	X-RAY DIFFRACTION	2.05
2R15	X-RAY DIFFRACTION	2.24
2Y23	X-RAY DIFFRACTION	2.5
6ZVA	X-RAY DIFFRACTION	2.68
5FM4	X-RAY DIFFRACTION	2.8
5FM5	X-RAY DIFFRACTION	3.1
2Y25	X-RAY DIFFRACTION	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P52179-F1	69.52	0.18

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 (4): 113, 883, 887, 1054

Disulfide bonds (1): 1160–1210

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 143 (showing top): GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, MODULE_329, GOBP_SARCOMERE_ORGANIZATION, MODULE_70, CHEN_LVAD_SUPPORT_OF_FAILING_HEART_UP, GOBP_CELLULAR_COMPONENT_ASSEMBLY_INVOLVED_IN_MORPHOGENESIS, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, MODULE_202, BLALOCK_ALZHEIMERS_DISEASE_UP, KINSEY_TARGETS_OF_EWSR1_FLII_FUSION_DN, GOBP_SKELETAL_MUSCLE_ORGAN_DEVELOPMENT, GOBP_ACTOMYOSIN_STRUCTURE_ORGANIZATION, CAIRO_HEPATOBLASTOMA_DN

GO Biological Process (5): extraocular skeletal muscle development (GO:0002074), positive regulation of gene expression (GO:0010628), obsolete protein kinase A signaling (GO:0010737), sarcomere organization (GO:0045214), positive regulation of protein secretion (GO:0050714)

GO Molecular Function (6): structural constituent of muscle (GO:0008307), kinase binding (GO:0019900), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), structural molecule activity (GO:0005198), protein binding (GO:0005515)

GO Cellular Component (5): striated muscle myosin thick filament (GO:0005863), M band (GO:0031430), cytoplasm (GO:0005737), sarcomere (GO:0030017), myosin filament (GO:0032982)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
skeletal muscle tissue development	1
camera-type eye development	1
skeletal muscle organ development	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
myofibril assembly	1
actomyosin structure organization	1
protein secretion	1
regulation of protein secretion	1
positive regulation of protein transport	1
positive regulation of secretion by cell	1
structural molecule activity	1
enzyme binding	1
protein binding	1
identical protein binding	1
protein dimerization activity	1
molecular_function	1
binding	1
muscle myosin complex	1
sarcomere	1
myosin filament	1
myofilament	1
A band	1
intracellular anatomical structure	1
myofibril	1
myosin complex	1
supramolecular fiber	1

Protein interactions and networks

STRING

1032 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MYOM1	TTN	Q8WZ42	617
MYOM1	OBSCN	Q5VST9	536
MYOM1	MYOZ2	Q9NPC6	531
MYOM1	ACTN2	P35609	525
MYOM1	CLUL1	Q15846	518
MYOM1	MYH7	P12883	507
MYOM1	TCAP	O15273	480
MYOM1	MYL5	Q02045	480
MYOM1	PDLIM3	Q53GG5	479
MYOM1	MYL3	P08590	447
MYOM1	MYLK2	Q9H1R3	434
MYOM1	MYH6	P13533	432
MYOM1	MYL2	P10916	422
MYOM1	NEB	P20929	418
MYOM1	FLNC	Q14315	417
MYOM1	AKAIN1	P0CW23	417

IntAct

25 interactions, top by confidence:

A	B	Type	Score
MYOM1	MYOM1	psi-mi:“MI:0407”(direct interaction)	0.650
DYSF	MYOM1	psi-mi:“MI:2364”(proximity)	0.450
PCNA	MYOM1	psi-mi:“MI:0915”(physical association)	0.370
M		psi-mi:“MI:0914”(association)	0.350
LATS1	ATP2A1	psi-mi:“MI:0914”(association)	0.350
TSPAN33	ATP2A1	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
CSNK2B	TUBAL3	psi-mi:“MI:0914”(association)	0.350
FMR1	MYOM1	psi-mi:“MI:0915”(physical association)	0.000
MYOM1	ANKRD28	psi-mi:“MI:0915”(physical association)	0.000
MYOM1	C1QTNF9	psi-mi:“MI:0915”(physical association)	0.000
DNAJB6	MYOM1	psi-mi:“MI:0915”(physical association)	0.000
MYOM1	DYSF	psi-mi:“MI:0915”(physical association)	0.000
SYNE1	MYOM1	psi-mi:“MI:0915”(physical association)	0.000
TTN	MYOM1	psi-mi:“MI:0915”(physical association)	0.000
MYOM1	TTN	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (25): MYOM1 (Biochemical Activity), MYOM1 (Two-hybrid), MYOM1 (Two-hybrid), TRIM23 (Two-hybrid), MTUS2 (Two-hybrid), PPP1R16A (Two-hybrid), PDE4DIP (Two-hybrid), KRTAP1-1 (Two-hybrid), KRTAP5-7 (Two-hybrid), DYSF (Affinity Capture-Western), MYOM1 (Two-hybrid), MYOM1 (Two-hybrid), MYOM1 (Two-hybrid), MYOM1 (Two-hybrid), SYNE1 (Two-hybrid)

