GDI2

Chr 10

GDP dissociation inhibitor 2

Also known as: HEL-S-46e, RABGDIB

GDP dissociation inhibitor 2 regulates intracellular membrane trafficking by preventing GDP to GTP exchange of Rab proteins and negatively regulates protein transport to cilia through RAB8A inhibition. Mutations cause X-linked intellectual disability, often with additional features that may include autism spectrum disorder, seizures, and developmental delays. This gene shows high constraint against loss-of-function variants (pLI 0.85, LOEUF 0.38), indicating that such mutations are likely pathogenic.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
5
Pubs (1 yr)
25
P/LP submissions
0%
P/LP missense
0.38
LOEUF
Mechanism
Clinical SummaryGDI2
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.85) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
25 unique Pathogenic / Likely Pathogenic· 49 VUS of 98 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.38LOEUF
pLI 0.849
Z-score 3.76
OE 0.17 (0.080.38)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.72Z-score
OE missense 0.69 (0.610.79)
171 obs / 247.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.17 (0.080.38)
00.351.4
Missense OE0.69 (0.610.79)
00.61.4
Synonymous OE0.77
01.21.6
LoF obs/exp: 4 / 23.8Missense obs/exp: 171 / 247.0Syn Z: 1.70

ClinVar Variant Classifications

98 submitted variants in ClinVar

Classification Summary

Pathogenic23
Likely Pathogenic2
VUS49
Likely Benign1
Benign3
23
Pathogenic
2
Likely Pathogenic
49
VUS
1
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
23
0
23
Likely Pathogenic
0
0
2
0
2
VUS
0
39
10
0
49
Likely Benign
0
1
0
0
1
Benign
0
1
2
0
3
Total04137078

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

View in ClinVar →

Protein Context — Lollipop Plot

GDI2 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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