RRAGC

Chr 1AD

Ras related GTP binding C

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

NCBI Gene: 64121 ENSG00000116954 UniProt: Q9HB90 OMIM: 608267

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the GTR/RAG GTP-binding protein family. The encoded protein is a monomeric guanine nucleotide-binding protein which forms a heterodimer with RRAGA and RRAGB and is primarily localized to the cytoplasm. The encoded protein promotes intracellular localization of the mTOR complex. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2012]

OMIM ResearchGenerating clinical summary…

GOFmechanismADLOEUF 0.301 OMIM phenotype

Clinical Summary— RRAGC

⚡

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.

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.30LOEUF

pLI 0.975

Z-score 3.45

OE 0.06 (0.02–0.30)

Highly constrained

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

Missense Constraint?

2.46Z-score

OE missense 0.53 (0.45–0.62)

113 obs / 214.6 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.06 (0.02–0.30)

0≤0.351.4

Missense OE?0.53 (0.45–0.62)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

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

This gene — mechanism propensity

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.