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10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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RAB3GAP2
RAB3 GTPase activating non-catalytic protein subunit 2
Chromosome 1 Β· 1q41
NCBI Gene: 25782Ensembl: ENSG00000118873.18HGNC: HGNC:17168UniProt: Q9H2M9
104PubMed Papers
22Diseases
0Drugs
46Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
guanyl-nucleotide exchange factor activityprotein bindingsmall GTPase bindingestablishment of protein localization to endoplasmic reticulum membraneCataract - intellectual disability - hypogonadismMicro syndromeMartsolf syndromeneurodegenerative disease
✦AI Summary

RAB3GAP2 is the non-catalytic regulatory subunit of the RAB3GAP complex, which functions as a guanine nucleotide exchange factor (GEF) for RAB18 and a GTPase-activating protein (GAP) for various Rab proteins 1. The complex promotes GDP release from RAB18, converting inactive RAB18-GDP to active RAB18-GTP, and recruits RAB18 to the cis-Golgi membrane and endoplasmic reticulum where it maintains proper ER structure 1. RAB3GAP2 is essential for normal eye and brain development and modulates both basal and rapamycin-induced autophagy through effects on autophagosomal biogenesis 23. In skeletal muscle, RAB3GAP2 functions as a negative regulator of endothelial cell proliferation and angiogenesis, with lower expression associated with increased capillary-to-fiber ratio and elite endurance performance 4. RAB3GAP2 also participates in cholesterol biosynthesis through RAB18-dependent regulation of sterol mobilization 5. Biallelic RAB3GAP2 mutations cause Warburg Micro syndrome and Martsolf syndrome, autosomal recessive disorders characterized by congenital cataracts, intellectual disability, and hypogonadotropic hypogonadism 67. Disease severity correlates with mutation type, with complete loss-of-function mutations causing more severe Warburg Micro syndrome, while partially-preserved function variants cause milder Martsolf syndrome 78.

Sources cited
1
RAB3GAP2 is the regulatory subunit of the RAB3GAP complex with GEF activity toward RAB18 and GAP activity toward multiple Rab proteins
PMID: 39779760
2
RAB3GAP1 and RAB3GAP2 modulate autophagy and autophagosomal biogenesis
PMID: 25495476
3
RAB3GAP2 defects cause neurodevelopmental and neurodegenerative disorders related to autophagy dysfunction
PMID: 34130600
4
RAB3GAP2 is expressed in skeletal muscle endothelium and negatively regulates endothelial cell proliferation and angiogenesis
PMID: 41678332
5
RAB3GAP-RAB18 complex regulates cholesterol biosynthesis through interactions with sterol-modifying proteins
PMID: 37774976
6
RAB3GAP2 mutations cause Micro syndrome and Martsolf syndrome characterized by ocular and neurological abnormalities
PMID: 23176487
7
RAB3GAP2 mutations cause Warburg Micro syndrome and Martsolf syndrome with hypogonadotropic hypogonadism; severity correlates with degree of protein dysfunction
PMID: 32376645
8
RAB3GAP2 mutations account for 7% of Warburg Micro and Martsolf syndrome cases; phenotypic severity relates to mutation severity
PMID: 23420520
Disease Associationsβ“˜22
Cataract - intellectual disability - hypogonadismOpen Targets
0.80Strong
Micro syndromeOpen Targets
0.80Strong
Martsolf syndromeOpen Targets
0.72Strong
neurodegenerative diseaseOpen Targets
0.52Moderate
genetic disorderOpen Targets
0.45Moderate
Warburg micro syndromeOpen Targets
0.42Moderate
autosomal recessive spastic paraplegia type 69Open Targets
0.37Weak
Abnormality of the breastOpen Targets
0.32Weak
Breast hypertrophyOpen Targets
0.31Weak
actinic keratosisOpen Targets
0.28Weak
Neurodevelopmental delayOpen Targets
0.27Weak
esophageal atresia/tracheoesophageal fistulaOpen Targets
0.26Weak
Tracheoesophageal fistulaOpen Targets
0.26Weak
HerniaOpen Targets
0.23Weak
brain aneurysmOpen Targets
0.17Weak
ovarian dysfunctionOpen Targets
0.17Weak
microcephalyOpen Targets
0.16Weak
amenorrheaOpen Targets
0.15Weak
smoking initiationOpen Targets
0.14Weak
microphthalmiaOpen Targets
0.12Weak
Martsolf syndrome 1UniProt
Warburg micro syndrome 2UniProt
Pathogenic Variants46
NM_012414.4(RAB3GAP2):c.713-2A>CPathogenic
not provided|Warburg micro syndrome 2
β˜…β˜…β˜†β˜†2024
NM_012414.4(RAB3GAP2):c.1276C>T (p.Arg426Cys)Pathogenic
Martsolf syndrome|Martsolf syndrome;Warburg micro syndrome 2|Martsolf syndrome 1
β˜…β˜…β˜†β˜†2024β†’ Residue 426
NM_012414.4(RAB3GAP2):c.960+1G>ALikely pathogenic
Warburg micro syndrome 2;Martsolf syndrome
β˜…β˜†β˜†β˜†2025
NM_012414.4(RAB3GAP2):c.3225+1G>ALikely pathogenic
RAB3GAP2-related disorder
β˜…β˜†β˜†β˜†2025
NM_012414.4(RAB3GAP2):c.2950G>T (p.Glu984Ter)Likely pathogenic
Warburg micro syndrome 2
β˜…β˜†β˜†β˜†2025β†’ Residue 984
NM_012414.4(RAB3GAP2):c.3262-2A>GLikely pathogenic
Warburg micro syndrome 2;Martsolf syndrome
β˜…β˜†β˜†β˜†2025
NM_012414.4(RAB3GAP2):c.1715-1G>ALikely pathogenic
Martsolf syndrome;Warburg micro syndrome 2
β˜…β˜†β˜†β˜†2025
NM_012414.4(RAB3GAP2):c.2628G>A (p.Trp876Ter)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 876
NM_012414.4(RAB3GAP2):c.1348dup (p.Ser450fs)Pathogenic
Warburg micro syndrome 2;Martsolf syndrome
β˜…β˜†β˜†β˜†2025β†’ Residue 450
NM_012414.4(RAB3GAP2):c.340del (p.Met114fs)Pathogenic
Warburg micro syndrome 2;Martsolf syndrome
β˜…β˜†β˜†β˜†2024β†’ Residue 114
NM_012414.4(RAB3GAP2):c.359G>A (p.Trp120Ter)Likely pathogenic
Warburg micro syndrome 2
β˜…β˜†β˜†β˜†2024β†’ Residue 120
NM_012414.4(RAB3GAP2):c.3645+1delLikely pathogenic
Martsolf syndrome 1
β˜…β˜†β˜†β˜†2024
NM_012414.4(RAB3GAP2):c.2366_2370delinsGACTGTGGTTTT (p.Gln789fs)Pathogenic
Warburg micro syndrome 2
β˜…β˜†β˜†β˜†2023β†’ Residue 789
NM_012414.4(RAB3GAP2):c.3613del (p.Met1205fs)Pathogenic
Warburg micro syndrome 2;Martsolf syndrome
β˜…β˜†β˜†β˜†2023β†’ Residue 1205
NM_012414.4(RAB3GAP2):c.3249del (p.Arg1083fs)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 1083
NM_012414.4(RAB3GAP2):c.1201del (p.Ala400_Val401insTer)Likely pathogenic
Warburg micro syndrome 2
β˜…β˜†β˜†β˜†2023β†’ Residue 400
NM_012414.4(RAB3GAP2):c.2287_2291del (p.Ala762_Gly763insTer)Likely pathogenic
Martsolf syndrome 1
β˜…β˜†β˜†β˜†2023β†’ Residue 762
NM_012414.4(RAB3GAP2):c.1998+1G>APathogenic
Martsolf syndrome;Warburg micro syndrome 2
β˜…β˜†β˜†β˜†2022
NM_012414.4(RAB3GAP2):c.2095C>T (p.Arg699Ter)Likely pathogenic
RAB3GAP2-related disorder
β˜…β˜†β˜†β˜†2022β†’ Residue 699
NM_012414.4(RAB3GAP2):c.2091dup (p.Val698fs)Likely pathogenic
RAB3GAP2-related disorder
β˜…β˜†β˜†β˜†2022β†’ Residue 698
View on ClinVar β†—
Related Genes
DMXL1Protein interaction85%DMXL2Protein interaction85%RAB18Protein interaction82%RAB3AProtein interaction79%MADDProtein interaction79%WDR7Protein interaction79%
Tissue Expression6 tissues
Heart
100%
Brain
93%
Bone Marrow
83%
Lung
60%
Ovary
55%
Liver
54%
Gene Interaction Network
Click a node to explore
RAB3GAP2DMXL1DMXL2RAB18RAB3AMADDWDR7
PROTEIN STRUCTURE
Preparing viewer…
PDB8VYB Β· 3.37 Γ… Β· EM
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.54Moderately Constrained
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.44 [0.36–0.54]
RankingsWhere RAB3GAP2 stands among ~20K protein-coding genes
  • #4,612of 20,598
    Most Researched104 Β· top quartile
  • #1,403of 5,498
    Most Pathogenic Variants46
  • #3,362of 17,882
    Most Constrained (LOEUF)0.54 Β· top quartile
Genes detectedRAB3GAP2
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
Hypogonadotropic hypogonadism due to variants in
PMID: 32376645
Cold Spring Harb Mol Case Stud Β· 2020
0.80
4
Comparative proximity biotinylation implicates the small GTPase RAB18 in sterol mobilization and biosynthesis.
PMID: 37774976
J Biol Chem Β· 2023
0.70
5
RAB3GAP1 and RAB3GAP2 modulate basal and rapamycin-induced autophagy.
PMID: 25495476
Autophagy Β· 2014
0.60