RASGEF1A

Chr 10

RasGEF domain family member 1A

Also known as: CG4853

The RASGEF1A protein functions as a guanine nucleotide exchange factor that activates RAS family proteins (KRAS, HRAS, NRAS) and RAP2A, regulating cell migration and RAS signaling pathways. Mutations cause autosomal recessive neurodevelopmental disorder with microcephaly, seizures, and brain malformations. This gene is highly constrained against loss-of-function mutations, indicating that complete loss of protein function is likely pathogenic.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
1
Pubs (1 yr)
13
P/LP submissions
0%
P/LP missense
0.32
LOEUF· LoF intol.
Mechanism
Clinical SummaryRASGEF1A
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.97). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
13 unique Pathogenic / Likely Pathogenic· 47 VUS of 74 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.32LOEUF
pLI 0.974
Z-score 4.03
OE 0.12 (0.060.32)
Highly constrained

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

Missense Constraint
2.66Z-score
OE missense 0.56 (0.490.64)
160 obs / 286.8 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.12 (0.060.32)
00.351.4
Missense OE0.56 (0.490.64)
00.61.4
Synonymous OE0.98
01.21.6
LoF obs/exp: 3 / 24.5Missense obs/exp: 160 / 286.8Syn Z: 0.13

ClinVar Variant Classifications

74 submitted variants in ClinVar

Classification Summary

Pathogenic11
Likely Pathogenic2
VUS47
Likely Benign1
Benign1
11
Pathogenic
2
Likely Pathogenic
47
VUS
1
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
11
0
11
Likely Pathogenic
0
0
2
0
2
VUS
0
42
5
0
47
Likely Benign
0
1
0
0
1
Benign
0
0
1
0
1
Total04319062

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

View in ClinVar →

Protein Context — Lollipop Plot

RASGEF1A · 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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