MYH2

Summary

MYH2 (myosin heavy chain 2, HGNC:7572) is a protein-coding gene on chromosome 17p13.1, encoding Myosin-2 (Q9UKX2). Myosins are actin-based motor molecules with ATPase activity essential for muscle contraction.

Myosins are actin-based motor proteins that function in the generation of mechanical force in eukaryotic cells. Muscle myosins are heterohexamers composed of 2 myosin heavy chains and 2 pairs of nonidentical myosin light chains. This gene encodes a member of the class II or conventional myosin heavy chains, and functions in skeletal muscle contraction. This gene is found in a cluster of myosin heavy chain genes on chromosome 17. A mutation in this gene results in inclusion body myopathy-3. Multiple alternatively spliced variants, encoding the same protein, have been identified.

Source: NCBI Gene 4620 — RefSeq curated summary.

At a glance

• Gene–disease (curated): myopathy, proximal, and ophthalmoplegia (Definitive, ClinGen) — +2 more curated relationships
• Clinical variants (ClinVar): 986 total — 31 pathogenic, 23 likely-pathogenic
• Phenotypes (HPO): 21
• Druggable target: yes
• MANE Select transcript: NM_017534

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7572
Approved symbol	MYH2
Name	myosin heavy chain 2
Location	17p13.1
Locus type	gene with protein product
Status	Approved
Aliases	MYH2A, MYHSA2, MyHC-IIa, MYHas8, MyHC-2A
Ensembl gene	ENSG00000125414
Ensembl biotype	protein_coding
OMIM	160740
Entrez	4620

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 13 protein_coding

ENST00000245503, ENST00000397183, ENST00000420805, ENST00000532183, ENST00000578017, ENST00000622564, ENST00000936537, ENST00000965119, ENST00000965120, ENST00000965121, ENST00000965122, ENST00000965123, ENST00000965124

RefSeq mRNA: 2 — MANE Select: NM_017534 NM_001100112, NM_017534

CCDS: CCDS11156

Canonical transcript exons

ENST00000245503 — 40 exons

Exon	Start	End
ENSE00000855382	10547717	10547940
ENSE00000907720	10526938	10527056
ENSE00001362713	10549375	10549417
ENSE00001673106	10536530	10536606
ENSE00001752886	10537233	10537542
ENSE00002145256	10521148	10521432
ENSE00002164163	10549636	10549658
ENSE00002326361	10539928	10540066
ENSE00002333854	10543902	10544016
ENSE00002339806	10535278	10535365
ENSE00002342098	10543098	10543161
ENSE00002342503	10525451	10525616
ENSE00002346526	10529832	10530074
ENSE00002348575	10523496	10523666
ENSE00002349153	10533509	10533632
ENSE00002353273	10543711	10543803
ENSE00002356399	10529162	10529252
ENSE00002371003	10528690	10529079
ENSE00002377090	10523759	10523884
ENSE00002379529	10547475	10547618
ENSE00002380194	10544100	10544127
ENSE00002384080	10529336	10529481
ENSE00002384274	10531633	10531888
ENSE00002385948	10540594	10540697
ENSE00002388163	10526599	10526795
ENSE00002389372	10535073	10535190
ENSE00002393197	10525224	10525348
ENSE00002393986	10542875	10542973
ENSE00002394298	10529564	10529740
ENSE00002395852	10527748	10527874
ENSE00002399442	10524757	10525065
ENSE00002400742	10524466	10524669
ENSE00002401769	10525693	10525876
ENSE00002403463	10533285	10533421
ENSE00002404262	10523308	10523412
ENSE00002419682	10537665	10537835
ENSE00002419969	10545346	10545502
ENSE00002421119	10523090	10523185
ENSE00002425301	10539444	10539562
ENSE00002426473	10539205	10539354

Expression profiles

Bgee: expression breadth ubiquitous, 163 present calls, max score 99.99.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 7.1603 / max 2533.9549, expressed in 76 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
164594	5.1326	61
164595	1.4303	48
164596	0.4170	26
164573	0.0612	15
164571	0.0440	12
164593	0.0269	10
164572	0.0244	11
164597	0.0239	12

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.99	gold quality
biceps brachii	UBERON:0001507	99.98	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.98	gold quality
body of tongue	UBERON:0011876	99.98	gold quality
vastus lateralis	UBERON:0001379	99.97	gold quality
diaphragm	UBERON:0001103	99.95	gold quality
quadriceps femoris	UBERON:0001377	99.95	gold quality
triceps brachii	UBERON:0001509	99.91	gold quality
gluteal muscle	UBERON:0002000	99.89	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.84	gold quality
skeletal muscle tissue	UBERON:0001134	99.73	gold quality
deltoid	UBERON:0001476	99.60	gold quality
gastrocnemius	UBERON:0001388	99.19	gold quality
tibialis anterior	UBERON:0001385	98.52	gold quality
muscle organ	UBERON:0001630	98.16	gold quality
skeletal muscle organ	UBERON:0014892	98.16	gold quality
muscle of leg	UBERON:0001383	97.49	gold quality
larynx	UBERON:0001737	97.06	gold quality
pharyngeal mucosa	UBERON:0000355	93.22	gold quality
tongue	UBERON:0001723	91.82	gold quality
muscle tissue	UBERON:0002385	91.56	gold quality
tendon of biceps brachii	UBERON:0008188	87.20	gold quality
superior surface of tongue	UBERON:0007371	84.74	gold quality
oral cavity	UBERON:0000167	82.19	gold quality
trabecular bone tissue	UBERON:0002483	77.18	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	74.48	gold quality
minor salivary gland	UBERON:0001830	69.66	gold quality
mouth mucosa	UBERON:0003729	68.95	gold quality
saliva-secreting gland	UBERON:0001044	63.47	gold quality
apex of heart	UBERON:0002098	61.06	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ANGPT1, CTNNB1, MEF2A, MEF2C, MEF2D, POU2F1, TCF7L2, TEK

miRNA regulators (miRDB)

