RRAS2

Chr 11AD

RAS related 2

Also known as: NS12, TC21

NCBI Gene: 22800 ENSG00000133818 UniProt: P62070 OMIM: 600098

This gene encodes RRAS2, a small GTPase that regulates MAPK signaling pathways and controls craniofacial development. Mutations cause Noonan syndrome 12 with autosomal dominant inheritance. The gene is highly constrained against loss-of-function variation (pLI 0.97, LOEUF 0.26), indicating that complete loss of function is likely incompatible with normal development.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the R-Ras subfamily of Ras-like small GTPases. The encoded protein associates with the plasma membrane and may function as a signal transducer. This protein may play an important role in activating signal transduction pathways that control cell proliferation. Mutations in this gene are associated with the growth of certain tumors. Pseudogenes of this gene are found on chromosomes 1 and 2. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Apr 2010]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Noonan syndrome 12MIM #618624

Ovarian carcinoma

UniProtOvarian cancer

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.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.26

LOEUF· LoF intol.

GOF*

Mechanism· G2P

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GeneReview available — RRAS2