FIG4 Gene
FIG4 Phosphoinositide 5-Phosphatase
Gene Information Card
| Symbol | FIG4 |
|---|---|
| Full Name | FIG4 phosphoinositide 5-phosphatase |
| Gene Type | protein-coding |
| Chromosomal Location | 6q21 |
| NCBI Gene ID | 9896 ncbi.nlm.nih.gov/gene/9896 |
| Ensembl ID | ENSG00000112357 |
| UniProt ID | Q92561 |
| OMIM ID | 609390 |
| HGNC ID | 16873 |
| Aliases | SAC3, KIAA0274, dJ249I4.1 |
Description
The FIG4 gene encodes a phosphoinositide 5-phosphatase that regulates the levels of phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2), a signaling lipid involved in endosomal trafficking and lysosomal function. Mutations in FIG4 cause Charcot-Marie-Tooth disease type 4J (CMT4J), Yunis-Varon syndrome, and amyotrophic lateral sclerosis (ALS).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Charcot-Marie-Tooth disease type 4J | Loss of FIG4 function leads to impaired endosomal trafficking and accumulation of enlarged vacuoles in neurons | OMIM #611228 |
| Yunis-Varon syndrome | Biallelic FIG4 mutations disrupt PI(3,5)P2 metabolism, causing skeletal and neurological defects | OMIM #216340 |
| Amyotrophic lateral sclerosis (ALS) | Heterozygous FIG4 variants contribute to motor neuron degeneration | ClinVar, PMID: 19201763 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 8.2 | Medium |
| Testis | 6.5 | Medium |
| Lung | 4.1 | Low |
| Liver | 3.0 | Low |
| Kidney | 5.8 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 7.1 | Embryonic kidney |
| HeLa | 5.3 | Cervical carcinoma |
| SH-SY5Y | 6.8 | Neuroblastoma |
| HepG2 | 4.0 | Hepatocellular carcinoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.122T>C (p.Ile41Thr) | Missense | Rare | Reduced phosphatase activity; associated with CMT4J |
| c.963G>A (p.Trp321*) | Nonsense | Rare | Premature truncation; loss of function |
| c.1540C>T (p.Arg514Trp) | Missense | Rare | Impaired PI(3,5)P2 regulation; linked to ALS |
| c.2086C>T (p.Arg696Cys) | Missense | Rare | Dominant-negative effect; Yunis-Varon syndrome |
Mutation functional classification
Loss of Function (LOF)
Biallelic loss-of-function mutations cause CMT4J and Yunis-Varon syndrome by disrupting PI(3,5)P2 metabolism and endosomal trafficking.
Gain of Function (GOF)
No evidence of gain-of-function mutations in FIG4.
Dominant Negative (DN)
Heterozygous missense variants (e.g., p.Arg696Cys) may exert dominant-negative effects, contributing to ALS pathogenesis.
View complete mutation data：
Gene Ontology (GO)
| • phosphatidylinositol-3 | • 5-bisphosphate 5-phosphatase activity (GO:0052629) |
| • phosphatidylinositol phosphate phosphatase activity (GO:0052742) | • endosome to lysosome transport (GO:0008333) |
| • regulation of phosphatidylinositol 3-kinase signaling (GO:0014066) |
Pathways
• Phosphatidylinositol phosphate metabolism (Reactome: R-HSA-1483255)
• Endosomal trafficking (Reactome: R-HSA-199991)
Protein Summary
FIG4 is a 907-amino acid phosphoinositide 5-phosphatase that dephosphorylates PI(3,5)P2 to PI(3)P. It forms a complex with VAC14 and PIKFYVE to regulate endosomal membrane dynamics. Loss of FIG4 function leads to enlarged vacuoles and impaired lysosomal degradation, particularly in neurons.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FIG4 Knockout HEK293 Cell Line | EDJ-KQ3972 | Human | 9896 | Details Get a Quote |
| FIG4 Knockout A-549 Cell Line | EDJ-KQ24909 | Human | 9896 | Details Get a Quote |
| FIG4 Knockout HCT 116 Cell Line | EDJ-KQ26253 | Human | 9896 | Details Get a Quote |
| FIG4 Knockout HeLa Cell Line | EDJ-KQ26254 | Human | 9896 | Details Get a Quote |
| FIG4 Knockout HAP1 Cell Line | EDC07887 | Human | 9896 | Details Get a Quote |
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