RAB3GAP1

Chr 2AR

RAB3 GTPase activating protein catalytic subunit 1

Also known as: MARTS2, P130, RAB3GAP, RAB3GAP130, WARBM1

NCBI Gene: 22930ENSG00000115839UniProt: Q15042

This gene encodes the catalytic subunit of a Rab GTPase activating protein. The encoded protein forms a heterodimer with a non-catalytic subunit to specifically regulate the activity of members of the Rab3 subfamily of small G proteins. This protein mediates the hydrolysis of GTP bound Rab3 to the GDP bound form. Mutations in this gene are associated with Warburg micro syndrome. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Feb 2010]

Primary Disease Associations & Inheritance

Martsolf syndrome 2MIM #619420
AR
Warburg micro syndrome 1MIM #600118
AR
567
ClinVar variants
76
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— RAB3GAP1
🧬
Gene-Disease Validity (ClinGen)
Warburg micro syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
76 Pathogenic / Likely Pathogenic· 241 VUS of 567 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.54LOEUF
pLI 0.000
Z-score 4.50
OE 0.38 (0.27–0.54)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.18Z-score
OE missense 0.85 (0.79–0.92)
440 obs / 515.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.38 (0.27–0.54)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.85 (0.79–0.92)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.97
0≤1.21.6
LoF obs/exp: 23 / 60.9Missense obs/exp: 440 / 515.6Syn Z: 0.27

ClinVar Variant Classifications

567 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic53
Likely Pathogenic23
VUS241
Likely Benign197
Benign44
Conflicting9
53
Pathogenic
23
Likely Pathogenic
241
VUS
197
Likely Benign
44
Benign
9
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
18
0
35
0
53
Likely Pathogenic
14
1
8
0
23
VUS
4
184
50
3
241
Likely Benign
0
6
119
72
197
Benign
0
0
44
0
44
Conflicting
—9
Total3619125675567

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

RAB3GAP1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

RAB3GAP1-related Warburg micro syndrome

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersEye
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Martsolf syndrome 2

MIM #619420

Molecular basis of disorder known

Autosomal recessive

Warburg micro syndrome 1

MIM #600118

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — RAB3GAP1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The spectrum of neurodevelopmental, neuromuscular and neurodegenerative disorders due to defective autophagy.
Deneubourg C et al.·Autophagy
2022
Replication and meta-analysis of candidate loci identified variation at RAB3GAP1 associated with keratoconus.
Bae HA et al.·Invest Ophthalmol Vis Sci
2013Meta-analysis
Mutation spectrum in RAB3GAP1, RAB3GAP2, and RAB18 and genotype-phenotype correlations in warburg micro syndrome and Martsolf syndrome.
Handley MT et al.·Hum Mutat
2013
Exome sequencing identifies a novel pathogenic variant in RAB3GAP1 causing Warburg Micro syndrome in a Pakistani family.
Ullah W et al.·Int J Dev Neurosci
2023
Revealing the functions of novel mutations in RAB3GAP1 in Martsolf and Warburg micro syndromes.
Koparir A et al.·Am J Med Genet A
2019Case report
Whole-Exome Sequencing and Copy Number Analysis in a Patient with Warburg Micro Syndrome.
Wang Q et al.·Genes (Basel)
2022Case report
Micro and Martsolf syndromes in 34 new patients: Refining the phenotypic spectrum and further molecular insights.
Abdel-Hamid MS et al.·Clin Genet
2020Review
Next generation sequencing in children with isolated congenital cataract.
Amanova G et al.·Eur J Ophthalmol
2025
Neuronal migration disorders: clinical, neuroradiologic and genetics aspects.
Spalice A et al.·Acta Paediatr
2009Review
Novel, homozygous RAB3GAP1 c.2606 + 1G>A, p.Glu830ValfsTer9 variant and chromosome 3q29 duplication in a Turkish individual with Warburg micro syndrome.
Geckinli B et al.·Clin Dysmorphol
2023Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools