FHOD3

Chr 18AD

formin 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.

OMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismADLOEUF 0.371 OMIM phenotype
Clinical SummaryFHOD3
🧬
Gene-Disease Validity (ClinGen)
hypertrophic cardiomyopathy · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.25) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.37LOEUF
pLI 0.067
Z-score 5.63
OE 0.25 (0.170.37)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.88Z-score
OE missense 0.91 (0.860.97)
742 obs / 812.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.25 (0.170.37)
00.351.4
Missense OE0.91 (0.860.97)
00.61.4
Synonymous OE1.02
01.21.6
LoF obs/exp: 16 / 65.0Missense obs/exp: 742 / 812.3Syn Z: -0.28
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveFHOD3-related hypertrophic cardiomyopathyOTHERAD
DN
0.6357th %ile
GOF
0.6053th %ile
LOF
0.3843th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

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

0 submitted variants 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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