CHCHD6

protein-coding

coiled-coil-helix-coiled-coil-helix domain containing 6, the group of Mitochondrial contact site and cristae organizing system subunits|Protein phosphatase 1 regulatory subunits|Coiled-coil-helix-coiled-coil-helix domain containing proteins

Gene summary

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]

MANE transcript

NM_032343.3

Inheritance

—

ClinVar variants

U:39B:7

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.96

Max pathogenic AF

—

Genomic locus

chr3:126,704,240-126,960,420

External References & Databases

Ensembl (ENSG00000159685)

Transcript & Mutation Effects

hg38 • Region Span ~256.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CHCHD6 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 42

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_032343.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	1 clinvar	1 clinvar	4
missense			37 clinvar	5 clinvar		42
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	39	6	1	46

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 27 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_032343.3	RefSeq	NP_115719.1	8	MANE Select
ENST00000290913.8	Ensembl	ENSP00000290913.3	8	MANE Select
NM_001320610.2	RefSeq	NP_001307539.1	8	Standard
ENST00000503119.5	Ensembl	ENSP00000427517.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

cellular response to DNA damage stimulus
cristae formation

Molecular Function

protein binding

Cellular Component

mitochondrion
mitochondrial inner membrane
cytosol
MICOS complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000290913
Coding exons: 8
Length: 256187
Individuals with no LoFs: 125722
Homozygous LoFs: 0
Heterozygous LoFs: 26
Defined: 125748
p: 0.000103

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.616	160	140	1.15	0.00000825	1501
Missense (PolyPhen)		42	43.579	0.96377		521
Synonymous	-0.305	57	54.1	1.05	0.00000316	447
Loss of Function	0.137	13	13.5	0.960	6.58e-7	163

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000066	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00011	0.00011	rare
South Asian	0.00023	0.00023	rare
Other	0.00051	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Component of the MICOS complex, a large protein complex of the mitochondrial inner membrane that plays crucial roles in the maintenance of crista junctions, inner membrane architecture, and formation of contact sites to the outer membrane. {ECO:0000269|PubMed:22228767}.;

Recessive Scores

pRec: 0.0796

Intolerance Scores

LoFtool: 0.905
RVIS EVS: 0.75
RVIS percentile EVS: 86.65

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.847

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium