FHOD3

Chr 18AD

formin homology 2 domain containing 3

Also known as: CMH28, FHOS2, Formactin2

NCBI Gene: 80206 ENSG00000134775 UniProt: Q8IVF7 OMIM: 609691

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is a member of the diaphanous-related formins (DRF), and contains multiple domains, including GBD (GTPase-binding domain), DID (diaphanous inhibitory domain), FH1 (formin homology 1), FH2 (formin homology 2), and DAD (diaphanous auto-regulatory domain) domains. This protein is thought to play a role in actin filament polymerization in cardiomyocytes. Mutations in this gene have been associated with dilated cardiomyopathy (DCM), characterized by dilation of the ventricular chamber, leading to impairment of systolic pump function and subsequent heart failure. Increased levels of the protein encoded by this gene have been observed in individuals with hypertrophic cardiomyopathy (HCM). Alternative splicing results in multiple transcript variants encoding different isoforms. A muscle-specific isoform has been shown to possess a casein kinase 2 (CK2) phosphorylation site at the C-terminal end of the FH2 domain. Phosphorylation of this site alters its interaction with sequestosome 1 (SQSTM1), and targets this isoform to myofibrils, while other isoforms form cytoplasmic aggregates. [provided by RefSeq, Aug 2015]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Cardiomyopathy, familial hypertrophic, 28MIM #619402

Clinical highlights

Gene-disease validity (ClinGen)

hypertrophic cardiomyopathy · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.37

LOEUF

Mechanism· predicted