RAB3GAP2

Chr 1AR

RAB3 GTPase activating non-catalytic protein subunit 2

Also known as: MARTS1, RAB3-GAP150, RAB3GAP150, SPG69, WARBM2, p150

RAB3GAP2 encodes the regulatory subunit of the Rab3 GTPase-activating complex, which regulates neurotransmitter vesicle trafficking and maintains endoplasmic reticulum structure, with highest expression in brain during neurodevelopment. Biallelic mutations cause Martsolf syndrome and Warburg micro syndrome, both autosomal recessive conditions involving intellectual disability, eye abnormalities, and additional developmental features. The gene is highly constrained against loss-of-function variants (pLI 0.99, LOEUF 0.29), reflecting its critical role in normal development.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.292 OMIM phenotypes
Clinical SummaryRAB3GAP2
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Gene-Disease Validity (ClinGen)
Warburg micro syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.29LOEUF
pLI 0.987
Z-score 6.85
OE 0.19 (0.130.29)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
0.87Z-score
OE missense 0.91 (0.850.97)
645 obs / 710.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.19 (0.130.29)
00.351.4
Missense OE0.91 (0.850.97)
00.61.4
Synonymous OE0.92
01.21.6
LoF obs/exp: 16 / 83.6Missense obs/exp: 645 / 710.1Syn Z: 1.05
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveRAB3GAP2-related Martsolf syndromeLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.3196th %ile
GOF
0.3094th %ile
LOF
0.75top 10%

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

RAB3GAP2 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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