13 targeting MYH2, 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-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-2113	99.58	71.22	1521
HSA-MIR-10399-5P	99.17	69.87	2610
HSA-MIR-6504-3P	99.17	69.31	2891
HSA-MIR-4801	98.96	69.42	2096
HSA-MIR-3132	97.96	67.91	711
HSA-MIR-214-5P	97.34	66.50	617
HSA-MIR-3121-5P	97.30	66.62	1146
HSA-MIR-197-5P	97.23	68.10	596
HSA-MIR-550B-2-5P	96.56	64.61	646

Literature-anchored findings (GeneRIF, showing 28)

• investigated the relation between expression of the mutant MyHC IIa and pathologic changes in muscle (PMID:11889243)
• Data suggest that changes in intracellular calcium may play a role in shifts in myosin heavy chain IIa (MyHC IIa) expression during muscle activation. (PMID:12235157)
• IRF-2 is involved in up-regulation of nonmuscle myosin heavy chain II-A gene expression in cell differentiation (PMID:15496418)
• analysis of normal variation indicates that there is strong selective pressure against mutations in MYH2; On the basis of these results, we suggest that MyHC genes should be regarded as candidate genes in hereditary myopathies of unknown etiology. (PMID:15741996)
• Our results provide evidence that the pathogenesis of the MyHC IIa E706K myopathy involves defective function of the mutated myosin as well as alterations in the structural integrity of all muscle cells irrespective of MyHC isoform expression. (PMID:17005402)
• myosin II has a role in glioma invasion of the brain (PMID:18495866)
• Null mutations in the fast myosin heavy chain IIa gene cause early onset myopathy and demonstrate that this isoform is necessary for normal muscle development and function. (PMID:20418530)
• NMMII and actin isoform expression changes coordinately with the remodeling phase of repair, and NMMII is increased as matrix stiffness increases. As NMMII expression increases, so does the fibroblast contractility. (PMID:21102503)
• the expression levels of the MHC genes are associated with age and both PGC-1alpha and PGC-1beta and indicate that the MHC genes may to some extent be used to determine fibre-type composition in human skeletal muscle. (PMID:21470888)
• The human genioglossus muscle is composed of conventional myosin heavy chain isoforms and 3 primary myosin hevy chain phenotypes. (PMID:22337492)
• This study demonistrated that the missense mutation c.2542T>C (p.V805A) in the MYHC2A gene. (PMID:22349865)
• Phenotypic expression of alpha-smooth muscle actin, smooth muscle myosin heavy chain 2, and smoothelin were significantly decreased in the dissected media, whereas that of osteopontin was elevated. (PMID:22960022)
• Myosin heavy chain 2A transcripts decreased significantly in skeletal muscle tissue from overnight parenterally fed patients but did not change significantly in orally refed mice (PMID:23190566)
• A previously unrecognized interplay between actin and myosin IIA in podosomes, is demonstrated. (PMID:23361003)
• This study presented more case in MYH2 mutation in recessive myopathy with external ophthalmoplegia linked to chromosome 17p13.1-p12. (PMID:23388406)
• Data shoe that five of the patients were homozygous for myosin heavy chain 2 (MYH2) missense mutations, one patient was compound heterozygous for a missense and a nonsense mutation and one patient was homozygous for a frame-shift MYH2 mutation. (PMID:24193343)
• We have found that a greater MyH2 content in the vastus lateralis is accompanied by a higher oxygen cost of cycling during exercise performed below the lactate threshold. (PMID:24781731)
• Myosin isoforms impact single-fiber force generation and may lead to alterations in whole skeletal muscle performance. (PMID:25567808)
• Transcriptional levels of MHC-I, MHC-IIa, and MHC-IIb in denervation groups were significantly down-regulated compared with controls (PMID:26059207)
• differential regulation of PKA and cell stiffness in unconfined versus confined cells is abrogated by dual, but not individual, inhibition of Piezo1 and myosin II. (PMID:27160899)
• C-terminal Myosin IIA Heavy Chain phosphorylation sites are critical for recruitment of Myosin IIA to lamellar protrusions and for marginal paxillin phosphorylation during active cell spreading. (PMID:28053086)
• Exome analysis revealed homozygosity for a novel truncating mutation p.G800fs27* in the Myosin Heavy Chain 2 (MYH2) gene in both brothers, while parents and an unaffected sibling were heterozygous (PMID:28729039)
• Precise Tuning of Cortical Contractility Regulates Cell Shape during Cytokinesis. (PMID:32268086)
• Myosin post-translational modifications and function in the presence of myopathy-linked truncating MYH2 mutations. (PMID:36745529)
• MYH2-associated myopathy caused by a novel splice-site variant. (PMID:36774715)
• MYH2-related Myopathy: Expanding the Clinical Spectrum of Chronic Progressive External Ophthalmoplegia (CPEO). (PMID:37154181)
• Nonmuscle myosin 2 filaments are processive in cells. (PMID:37218133)
• Myosin heavy chain 2 (MYH2) expression in hypertrophic chondrocytes of soft callus provokes endochondral bone formation in fracture. (PMID:37871676)

Cross-species orthologs

0 orthologs

Paralogs (44): MYH13 (ENSG00000006788), MYO16 (ENSG00000041515), MYO9A (ENSG00000066933), MYO3B (ENSG00000071909), MYH7B (ENSG00000078814), MYO15A (ENSG00000091536), MYH7 (ENSG00000092054), MYO3A (ENSG00000095777), MYO9B (ENSG00000099331), MYH9 (ENSG00000100345), MYH14 (ENSG00000105357), MYH1 (ENSG00000109061), MYH3 (ENSG00000109063), 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-2 — Q9UKX2 (reviewed: Q9UKX2)

Alternative names: Myosin heavy chain 2, Myosin heavy chain 2a, Myosin heavy chain IIa, Myosin heavy chain, skeletal muscle, adult 2

All UniProt accessions (3): Q9UKX2, E7EX84, J3QLR0

UniProt curated annotations — full annotation on UniProt →

Function. Myosins are actin-based motor molecules with ATPase activity essential for 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). Interacts with GCSAM.

