RAPGEF1

Chr 9

Rap guanine nucleotide exchange factor 1

This gene encodes a guanine nucleotide exchange factor that transduces signals from CRK to activate RAS family GTPases and is essential for nerve growth factor-induced neurite outgrowth, cell adhesion, and endothelial barrier function. The extremely high pLI score (1.0) and low LOEUF score (0.222) indicate the gene is highly intolerant to loss-of-function mutations, suggesting pathogenic variants would likely cause autosomal dominant disease. However, specific neurogenetic disorders caused by RAPGEF1 mutations have not yet been clinically characterized.

Summary from RefSeq, UniProt
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0
Active trials
5
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.22
LOEUF· LoF intol.
Mechanism
Clinical SummaryRAPGEF1
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.
Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 502 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.22LOEUF
pLI 1.000
Z-score 6.28
OE 0.12 (0.070.22)
Highly constrained

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

Missense Constraint
3.13Z-score
OE missense 0.66 (0.610.71)
431 obs / 656.7 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.12 (0.070.22)
00.351.4
Missense OE0.66 (0.610.71)
00.61.4
Synonymous OE0.94
01.21.6
LoF obs/exp: 7 / 59.1Missense obs/exp: 431 / 656.7Syn Z: 0.82

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

RAPGEF1 · 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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