CCDC22

Chr XXLR

CCC complex scaffolding subunit CCDC22

Also known as: CXorf37, JM1, RTSC2

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).

OMIMResearchSummary from RefSeq, OMIM, UniProt
XLRLOEUF 0.121 OMIM phenotype
Clinical SummaryCCDC22
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Gene-Disease Validity (ClinGen)
Ritscher-Schinzel syndrome 2 · XLModerate

Moderate evidence — consider for supplementary testing

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.12LOEUF
pLI 1.000
Z-score 4.56
OE 0.00 (0.000.12)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
1.29Z-score
OE missense 0.78 (0.700.87)
211 obs / 270.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.000.12)
00.351.4
Missense OE0.78 (0.700.87)
00.61.4
Synonymous OE1.01
01.21.6
LoF obs/exp: 0 / 24.2Missense obs/exp: 211 / 270.7Syn Z: -0.09

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

CCDC22 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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