MYH9

Chr 22AD

myosin heavy chain 9

Also known as: BDPLT6, DFNA17, EPSTS, FTNS, MATINS, MHA, NMHC-II-A, NMMHC-IIA

NCBI Gene: 4627ENSG00000100345UniProt: P35579

This gene encodes a conventional non-muscle myosin; this protein should not be confused with the unconventional myosin-9a or 9b (MYO9A or MYO9B). The encoded protein is a myosin IIA heavy chain that contains an IQ domain and a myosin head-like domain which is involved in several important functions, including cytokinesis, cell motility and maintenance of cell shape. Defects in this gene have been associated with non-syndromic sensorineural deafness autosomal dominant type 17, Epstein syndrome, Alport syndrome with macrothrombocytopenia, Sebastian syndrome, Fechtner syndrome and macrothrombocytopenia with progressive sensorineural deafness. [provided by RefSeq, Dec 2011]

Primary Disease Associations & Inheritance

Deafness, autosomal dominant 17MIM #603622
AD
Macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing lossMIM #155100
AD
572
ClinVar variants
9
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— MYH9
🧬
Gene-Disease Validity (ClinGen)
macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
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.
📋
ClinVar Variants
9 Pathogenic / Likely Pathogenic· 282 VUS of 572 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.
0.09LOEUF
pLI 1.000
Z-score 9.11
OE 0.04 (0.02–0.09)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

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.
3.47Z-score
OE missense 0.71 (0.67–0.75)
820 obs / 1151.7 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.0.04 (0.02–0.09)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.71 (0.67–0.75)
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.1.18
0≤1.21.6
LoF obs/exp: 4 / 104.4Missense obs/exp: 820 / 1151.7Syn Z: -3.16

ClinVar Variant Classifications

572 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5
Likely Pathogenic4
VUS282
Likely Benign228
Benign27
Conflicting26
5
Pathogenic
4
Likely Pathogenic
282
VUS
228
Likely Benign
27
Benign
26
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
1
2
0
5
Likely Pathogenic
0
3
1
0
4
VUS
6
234
34
8
282
Likely Benign
0
26
96
106
228
Benign
0
10
0
17
27
Conflicting
—26
Total8274133131572

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

View in ClinVar →

Protein Context — Lollipop Plot

MYH9 · protein map & ClinVar variants

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

Gene2Phenotype Curations

MYH9-related deafness

definitive
ADUndeterminedUncertain
Ear
G2P ↗

MYH9-related macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss

definitive
ADLoss Of FunctionAbsent Gene Product, Altered Gene Product Structure
Dev. DisordersEyeEar
G2P ↗
missense variantinframe deletioninframe insertion

MYH9-related elastin aggregation syndrome

moderate
ADUndeterminedAltered Gene Product Structure
Skin
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Deafness, autosomal dominant 17

MIM #603622

Molecular basis of disorder known

Autosomal dominant

Macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss

MIM #155100

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — MYH9
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The p-MYH9/USP22/HIF-1α axis promotes lenvatinib resistance and cancer stemness in hepatocellular carcinoma.
Shan Q et al.·Signal Transduct Target Ther
2024
The tumor-enriched small molecule gambogic amide suppresses glioma by targeting WDR1-dependent cytoskeleton remodeling.
Qu J et al.·Signal Transduct Target Ther
2023Functional
Update on the Use of Thrombopoietin-Receptor Agonists in Pediatrics.
Gebetsberger J et al.·Hamostaseologie
2024Review
Myosins and Hearing.
Friedman TB et al.·Adv Exp Med Biol
2020Review
OLFM4 promotes the progression of intestinal metaplasia through activation of the MYH9/GSK3β/β-catenin pathway.
Wei H et al.·Mol Cancer
2024
Novel function of MOTS-c in mitochondrial remodelling contributes to its antiviral role during HBV infection.
Lin C et al.·Gut
2024Functional
ACTN1 promotes HNSCC tumorigenesis and cisplatin resistance by enhancing MYH9-dependent degradation of GSK-3β and integrin β1-mediated phosphorylation of FAK.
Cui L et al.·J Exp Clin Cancer Res
2023
[Congenital thrombocytopenia].
Kunishima S·Rinsho Ketsueki
2018Review
Kidney Organoid Modeling of WT1 Mutations Reveals Key Regulatory Paths Underlying Podocyte Development.
Wang G et al.·Adv Sci (Weinh)
2024Functional
Targeting the SPC25/RIOK1/MYH9 Axis to Overcome Tumor Stemness and Platinum Resistance in Epithelial Ovarian Cancer.
Jiang X et al.·Adv Sci (Weinh)
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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