CNKSR2

Chr XX-linked

connector enhancer of kinase suppressor of Ras 2

Also known as: CNK2, KSR2, MAGUIN, MRXSHG

NCBI Gene: 22866 ENSG00000149970 UniProt: Q8WXI2 OMIM: 300724

This protein functions as a scaffold protein that mediates mitogen-activated protein kinase pathways downstream from Ras and may regulate synaptic protein assembly at the postsynaptic membrane. Mutations cause X-linked syndromic intellectual developmental disorder (Houge type), inherited in an X-linked pattern. The gene is highly constrained against loss-of-function variants, indicating intolerance to protein-disrupting mutations.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a multidomain protein that functions as a scaffold protein to mediate the mitogen-activated protein kinase pathways downstream from Ras. This gene product is induced by vitamin D and inhibits apoptosis in certain cancer cells. It may also play a role in ternary complex assembly of synaptic proteins at the postsynaptic membrane and coupling of signal transduction to membrane/cytoskeletal remodeling. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2009]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Intellectual developmental disorder, X-linked syndromic, Houge typeMIM #301008

X-linked

Clinical highlights

Gene-disease validity (ClinGen)

X-linked complex neurodevelopmental disorder · XLDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

—

LOEUF

LOF

Mechanism· G2P

Some data sources returned errors (1)

gnomad: TimeoutError: The operation was aborted due to timeout