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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
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RAB3GAP1
RAB3 GTPase activating protein catalytic subunit 1
Chromosome 2 Β· 2q21.3
NCBI Gene: 22930Ensembl: ENSG00000115839.20HGNC: HGNC:17063UniProt: A0A8J9AUI2
127PubMed Papers
22Diseases
0Drugs
75Pathogenic Variants
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
endoplasmic reticulum tubular networkextracellular exosomeGolgi apparatuscis-Golgi networkWarburg micro syndrome 1Micro syndromeWarburg micro syndromeMartsolf syndrome 2
✦AI Summary

RAB3GAP1 encodes the catalytic subunit of the RAB3 GTPase-activating protein complex that plays critical roles in membrane trafficking and neurodevelopment. The protein functions as both a GTPase-activating protein (GAP) for RAB3 subfamily members and a guanine nucleotide exchange factor (GEF) for RAB18, regulating vesicular transport at the endoplasmic reticulum and Golgi apparatus 1. RAB3GAP1 is essential for autophagy regulation, modulating both basal and rapamycin-induced autophagosome formation through interactions with ATG proteins and lipid droplet organization 2. The protein promotes phagophore biogenesis by facilitating endosome-ER contact sites and creating localized environments for autophagy initiation 3. In neurons, RAB3GAP1 regulates neurite outgrowth and complexity through interactions with axon elongation factors like DOCK7 and ER-Golgi trafficking modulators like TMF1 4. Loss-of-function mutations in RAB3GAP1 cause Warburg Micro syndrome, characterized by microcephaly, intellectual disability, and ocular abnormalities 56. The protein is also implicated in cholesterol biosynthesis, as RAB3GAP1-deficient cells accumulate cholesterol precursors and show impaired de novo cholesterol synthesis 1. Additionally, RAB3GAP1 dysfunction contributes to congenital disorders of autophagy, representing a novel class of neurodevelopmental conditions 7.

Sources cited
1
RAB3GAP1 functions as GAP for RAB3 and GEF for RAB18, and its loss causes cholesterol biosynthesis defects
PMID: 37774976
2
RAB3GAP1 modulates basal and rapamycin-induced autophagy through interactions with ATG proteins
PMID: 25495476
3
RAB3GAP1 promotes phagophore biogenesis through ER-endosome contact sites
PMID: 40644301
4
RAB3GAP1 regulates neuronal morphogenesis and neurite outgrowth through interactions with DOCK7 and TMF1
PMID: 37385458
5
RAB3GAP1 mutations cause Warburg Micro syndrome with ocular and neurological abnormalities
PMID: 23176487
6
RAB3GAP1 mutations cause similar syndrome with polyneuropathy and neuronal vacuolation in animal models
PMID: 26607784
7
RAB3GAP1 dysfunction contributes to congenital disorders of autophagy
PMID: 34130600
Disease Associationsβ“˜22
Warburg micro syndrome 1Open Targets
0.81Strong
Micro syndromeOpen Targets
0.73Strong
Warburg micro syndromeOpen Targets
0.62Moderate
Martsolf syndrome 2Open Targets
0.60Moderate
genetic disorderOpen Targets
0.51Moderate
Cataract - intellectual disability - hypogonadismOpen Targets
0.37Weak
neurodegenerative diseaseOpen Targets
0.37Weak
Developmental cataractOpen Targets
0.33Weak
Abnormal corpus callosum morphologyOpen Targets
0.33Weak
Absent speechOpen Targets
0.33Weak
Bilateral microphthalmosOpen Targets
0.33Weak
cleft palateOpen Targets
0.33Weak
Cortical thickening of humeral diaphysisOpen Targets
0.33Weak
early-onset non-syndromic cataractOpen Targets
0.33Weak
Epileptic encephalopathy with global cerebral demyelinationOpen Targets
0.33Weak
hypertrichosisOpen Targets
0.33Weak
hypotonia, infantile, with psychomotor retardation and characteristic faciesOpen Targets
0.33Weak
RigidityOpen Targets
0.33Weak
Severe intellectual disabilityOpen Targets
0.33Weak
SpasticityOpen Targets
0.33Weak
Martsolf syndrome 2UniProt
Warburg micro syndrome 1UniProt
Pathogenic Variants75
NM_012233.3(RAB3GAP1):c.899+1G>APathogenic
Warburg micro syndrome 1|not provided
β˜…β˜…β˜†β˜†2026
NM_012233.3(RAB3GAP1):c.748+1G>APathogenic
Warburg micro syndrome 1|not provided|Inborn genetic diseases
β˜…β˜…β˜†β˜†2025
NM_012233.3(RAB3GAP1):c.691C>T (p.Arg231Ter)Pathogenic
not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 231
NM_012233.3(RAB3GAP1):c.1174C>T (p.Arg392Ter)Pathogenic
not provided|Warburg micro syndrome 1
β˜…β˜…β˜†β˜†2025β†’ Residue 392
NM_012233.3(RAB3GAP1):c.1039C>T (p.Arg347Ter)Pathogenic
Warburg micro syndrome 1|not provided|Warburg micro syndrome 1;Martsolf syndrome 2|Inborn genetic diseases
β˜…β˜…β˜†β˜†2025β†’ Residue 347
NM_012233.3(RAB3GAP1):c.559C>T (p.Arg187Ter)Pathogenic
Warburg micro syndrome 1|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 187
NM_012233.3(RAB3GAP1):c.18+1G>CLikely pathogenic
RAB3GAP1-related disorder|not provided
β˜…β˜…β˜†β˜†2025
NM_012233.3(RAB3GAP1):c.520C>T (p.Arg174Ter)Pathogenic
not provided|RAB3GAP1-related disorder
β˜…β˜…β˜†β˜†2024β†’ Residue 174
NM_012233.3(RAB3GAP1):c.1471C>T (p.Arg491Ter)Pathogenic
Inborn genetic diseases|not provided|RAB3GAP1-related disorder
β˜…β˜…β˜†β˜†2024β†’ Residue 491
NM_012233.3(RAB3GAP1):c.1009C>T (p.Arg337Ter)Pathogenic
not provided|Warburg micro syndrome 1
β˜…β˜…β˜†β˜†2024β†’ Residue 337
NM_012233.3(RAB3GAP1):c.68G>A (p.Trp23Ter)Pathogenic
not provided
β˜…β˜…β˜†β˜†2023β†’ Residue 23
NM_012233.3(RAB3GAP1):c.659del (p.Pro219_Leu220insTer)Pathogenic
not provided|Warburg micro syndrome 1
β˜…β˜…β˜†β˜†2023β†’ Residue 219
NM_012233.3(RAB3GAP1):c.2343_2347del (p.Pro782fs)Pathogenic
not provided
β˜…β˜…β˜†β˜†2023β†’ Residue 782
NM_012233.3(RAB3GAP1):c.630_631insC (p.Ile211fs)Pathogenic
not provided|Warburg micro syndrome 1|RAB3GAP1-related disorder
β˜…β˜…β˜†β˜†2023β†’ Residue 211
NM_012233.3(RAB3GAP1):c.1185_1186del (p.Gly396fs)Pathogenic
not provided|RAB3GAP1-related disorder
β˜…β˜…β˜†β˜†2023β†’ Residue 396
NM_012233.3(RAB3GAP1):c.519G>A (p.Trp173Ter)Pathogenic
not provided|Warburg micro syndrome 1;Martsolf syndrome 2
β˜…β˜…β˜†β˜†2023β†’ Residue 173
NM_012233.3(RAB3GAP1):c.429dup (p.Lys144Ter)Pathogenic
Warburg micro syndrome 1
β˜…β˜…β˜†β˜†2021β†’ Residue 144
NM_012233.3(RAB3GAP1):c.1908C>G (p.Tyr636Ter)Pathogenic
Warburg micro syndrome 1|not provided
β˜…β˜…β˜†β˜†2019β†’ Residue 636
NM_012233.3(RAB3GAP1):c.2642T>G (p.Leu881Ter)Pathogenic
Warburg micro syndrome 1
β˜…β˜…β˜†β˜†2015β†’ Residue 881
NM_012233.3(RAB3GAP1):c.107_114del (p.Asp36fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2026β†’ Residue 36
View on ClinVar β†—
Related Genes
DMXL1Protein interaction100%DMXL2Protein interaction94%RAB3AProtein interaction88%MADDProtein interaction88%VAPBProtein interaction73%VAPAProtein interaction73%
Tissue Expression6 tissues
Heart
100%
Brain
78%
Ovary
51%
Lung
45%
Bone Marrow
38%
Liver
31%
Gene Interaction Network
Click a node to explore
RAB3GAP1DMXL1DMXL2RAB3AMADDVAPBVAPA
PROTEIN STRUCTURE
Preparing viewer…
PDB8VYB Β· 3.37 Γ… Β· EM
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.80LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.66 [0.55–0.80]
RankingsWhere RAB3GAP1 stands among ~20K protein-coding genes
  • #3,701of 20,598
    Most Researched127 Β· top quartile
  • #981of 5,498
    Most Pathogenic Variants75 Β· top quartile
  • #6,628of 17,882
    Most Constrained (LOEUF)0.80
Genes detectedRAB3GAP1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
The spectrum of neurodevelopmental, neuromuscular and neurodegenerative disorders due to defective autophagy.
PMID: 34130600
Autophagy Β· 2022
1.00
2
RAB3GAP1, RAB3GAP2 and RAB18: disease genes in Micro and Martsolf syndromes.
PMID: 23176487
Biochem Soc Trans Β· 2012
0.90
3
A mutation in the Warburg syndrome gene, RAB3GAP1, causes a similar syndrome with polyneuropathy and neuronal vacuolation in Black Russian Terrier dogs.
PMID: 26607784
Neurobiol Dis Β· 2016
0.80
4
Replication and meta-analysis of candidate loci identified variation at RAB3GAP1 associated with keratoconus.
PMID: 23833071
Invest Ophthalmol Vis Sci Β· 2013
0.70
5
Comparative proximity biotinylation implicates the small GTPase RAB18 in sterol mobilization and biosynthesis.
PMID: 37774976
J Biol Chem Β· 2023
0.60