RIT1

Chr 1AD

Ras like without CAAX 1

Also known as: NS8, RIBB, RIT, ROC1

NCBI Gene: 6016ENSG00000143622UniProt: Q9C0K0OMIM: 609591

This gene encodes a member of a subfamily of Ras-related GTPases. The encoded protein is involved in regulating p38 MAPK-dependent signaling cascades related to cellular stress. This protein also cooperates with nerve growth factor to promote neuronal development and regeneration. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Feb 2012]

GeneReviewsOMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Noonan syndrome 8MIM #615355
AD
UniProtImmunodeficiency 49, severe combined
UniProtIntellectual developmental disorder with speech delay, dysmorphic facies, and T-cell abnormalities

Clinical highlights

Gene-disease validity (ClinGen)
Noonan syndrome · ADDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Gain of function is the curated mechanism (Gene2Phenotype), so a variant that simply removes the protein may not be the pathogenic class here — missense variants in functional domains often carry more weight.Curated gene-level mechanism — a prior for triage, not a per-variant call.
1
Active trials
46
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.65
LOEUF
GOF*
Mechanism· G2P
📖
GeneReview available — RIT1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?
0.65LOEUF
pLI 0.133
Z-score 2.51
OE 0.28 (0.14–0.65)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
2.08Z-score
OE missense 0.52 (0.43–0.63)
75 obs / 145.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?
LoF OE?0.28 (0.14–0.65)
0≤0.351.4
Missense OE?0.52 (0.43–0.63)
0≤0.61.4
Synonymous OE?0.98
0≤1.21.6
LoF obs/exp: 4 / 14.2Missense obs/exp: 75 / 145.4Syn Z: 0.09

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

RIT1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

VCEP specificationsRASopathyPilot
Specifications ↗Panel ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients