MYH4

Summary

MYH4 (myosin heavy chain 4, HGNC:7574) is a protein-coding gene on chromosome 17p13.1, encoding Myosin-4 (Q9Y623). Muscle contraction.

Enables double-stranded RNA binding activity. Involved in muscle contraction. Located in myofibril.

Source: NCBI Gene 4622 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 259 total
• MANE Select transcript: NM_017533

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7574
Approved symbol	MYH4
Name	myosin heavy chain 4
Location	17p13.1
Locus type	gene with protein product
Status	Approved
Aliases	MYH2B, MyHC-2B, MyHC-IIb
Ensembl gene	ENSG00000264424
Ensembl biotype	protein_coding
OMIM	160742
Entrez	4622

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000255381

RefSeq mRNA: 1 — MANE Select: NM_017533 NM_017533

CCDS: CCDS11154

Canonical transcript exons

ENST00000255381 — 40 exons

Exon	Start	End
ENSE00000855197	10447818	10448126
ENSE00000855209	10448618	10448783
ENSE00000907623	10443290	10443527
ENSE00000907639	10454941	10455077
ENSE00000907649	10457420	10457729
ENSE00000907655	10460203	10460321
ENSE00000907675	10466542	10466784
ENSE00001362985	10469288	10469336
ENSE00001363001	10469537	10469559
ENSE00002326294	10448396	10448520
ENSE00002328938	10444976	10445146
ENSE00002329629	10448864	10449047
ENSE00002330718	10462865	10462968
ENSE00002330786	10445237	10445362
ENSE00002331010	10463551	10463643
ENSE00002334772	10464681	10464708
ENSE00002336006	10460916	10461054
ENSE00002336865	10459251	10459421
ENSE00002340282	10447013	10447216
ENSE00002347702	10452416	10452506
ENSE00002349278	10454555	10454810
ENSE00002350715	10450453	10450649
ENSE00002351254	10450777	10450895
ENSE00002353818	10453152	10453328
ENSE00002355686	10451326	10451452
ENSE00002358863	10465442	10465598
ENSE00002362925	10444795	10444899
ENSE00002364139	10455614	10455731
ENSE00002378114	10455814	10455901
ENSE00002388015	10463090	10463188
ENSE00002395032	10455172	10455295
ENSE00002400258	10456485	10456555
ENSE00002407011	10451941	10452330
ENSE00002409371	10453643	10453885
ENSE00002413486	10444604	10444699
ENSE00002415932	10459952	10460101
ENSE00002416224	10464472	10464586
ENSE00002426691	10452787	10452932
ENSE00002429461	10463338	10463401
ENSE00003199984	10466273	10466416

Expression profiles

Bgee: expression breadth broad, 32 present calls, max score 93.94.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0216 / max 22.3232, expressed in 5 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
164567	0.0216	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	93.94	gold quality
vastus lateralis	UBERON:0001379	91.26	gold quality
quadriceps femoris	UBERON:0001377	90.05	gold quality
biceps brachii	UBERON:0001507	84.21	silver quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	83.13	gold quality
skeletal muscle tissue	UBERON:0001134	81.86	gold quality
deltoid	UBERON:0001476	80.70	silver quality
muscle tissue	UBERON:0002385	76.86	gold quality
gluteal muscle	UBERON:0002000	75.57	gold quality
hindlimb stylopod muscle	UBERON:0004252	73.23	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	71.90	gold quality
diaphragm	UBERON:0001103	71.21	silver quality
tibialis anterior	UBERON:0001385	71.11	silver quality
muscle organ	UBERON:0001630	68.51	gold quality
muscle of leg	UBERON:0001383	62.02	gold quality
gastrocnemius	UBERON:0001388	60.80	gold quality
heart right ventricle	UBERON:0002080	58.75	silver quality
lower lobe of lung	UBERON:0008949	58.21	silver quality
jejunum	UBERON:0002115	54.04	silver quality
pancreatic ductal cell	CL:0002079	53.29	silver quality
synovial joint	UBERON:0002217	53.22	silver quality
cortical plate	UBERON:0005343	51.21	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	50.91	gold quality
epithelial cell of pancreas	CL:0000083	50.03	gold quality
layer of synovial tissue	UBERON:0007616	49.89	gold quality
buccal mucosa cell	CL:0002336	49.80	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
hair follicle	UBERON:0002073	49.18	gold quality
oocyte	CL:0000023	49.07	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.03

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MEF2A, NFATC1, SRF, YY1

Literature-anchored findings (GeneRIF, showing 3)

• 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)
• MyHC-2b was always co-expressed with the major MyHC isoforms, not only with the fast ones (MyHC-2a and -2x) but with the slow isoform (MyHC-1) as well. (PMID:23796659)
• Transcriptional levels of MHC-I, MHC-IIa, and MHC-IIb in denervation groups were significantly down-regulated compared with controls (PMID:26059207)

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), 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)

Protein

Protein identifiers

Myosin-4 — Q9Y623 (reviewed: Q9Y623)

Alternative names: Myosin heavy chain 2b, Myosin heavy chain 4, Myosin heavy chain IIb, Myosin heavy chain, skeletal muscle, fetal

All UniProt accessions (1): Q9Y623

UniProt curated annotations — full annotation on UniProt →

Function. 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. Cytoplasm. Myofibril.

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.

RefSeq proteins (1): NP_060003* (*=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 (63 total): modified residue 46, sequence variant 8, domain 3, region of interest 2, chain 1, coiled-coil region 1, sequence conflict 1, binding site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y623-F1	74.39	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): 179–186

Post-translational modifications (46): 79, 130, 389, 391, 392, 419, 424, 625, 757, 776, 1092, 1162, 1237, 1241, 1243, 1255, 1261, 1265, 1278, 1286 …

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 124 (showing top): YAATNRNNNYNATT_UNKNOWN, HUMMERICH_BENIGN_SKIN_TUMOR_DN, KEGG_TIGHT_JUNCTION, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, CAGCTG_AP4_Q5, HUMMERICH_SKIN_CANCER_PROGRESSION_DN, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, CEBPB_01, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, TCF4_Q5, KEGG_VIRAL_MYOCARDITIS, GOBP_MUSCLE_CONTRACTION, GOBP_NUCLEOSIDE_TRIPHOSPHATE_METABOLIC_PROCESS, GOMF_CYTOSKELETAL_MOTOR_ACTIVITY, GOBP_ACTIN_MEDIATED_CELL_CONTRACTION

GO Biological Process (4): muscle contraction (GO:0006936), actin filament-based movement (GO:0030048), muscle filament sliding (GO:0030049), ATP metabolic process (GO:0046034)

GO Molecular Function (9): microfilament motor activity (GO:0000146), double-stranded RNA binding (GO:0003725), calmodulin binding (GO:0005516), ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), actin filament binding (GO:0051015), nucleotide binding (GO:0000166), cytoskeletal motor activity (GO:0003774), actin binding (GO:0003779)

GO Cellular Component (7): cytoplasm (GO:0005737), muscle myosin complex (GO:0005859), myosin II complex (GO:0016460), myofibril (GO:0030016), sarcomere (GO:0030017), myosin filament (GO:0032982), myosin complex (GO:0016459)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
ATP-dependent activity	2
cellular anatomical structure	2
contractile muscle fiber	2
myosin complex	2
muscle system process	1
actin filament-based process	1
muscle contraction	1
actin-myosin filament sliding	1
purine ribonucleotide metabolic process	1
purine ribonucleoside triphosphate metabolic process	1
cytoskeletal motor activity	1
polypeptide conformation or assembly isomerase activity	1
RNA binding	1
protein binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ribonucleoside triphosphate phosphatase activity	1
actin binding	1
protein-containing complex binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
molecular_function	1
cytoskeletal protein binding	1
intracellular anatomical structure	1
myosin II complex	1
myofibril	1
supramolecular fiber	1
actin cytoskeleton	1
protein-containing complex	1

Protein interactions and networks

STRING

1590 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MYH4	MUTYH	Q9UIF7	798
MYH4	MYOG	P15173	675
MYH4	MYOD1	P15172	647
MYH4	MYOZ1	Q9NP98	646
MYH4	TNNI2	P48788	625
MYH4	MYL2	P10916	615
MYH4	TNNI1	P19237	615
MYH4	MYF5	P13349	598
MYH4	TTN	Q8WZ42	593
MYH4	TNNT3	P45378	592
MYH4	MYL3	P08590	587
MYH4	TNNC2	P02585	585
MYH4	PAX7	P23759	573
MYH4	MYL1	P05976	569
MYH4	ACTN3	Q08043	545

IntAct

76 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
LIMS1	TYMS	psi-mi:“MI:0914”(association)	0.530
SYT3	PGK2	psi-mi:“MI:0914”(association)	0.530
HSPB8	VWA8	psi-mi:“MI:0914”(association)	0.530
TGS1	SNRNP70	psi-mi:“MI:0914”(association)	0.530
TAF6L	SUPT3H	psi-mi:“MI:0914”(association)	0.530
ESR2	FBLL1	psi-mi:“MI:0914”(association)	0.460
EIF4ENIF1	MCRIP1	psi-mi:“MI:0915”(physical association)	0.400
Kif13b	TCF3	psi-mi:“MI:0914”(association)	0.350
LDHD	METTL8	psi-mi:“MI:0914”(association)	0.350
CDCA8	DCLK1	psi-mi:“MI:0914”(association)	0.350
HIF1A	MYL1	psi-mi:“MI:0914”(association)	0.350
SIX1	EYA4	psi-mi:“MI:0914”(association)	0.350
TLE3	ATP2A1	psi-mi:“MI:0914”(association)	0.350
AKAP17A	NOS1AP	psi-mi:“MI:0914”(association)	0.350
AURKC	USP19	psi-mi:“MI:0914”(association)	0.350
TMEM260	MYH3	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

BioGRID (83): MYH4 (Affinity Capture-MS), MYH4 (Affinity Capture-MS), MYH4 (Affinity Capture-MS), MYH4 (Affinity Capture-MS), ACTN2 (Co-fractionation), MYH4 (Co-fractionation), MYH4 (Affinity Capture-MS), MYH4 (Affinity Capture-MS), MYH4 (Affinity Capture-MS), MYH4 (Affinity Capture-MS), MYH4 (Affinity Capture-MS), MYH4 (Affinity Capture-MS), MYH4 (Affinity Capture-MS), MYH4 (Affinity Capture-MS), MYH4 (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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	244
Likely benign	6
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

3716 predictions. Top by Δscore:

Variant	Effect	Δscore
17:10443525:CTC:C	acceptor_gain	1.0000
17:10443527:CCTG:C	acceptor_loss	1.0000
17:10443528:CTGA:C	acceptor_loss	1.0000
17:10444597:TAC:T	donor_loss	1.0000
17:10444598:ACT:A	donor_loss	1.0000
17:10444599:CTC:C	donor_loss	1.0000
17:10444602:A:AC	donor_gain	1.0000
17:10444602:A:T	donor_loss	1.0000
17:10444602:ACAG:A	donor_gain	1.0000
17:10444602:ACAGC:A	donor_gain	1.0000
17:10444603:C:CA	donor_gain	1.0000
17:10444603:CA:C	donor_gain	1.0000
17:10444603:CAG:C	donor_gain	1.0000
17:10444603:CAGC:C	donor_gain	1.0000
17:10444603:CAGCC:C	donor_gain	1.0000
17:10444790:GTCAC:G	donor_loss	1.0000
17:10444791:TCA:T	donor_loss	1.0000
17:10444792:CA:C	donor_loss	1.0000
17:10444793:ACCT:A	donor_loss	1.0000
17:10444794:C:CT	donor_loss	1.0000
17:10444897:CACCT:C	acceptor_loss	1.0000
17:10444898:ACCT:A	acceptor_loss	1.0000
17:10444899:CCTG:C	acceptor_loss	1.0000
17:10444900:C:A	acceptor_loss	1.0000
17:10444901:T:C	acceptor_loss	1.0000
17:10444970:ACCTA:A	donor_loss	1.0000
17:10444971:CCTAC:C	donor_loss	1.0000
17:10444973:TA:T	donor_loss	1.0000
17:10444974:A:AC	donor_gain	1.0000
17:10444974:A:T	donor_loss	1.0000

AlphaMissense

12962 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:10455675:C:G	G705R	1.000
17:10455686:C:A	G701V	1.000
17:10455686:C:T	G701D	1.000
17:10455687:C:A	G701C	1.000
17:10455687:C:G	G701R	1.000
17:10455688:G:C	N700K	1.000
17:10455688:G:T	N700K	1.000
17:10455691:A:C	C699W	1.000
17:10455693:A:G	C699R	1.000
17:10455698:A:G	L697P	1.000
17:10455842:G:C	C676W	1.000
17:10455843:C:T	C676Y	1.000
17:10455844:A:G	C676R	1.000
17:10455851:A:C	F673L	1.000
17:10455851:A:T	F673L	1.000
17:10455853:A:G	F673L	1.000
17:10455885:A:G	L662P	1.000
17:10457531:A:G	W596R	1.000
17:10457531:A:T	W596R	1.000
17:10457560:G:T	A586D	1.000
17:10457707:A:G	L537P	1.000
17:10459261:A:G	L526P	1.000
17:10459290:G:C	F516L	1.000
17:10459290:G:T	F516L	1.000
17:10459292:A:G	F516L	1.000
17:10459305:C:A	W511C	1.000
17:10459305:C:G	W511C	1.000
17:10459307:A:G	W511R	1.000
17:10459307:A:T	W511R	1.000
17:10459347:G:C	F497L	1.000

dbSNP variants (sampled 300 via entrez): RS1000053177 (17:10457977 T>C), RS1000269689 (17:10466439 G>A,C), RS1000435433 (17:10444437 T>C), RS1000635042 (17:10454153 A>G), RS1000743315 (17:10461119 G>C), RS1000868624 (17:10467948 C>A), RS1001007128 (17:10454506 A>G), RS1001302278 (17:10468304 C>T), RS1001574167 (17:10447348 T>C), RS1001797348 (17:10459162 T>C), RS1001932871 (17:10460430 A>G,T), RS1001962510 (17:10460751 C>G,T), RS1002024874 (17:10460800 C>G,T), RS1002098326 (17:10460372 A>T), RS1002235519 (17:10453465 G>A,C,T)

Disease associations

OMIM: gene MIM:160742 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression	1
CGP 52608	affects binding, increases reaction	1
Ethanol	decreases expression	1
N-Nitrosopyrrolidine	increases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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