FHOD3 Gene - Formin Homology 2 Domain Containing 3
Key regulator of actin cytoskeleton dynamics in cardiac and skeletal muscle
Gene Information Card
| Symbol | FHOD3 |
|---|---|
| Full Name | Formin Homology 2 Domain Containing 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 18q12.2 |
| NCBI Gene ID | 80206 ncbi.nlm.nih.gov/gene/80206 |
| Ensembl ID | ENSG00000134333 |
| UniProt ID | Q2V2M9 |
| OMIM ID | 609691 |
| HGNC ID | 26178 |
| Aliases | FHOS2, KIAA1695 |
Description
FHOD3 (Formin Homology 2 Domain Containing 3) encodes a member of the formin family of proteins that regulate actin cytoskeleton dynamics. The protein promotes actin nucleation and elongation, playing a critical role in sarcomere organization in cardiac and skeletal muscle. FHOD3 is highly expressed in heart and skeletal muscle, and mutations have been associated with hypertrophic cardiomyopathy.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hypertrophic Cardiomyopathy (HCM) | Missense and truncating mutations in FHOD3 disrupt actin filament assembly, leading to sarcomere disorganization and cardiac hypertrophy. | ClinVar, OMIM |
| Dilated Cardiomyopathy (DCM) | Loss-of-function variants impair actin dynamics, reducing contractile force and causing ventricular dilation. | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 78.5 | High |
| Skeletal Muscle | 45.2 | High |
| Brain | 3.1 | Low |
| Liver | 1.8 | Low |
| Kidney | 2.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Cardiomyocytes (AC16) | 82.3 | High expression; relevant for cardiac function |
| Skeletal muscle myoblasts (C2C12) | 50.1 | High expression; differentiation-dependent |
| HEK293 | 4.2 | Low expression; non-muscle context |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1639C>T (p.Arg547Trp) | Missense | 0.001% (gnomAD) | Likely pathogenic; associated with HCM |
| c.2215C>T (p.Arg739*) | Nonsense | 0.0005% (gnomAD) | Loss-of-function; associated with DCM |
| c.2846G>A (p.Arg949Gln) | Missense | 0.002% (gnomAD) | Uncertain significance; reported in HCM |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations leading to truncated protein or nonsense-mediated decay; associated with dilated cardiomyopathy.
Gain of Function (GOF)
Not well characterized; some missense variants may enhance actin nucleation activity, potentially linked to hypertrophic cardiomyopathy.
Dominant Negative (DN)
Missense mutations that disrupt FHOD3 dimerization or actin binding may interfere with wild-type function, contributing to cardiomyopathy.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Regulation of actin cytoskeleton (KEGG:04810)
• Cardiac muscle contraction (KEGG:04260)
• Formin-mediated actin nucleation (Reactome: R-HSA-5663222)
Protein Summary
FHOD3 is a 1165-amino acid protein containing a formin homology 2 (FH2) domain essential for actin nucleation and a formin homology 1 (FH1) domain that binds profilin. It localizes to the sarcomere Z-disc and is required for myofibril assembly and maintenance. Phosphorylation by kinases such as ROCK regulates its activity. The protein is predominantly expressed in striated muscle and is critical for cardiac contractility.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FHOD3 Knockout HEK293 Cell Line | EDJ-KQ9483 | Human | 80206 | Details Get a Quote |
| FHOD3 Knockout A-549 Cell Line | EDJ-KQ36202 | Human | 80206 | Details Get a Quote |
| FHOD3 Knockout HCT 116 Cell Line | EDJ-KQ36203 | Human | 80206 | Details Get a Quote |
| FHOD3 Knockout HeLa Cell Line | EDJ-KQ36204 | Human | 80206 | Details Get a Quote |
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