C12ORF71

Chr 12

chromosome 12 open reading frame 71

NCBI Gene: 728858 ENSG00000214700 UniProt: A8MTZ7

The C12ORF71 protein is involved in mitochondrial ribosome assembly and function. Mutations cause autosomal recessive spastic paraplegia with optic atrophy, cerebellar ataxia, and neuropathy, typically presenting in childhood to early adulthood. The gene shows low constraint against loss-of-function variants, consistent with its recessive inheritance pattern.

Research

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.72

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.72LOEUF

pLI 0.003

Z-score 0.33

OE 0.84 (0.41–1.72)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.36Z-score

OE missense 0.91 (0.79–1.06)

132 obs / 144.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.84 (0.41–1.72)

0≤0.351.4

Missense OE?0.91 (0.79–1.06)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 4 / 4.8Missense obs/exp: 132 / 144.3Syn Z: -0.11

Background carrier burden — how many people carry a rare variant somewhere in C12ORF71?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 140

321 rare PASS variants

Rare truncating (LoF)

1 in 3,300

40 rare PASS variants

Rare synonymous (reference)

1 in 390

118 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for C12ORF71. 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 230	1 in 3,500
South Asian	~43k	1 in 130	1 in 3,900
Remaining (unassigned)	~30k	1 in 160	1 in 2,700
European (Finnish)	~27k	1 in 950	1 in 4,400
Admixed American	~22k	1 in 290	≈ 1 in 7,500
African / African American	~21k	1 in 210	1 in 1,000
East Asian	~20k	1 in 320	1 in 1,800
Ashkenazi Jewish	~13k	1 in 460	none seen
Middle Eastern	~2,884	1 in 160	≈ 1 in 2,900

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