CHCHD4

coiled-coil-helix-coiled-coil-helix domain containing 4, the group of Coiled-coil-helix-coiled-coil-helix domain containing proteins

Basic information

Region (hg38): 3:14112077-14124870

Links

ENSG00000163528 ∙ NCBI:131474 ∙ OMIM:611077 ∙ HGNC:26467 ∙ Uniprot:Q8N4Q1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CHCHD4 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CHCHD4 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense			10			10
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding			3		1	4
Total	0	0	13	0	1

Variants in CHCHD4

This is a list of pathogenic ClinVar variants found in the CHCHD4 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
3-14112958-G-C		not specified	Uncertain significance (Jan 10, 2022)
3-14112970-T-C		not specified	Uncertain significance (Dec 03, 2024)
3-14113024-T-G		not specified	Uncertain significance (Jul 25, 2023)
3-14113033-G-C		not specified	Uncertain significance (Jan 21, 2025)
3-14113041-C-T		not specified	Uncertain significance (Dec 22, 2024)
3-14113042-G-A		not specified	Uncertain significance (Aug 11, 2022)
3-14113080-G-A		not specified	Uncertain significance (Dec 12, 2023)
3-14113132-C-T		not specified	Uncertain significance (Jul 12, 2023)
3-14113201-C-T			Benign (Apr 17, 2018)
3-14116443-T-C		not specified	Uncertain significance (Dec 17, 2024)
3-14116446-T-C		not specified	Uncertain significance (Nov 11, 2024)
3-14116497-T-G		not specified	Uncertain significance (Jan 20, 2023)
3-14116518-T-G		not specified	Uncertain significance (Nov 09, 2024)
3-14121926-C-T		not specified	Uncertain significance (Feb 23, 2023)
3-14121962-A-G		not specified	Uncertain significance (Feb 06, 2024)
3-14121967-G-A		not specified	Uncertain significance (May 13, 2024)
3-14124780-C-T			Benign (Jun 14, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CHCHD4	protein_coding	protein_coding	ENST00000295767	3	12791

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.187	0.767	125744	0	4	125748	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.880	63	85.9	0.733	0.00000427	1023
Missense in Polyphen		14	22.852	0.61264		295
Synonymous	-0.653	36	31.3	1.15	0.00000183	271
Loss of Function	1.66	2	6.60	0.303	3.45e-7	76

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000176	0.0000176
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Functions as chaperone and catalyzes the formation of disulfide bonds in substrate proteins, such as COX17, COX19 and MICU1 (PubMed:16185709, PubMed:26387864, PubMed:19182799, PubMed:21059946, PubMed:23186364, PubMed:23676665). Required for the import and folding of small cysteine-containing proteins (small Tim) in the mitochondrial intermembrane space (IMS). Precursor proteins to be imported into the IMS are translocated in their reduced form into the mitochondria. The oxidized form of CHCHD4/MIA40 forms a transient intermolecular disulfide bridge with the reduced precursor protein, resulting in oxidation of the precursor protein that now contains an intramolecular disulfide bond and is able to undergo folding in the IMS (PubMed:16185709, PubMed:19182799, PubMed:21059946, PubMed:23676665). Reduced CHCHD4/MIA40 is then reoxidized by GFER/ERV1 via a disulfide relay system (PubMed:23186364). Mediates formation of disulfide bond in MICU1 in the IMS, promoting formation of the MICU1-MICU2 heterodimer that regulates mitochondrial calcium uptake (PubMed:26387864). {ECO:0000269|PubMed:16185709, ECO:0000269|PubMed:19182799, ECO:0000269|PubMed:21059946, ECO:0000269|PubMed:23186364, ECO:0000269|PubMed:23676665, ECO:0000269|PubMed:26387864}.
• Pathway: Metabolism of proteins;Mitochondrial protein import (Consensus)

Recessive Scores

• pRec: 0.0959

Intolerance Scores

• loftool: 0.312
• rvis_EVS: -0.01
• rvis_percentile_EVS: 53.19

Haploinsufficiency Scores

• pHI: 0.116
• hipred: N
• hipred_score: 0.477
• ghis: 0.610

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.791

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Chchd4

Gene ontology

• Biological process: peptidyl-cysteine oxidation;protein maturation by protein folding;protein import into mitochondrial intermembrane space;'de novo' posttranslational protein folding
• Cellular component: mitochondrion;mitochondrial intermembrane space
• Molecular function: protein binding;protein disulfide oxidoreductase activity