CHCHD6

Chr 3

coiled-coil-helix-coiled-coil-helix domain containing 6

Also known as: CHCM1, MICOS25, Mic25, PPP1R23

NCBI Gene: 84303 ENSG00000159685 UniProt: Q9BRQ6 OMIM: 615634

The CHCHD6 protein is a component of the MICOS complex that maintains mitochondrial inner membrane architecture and crista junctions. Mutations cause autosomal recessive mitochondrial complex IV deficiency presenting in infancy with severe neurodegeneration, developmental delay, and early lethality. This gene shows low constraint against loss-of-function variants.

OMIM ResearchSummary from RefSeq, UniProt

Involved in DNA damage response and cristae formation. Located in mitochondrial inner membrane. Part of MICOS complex. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.52

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.52LOEUF

pLI 0.000

Z-score 0.14

OE 0.96 (0.62–1.52)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.62Z-score

OE missense 1.15 (1.01–1.31)

160 obs / 139.5 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.96 (0.62–1.52)

0≤0.351.4

Missense OE?1.15 (1.01–1.31)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 13 / 13.5Missense obs/exp: 160 / 139.5Syn Z: -0.31

Background carrier burden — how many people carry a rare variant somewhere in CHCHD6?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

378 rare PASS variants

Rare truncating (LoF)

1 in 2,200

63 rare PASS variants

Rare synonymous (reference)

1 in 370

140 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CHCHD6. 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 210	1 in 2,300
South Asian	~43k	1 in 98	1 in 1,900
Remaining (unassigned)	~30k	1 in 96	1 in 640
European (Finnish)	~27k	1 in 420	≈ 1 in 6,300
Admixed American	~22k	1 in 110	1 in 4,300
African / African American	~21k	1 in 77	1 in 2,600
East Asian	~20k	1 in 110	1 in 2,300
Ashkenazi Jewish	~13k	1 in 450	none seen
Middle Eastern	~2,884	1 in 110	1 in 500

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): 7 of 8 coding exons well covered in gnomAD exomes; exon 6 marginal. Genomes: all 8.? see exons ↓