RAB3GAP1
RAB3 GTPase Activating Protein Catalytic Subunit 1
Gene Information Card
| Symbol | RAB3GAP1 |
|---|---|
| Full Name | RAB3 GTPase activating protein catalytic subunit 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 2q21.3 |
| NCBI Gene ID | 22930 ncbi.nlm.nih.gov/gene/22930 |
| Ensembl ID | ENSG00000115966 |
| UniProt ID | Q15042 |
| OMIM ID | 602536 |
| HGNC ID | 30246 |
| Aliases | KIAA0066, RAB3GAP, p150 |
Description
RAB3GAP1 encodes the catalytic subunit of the RAB3 GTPase-activating protein complex, which specifically inactivates RAB3 proteins by converting them from the active GTP-bound form to the inactive GDP-bound form. This regulation is critical for calcium-dependent exocytosis of neurotransmitters and hormones. Mutations in this gene cause Warburg Micro syndrome and Martsolf syndrome, characterized by ocular, neurological, and developmental abnormalities.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Warburg Micro syndrome | Loss-of-function mutations in RAB3GAP1 impair RAB3 inactivation, disrupting synaptic vesicle exocytosis and leading to microcephaly, microphthalmia, and congenital cataracts. | ClinVar, OMIM |
| Martsolf syndrome | Hypomorphic mutations reduce RAB3GAP1 activity, causing 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 |
| Pancreas | 8.5 | Medium |
| Liver | 6.3 | Low |
| Heart | 5.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y | 12.4 | Neuronal cell line |
| HeLa | 7.8 | Cervical carcinoma |
| HEK293 | 6.5 | Embryonic kidney |
| HepG2 | 4.2 | Hepatocellular carcinoma |
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; associated with Warburg Micro syndrome |
| c.1192G>A (p.Gly398Arg) | Missense | Rare | Impaired catalytic activity; Martsolf syndrome |
| c.1666C>T (p.Arg556Trp) | Missense | Rare | Reduced protein stability; Warburg Micro syndrome |
Mutation functional classification
Loss of Function (LOF)
Most pathogenic mutations in RAB3GAP1 are loss-of-function, leading to reduced or absent catalytic activity and impaired RAB3 inactivation.
Gain of Function (GOF)
No gain-of-function mutations have been reported for RAB3GAP1.
Dominant Negative (DN)
No dominant-negative mutations have been described; inheritance is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • GTPase activator activity | • Rab GTPase binding |
| • intracellular protein transport | • synaptic vesicle exocytosis |
| • cytosol | • Golgi apparatus |
Pathways
• RAB3-mediated exocytosis
• Neurotransmitter release cycle
Protein Summary
The RAB3GAP1 protein (150 kDa) is the catalytic subunit of the heterodimeric RAB3 GTPase-activating protein complex. It contains a conserved TBC (Tre-2/Bub2/Cdc16) domain responsible for GAP activity toward RAB3A, RAB3B, RAB3C, and RAB3D. The protein is ubiquitously expressed, with highest levels in brain and endocrine tissues, and localizes to the cytosol and Golgi apparatus. Defects in RAB3GAP1 disrupt regulated secretion, leading to neurodevelopmental and ocular disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RAB3GAP1 Knockout HEK293 Cell Line | EDJ-KQ7751 | Human | 22930 | Details Get a Quote |
| RAB3GAP1 Knockout HCT 116 Cell Line | EDJ-KQ33189 | Human | 22930 | Details Get a Quote |
| RAB3GAP1 Knockout HeLa Cell Line | EDJ-KQ33190 | Human | 22930 | Details Get a Quote |
| RAB3GAP1 Knockout A-549 Cell Line | EDJ-KQ31868 | Human | 22930 | Details Get a Quote |
