GDI1

Chr XXLD

GDP dissociation inhibitor 1

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

NCBI Gene: 2664 ENSG00000203879 UniProt: P31150 OMIM: 300104

GDP dissociation inhibitor 1 regulates the GDP/GTP exchange reaction of Rab proteins, which are essential for vesicular trafficking between cellular organelles. Mutations cause X-linked intellectual developmental disorder, with the gene being highly constrained against loss-of-function variants (pLI 0.99, LOEUF 0.19). The protein is expressed primarily in neural and sensory tissues and follows X-linked inheritance.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOFmechanismXLDLOEUF 0.191 OMIM phenotype

Clinical Summary— GDI1

🧬

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.

📋

ClinVar Variants

12 unique Pathogenic / Likely Pathogenic· 81 VUS of 244 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

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?

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?

LoF OE?0.00 (0.00–0.19)

0≤0.351.4

Missense OE?0.35 (0.29–0.42)

0≤0.61.4

Synonymous OE?1.24

0≤1.21.6

LoF obs/exp: 0 / 15.6Missense obs/exp: 70 / 201.4Syn Z: -1.73

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

limitedGDI1-related intellectual developmental disorderLOFXLR

This gene — mechanism propensity

0.2499th %ile

GOF

0.4282th %ile

LOF

0.71top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 75% of P/LP variants are LoF · LOEUF 0.19

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

244 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4

Likely Pathogenic8

VUS81

Likely Benign32

Benign4

Conflicting10

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	4	0	0	0	4
Likely Pathogenic	5	3	0	0	8
VUS	0	71	8	2	81
Likely Benign	0	3	4	25	32
Benign	0	0	2	2	4
Conflicting	—				10
Total	9	77	14	29	139

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

View in ClinVar →

142 pathogenic / likely-pathogenic (of 156) ClinVar copy-number / structural variants overlap GDI1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →