RAB3GAP1

Chr 2

RAB3 GTPase activating protein catalytic subunit 1

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

NCBI Gene: 22930 ENSG00000115839 UniProt: Q15042

The protein functions as the catalytic subunit of a Rab3 GTPase-activating complex that regulates GTP hydrolysis by Rab proteins and has guanine nucleotide exchange factor activity toward RAB18, playing essential roles in eye and brain development. Mutations cause Warburg micro syndrome 1 and Martsolf syndrome 2, both autosomal recessive disorders affecting neurodevelopment with ocular abnormalities. The gene is highly constrained against loss-of-function variants (LOEUF 0.535), reflecting its critical developmental functions.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.54

Clinical Summary— RAB3GAP1

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Gene-Disease Validity (ClinGen)

Warburg micro syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

84 unique Pathogenic / Likely Pathogenic· 250 VUS of 639 total submissions

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GeneReview available — RAB3GAP1

Authoritative clinical overview · Recommended first read

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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

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?

1.18Z-score

OE missense 0.85 (0.79–0.92)

440 obs / 515.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.38 (0.27–0.54)

0≤0.351.4

Missense OE?0.85 (0.79–0.92)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 23 / 60.9Missense obs/exp: 440 / 515.6Syn Z: 0.27

ClinVar Variant Classifications

639 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic57

Likely Pathogenic27

VUS250

Likely Benign204

Benign55

Conflicting14

Pathogenic

Likely Pathogenic

250

VUS

204

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	49	2	6	0	57
Likely Pathogenic	25	1	1	0	27
VUS	5	201	38	6	250
Likely Benign	0	9	121	74	204
Benign	0	3	48	4	55
Conflicting	—				14
Total	79	216	214	84	607

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

View in ClinVar →

13 pathogenic / likely-pathogenic (of 27) ClinVar copy-number / structural variants overlap RAB3GAP1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →