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| INF2 |
|---|
| Gene Symbol | INF2 |
| Full Name | Inverted Formin 2 |
| Aliases | C14FDF7, hINF2 |
| Chromosomal Location | 14q12 |
| Gene Type | Protein coding |
| NCBI Gene ID | [84623](https://www.ncbi.nlm.nih.gov/gene/84623) |
| OMIM | [614098](https://omim.org/entry/614098) |
| Ensembl ID | ENSG00000126777 |
| UniProt ID | [Q9P2R3](https://www.uniprot.org/uniprot/Q9P2R3) |
| Associated Diseases | [Charcot-Marie-Tooth disease](/diseases/charcot-marie-tooth-disease), [FSGS](/diseases/focal-segmental-glomerulosclerosis), [ALS](/diseases/ALS), Parkinson's disease |
INF2 (Inverted Formin 2) is a member of the formin family of actin-nucleating proteins. Unlike other formins that promote actin polymerization, INF2 functions as both an actin polymerizer and depolymerizer, depending on context. It plays critical roles in cytoskeletal dynamics, cell division, and organelle trafficking.
INF2 has unique structural features:
- N-terminal Diaphanous Auto-regulatory Domain (DAD): Inhibits activity
- Formin Homology 1 (FH1) domain: Proline-rich, binds profilin
- Formin Homology 2 (FH2) domain: Binds actin
- C-terminal DAD: Regulatory region
INF2 is unique among formins:
- Inverted function: Can both polymerize and depolymerize actin
- ER morphology: Regulates endoplasmic reticulum shape
- Mitochondrial dynamics: Affects mitochondrial fission
- Cytokinesis: Essential for cell division
In neurons, INF2 is important for:
- Axonal transport: Regulation of cytoskeletal tracks
- Dendritic morphology: Shapes dendritic arborization
- Synaptic function: Affects presynaptic terminals
- Mitochondrial distribution: Maintains neuronal energy requirements
INF2 is a major gene for CMT disease type 2 (demyelinating):
- Dominant mutations: Cause CMT2 with intermediate demyelination
- Glomerulopathy: Associated with FSGS
- Phenotype: Peripheral neuropathy, foot deformities
- Pathogenesis: Altered actin dynamics in Schwann cells
- Motor neuron vulnerability: INF2 mutations affect cytoskeleton
- Axonal transport defects: Altered actin regulation
- Disease progression: Role in sporadic ALS
- Mitochondrial dysfunction: INF2 affects mitochondrial dynamics
- Neuronal survival: Altered mitophagy in PD models
- Synaptic dysfunction: Effects on dopaminergic synapses
- FSGS: Focal segmental glomerulosclerosis
- Kidney disease: Secondary to CMT
INF2 is widely expressed:
| Tissue |
Expression Level |
| Brain |
High |
| Kidney |
High |
| Heart |
Moderate |
| Muscle |
Moderate |
| Peripheral nerve |
High (Schwann cells) |
In brain: neurons, astrocytes, and glial cells.
- Formin modulators: Being developed for cytoskeletal disorders
- Actin-targeting compounds: Therapeutic potential
- INF2 mutations as genetic screening for CMT
- Expression changes in neurodegenerative diseases