Subcellular location. Cytoplasm. Myofibril.

Disease relevance. Congenital myopathy 6 with ophthalmoplegia (CMYO6) [MIM:605637] A muscular disorder characterized by mild-to-moderate muscle weakness, ophthalmoplegia, and contractures at birth in some patients. Muscle biopsies from patients show predominance of type 1 fibers and small or absent type 2A fibers. The disease is non-progressive or it progresses very slowly. Inheritance is autosomal dominant or recessive. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The rodlike tail sequence is highly repetitive, showing cycles of a 28-residue repeat pattern composed of 4 heptapeptides, characteristic for alpha-helical coiled coils. Limited proteolysis of myosin heavy chain produces 1 light meromyosin (LMM) and 1 heavy meromyosin (HMM). HMM can be further cleaved into 2 globular subfragments (S1) and 1 rod-shaped subfragment (S2).

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UKX2-1	1	yes
Q9UKX2-2	2

RefSeq proteins (2): NP_001093582, NP_060004* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000048	IQ_motif_EF-hand-BS	Binding_site
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 (55 total): modified residue 37, region of interest 4, sequence variant 4, domain 3, sequence conflict 2, chain 1, binding site 1, splice variant 1, coiled-coil region 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UKX2-F1	73.51	0.10

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): 179–186

Post-translational modifications (37): 64, 69, 130, 389, 392, 419, 625, 759, 1094, 1098, 1164, 1239, 1243, 1245, 1257, 1263, 1288, 1290, 1294, 1305 …

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-2029482	Regulation of actin dynamics for phagocytic cup formation
R-HSA-9664422	FCGR3A-mediated phagocytosis
R-HSA-1643685	Disease
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-2029480	Fcgamma receptor (FCGR) dependent phagocytosis
R-HSA-5663205	Infectious disease
R-HSA-9658195	Leishmania infection
R-HSA-9664407	Parasite infection
R-HSA-9664417	Leishmania phagocytosis
R-HSA-9824443	Parasitic Infection Pathways

MSigDB gene sets: 195 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, HUMMERICH_BENIGN_SKIN_TUMOR_DN, HUMMERICH_MALIGNANT_SKIN_TUMOR_DN, KEGG_TIGHT_JUNCTION, MORF_RAD51L3, KEGG_VIRAL_MYOCARDITIS, GOBP_MUSCLE_CONTRACTION, MORF_CTSB, BRN2_01, MORF_IL4, GOMF_CYTOSKELETAL_MOTOR_ACTIVITY, HP1SITEFACTOR_Q6, GOBP_ACTIN_MEDIATED_CELL_CONTRACTION, MORF_THPO, NKX22_01

GO Biological Process (2): muscle contraction (GO:0006936), muscle filament sliding (GO:0030049)

GO Molecular Function (8): microfilament motor activity (GO:0000146), calmodulin binding (GO:0005516), 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 (11): cytoplasm (GO:0005737), cytosol (GO:0005829), muscle myosin complex (GO:0005859), cell-cell junction (GO:0005911), myosin II complex (GO:0016460), myofibril (GO:0030016), sarcomere (GO:0030017), myosin filament (GO:0032982), protein-containing complex (GO:0032991), myosin complex (GO:0016459), supramolecular fiber (GO:0099512)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Fcgamma receptor (FCGR) dependent phagocytosis	1
Leishmania phagocytosis	1
Immune System	1
Innate Immune System	1
Disease	1
Parasitic Infection Pathways	1
Leishmania infection	1
Parasite infection	1
Infectious disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
contractile muscle fiber	2
myosin complex	2
muscle system process	1
muscle contraction	1
actin-myosin filament sliding	1
cytoskeletal motor activity	1
polypeptide conformation or assembly isomerase activity	1
ATP-dependent activity	1
protein binding	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
cytoplasm	1
myosin II complex	1
anchoring junction	1
myofibril	1
supramolecular fiber	1
cellular_component	1
actin cytoskeleton	1
protein-containing complex	1
supramolecular polymer	1

Protein interactions and networks

STRING

1894 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MYH2	MUTYH	Q9UIF7	758
MYH2	MYL1	P05976	756
MYH2	GNE	Q9Y223	727
MYH2	MYF6	P23409	707
MYH2	MYOG	P15173	704
MYH2	ACTA1	P02568	695
MYH2	TRIM63	Q969Q1	679
MYH2	MYOD1	P15172	677
MYH2	TTN	Q8WZ42	651
MYH2	DIXDC1	Q155Q3	639
MYH2	MYL3	P08590	625
MYH2	TNNT1	P13805	613
MYH2	TNNI1	P19237	611
MYH2	MYF5	P13349	608
MYH2	TNNI2	P48788	607

IntAct

67 interactions, top by confidence:

