MYH4

protein-coding

myosin heavy chain 4, the group of Myosin heavy chains, class II

Gene summary

Enables double-stranded RNA binding activity. Involved in muscle contraction. Located in myofibril. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_017533.2

Inheritance

—

ClinVar variants

U:301B:14

Top phenotype

EBV-positive nodal T- and NK-cell lymphoma

gnomAD constraint

pLI —, LoF o/e 0.88

Max pathogenic AF

—

Genomic locus

chr17:10,443,290-10,469,559

External References & Databases

Ensembl (ENSG00000264424)

Transcript & Mutation Effects

hg38 • Region Span ~26.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MYH4 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 297

not providedTotal: 18

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_017533.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				2 clinvar	2 clinvar	4
missense			294 clinvar	6 clinvar	4 clinvar	304
nonsense			3 clinvar			3
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	301	8	6	315

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 3 of 3 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_017533.2	RefSeq	NP_060003.2	38	MANE Select
ENST00000255381.2	Ensembl	ENSP00000255381.2	38	MANE Select
XM_017024676.2	RefSeq	XP_016880165.1	38	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
myhz2	Danio rerio	Structure: muscle cell Quality: deformed abnormal

Gene / Model

Organism

Observed Phenotype

myhz2

Danio rerio

Structure: muscle cell

Quality: deformed

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Tight junction - Homo sapiens (human)

Biological Process

muscle contraction
actin filament-based movement
muscle filament sliding
ATP metabolic process

Molecular Function

microfilament motor activity
double-stranded RNA binding
calmodulin binding
ATP binding
ATPase activity

Cellular Component

muscle myosin complex
myofibril
sarcomere
myosin filament

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000255381
Coding exons: 38
Length: 26270
Individuals with no LoFs: 125039
Homozygous LoFs: 0
Heterozygous LoFs: 709
Defined: 125748
p: 0.00282

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.111	1020	1.03e+3	0.990	0.0000571	12912
Missense (PolyPhen)		418	419.9	0.99548		5425
Synonymous	0.0244	382	383	0.998	0.0000213	3514
Loss of Function	1.18	92	105	0.876	0.00000584	1242

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0040	0.0040	notable
Latino/Admixed American	0.0025	0.0023	notable
Ashkenazi Jewish	0.0061	0.0061	notable
East Asian	0.0024	0.0024	notable
Finnish	0.00065	0.00065	rare
European (Non-Finnish)	0.0033	0.0033	notable
South Asian	0.0023	0.0021	notable
Other	0.0016	0.0015	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Muscle contraction.;

Recessive Scores

pRec: 0.188

Intolerance Scores

LoFtool: 0.123
RVIS EVS: 0.14
RVIS percentile EVS: 63.62

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.653

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	High	Medium	High