ESM2 similar proteins: A0A087WV53, A2AAJ9, A2ABU4, A2RUH7, E7F6H7, O00423, O01761, O14576, O54785, O70468, O88485, O88599, P16419, P22607, P26453, P52179, P53670, P53671, P54296, P56741, P70402, Q00872, Q02173, Q05623, Q05BC3, Q0DYP5, Q13203, Q14168, Q14324, Q14896, Q29RQ3, Q32L23, Q4V8C3, Q5FW53, Q5PQM4, Q5VST9, Q5VTT5, Q5XI81, Q5XKE0, Q60992

Diamond homologs: A0A087WV53, A2AAJ9, A2ASS6, A2RUH7, O75147, O94856, O94898, P05548, P52179, P54296, P97685, Q00872, Q23551, Q52KR2, Q5VST9, Q62234, Q80W87, Q810U3, Q8WX93, Q92626, A2ABU4, O88599, P12960, P14781, P28685, P68500, P70402, P97527, P97528, Q02173, Q07409, Q12860, Q13203, Q14896, Q28106, Q2EY15, Q2VWP7, Q2VWP9, Q589G5, Q5PQM4

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
MYOM1	“up-regulates quantity”	OBSCN	relocalization
PKA	“down-regulates activity”	MYOM1	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

2192 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	1226
Likely benign	682
Benign	178

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1452047	NC_000018.9:g.(?2847807)(3582246_?)del	Pathogenic

SpliceAI

5404 predictions. Top by Δscore:

Variant	Effect	Δscore
18:3067570:T:TC	acceptor_gain	1.0000
18:3075483:T:TC	acceptor_gain	1.0000
18:3083783:ACTT:A	donor_loss	1.0000
18:3083784:CT:C	donor_loss	1.0000
18:3083785:TT:T	donor_loss	1.0000
18:3083787:A:AC	donor_gain	1.0000
18:3083787:A:T	donor_loss	1.0000
18:3083788:C:CA	donor_gain	1.0000
18:3083788:C:T	donor_loss	1.0000
18:3083890:CAAAG:C	acceptor_gain	1.0000
18:3083891:AAAG:A	acceptor_gain	1.0000
18:3083892:AAG:A	acceptor_gain	1.0000
18:3083892:AAGC:A	acceptor_loss	1.0000
18:3083893:AG:A	acceptor_gain	1.0000
18:3083893:AGC:A	acceptor_loss	1.0000
18:3083894:GC:G	acceptor_loss	1.0000
18:3083895:C:CC	acceptor_gain	1.0000
18:3083895:C:CG	acceptor_loss	1.0000
18:3086034:CTA:C	donor_loss	1.0000
18:3086037:CCT:C	donor_gain	1.0000
18:3086066:T:A	donor_gain	1.0000
18:3086149:CACCT:C	acceptor_loss	1.0000
18:3086150:ACCTA:A	acceptor_loss	1.0000
18:3086151:CCTAG:C	acceptor_loss	1.0000
18:3086152:CTA:C	acceptor_loss	1.0000
18:3086153:T:A	acceptor_loss	1.0000
18:3089531:TTTTA:T	donor_loss	1.0000
18:3089532:TTTA:T	donor_loss	1.0000
18:3089533:TTA:T	donor_loss	1.0000
18:3089534:TAC:T	donor_loss	1.0000

AlphaMissense

11044 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:3079280:A:G	L1516P	0.999
18:3119961:A:G	F1009S	0.999
18:3126774:C:G	R973P	0.999
18:3126832:A:G	W954R	0.999
18:3126832:A:T	W954R	0.999
18:3131452:C:G	R810P	0.999
18:3131455:A:G	F809S	0.999
18:3135621:A:T	V712D	0.999
18:3135624:C:G	R711P	0.999
18:3135627:A:G	F710S	0.999
18:3168829:A:G	W443R	0.999
18:3168829:A:T	W443R	0.999
18:3187481:A:G	W310R	0.999
18:3187481:A:T	W310R	0.999
18:3067504:A:G	W1606R	0.998
18:3067504:A:T	W1606R	0.998
18:3116459:A:G	W1059R	0.998
18:3116459:A:T	W1059R	0.998
18:3126830:C:A	W954C	0.998
18:3126830:C:G	W954C	0.998
18:3134685:C:A	W783C	0.998
18:3134685:C:G	W783C	0.998
18:3134759:A:G	W759R	0.998
18:3134759:A:T	W759R	0.998
18:3134764:A:T	V757D	0.998
18:3141992:A:G	W658R	0.998
18:3141992:A:T	W658R	0.998
18:3151789:C:G	R583P	0.998
18:3151792:A:G	F582S	0.998
18:3155002:A:G	W530R	0.998