A	B	Type	Score
HDAC1	CDK2AP1	psi-mi:“MI:0914”(association)	0.840
PRKAG2	PRKAB2	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
YWHAZ	LMNA	psi-mi:“MI:0914”(association)	0.560
HSPB8	VWA8	psi-mi:“MI:0914”(association)	0.530
TMEM200A	PPP3CB	psi-mi:“MI:0914”(association)	0.530
MYH2	H2BC9	psi-mi:“MI:0915”(physical association)	0.400
DUX4L9	MYH2	psi-mi:“MI:0915”(physical association)	0.370
LRRC39	MYH2	psi-mi:“MI:0915”(physical association)	0.370
	PGRMC1	psi-mi:“MI:0914”(association)	0.350
IFIT3	HSPA1B	psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350
HIF1A	MYL1	psi-mi:“MI:0914”(association)	0.350
TLE3	ATP2A1	psi-mi:“MI:0914”(association)	0.350
USP15	KRT35	psi-mi:“MI:0914”(association)	0.350
P		psi-mi:“MI:0914”(association)	0.350
PRKACB	MYL1	psi-mi:“MI:0914”(association)	0.350
AXL		psi-mi:“MI:0914”(association)	0.350
SNRK	PRPF6	psi-mi:“MI:0914”(association)	0.350
ATG101	FOXO3	psi-mi:“MI:0914”(association)	0.350
CFTR	MYH7B	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350

BioGRID (47): ACTN1 (Co-fractionation), ACTN2 (Co-fractionation), ACTN4 (Co-fractionation), MYH2 (Co-fractionation), MYH2 (Co-fractionation), TPM1 (Co-fractionation), MYH2 (Affinity Capture-MS), MYH2 (Affinity Capture-MS), MYH2 (Affinity Capture-MS), MYH2 (Affinity Capture-MS), MYH2 (Affinity Capture-MS), MYH2 (Affinity Capture-MS), MYH2 (Affinity Capture-MS), MYH2 (Proximity Label-MS), MYH2 (Two-hybrid)

ESM2 similar proteins: A1C4A5, A1DBH2, A2R5J1, A3LYL7, A4RE77, A5DKH0, A5E4A8, A6SED8, A6ZMG6, A7EK16, A8N2Y6, A8PWF6, B0CRJ3, B0Y9Q4, E1BPK6, E9Q634, G3UW82, O00160, P0CP00, P0CP01, P12882, P13538, P49824, Q00647, Q04439, Q076A6, Q076A7, Q0CEX5, Q12965, Q1DLP2, Q28641, Q2HDI2, Q2US45, Q4WC55, Q59MQ0, Q63356, Q64331, Q6BUQ2, Q6C7C0, Q6CVE9

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

6 interactions.

A	Effect	B	Mechanism
MEF2A	“up-regulates quantity by expression”	MYH2	“transcriptional regulation”
MEF2D	“up-regulates quantity by expression”	MYH2	“transcriptional regulation”
MEF2C	“up-regulates quantity by expression”	MYH2	“transcriptional regulation”
POU2F1	“up-regulates quantity by expression”	MYH2	“transcriptional regulation”
TEK	“up-regulates quantity by expression”	MYH2	“transcriptional regulation”
ANGPT1	“up-regulates quantity by expression”	MYH2	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 70 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
protein phosphorylation	8	8.5×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	31
Likely pathogenic	23
Uncertain significance	567
Likely benign	268
Benign	51

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1210048	NM_017534.6(MYH2):c.1920del (p.Gly642fs)	Pathogenic
1391790	NM_017534.6(MYH2):c.3757A>T (p.Lys1253Ter)	Pathogenic
1399827	NM_017534.6(MYH2):c.2365del (p.Gln789fs)	Pathogenic
14137	NM_017534.6(MYH2):c.2116G>A (p.Glu706Lys)	Pathogenic
1453954	NC_000017.11:g.10535371_10535372insGGAGGGAGGAGCCAAGATGGCCGAATAGGAACAGCTCCGGTCTACAGCTCCCAGCGTGAGCGACGCAGAAGACGGTGATTTCTGCATTTCCATCTGAGGTACCGGGTTCANNNNNNNNNNAAAAAAAAAAAAAAAAAAAAAAATTCTCCTGTAA	Pathogenic
1459021	NC_000017.10:g.(?10424597)(10451237_?)del	Pathogenic
183660	NM_017534.6(MYH2):c.5609T>C (p.Leu1870Pro)	Pathogenic
183662	NM_017534.6(MYH2):c.2347C>T (p.Arg783Ter)	Pathogenic
183664	NM_017534.6(MYH2):c.2405T>A (p.Leu802Ter)	Pathogenic
2172073	NM_017534.6(MYH2):c.2418del (p.Glu806fs)	Pathogenic
2420285	NM_017534.6(MYH2):c.5554C>T (p.Arg1852Ter)	Pathogenic
2817017	NM_017534.6(MYH2):c.2956dup (p.Glu986fs)	Pathogenic
2851422	NM_017534.6(MYH2):c.3467_3476del (p.Leu1156fs)	Pathogenic
2984803	NM_017534.6(MYH2):c.3126del (p.Ser1043fs)	Pathogenic
3012196	NM_017534.6(MYH2):c.2219_2220del (p.Gln740fs)	Pathogenic
3015951	NM_017534.6(MYH2):c.4302_4303insG (p.Met1435fs)	Pathogenic
3377394	NM_017534.6(MYH2):c.985C>T (p.Gln329Ter)	Pathogenic
3606820	NM_017534.6(MYH2):c.3817C>T (p.Gln1273Ter)	Pathogenic
3623063	NM_017534.6(MYH2):c.2104_2111del (p.Asn702fs)	Pathogenic
3671674	NM_017534.6(MYH2):c.95_96del (p.Pro31_Phe32insTer)	Pathogenic
4720717	NM_017534.6(MYH2):c.1837C>T (p.Gln613Ter)	Pathogenic
4720875	NM_017534.6(MYH2):c.1253del (p.Gln418fs)	Pathogenic
4727348	NM_017534.6(MYH2):c.5138dup (p.Asp1714fs)	Pathogenic
4734856	NM_017534.6(MYH2):c.3352C>T (p.Gln1118Ter)	Pathogenic
4748128	NM_017534.6(MYH2):c.2543_2549del (p.Ser848fs)	Pathogenic
4768881	NM_017534.6(MYH2):c.5162del (p.Leu1721fs)	Pathogenic
4804918	NM_017534.6(MYH2):c.1296del (p.Ala433fs)	Pathogenic
523864	NM_017534.6(MYH2):c.3238C>T (p.Gln1080Ter)	Pathogenic
578108	NM_017534.6(MYH2):c.3014del (p.Leu1005fs)	Pathogenic
625152	NM_017534.6(MYH2):c.2377C>T (p.Arg793Ter)	Pathogenic

