RALGDS

Chr 9

ral guanine nucleotide dissociation stimulator

Also known as: RGDS, RGF, RalGEF

This protein functions as a guanine nucleotide exchange factor that activates RalA and RalB GTPases, playing important roles in intracellular transport and bacterial clearance through exocyst complex assembly. Pathogenic variants cause intellectual disability with seizures, hypotonia, and cerebellar atrophy, following an autosomal dominant inheritance pattern. The gene is highly constrained against loss-of-function variants, indicating that such mutations are likely to cause significant developmental effects.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 0.34
Clinical SummaryRALGDS
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.89) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
36 unique Pathogenic / Likely Pathogenic· 132 VUS of 220 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.34LOEUF
pLI 0.888
Z-score 4.89
OE 0.19 (0.110.34)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
1.47Z-score
OE missense 0.82 (0.760.89)
424 obs / 517.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.19 (0.110.34)
00.351.4
Missense OE0.82 (0.760.89)
00.61.4
Synonymous OE1.11
01.21.6
LoF obs/exp: 8 / 42.4Missense obs/exp: 424 / 517.9Syn Z: -1.23

ClinVar Variant Classifications

220 submitted variants in ClinVar

Classification Summary

Pathogenic35
Likely Pathogenic1
VUS132
Likely Benign23
Benign13
35
Pathogenic
1
Likely Pathogenic
132
VUS
23
Likely Benign
13
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
35
0
35
Likely Pathogenic
0
0
1
0
1
VUS
0
121
10
1
132
Likely Benign
0
9
1
13
23
Benign
0
1
0
12
13
Total01314726204

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

View in ClinVar →

Protein Context — Lollipop Plot

RALGDS · 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.

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Clinical Literature
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