RAB3GAP2: RAB3 GTPase Activating Non-Catalytic Protein Subunit 2
A key regulator of RAB3-mediated vesicle trafficking, implicated in Warburg Micro Syndrome and Martsolf Syndrome.
Gene Information Card
| Symbol | RAB3GAP2 |
|---|---|
| Full Name | RAB3 GTPase activating non-catalytic protein subunit 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 1q41 |
| NCBI Gene ID | 25782 ncbi.nlm.nih.gov/gene/25782 |
| Ensembl ID | ENSG00000118873 |
| UniProt ID | Q9H2M9 |
| OMIM ID | 609275 |
| HGNC ID | 17168 |
| Aliases | KIAA0839, p150, RAB3-GAP150 |
Description
RAB3GAP2 encodes the non-catalytic subunit of the RAB3 GTPase-activating protein (RAB3GAP) complex. This complex, together with the catalytic subunit RAB3GAP1, regulates the GTP/GDP cycle of RAB3 proteins, which are critical for calcium-dependent exocytosis of neurotransmitters and hormones. Mutations in RAB3GAP2 cause autosomal recessive Warburg Micro Syndrome and Martsolf Syndrome, characterized by intellectual disability, microcephaly, cataracts, and hypotonia.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Warburg Micro Syndrome | Loss-of-function mutations in RAB3GAP2 disrupt RAB3GAP complex activity, impairing vesicle trafficking and neurotransmitter release, leading to severe neurodevelopmental defects. | ClinVar, OMIM |
| Martsolf Syndrome | Hypomorphic mutations in RAB3GAP2 reduce but do not abolish RAB3GAP complex function, resulting in a milder phenotype with intellectual disability, cataracts, and hypotonia. | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 15.2 | Medium |
| Testis | 10.8 | Medium |
| Kidney | 8.5 | Medium |
| Liver | 6.3 | Low |
| Heart | 5.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 12.4 | Neuronal model |
| HeLa (cervical carcinoma) | 9.8 | Epithelial |
| HEK293 (embryonic kidney) | 8.1 | Common cell line |
| HepG2 (hepatocellular carcinoma) | 6.7 | Liver model |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.748C>T (p.Arg250*) | Nonsense | Rare | Loss of function; truncation of protein |
| c.1000_1001del (p.Leu334Valfs*3) | Frameshift | Rare | Loss of function; premature termination |
| c.1687C>T (p.Arg563Trp) | Missense | Rare | Likely loss of function; disrupts complex formation |
Mutation functional classification
Loss of Function (LOF)
Most reported mutations in RAB3GAP2 are loss-of-function (nonsense, frameshift, splice-site), leading to reduced or absent protein, impairing RAB3GAP complex activity and causing Warburg Micro Syndrome or Martsolf Syndrome.
Gain of Function (GOF)
No gain-of-function mutations have been reported for RAB3GAP2.
Dominant Negative (DN)
No dominant-negative mutations have been described for RAB3GAP2.
View complete mutation data：
Gene Ontology (GO)
| • GTPase activator activity | • RAB3 GTPase binding |
| • intracellular protein transport | • synaptic vesicle exocytosis |
| • regulation of exocytosis |
Pathways
• RAB3GAP complex-mediated RAB3 regulation
• Vesicle-mediated transport
• Neurotransmitter release cycle
Protein Summary
RAB3GAP2 is a 150 kDa non-catalytic subunit of the RAB3GAP heterodimer. It binds to the catalytic subunit RAB3GAP1 and is essential for complex stability and localization. The complex acts as a GTPase-activating protein (GAP) for RAB3A, RAB3B, RAB3C, and RAB3D, converting them from the active GTP-bound state to the inactive GDP-bound state, thereby regulating vesicle docking and fusion. Defects in this protein lead to impaired neurotransmitter release and neurodevelopmental disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RAB3GAP2 Knockout HEK293 Cell Line | EDJ-KQ8223 | Human | 25782 | Details Get a Quote |
| RAB3GAP2 Knockout A-549 Cell Line | EDJ-KQ34123 | Human | 25782 | Details Get a Quote |
| RAB3GAP2 Knockout HCT 116 Cell Line | EDJ-KQ34124 | Human | 25782 | Details Get a Quote |
| RAB3GAP2 Knockout HeLa Cell Line | EDJ-KQ32810 | Human | 25782 | Details Get a Quote |
