MYO5A

Chr 15AR

myosin VA

Also known as: GS1, MYH12, MYO5, MYR12

NCBI Gene: 4644 ENSG00000197535 UniProt: Q9Y4I1 OMIM: 160777

This gene encodes a processive actin-based motor protein that transports melanosomes and vesicles to the plasma membrane and is involved in dendrite formation. Mutations cause Griscelli syndrome type 1, characterized by hypopigmentation and severe neurological abnormalities, inherited in an autosomal recessive pattern. The gene is highly constrained against loss-of-function variation (pLI 0.94, LOEUF 0.30), reflecting its critical role in neuronal and melanocyte function.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene is one of three myosin V heavy-chain genes, belonging to the myosin gene superfamily. Myosin V is a class of actin-based motor proteins involved in cytoplasmic vesicle transport and anchorage, spindle-pole alignment and mRNA translocation. The protein encoded by this gene is abundant in melanocytes and nerve cells. Mutations in this gene cause Griscelli syndrome type-1 (GS1) and neuroectodermal melanolysosomal disease, or Elejalde disease. [provided by RefSeq, Sep 2023]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.291 OMIM phenotype

Clinical Summary— MYO5A

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Gene-Disease Validity (ClinGen)

Griscelli syndrome type 1 · ARDefinitive

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 0.94). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

11 unique Pathogenic / Likely Pathogenic· 242 VUS of 549 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.29LOEUF

pLI 0.944

Z-score 7.71

OE 0.21 (0.15–0.29)

Highly constrained

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

Missense Constraint?

3.10Z-score

OE missense 0.72 (0.68–0.77)

723 obs / 998.3 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.21 (0.15–0.29)

0≤0.351.4

Missense OE?0.72 (0.68–0.77)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 23 / 110.5Missense obs/exp: 723 / 998.3Syn Z: 1.06

ClinVar Variant Classifications

549 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic8

Likely Pathogenic3

VUS242

Likely Benign132

Benign127

Conflicting9

Pathogenic

Likely Pathogenic

242

VUS

132

Likely Benign

127

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	6	1	1	0	8
Likely Pathogenic	2	1	0	0	3
VUS	2	232	7	1	242
Likely Benign	0	8	55	69	132
Benign	0	6	106	15	127
Conflicting	—				9
Total	10	248	169	85	521

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

View in ClinVar →

20 pathogenic / likely-pathogenic (of 28) ClinVar copy-number / structural variants overlap MYO5A — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →