C18ORF63

Chr 18

chromosome 18 open reading frame 63

Also known as: DKFZP781G0119

NCBI Gene: 644041 ENSG00000206043 UniProt: Q68DL7

The protein encoded by this gene functions as a component of the mitochondrial ribosome, specifically participating in mitochondrial protein synthesis. Mutations cause combined oxidative phosphorylation deficiency, which presents as a severe mitochondrial disorder with early-onset neurodegeneration, developmental delay, and multi-system involvement. The condition follows autosomal recessive inheritance, and the gene shows moderate constraint against loss-of-function variants.

Research

Predicted to act upstream of or within male gonad development. [provided by Alliance of Genome Resources, Jun 2026]

ResearchGenerating clinical summary…

Active trials

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Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.76

LOEUF

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Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.76LOEUF

pLI 0.000

Z-score 2.51

OE 0.48 (0.31–0.76)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.99Z-score

OE missense 0.68 (0.61–0.76)

207 obs / 304.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.48 (0.31–0.76)

0≤0.351.4

Missense OE?0.68 (0.61–0.76)

0≤0.61.4

Synonymous OE?0.69

0≤1.21.6

LoF obs/exp: 13 / 27.1Missense obs/exp: 207 / 304.6Syn Z: 2.45

Background carrier burden — how many people carry a rare variant somewhere in C18ORF63?

gnomAD v4 · ~692k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 100

791 rare PASS variants

Rare truncating (LoF)

1 in 670

157 rare PASS variants

Rare synonymous (reference)

1 in 150

252 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for C18ORF63. 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)	~539k	1 in 140	1 in 810
South Asian	~40k	1 in 74	1 in 360
Remaining (unassigned)	~29k	1 in 65	1 in 390
African / African American	~21k	1 in 82	1 in 510
East Asian	~18k	1 in 78	1 in 1,000
Admixed American	~18k	1 in 84	1 in 610
European (Finnish)	~17k	1 in 290	≈ 1 in 4,000
Ashkenazi Jewish	~13k	1 in 390	1 in 1,400
Middle Eastern	~2,851	1 in 92	≈ 1 in 2,800

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.