FHOD3
Chr 18ADformin homology 2 domain containing 3
Also known as: CMH28, FHOS2, Formactin2
FHOD3 encodes a formin protein that regulates actin filament polymerization in cardiomyocytes and controls cell morphology, cytoskeletal organization, and developmental angiogenesis. Mutations cause familial hypertrophic cardiomyopathy with autosomal dominant inheritance. The gene shows significant constraint against loss-of-function variants (LOEUF 0.374), reflecting its essential role in cardiac muscle function.
Primary Disease Associations & Inheritance
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
The highest-scoring mechanism for this gene is dominant-negative.
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.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
400 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 9 | 0 | 9 |
Likely Pathogenic | 2 | 2 | 2 | 0 | 6 |
VUS | 4 | 195 | 9 | 2 | 210 |
Likely Benign | 0 | 17 | 8 | 26 | 51 |
Benign | 0 | 4 | 79 | 13 | 96 |
Conflicting | — | 4 | |||
| Total | 6 | 218 | 107 | 41 | 376 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
FHOD3 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools