MYO5A

Chr 15AR

myosin VA

Also known as: GS1, MYH12, MYO5, MYR12

NCBI Gene: 4644ENSG00000197535UniProt: Q9Y4I1

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]

Primary Disease Associations & Inheritance

Griscelli syndrome, type 1MIM #214450
AR
545
ClinVar variants
31
Pathogenic / LP
0.94
pLI score· haploinsufficient
0
Active trials
Clinical Summary— MYO5A
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Gene-Disease Validity (ClinGen)
Griscelli syndrome type 1 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
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.
📋
ClinVar Variants
31 Pathogenic / Likely Pathogenic· 247 VUS of 545 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
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?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.21 (0.15–0.29)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.72 (0.68–0.77)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.93
0≤1.21.6
LoF obs/exp: 23 / 110.5Missense obs/exp: 723 / 998.3Syn Z: 1.06

ClinVar Variant Classifications

545 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic26
Likely Pathogenic5
VUS247
Likely Benign131
Benign127
Conflicting9
26
Pathogenic
5
Likely Pathogenic
247
VUS
131
Likely Benign
127
Benign
9
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
1
23
0
26
Likely Pathogenic
0
1
4
0
5
VUS
1
229
16
1
247
Likely Benign
0
8
55
68
131
Benign
0
6
106
15
127
Conflicting
—9
Total324520484545

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

View in ClinVar →

Protein Context — Lollipop Plot

MYO5A · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

MYO5A-related Griscelli syndrome

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersSkin
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
MYOSIN VA; MYO5A
MIM #160777 · *

Griscelli syndrome, type 1

MIM #214450

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
BAG5 regulates HSPA8-mediated protein folding required for sperm head-tail coupling apparatus assembly.
Gan S et al.·EMBO Rep
2024
Griscelli syndrome type 1: a novel pathogenic variant, and review of literature.
Khorram E et al.·Mol Genet Genomics
2023Review
Clinical, Morphologic, and Genomic Findings in Spitz Tumors With RET Fusion: A Series of 31 Cases.
Donati M et al.·Mod Pathol
2025Cohort
Cardiac dysfunction related to cardiac mRNA and protein traffic impairment due to reduced unconventional motor protein myosin-5b expression.
Heimerl M et al.·Eur Heart J
2025
Central nervous system ganglioneuroblastoma harboring MYO5A-NTRK3 fusion.
Ito J et al.·Brain Tumor Pathol
2020Case report
MYO5A Frameshift Variant in a Miniature Dachshund with Coat Color Dilution and Neurological Defects Resembling Human Griscelli Syndrome Type 1.
Christen M et al.·Genes (Basel)
2021
Genomic Fusions in Pigmented Spindle Cell Nevus of Reed.
VandenBoom T et al.·Am J Surg Pathol
2018
Genome-Wide Association and Inheritance-Based Analyses Implicate Unconventional Myosin Genes in Hypoplastic Left Heart Syndrome.
Theis JL et al.·Circ Genom Precis Med
2023
Radiolabeling molecular biomarkers of invasive pituitary adenomas: a narrative review.
Marche C et al.·Pituitary
2025Review
Clinical, Morphologic, and Molecular Findings in Neurotrophic Tyrosine Receptor Kinase 3 (NTRK3) Fusion Spitz Neoplasms.
Addo AK et al.·Mod Pathol
2025Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
MYO5A-mediated stabilization promotes the acquisition of fusion competence in sealed autophagosomes.
Nambiar A et al.·EMBO J
2026🔓 Open Access
A novel, rapidly progressive ataxia due to a spontaneous Myo5a mutation in mice impairs transport proteins and alters mitochondria.
Telenson AM et al.·FASEB J
2025
Rare variant of large pediatric glioneuronal tumor with novel MYO5A::NTRK3 fusion: illustrative case.
Chenoweth D et al.·J Neurosurg Case Lessons
2024🔓 Open Access
MYO5A overexpression promotes invasion and correlates with low lymphocyte infiltration in head and neck squamous carcinoma.
Xing J et al.·BMC Cancer
2023🔓 Open Access
MYO5A Inhibition by miR-145 Acts as a Predictive Marker of Occult Neck Lymph Node Metastasis in Human Laryngeal Squamous Cell Carcinoma [Retraction].
·Onco Targets Ther
2023🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools