VIPAS39: VPS33B Interacting Protein, Apical-Basolateral Polarity Regulator, Spe-39 Homolog
Key regulator of endosomal-lysosomal trafficking and epithelial cell polarity; associated with ARC syndrome and related disorders.
Gene Information Card
| Symbol | VIPAS39 |
|---|---|
| Full Name | VPS33B Interacting Protein, Apical-Basolateral Polarity Regulator, Spe-39 Homolog |
| Gene Type | Protein coding |
| Chromosomal Location | 14q31.3 |
| NCBI Gene ID | 63894 ncbi.nlm.nih.gov/gene/63894 |
| Ensembl ID | ENSG00000100823 |
| UniProt ID | Q9H9C1 |
| OMIM ID | 613401 |
| HGNC ID | 20347 |
| Aliases | SPE-39, hSPE-39, VIPAR, VPS33B-interacting protein, apical-basolateral polarity regulator |
Description
VIPAS39 (VPS33B Interacting Protein, Apical-Basolateral Polarity Regulator, Spe-39 Homolog) encodes a protein that interacts with VPS33B to regulate endosomal-lysosomal trafficking and maintain apical-basolateral polarity in epithelial cells. The protein is part of the HOPS (homotypic fusion and protein sorting) complex and is essential for proper lysosome biogenesis and function. Mutations in VIPAS39 cause arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome, a severe multisystem disorder.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome | Loss-of-function mutations disrupt endosomal-lysosomal trafficking, leading to impaired bile acid secretion, renal tubular dysfunction, and joint contractures. | ClinVar, OMIM |
| Cholestasis, progressive familial intrahepatic 9 | Defects in VIPAS39 impair bile canalicular formation and bile acid transport. | OMIM #619849 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Kidney | 10.2 | Medium |
| Small intestine | 8.9 | Medium |
| Pancreas | 7.3 | Low |
| Brain | 5.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver) | 14.8 | Hepatocyte model |
| HEK 293 (embryonic kidney) | 11.3 | Epithelial cell line |
| Caco-2 (colon) | 9.6 | Intestinal epithelial model |
| SH-SY5Y (neuroblastoma) | 4.2 | Neuronal model |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.743G>A (p.Arg248Gln) | Missense | Rare | Loss of VPS33B interaction; causes ARC syndrome |
| c.1A>G (p.Met1?) | Start loss | Rare | Complete loss of protein; ARC syndrome |
| c.112C>T (p.Arg38*) | Nonsense | Rare | Premature truncation; ARC syndrome |
| c.497_498del (p.Val166Alafs*5) | Frameshift | Rare | Loss of function; ARC syndrome |
Mutation functional classification
Loss of Function (LOF)
Most reported mutations are loss-of-function (nonsense, frameshift, start loss, missense disrupting VPS33B binding), leading to ARC syndrome.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported; inheritance is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Endosomal-lysosomal trafficking (HOPS complex)
• Apical-basolateral polarity establishment
• Lysosome biogenesis
Protein Summary
VIPAS39 (SPE-39) is a 492-amino acid protein that localizes to endosomes and lysosomes. It directly binds VPS33B, a class C VPS protein, to form a complex essential for endosome-lysosome fusion and lysosomal maturation. The protein also regulates epithelial cell polarity by controlling the trafficking of apical and basolateral membrane proteins. Loss of VIPAS39 function leads to defective bile canaliculi formation, renal tubular dysfunction, and impaired joint development, characteristic of ARC syndrome.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| VIPAS39 Knockout HEK293 Cell Line | EDJ-KQ15317 | Human | 63894 | Details Get a Quote |
| VIPAS39 Knockout A-549 Cell Line | EDJ-KQ47251 | Human | 63894 | Details Get a Quote |
| VIPAS39 Knockout HCT 116 Cell Line | EDJ-KQ47252 | Human | 63894 | Details Get a Quote |
| VIPAS39 Knockout HeLa Cell Line | EDJ-KQ47253 | Human | 63894 | Details Get a Quote |
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