dbSNP variants (sampled 300 via entrez): RS1000006006 (18:3130585 G>A), RS1000025241 (18:3242070 T>C), RS1000027144 (18:3159814 G>C), RS1000031407 (18:3120049 T>C), RS1000044815 (18:3248054 C>T), RS1000070283 (18:3199363 C>A,T), RS1000073338 (18:3132175 G>A), RS1000096580 (18:3248301 G>A), RS1000103173 (18:3077138 G>A,C), RS1000104047 (18:3130924 T>C), RS1000150157 (18:3114617 C>T), RS1000155826 (18:3169498 G>A), RS1000165405 (18:3215906 CAT>C), RS1000172570 (18:3095580 A>G), RS1000230322 (18:3236052 TC>T)

Disease associations

OMIM: gene MIM:603508 | disease phenotypes: MIM:142946, MIM:192600, MIM:236750, MIM:613765

GenCC curated gene-disease

Disease	Classification	Inheritance
hypertrophic cardiomyopathy	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
hypertrophic cardiomyopathy	Disputed	AD

Mondo (11): hypertrophic cardiomyopathy (MONDO:0005045), holoprosencephaly 4 (MONDO:0007734), dilated cardiomyopathy (MONDO:0005021), familial hypertrophic cardiomyopathy (MONDO:0024573), non-immune hydrops fetalis (MONDO:0009369), arrhythmogenic right ventricular cardiomyopathy (MONDO:0016587), cardiac arrest (MONDO:0000745), cardiomyopathy (MONDO:0004994), hypertrophic cardiomyopathy 9 (MONDO:0013412), hypoglycemia (MONDO:0004946), liver disorder (MONDO:0005154)

Orphanet (8): Rare hypertrophic cardiomyopathy (Orphanet:217569), Holoprosencephaly (Orphanet:2162), Dilated cardiomyopathy (Orphanet:217604), Rare familial disorder with hypertrophic cardiomyopathy (Orphanet:99739), Non-immune hydrops fetalis (Orphanet:363999), Inherited arrhythmogenic cardiomyopathy (Orphanet:247), Rare cardiomyopathy (Orphanet:167848), NON RARE IN EUROPE: Familial isolated hypertrophic cardiomyopathy (Orphanet:155)

HPO phenotypes

2 total (2 of 2 shown, HPO-id order):

HPO	Term
HP:0001639	Hypertrophic cardiomyopathy
HP:0001644	Dilated cardiomyopathy

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST003254_1	Urinary albumin-to-creatinine ratio in non-diabetics	9.000000e-06
GCST003542_27	Night sleep phenotypes	9.000000e-06
GCST004795_4	Brain volume in infants (white matter)	1.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007778	urinary albumin to creatinine ratio
EFO:0007827	nighttime rest measurement
EFO:0008370	infant white matter volume measurement

MeSH disease descriptors (10)

Descriptor	Name	Tree numbers
D019571	Arrhythmogenic Right Ventricular Dysplasia	C14.240.400.145; C14.280.238.028; C14.280.400.145; C16.131.240.400.145
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
D007003	Hypoglycemia	C18.452.394.984
D008107	Liver Diseases	C06.552
C566044	Cardiomyopathy, Familial Hypertrophic, 9 (supp.)
C564180	Holoprosencephaly 4 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	decreases expression, increases expression, increases methylation	3
Benzo(a)pyrene	affects methylation, increases methylation	2
Valproic Acid	affects cotreatment, increases expression, decreases expression	2
GSK-J4	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
sodium arsenite	increases expression	1
manganese chloride	increases expression	1
di-n-butylphosphoric acid	affects expression	1
incobotulinumtoxinA	decreases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	decreases expression, affects cotreatment	1
Doxorubicin	decreases expression	1
Estradiol	decreases expression	1
Hydralazine	affects cotreatment, increases expression	1
Manganese	increases expression	1
Nickel	decreases expression	1
Oxygen	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	affects cotreatment, decreases expression	1
Triclosan	decreases expression	1
Urethane	decreases expression	1
Cyclosporine	increases expression	1
Sodium Selenite	decreases expression	1
Okadaic Acid	decreases expression	1
Magnetite Nanoparticles	decreases expression	1

Clinical trials (associated diseases)

227 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