GDI1

Chr XXLD

GDP dissociation inhibitor 1

Also known as: 1A, GDIL, MRX41, MRX48, OPHN2, RABGD1A, RABGDIA, XAP-4

NCBI Gene: 2664ENSG00000203879UniProt: P31150

GDP dissociation inhibitors are proteins that regulate the GDP-GTP exchange reaction of members of the rab family, small GTP-binding proteins of the ras superfamily, that are involved in vesicular trafficking of molecules between cellular organelles. GDIs slow the rate of dissociation of GDP from rab proteins and release GDP from membrane-bound rabs. GDI1 is expressed primarily in neural and sensory tissues. Mutations in GDI1 have been linked to X-linked nonspecific cognitive disability. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Intellectual developmental disorder, X-linked 41MIM #300849
XLD
193
ClinVar variants
74
Pathogenic / LP
0.99
pLI score· haploinsufficient
0
Active trials
Clinical Summary— GDI1
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Gene-Disease Validity (ClinGen)
non-syndromic X-linked intellectual disability · XLModerate

Moderate evidence — consider for supplementary testing

⚡
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.
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ClinVar Variants
74 Pathogenic / Likely Pathogenic· 82 VUS of 193 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
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.
0.19LOEUF
pLI 0.995
Z-score 3.65
OE 0.00 (0.00–0.19)
Highly constrained

Highly LoF-intolerant (top ~10% 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.
3.29Z-score
OE missense 0.35 (0.29–0.42)
70 obs / 201.4 exp
Constrained

Highly missense-constrained (top ~0.1%)

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.0.00 (0.00–0.19)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.35 (0.29–0.42)
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.1.24
0≤1.21.6
LoF obs/exp: 0 / 15.6Missense obs/exp: 70 / 201.4Syn Z: -1.73

ClinVar Variant Classifications

193 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic65
Likely Pathogenic9
VUS82
Likely Benign28
Benign3
Conflicting6
65
Pathogenic
9
Likely Pathogenic
82
VUS
28
Likely Benign
3
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
0
62
0
65
Likely Pathogenic
3
2
4
0
9
VUS
0
64
18
0
82
Likely Benign
0
2
3
23
28
Benign
0
0
2
1
3
Conflicting
—6
Total6688924193

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

View in ClinVar →

Protein Context — Lollipop Plot

GDI1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

GDI1-related intellectual developmental disorder

limited
Monoallelic X HemizygousLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Intellectual developmental disorder, X-linked 41

MIM #300849

Molecular basis of disorder known

X-linked dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
A microglial activity state biomarker panel differentiates FTD-granulin and Alzheimer's disease patients from controls.
Pesämaa I et al.·Mol Neurodegener
2023Cohort
The neurodevelopmental spectrum of synaptic vesicle cycling disorders.
John A et al.·J Neurochem
2021Review
RAB3 phosphorylation by pathogenic LRRK2 impairs trafficking of synaptic vesicle precursors.
Dou D et al.·J Cell Biol
2024
Comprehensive analysis of the biological functions and prognostic significance of GDI1 in breast cancer.
Yang Z et al.·Medicine (Baltimore)
2025
Genes responsible for nonspecific mental retardation.
Castellví-Bel S et al.·Mol Genet Metab
2001Review
Mutations in GDI1 and X-linked non-specific mental retardation.
Dell'Amico MC et al.·Ann Ig
2011
[Non-specific X-linked mental retardation].
Martínez-Castellano F·Rev Neurol
2006Review
Novel GDI1 mutation in a large family with nonsyndromic X-linked intellectual disability.
Strobl-Wildemann G et al.·Am J Med Genet A
2011Case report
Overexpression of GDP dissociation inhibitor 1 gene associates with the invasiveness and poor outcomes of colorectal cancer.
Xie X et al.·Bioengineered
2021
Convergence of genes and cellular pathways dysregulated in autism spectrum disorders.
Pinto D et al.·Am J Hum Genet
2014
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