RABGAP1

Chr 9

RAB GTPase activating protein 1

Also known as: GAPCENA, TBC1D11

The protein functions as a GTPase-activating protein for RAB6A and participates in microtubule nucleation by the centrosome and the metaphase-anaphase transition during cell division. Loss-of-function mutations in RABGAP1 cause autosomal recessive neurodevelopmental disorders. The gene is highly intolerant to loss-of-function variants, indicating that haploinsufficiency is the likely pathogenic mechanism.

OMIMResearchSummary from RefSeq, UniProt, Mechanism
LOFmechanismLOEUF 0.08
Clinical SummaryRABGAP1
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
32 unique Pathogenic / Likely Pathogenic· 150 VUS of 217 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.08LOEUF
pLI 1.000
Z-score 7.12
OE 0.02 (0.010.08)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
2.96Z-score
OE missense 0.65 (0.600.71)
368 obs / 566.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.02 (0.010.08)
00.351.4
Missense OE0.65 (0.600.71)
00.61.4
Synonymous OE0.96
01.21.6
LoF obs/exp: 1 / 61.1Missense obs/exp: 368 / 566.4Syn Z: 0.41
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
moderateRABGAP1-related neurodevelopmental disorder with microcephaly and sensorineural hearing lossOTHERAR

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

DN
0.4685th %ile
GOF
0.5267th %ile
LOF
0.65top 25%

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

217 submitted variants in ClinVar

Classification Summary

Pathogenic30
Likely Pathogenic2
VUS150
Likely Benign7
Benign1
30
Pathogenic
2
Likely Pathogenic
150
VUS
7
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
29
0
30
Likely Pathogenic
1
0
1
0
2
VUS
2
143
5
0
150
Likely Benign
0
6
0
1
7
Benign
0
0
0
1
1
Total4149352190

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

View in ClinVar →

Protein Context — Lollipop Plot

RABGAP1 · 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.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC