RRAS

Chr 19

RAS related

Also known as: R-Ras, RRAS1

The protein encoded by this gene is a small GTPase involved in diverse processes including angiogenesis, vascular homeostasis and regeneration, cell adhesion, and neuronal axon guidance. Mutations in this gene are found in many invasive cancers. [provided by RefSeq, Jul 2015]

0
Active trials
27
Pubs (1 yr)
4
P/LP submissions
0%
P/LP missense
1.10
LOEUF
GOF*
Mechanism· G2P
Clinical SummaryRRAS
🧬
Gene-Disease Validity (ClinGen)
Noonan syndrome · ADLimited

Limited evidence — not for standalone diagnostic reporting

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
4 unique Pathogenic / Likely Pathogenic· 107 VUS of 200 total submissions
📖
GeneReview available — RRAS
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.10LOEUF
pLI 0.005
Z-score 1.37
OE 0.52 (0.271.10)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.68Z-score
OE missense 0.83 (0.710.98)
110 obs / 131.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.52 (0.271.10)
00.351.4
Missense OE0.83 (0.710.98)
00.61.4
Synonymous OE1.01
01.21.6
LoF obs/exp: 5 / 9.6Missense obs/exp: 110 / 131.8Syn Z: -0.04
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongRRAS-related atypical Noonan syndromeGOFAD
DN
0.78top 25%
GOF
0.78top 25%
LOF
0.2970th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

200 submitted variants in ClinVar

Classification Summary

Pathogenic2
Likely Pathogenic2
VUS107
Likely Benign79
Benign2
Conflicting1
2
Pathogenic
2
Likely Pathogenic
107
VUS
79
Likely Benign
2
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
2
0
2
Likely Pathogenic
0
0
2
0
2
VUS
2
95
9
1
107
Likely Benign
0
0
30
49
79
Benign
0
0
2
0
2
Conflicting
1
Total2954550193

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

View in ClinVar →

Protein Context — Lollipop Plot

RRAS · 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.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →