CHCHD3

protein-coding

coiled-coil-helix-coiled-coil-helix domain containing 3, the group of Protein phosphatase 1 regulatory subunits|Mitochondrial contact site and cristae organizing system subunits|Coiled-coil-helix-coiled-coil-helix domain containing proteins|MicroRNA protein coding host genes

Gene summary

The protein encoded by this gene is an inner mitochondrial membrane scaffold protein. Absence of the encoded protein affects the structural integrity of mitochondrial cristae and leads to reductions in ATP production, cell growth, and oxygen consumption. This protein is part of the mitochondrial contact site and cristae organizing system (MICOS). Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2015]

MANE transcript

NM_017812.4

Inheritance

—

ClinVar variants

U:40

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.32

Max pathogenic AF

—

Genomic locus

chr7:132,784,870-133,082,090

External References & Databases

Ensembl (ENSG00000106554)

Transcript & Mutation Effects

hg38 • Region Span ~297.2 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 CHCHD3 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 33

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_017812.4. 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			1 clinvar			1
missense			36 clinvar			36
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	40	0	0	40

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 58 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_017812.4	RefSeq	NP_060282.1	8	MANE Select
ENST00000262570.10	Ensembl	ENSP00000262570.5	8	MANE Select
NM_001317177.2	RefSeq	NP_001304106.1	9	Standard
NM_001317178.2	RefSeq	NP_001304107.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Metabolism of proteins
Mitochondrial protein import

Biological Process

negative regulation of transcription by RNA polymerase II
inner mitochondrial membrane organization
mitochondrial fusion
cristae formation

Molecular Function

DNA-binding transcription repressor activity, RNA polymerase II-specific
protein binding
phosphatase binding
protein-containing complex scaffold activity

Cellular Component

nucleus
cytoplasm
mitochondrion
mitochondrial inner membrane
MICOS complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000262570
Coding exons: 8
Length: 297220
Individuals with no LoFs: 125733
Homozygous LoFs: 0
Heterozygous LoFs: 11
Defined: 125744
p: 0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.369	114	126	0.907	0.00000685	1454
Missense (PolyPhen)		35	34.333	1.0194		477
Synonymous	0.666	40	45.7	0.875	0.00000240	412
Loss of Function	2.69	6	18.5	0.325	0.00000120	188

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000026	0.000026	rare
South Asian	0.00013	0.00013	rare
Other	0.00016	0.00016	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. Has also been shown to function as a transcription factor which binds to the BAG1 promoter and represses BAG1 transcription. Plays an important role in the maintenance of the MICOS complex stability and the mitochondrial cristae morphology (PubMed:25781180). {ECO:0000269|PubMed:22567091, ECO:0000269|PubMed:25781180}.;

Recessive Scores

pRec: 0.107

Intolerance Scores

LoFtool: 0.551
RVIS EVS: 0.01
RVIS percentile EVS: 54.95

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): K
Indispensability pred.: E
Indispensability score: 0.579

Gene Damage Prediction

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