RALGPS1

Chr 9

Ral GEF with PH domain and SH3 binding motif 1

Also known as: RALGEF2, RALGPS1A

The protein functions as a guanine nucleotide exchange factor for the small GTPase RALA and is involved in cytoskeletal organization. Loss-of-function mutations in RALGPS1 cause autosomal dominant neurodevelopmental disorder, as the gene is highly intolerant to loss-of-function variation (pLI=1.0, LOEUF=0.127). The pathogenic mechanism involves haploinsufficiency affecting Ral protein signal transduction pathways critical for normal neuronal development.

Summary from RefSeq, UniProt, Mechanism
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0
Active trials
1
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.13
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical SummaryRALGPS1
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.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.13LOEUF
pLI 1.000
Z-score 5.51
OE 0.03 (0.010.13)
Highly constrained

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

Missense Constraint
3.09Z-score
OE missense 0.51 (0.450.58)
163 obs / 318.2 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.03 (0.010.13)
00.351.4
Missense OE0.51 (0.450.58)
00.61.4
Synonymous OE0.89
01.21.6
LoF obs/exp: 1 / 37.3Missense obs/exp: 163 / 318.2Syn Z: 0.99
DN
0.4487th %ile
GOF
0.4875th %ile
LOF
0.68top 10%

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

LOFprediction above median · LOEUF 0.13

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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

RALGPS1 · 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.

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Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found