C3ORF22

Chr 3

chromosome 3 open reading frame 22

NCBI Gene: 152065 ENSG00000180697 UniProt: Q8N5N4

The function of the C3ORF22 protein is not well characterized based on the available information, with only cytoplasmic localization currently established. Clinical phenotypes associated with mutations in this gene have not been clearly defined in the provided data. The gene shows tolerance to loss-of-function variants (pLI = 0.10, LOEUF = 1.28), suggesting it may not be essential for normal development.

ResearchSummary from RefSeq

Located in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

LOEUF 1.27

Clinical Summary— C3ORF22

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Population Constraint (gnomAD)

Low constraint (pLI 0.10) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

57 VUS of 63 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.27LOEUF

pLI 0.100

Z-score 1.21

OE 0.41 (0.17–1.27)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.04Z-score

OE missense 1.01 (0.85–1.21)

87 obs / 86.0 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.41 (0.17–1.27)

0≤0.351.4

Missense OE?1.01 (0.85–1.21)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 2 / 4.9Missense obs/exp: 87 / 86.0Syn Z: 0.10

ClinVar Variant Classifications

63 submitted variants in ClinVar

ClinVar

Classification Summary

VUS57

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	57	57
Likely Benign	0	0
Benign	0	0
Total	57	57

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

13 pathogenic / likely-pathogenic (of 19) ClinVar copy-number / structural variants overlap C3ORF22 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →