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…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.27

LOEUF

—

Mechanism

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

Background carrier burden — how many people carry a rare variant somewhere in C3ORF22?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 420

226 rare PASS variants

Rare truncating (LoF)

1 in 5,800

40 rare PASS variants

Rare synonymous (reference)

1 in 450

95 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for C3ORF22. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 550	1 in 8,500
South Asian	~43k	1 in 270	1 in 1,500
Remaining (unassigned)	~30k	1 in 330	1 in 4,200
European (Finnish)	~27k	1 in 1,100	≈ 1 in 27,000
Admixed American	~22k	1 in 270	≈ 1 in 7,400
African / African American	~21k	1 in 240	1 in 3,800
East Asian	~20k	1 in 200	1 in 3,900
Ashkenazi Jewish	~13k	1 in 410	none seen
Middle Eastern	~2,884	1 in 240	≈ 1 in 2,200

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 3 coding exons well covered in gnomAD exomes and genomes.? see exons ↓