SpliceAI

3522 predictions. Top by Δscore:

Variant	Effect	Δscore
17:10521430:CTC:C	acceptor_gain	1.0000
17:10521431:TC:T	acceptor_gain	1.0000
17:10521432:CC:C	acceptor_gain	1.0000
17:10521432:CCTGA:C	acceptor_loss	1.0000
17:10521433:C:CC	acceptor_gain	1.0000
17:10521433:CT:C	acceptor_loss	1.0000
17:10523081:AATAC:A	donor_loss	1.0000
17:10523082:ATACT:A	donor_loss	1.0000
17:10523083:TACTT:T	donor_loss	1.0000
17:10523084:ACTTA:A	donor_loss	1.0000
17:10523085:CTTAC:C	donor_loss	1.0000
17:10523086:T:TA	donor_loss	1.0000
17:10523087:T:TG	donor_loss	1.0000
17:10523088:A:AC	donor_gain	1.0000
17:10523088:AC:A	donor_loss	1.0000
17:10523088:ACAG:A	donor_gain	1.0000
17:10523088:ACAGC:A	donor_gain	1.0000
17:10523089:C:A	donor_loss	1.0000
17:10523089:C:CG	donor_gain	1.0000
17:10523089:CA:C	donor_gain	1.0000
17:10523089:CAG:C	donor_gain	1.0000
17:10523089:CAGC:C	donor_gain	1.0000
17:10523089:CAGCC:C	donor_gain	1.0000
17:10523182:CCGT:C	acceptor_gain	1.0000
17:10523183:CGTC:C	acceptor_gain	1.0000
17:10523184:GTCT:G	acceptor_loss	1.0000
17:10523185:TCTGA:T	acceptor_loss	1.0000
17:10523186:CTGA:C	acceptor_loss	1.0000
17:10523187:T:A	acceptor_loss	1.0000
17:10523491:CCCA:C	donor_loss	1.0000

AlphaMissense

12943 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:10533519:C:T	G765E	1.000
17:10535127:C:G	R709P	1.000
17:10535134:C:G	G707R	1.000
17:10535145:C:A	G703V	1.000
17:10535145:C:T	G703D	1.000
17:10535146:C:A	G703C	1.000
17:10535146:C:G	G703R	1.000
17:10535147:G:C	N702K	1.000
17:10535147:G:T	N702K	1.000
17:10535157:A:G	L699P	1.000
17:10535306:A:C	C678W	1.000
17:10535308:A:G	C678R	1.000
17:10535310:C:A	R677M	1.000
17:10535315:A:C	F675L	1.000
17:10535315:A:T	F675L	1.000
17:10535317:A:G	F675L	1.000
17:10535349:A:G	L664P	1.000
17:10537373:G:T	A586D	1.000
17:10537675:A:G	L526P	1.000
17:10537704:G:C	F516L	1.000
17:10537704:G:T	F516L	1.000
17:10537706:A:G	F516L	1.000
17:10537719:C:A	W511C	1.000
17:10537719:C:G	W511C	1.000
17:10537721:A:G	W511R	1.000
17:10537721:A:T	W511R	1.000
17:10537761:G:C	F497L	1.000
17:10537761:G:T	F497L	1.000
17:10537762:A:C	F497C	1.000
17:10537762:A:G	F497S	1.000

dbSNP variants (sampled 300 via entrez): RS1000266108 (17:10530256 T>C), RS1000311938 (17:10538929 C>G), RS1000404244 (17:10536663 G>A), RS1000488107 (17:10532708 C>T), RS1000681292 (17:10550300 A>G), RS1000715120 (17:10534729 C>T), RS1000722293 (17:10530608 A>G), RS1000734564 (17:10550632 A>G), RS1000747890 (17:10534094 GCCA>G), RS1000810094 (17:10534504 A>C), RS1001051198 (17:10540624 G>A,T), RS1001078753 (17:10520842 T>C), RS1001288027 (17:10523034 G>A,T), RS1001385696 (17:10522161 G>A,T), RS1001417034 (17:10522551 T>A)

Disease associations

OMIM: gene MIM:160740 | disease phenotypes: MIM:605637, MIM:616649

GenCC curated gene-disease

Disease	Classification	Inheritance
myopathy, proximal, and ophthalmoplegia	Strong	Semidominant
hereditary inclusion body myopathy-joint contractures-ophthalmoplegia syndrome	Supportive	Autosomal dominant
childhood-onset autosomal recessive myopathy with external ophthalmoplegia	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
myopathy, proximal, and ophthalmoplegia	Moderate	AD
myopathy, proximal, and ophthalmoplegia	Definitive	AR

