MYH10

Chr 17

myosin heavy chain 10

Also known as: NMMHC-IIB, NMMHCB

NCBI Gene: 4628 ENSG00000133026 UniProt: P35580 OMIM: 160776

This protein is a cellular myosin that functions in cytokinesis, cell shape maintenance, and cytoskeletal reorganization during cell spreading. Mutations cause autosomal dominant May-Hegglin anomaly and related macrothrombocytopenia syndromes characterized by bleeding disorders due to large platelets and low platelet counts. The gene is highly constrained against loss-of-function variants, indicating that such mutations are likely to be severe.

OMIM ResearchSummary from UniProt

This gene encodes a member of the myosin superfamily. The protein represents a conventional non-muscle myosin; it should not be confused with the unconventional myosin-10 (MYO10). Myosins are actin-dependent motor proteins with diverse functions including regulation of cytokinesis, cell motility, and cell polarity. Mutations in this gene have been associated with May-Hegglin anomaly and developmental defects in brain and heart. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.17

Clinical Summary— MYH10

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Gene-Disease Validity (ClinGen)

complex neurodevelopmental disorder with or without congenital anomalies · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

15 unique Pathogenic / Likely Pathogenic· 278 VUS of 368 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.17LOEUF

pLI 1.000

Z-score 8.96

OE 0.10 (0.07–0.17)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

5.01Z-score

OE missense 0.58 (0.55–0.62)

671 obs / 1148.4 exp

Constrained

Extremely missense-constrained (top ~0.01%)

Observed / Expected Ratios?

LoF OE?0.10 (0.07–0.17)

0≤0.351.4

Missense OE?0.58 (0.55–0.62)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 12 / 116.2Missense obs/exp: 671 / 1148.4Syn Z: 1.19

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

moderateMYH10-related multiple congenital anomaliesDNAD

This gene — mechanism propensity

0.5967th %ile

GOF

0.4283th %ile

LOF

0.57top 25%

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and dominant-negative). The Badonyi & Marsh model scores dominant-negative highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports loss-of-function (haploinsufficiency). Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOF47% of P/LP variants are LoF · LOEUF 0.17

DN1 literature citation

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Literature Evidence

DNMYH10 variant overexpression produced a dominant-negative effect on ciliary length.1

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

References

1.PMID 35980381 ↗

ClinVar Variant Classifications

368 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6

Likely Pathogenic9

VUS278

Likely Benign26

Benign16

Conflicting1

Pathogenic

Likely Pathogenic

278

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	4	2	0	0	6
Likely Pathogenic	3	6	0	0	9
VUS	19	256	2	1	278
Likely Benign	0	5	8	13	26
Benign	0	3	5	8	16
Conflicting	—				1
Total	26	272	15	22	336

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

11 pathogenic / likely-pathogenic (of 16) ClinVar copy-number / structural variants overlap MYH10 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →