RRAGC

Chr 1AD

Ras related GTP binding C

Also known as: GTR2, LNGODS, LNGOS, RAGC, TIB929

This protein is a guanine nucleotide-binding protein that regulates mTORC1 signaling in response to amino acid availability by promoting recruitment of mTORC1 to lysosomes when in its active GDP-bound state. Mutations cause Long-Olsen-Distelmaier syndrome with autosomal dominant inheritance. The gene is highly constrained against loss-of-function variants (pLI = 0.98), indicating that such variants are likely to be pathogenic.

OMIMResearchSummary from RefSeq, OMIM, UniProt
GOFmechanismADLOEUF 0.301 OMIM phenotype
Clinical SummaryRRAGC
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.30LOEUF
pLI 0.975
Z-score 3.45
OE 0.06 (0.020.30)
Highly constrained

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

Missense Constraint
2.46Z-score
OE missense 0.53 (0.450.62)
113 obs / 214.6 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.06 (0.020.30)
00.351.4
Missense OE0.53 (0.450.62)
00.61.4
Synonymous OE0.91
01.21.6
LoF obs/exp: 1 / 15.8Missense obs/exp: 113 / 214.6Syn Z: 0.62
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
moderateRRAGC-related congenital dilated cardiomyopathy with hyperlactatemia, deranged liver function and cataractsGOFAD
DN
0.5082th %ile
GOF
0.5955th %ile
LOF
0.64top 25%

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

LOFprediction above median · LOEUF 0.30

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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

RRAGC · 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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