Mondo (7): myopathy, proximal, and ophthalmoplegia (MONDO:0011577), limb-girdle muscular dystrophy (MONDO:0016971), hereditary spherocytosis type 2 (MONDO:0000913), muscular dystrophy (MONDO:0020121), childhood-onset autosomal recessive myopathy with external ophthalmoplegia (MONDO:0018206), myopathy (MONDO:0005336), hereditary inclusion body myopathy-joint contractures-ophthalmoplegia syndrome (MONDO:0019195)

Orphanet (5): Childhood-onset autosomal recessive myopathy with external ophthalmoplegia (Orphanet:363677), Hereditary inclusion body myopathy-joint contractures-ophthalmoplegia syndrome (Orphanet:79091), Limb-girdle muscular dystrophy (Orphanet:263), Hereditary spherocytosis (Orphanet:822), Muscular dystrophy (Orphanet:98473)

HPO phenotypes

21 total (21 of 21 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000218	High palate
HP:0000467	Neck muscle weakness
HP:0000508	Ptosis
HP:0000602	Ophthalmoplegia
HP:0001290	Generalized hypotonia
HP:0002015	Dysphagia
HP:0002058	Myopathic facies
HP:0002460	Distal muscle weakness
HP:0002515	Waddling gait
HP:0002650	Scoliosis
HP:0002803	Congenital contracture
HP:0003198	Myopathy
HP:0003324	Generalized muscle weakness
HP:0003557	Increased variability in muscle fiber diameter
HP:0003577	Congenital onset
HP:0003691	Scapular winging
HP:0003701	Proximal muscle weakness
HP:0003803	Type 1 muscle fiber predominance
HP:0100299	Muscle fiber inclusion bodies

GWAS associations

0 associations (top):

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D009136	Muscular Dystrophies	C05.651.534.500; C10.668.491.175.500; C16.320.577
D049288	Muscular Dystrophies, Limb-Girdle	C05.651.534.500.280; C10.668.491.175.500.149; C16.320.577.280
C565311	Inclusion Body Myopathy 3, Autosomal Dominant (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295980 (SINGLE PROTEIN)

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

Binding affinities (BindingDB)

50 measured of 50 human assays (50 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(3aS)-3a-hydroxy-6,7-dimethyl-1-(2-methylquinolin-6-yl)-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	410 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-3a-hydroxy-6-methyl-1-thieno[2,3-b]pyridin-2-yl-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	680 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-3a-hydroxy-1-(2-methoxyquinolin-6-yl)-6-methyl-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	800 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-3a-hydroxy-6-methyl-1-(3-methyl-1,2-benzoxazol-6-yl)-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	820 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-3a-hydroxy-6,7-dimethyl-1-pyrazolo[1,5-a]pyridin-5-yl-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	900 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-3a-hydroxy-6,7-dimethyl-1-quinolin-6-yl-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	1000 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-3a-hydroxy-1-(2-methoxyquinolin-6-yl)-6,7-dimethyl-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	1000 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-3a-hydroxy-6-methyl-1-thieno[3,2-b]pyridin-2-yl-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	1200 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
5-[(3aS)-3a-hydroxy-6-methyl-4-oxo-2,3-dihydropyrrolo[2,3-b]quinolin-1-yl]-3-chloropyridine-2-carbonitrile	KI	1300 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-1-(2-ethylquinolin-6-yl)-3a-hydroxy-6,7-dimethyl-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	1300 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-3a-hydroxy-6,7-dimethyl-1-(2-propan-2-yl-1,3-benzothiazol-5-yl)-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	1400 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(9S)-12-(4-chlorophenyl)-5-ethyl-9-hydroxy-4-thia-2,12-diazatricyclo[7.3.0.03,7]dodeca-1,3(7),5-trien-8-one	KI	1500 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-6-fluoro-3a-hydroxy-7-methyl-1-quinolin-6-yl-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	2400 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
6-[(3aS)-3a-hydroxy-6,7-dimethyl-4-oxo-2,3-dihydropyrrolo[2,3-b]quinolin-1-yl]quinoline-2-carbonitrile	KI	2600 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(7S)-7-hydroxy-11-methyl-4-(2-methylquinolin-6-yl)-10-thia-2,4-diazatricyclo[7.3.0.03,7]dodeca-1(9),2,11-trien-8-one	KI	2800 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-1-(5-chloro-6-methoxy-3-pyridinyl)-3a-hydroxy-6,7-dimethyl-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	3000 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
2-chloro-4-[(9S)-9-hydroxy-5,6-dimethyl-8-oxo-4-thia-2,12-diazatricyclo[7.3.0.03,7]dodeca-1,3(7),5-trien-12-yl]benzonitrile	KI	3700 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-1-(2-aminoquinolin-6-yl)-3a-hydroxy-6,7-dimethyl-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	3800 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-1-(1-benzothiophen-5-yl)-3a-hydroxy-6-methyl-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	3900 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-3a-hydroxy-6,7-dimethyl-1-(5,6,7,8-tetrahydroquinolin-3-yl)-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	3900 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-1-(1-benzothiophen-6-yl)-3a-hydroxy-6-methyl-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	4300 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-6-fluoro-3a-hydroxy-7-methyl-1-(2-methyl-1-benzofuran-5-yl)-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	4400 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-1-(2-aminoquinolin-6-yl)-3a-hydroxy-6-methyl-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	4700 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-1-(1-benzofuran-5-yl)-3a-hydroxy-6-methyl-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	4800 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-1-(4-chlorophenyl)-3a-hydroxy-6-methyl-7-(trifluoromethyl)-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	4800 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-1-(1-benzofuran-5-yl)-3a-hydroxy-6-methyl-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	5000 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
4-[(15S)-15-hydroxy-16-oxo-8-thia-10,12-diazatetracyclo[7.7.0.02,7.011,15]hexadeca-1(9),2(7),10-trien-12-yl]benzonitrile	KI	5000 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-1-(3,4-dimethylphenyl)-6-fluoro-3a-hydroxy-7-methyl-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	5800 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-1-(3-chloro-4-methylphenyl)-3a-hydroxy-6-methyl-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	7700 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-3a-hydroxy-1-isoquinolin-7-yl-6-methyl-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	10000 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-1-(1-benzofuran-6-yl)-3a-hydroxy-6-methyl-7-(trifluoromethyl)-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	10000 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-1-(3,4-dimethylphenyl)-3a-hydroxy-6-methyl-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	11000 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-1-(1-benzothiophen-6-yl)-6-chloro-3a-hydroxy-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	12000 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-1-(1,3-benzothiazol-6-yl)-6-fluoro-3a-hydroxy-7-methyl-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	12000 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-1-(2-ethyl-4-pyridinyl)-3a-hydroxy-6,7-dimethyl-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	12000 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-1-(4-chloro-3-methylphenyl)-3a-hydroxy-6-methyl-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	13000 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
4-[(3aS)-6-chloro-3a-hydroxy-4-oxo-2,3-dihydropyrrolo[2,3-b]quinolin-1-yl]-2-methylbenzonitrile	KI	15000 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(15S)-15-hydroxy-12-phenyl-8-thia-10,12-diazatetracyclo[7.7.0.02,7.011,15]hexadeca-1(9),2(7),10-trien-16-one	KI	15000 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-6-fluoro-3a-hydroxy-7-methyl-1-(3-methylphenyl)-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	16000 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-3a-hydroxy-1-(2-methoxy-4-pyridinyl)-6-methyl-7-(trifluoromethyl)-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	18000 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-1-(1-benzofuran-6-yl)-3a-hydroxy-6-(trifluoromethyl)-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	20000 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
4-[(3aS)-3a-hydroxy-6-methyl-4-oxo-7-(trifluoromethyl)-2,3-dihydropyrrolo[2,3-b]quinolin-1-yl]benzonitrile	KI	20000 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-1-(1-benzothiophen-5-yl)-6-chloro-3a-hydroxy-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	22000 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-1-(3-chlorophenyl)-3a-hydroxy-6,7-dimethyl-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	23000 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(9S)-12-(1-benzofuran-6-yl)-5-ethyl-9-hydroxy-4-thia-2,12-diazatricyclo[7.3.0.03,7]dodeca-1,3(7),5-trien-8-one	KI	23000 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-1-(3-bromophenyl)-3a-hydroxy-6,7-dimethyl-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	33000 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-3a-hydroxy-1-quinolin-6-yl-6-(trifluoromethyl)-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	40000 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-3a-hydroxy-1-(2-methoxy-4-pyridinyl)-6-(trifluoromethyl)-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	60000 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(9S)-9-hydroxy-4-methyl-12-phenyl-2,4,5,12-tetrazatricyclo[7.3.0.03,7]dodeca-1,3(7),5-trien-8-one	KI	330000 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-1-[3-[(dimethylamino)methyl]quinolin-6-yl]-3a-hydroxy-6,7-dimethyl-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	400000 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, decreases expression	2
Benzo(a)pyrene	affects methylation, decreases methylation, increases mutagenesis	2
2,4,6-tribromophenol	decreases expression	1
decabromobiphenyl ether	decreases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
trichostatin A	decreases expression	1
sodium arsenite	affects binding, increases reaction	1
tetrabromobisphenol A	decreases expression	1
ML 7	decreases activity, affects localization	1
CGP 52608	affects binding, increases reaction	1
Y 27632	affects localization	1
monomethylarsonous acid	increases expression	1
blebbistatin	decreases activity	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
incobotulinumtoxinA	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Copper	affects cotreatment, decreases expression	1
Phenobarbital	increases expression	1
Silicon Dioxide	decreases expression	1
Tobacco Smoke Pollution	affects expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4155516	Binding	Inhibition of human myosin 2a ATPase activity	Medicinal Chemistry and Use of Myosin II Inhibitor ( S)-Blebbistatin and Its Derivatives. — J Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1GJ	Abcam A-549 MYH2 KO 2	Cancer cell line	Male
CVCL_B2P2	Abcam A-549 MYH2 KO 1	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01882400	PHASE4	COMPLETED	Assessment of Response to Treatment of Osteoporosis With Oral Bisphosphonates in Patients With Muscular Dystrophy
NCT00120055	PHASE4	COMPLETED	Association Between Systemic Exposure of Atorvastatin and Metabolites and Atorvastatin-induced Myotoxicity
NCT03633565	PHASE4	UNKNOWN	Comparative Study of Strategies for Management of Duchenne Myopathy (DM)
NCT03783923	PHASE3	TERMINATED	A Study of Deflazacort (Emflaza®) in Participants With Limb-Girdle Muscular Dystrophy 2I (LGMD2I)
NCT06246513	PHASE3	ACTIVE_NOT_RECRUITING	A Trial to Learn More About an Experimental Gene Therapy Called Bidridistrogene Xeboparvovec (SRP-9003) as a Possible Treatment for Limb Girdle Muscular Dystrophy 2E/R4
NCT01254019	PHASE3	COMPLETED	A Clinical Study to Assess the Efficacy and Safety of GSK2402968 in Subjects With Duchenne Muscular Dystrophy
NCT01480245	PHASE3	TERMINATED	Open Label Study of GSK2402968 in Subjects With Duchenne Muscular Dystrophy
NCT01803412	PHASE3	TERMINATED	A Study of the Safety, Tolerability & Efficacy of Long-term Administration of Drisapersen in US & Canadian Subjects
NCT01826487	PHASE3	COMPLETED	Phase 3 Study of Ataluren in Participants With Nonsense Mutation Duchenne Muscular Dystrophy (nmDMD)
NCT01890798	PHASE3	WITHDRAWN	Drisapersen Duchenne Muscular Dystrophy (DMD) Treatment Protocol
NCT02090959	PHASE3	TERMINATED	An Extension Study of Ataluren (PTC124) in Participants With Nonsense Mutation Dystrophinopathy
NCT02432885	PHASE3	COMPLETED	Myocardial Fibrosis Progression in Duchenne and Becker Muscular Dystrophy - ACE Inhibitor Therapy Trial
NCT03179631	PHASE3	COMPLETED	Long-Term Outcomes of Ataluren in Duchenne Muscular Dystrophy
NCT05126758	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Deramiocel (CAP-1002) in Ambulatory and Non-Ambulatory Patients With Duchenne Muscular Dystrophy
NCT07587242	PHASE3	NOT_YET_RECRUITING	A Phase 3 Study to Evaluate the Safety and Efficacy of AOC 1044 (Also Referred to as Delpacibart Zotadirsen) in Participants With DMD With Gene Mutations Amenable to Exon 44 Skipping
NCT07608432	PHASE3	RECRUITING	Efficacy, Safety, and Tolerability of Zeleciment Rostudirsen (DYNE-251) Administered Intravenously Every 4 Weeks in Ambulatory Participants With Duchenne Muscular Dystrophy (FORZETTO)
NCT01225614	PHASE3	UNKNOWN	Efficacy and Tolerance of Early Launching of Nocturnal Non Invasive
NCT04054375	PHASE2	COMPLETED	Weekly Steroids in Muscular Dystrophy
NCT01153932	PHASE2	COMPLETED	Phase II Doubleblind Exploratory Study of GSK2402968 in Ambulant Subjects With Duchenne Muscular Dystrophy
NCT01462292	PHASE2	COMPLETED	A Clinical Study to Assess Two Doses of GSK2402968 in Subjects With Duchenne Muscular Dystrophy (DMD)
NCT01910649	PHASE2	TERMINATED	A Phase I/II, Open Label, Escalating Dose, Pilot Study to Assess Effect, Safety, Tolerability and PK of Multiple SC Doses of Drisapersen in Patients With Duchenne Muscular Dystrophy and to Assess the Potential for IV Dosing as an Alternative Route of Administration
NCT03406780	PHASE2	COMPLETED	A Study of CAP-1002 in Ambulatory and Non-Ambulatory Patients With Duchenne Muscular Dystrophy
NCT05479981	PHASE2	COMPLETED	Extension of AOC 1001-CS1 (MARINA) Study in Adult Myotonic Dystrophy Type 1 (DM1) Patients
NCT06290713	PHASE2	RECRUITING	Vasodilator and Exercise Study for DMD (VASO-REx)
NCT06547216	PHASE2	ACTIVE_NOT_RECRUITING	Phase 2 Open-label Extension Study of AOC 1020 in Participants With Facioscapulohumeral Muscular Dystrophy (FSHD)
NCT07287189	PHASE2	RECRUITING	Phase 2 Study of SAT-3247 in Pediatric Ambulatory Patients
NCT00873782	PHASE1	COMPLETED	Safety Study of Transvenous Limb Perfusion in Human Muscular Dystrophy
NCT01344798	PHASE1	COMPLETED	Clinical Study of AAV1-gamma-sarcoglycan Gene Therapy for Limb Girdle Muscular Dystrophy Type 2C
NCT02050776	PHASE1	WITHDRAWN	Stem Cell Therapy in Limb Girdle Muscular Dystrophy
NCT02245711	PHASE1	WITHDRAWN	Cell Therapy in Limb Girdle Muscular Dystrophy
NCT05876780	PHASE1	ACTIVE_NOT_RECRUITING	A Gene Transfer Single Dose Study to Evaluate the Safety, Tolerability and Efficacy of SRP-9003 in Non-Ambulatory and Ambulatory Participants With Limb Girdle Muscular Dystrophy, Type 2E/R4 (Beta-Sarcoglycan [β-SG] Deficiency)
NCT05906251	PHASE1	TERMINATED	A Gene Transfer Study to Evaluate the Safety, Tolerability and Efficacy of SRP-6004 in Ambulatory Participants With Limb Girdle Muscular Dystrophy, Type 2B/R2 (LGMD2B/R2, Dysferlin [DYSF] Related)
NCT06747273	PHASE1	TERMINATED	Study to Evaluate the Safety, Tolerability, and Efficacy of SRP-9004 Administered by Systemic Infusion in Limb Girdle Muscular Dystrophy Type 2D/R3 Participants in the United States
NCT00494195	PHASE1	COMPLETED	Gene Transfer Therapy for Treating Children and Adults With Limb Girdle Muscular Dystrophy Type 2D (LGMD2D)
NCT00674843	PHASE1	UNKNOWN	The Efficacy of Using Far Infrared Radiation to Manage Muscular Dystrophies
NCT01128855	PHASE1	COMPLETED	A Double-blind, Escalating Dose, Randomized, Placebo-controlled Study Assessing PK, Safety, Tolerability in Non-ambulant DMD Subjects
NCT02241928	PHASE1	WITHDRAWN	Stem Cell Therapy in Muscular Dystrophy
NCT03627494	PHASE1	COMPLETED	First Time in Human (FTIH) Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Single and Repeat Doses of GSK3439171A in Healthy Subjects and to Assess Food Effect
NCT05492734	PHASE1	COMPLETED	A Study to Assess the Feasibility of Non-invasive Dried Blood Sampling
NCT05730842	PHASE1	COMPLETED	Absorption, Metabolism, Excretion and Absolute Bioavailability of EDG-5506 in Healthy Volunteers