C12ORF60

Chr 12

chromosome 12 open reading frame 60

NCBI Gene: 144608 ENSG00000182993 UniProt: Q5U649

This gene encodes a mitochondrial ribosomal protein that is essential for mitochondrial protein synthesis and ribosome assembly. Mutations cause autosomal recessive mitochondrial complex I deficiency, typically presenting in infancy with severe neurological manifestations including developmental delay, seizures, and progressive encephalopathy. The gene shows low constraint against loss-of-function variants in the general population.

Research

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

1.69

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?

1.69LOEUF

pLI 0.048

Z-score 0.63

OE 0.62 (0.25–1.69)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.01Z-score

OE missense 1.00 (0.87–1.16)

125 obs / 124.7 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.62 (0.25–1.69)

0≤0.351.4

Missense OE?1.00 (0.87–1.16)

0≤0.61.4

Synonymous OE?1.14

0≤1.21.6

LoF obs/exp: 2 / 3.2Missense obs/exp: 125 / 124.7Syn Z: -0.70

Background carrier burden — how many people carry a rare variant somewhere in C12ORF60?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 190

309 rare PASS variants

Rare truncating (LoF)

1 in 2,800

49 rare PASS variants

Rare synonymous (reference)

1 in 980

104 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for C12ORF60. 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 370	1 in 5,000
South Asian	~43k	1 in 120	1 in 1,100
Remaining (unassigned)	~30k	1 in 170	1 in 2,700
European (Finnish)	~27k	1 in 1,400	1 in 1,300
Admixed American	~22k	1 in 160	≈ 1 in 7,500
African / African American	~21k	1 in 170	1 in 1,700
East Asian	~20k	1 in 240	≈ 1 in 6,600
Ashkenazi Jewish	~13k	1 in 620	none seen
Middle Eastern	~2,884	1 in 160	none seen

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 1 coding exons well covered in gnomAD exomes and genomes.? see exons ↓