CCDC22

Chr XXLR

CCC complex scaffolding subunit CCDC22

Also known as: CXorf37, JM1, RTSC2

NCBI Gene: 28952 ENSG00000101997 UniProt: O60826 OMIM: 300859

This protein is a component of the commander complex that regulates endosomal recycling of transmembrane proteins and NF-kappa-B signaling. Mutations cause Ritscher-Schinzel syndrome 2, a syndromic X-linked intellectual disability disorder. The gene follows X-linked recessive inheritance and is highly constrained against loss-of-function variants (pLI = 1.00, LOEUF = 0.12).

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a protein containing a coiled-coil domain. The encoded protein functions in the regulation of NF-kB (nuclear factor kappa-light-chain-enhancer of activated B cells) by interacting with COMMD (copper metabolism Murr1 domain-containing) proteins. The mouse orthologous protein has been shown to bind copines, which are calcium-dependent, membrane-binding proteins that may function in calcium signaling. This human gene has been identified as a novel candidate gene for syndromic X-linked intellectual disability. [provided by RefSeq, Aug 2013]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Ritscher-Schinzel syndrome 2MIM #300963

XLR

Clinical highlights

Gene-disease validity (ClinGen)

Ritscher-Schinzel syndrome 2 · XLModerateconsider for supplementary testing

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.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

0.12

LOEUF· LoF intol.

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Mechanism

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GeneReview available — CCDC22