CHCHD4 coiled-coil-helix-coiled-coil-helix domain containing 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: CHCHD4provided by HGNC
Official Full Name: coiled-coil-helix-coiled-coil-helix domain containing 4provided by HGNC
Primary source: HGNC:HGNC:26467
See related: Ensembl:ENSG00000163528 MIM:611077; AllianceGenome:HGNC:26467
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: MIA40; TIMM40
Summary: CHCHD4, a component of human mitochondria, belongs to a protein family whose members share 6 highly conserved cysteine residues constituting a -CXC-CX(9)C-CX(9)C- motif in the C terminus (Hofmann et al., 2005 [PubMed 16185709]).[supplied by OMIM, Mar 2008]
Expression: Ubiquitous expression in kidney (RPKM 8.0), duodenum (RPKM 6.4) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 3p25.1

Exon count:: 4

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	3	NC_000003.12 (14112077..14124870, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	3	NC_060927.1 (14114022..14126815, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	3	NC_000003.11 (14153577..14166370, complement)

Chromosome 3 - NC_000003.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

[The glutathionylation of the human mitochondrial protein MIA40 regulates ROS homeostasis].
Title: [The glutathionylation of the human mitochondrial protein MIA40 regulates ROS homeostasis].
Impaired AIF-CHCHD4 interaction and mitochondrial calcium overload contribute to auditory neuropathy spectrum disorder in patient-iPSC-derived neurons with AIFM1 variant.
Title: Impaired AIF-CHCHD4 interaction and mitochondrial calcium overload contribute to auditory neuropathy spectrum disorder in patient-iPSC-derived neurons with AIFM1 variant.
CHCHD4 (MIA40) and the mitochondrial disulfide relay system.
Title: CHCHD4 (MIA40) and the mitochondrial disulfide relay system.
AIF meets the CHCHD4/Mia40-dependent mitochondrial import pathway.
Title: AIF meets the CHCHD4/Mia40-dependent mitochondrial import pathway.
First group to discover the expression of the human CHCHD4 isoforms and first to call the human gene CHCHD4, and to clone and show the expression of its alternatively expressed CHCHD4 isoforms (CHCHD4.1 and CHCHD4.2).
Title: Human CHCHD4 mitochondrial proteins regulate cellular oxygen consumption rate and metabolism and provide a critical role in hypoxia signaling and tumor progression.
Compared to wild type control littermates, mice with a knockout of CHCHD4 exhibit reduced weight gain when fed a high-fat diet.
Title: Metabolic epistasis among apoptosis-inducing factor and the mitochondrial import factor CHCHD4.
Data show that the redox state of cytochrome c oxidase assembly protein 17 (Cox17), mitochondrial membrane transport protein Mia40 and superoxide dismutase 1 (SOD1) in the cytoplasm were directly observed with in-cell NMR spectroscopy.
Title: Direct structural evidence of protein redox regulation obtained by in-cell NMR.
our findings suggest that MIA40 reduction contributes to the effects of AIF deficiency on OXPHOS, as it may impact on the correct assembly and maintenance of the respiratory subunits.
Title: Loss of apoptosis-inducing factor critically affects MIA40 function.
results demonstrate an indispensable role for hMIA40 for the export of Fe-S clusters from mitochondria.
Title: Human mitochondrial MIA40 (CHCHD4) is a component of the Fe-S cluster export machinery.
Data indicate that poptosis-inducing factor (AIF) controls the mitochondrial import of mitochondrial membrane transport protein CHCHD4.
Title: Interaction between AIF and CHCHD4 Regulates Respiratory Chain Biogenesis.

Submit: New GeneRIF Correction See all GeneRIFs (21)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein-disulfide reductase activity	IBA Inferred from Biological aspect of Ancestor more info
enables protein-disulfide reductase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein-disulfide reductase activity	IMP Inferred from Mutant Phenotype more info	PubMed

Process	Evidence Code	Pubs
involved_in 'de novo' post-translational protein folding	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to leukemia inhibitory factor	IEA Inferred from Electronic Annotation more info
involved_in cellular response to oxidative stress	IEA Inferred from Electronic Annotation more info
involved_in mitochondrial DNA repair	IEA Inferred from Electronic Annotation more info
involved_in mitochondrial respiratory chain complex assembly	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in peptidyl-cysteine oxidation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of cellular respiration	IEA Inferred from Electronic Annotation more info
involved_in protein import into mitochondrial intermembrane space	IBA Inferred from Biological aspect of Ancestor more info
involved_in protein import into mitochondrial intermembrane space	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein maturation by protein folding	IBA Inferred from Biological aspect of Ancestor more info
involved_in protein maturation by protein folding	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of protein export from nucleus	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
is_active_in mitochondrial intermembrane space	IBA Inferred from Biological aspect of Ancestor more info
located_in mitochondrial intermembrane space	IDA Inferred from Direct Assay more info	PubMed
located_in mitochondrion	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: mitochondrial intermembrane space import and assembly protein 40

Names: coiled-coil-helix-coiled-coil-helix domain-containing protein 4; translocase of inner mitochondrial membrane 40 homolog

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001098502.2 → NP_001091972.1 mitochondrial intermembrane space import and assembly protein 40 isoform 1

See identical proteins and their annotated locations for NP_001091972.1

Status: VALIDATED

Description

Transcript Variant: This variant (1) is the predominant transcript. It does not contain an N-terminal, cleavable mitochondrial target sequence, yet experimental studies have determined that the encoded protein (isoform 1) is found within the intermembrane space of the mitochondrion.

Source sequence(s)

BC017082, BC033775, DB452249, DB501565

Consensus CDS

CCDS43054.1

UniProtKB/Swiss-Prot

A8K3Z9, Q8N4Q1, Q96AI2, Q96MY6

Related

ENSP00000380122.3, ENST00000396914.4

Conserved Domains (1) summary

pfam06747
Location:64 → 100

CHCH; CHCH domain
NM_144636.3 → NP_653237.1 mitochondrial intermembrane space import and assembly protein 40 isoform 2

See identical proteins and their annotated locations for NP_653237.1

Status: VALIDATED

Description

Transcript Variant: This variant (2) contains an alternate segment for the 5' coding region and uses a downstream start codon, compared to variant 1. Variant 2 is found at a much lower frequency than variant 1. The predicted protein (isoform 2) is longer and has a distinct and longer N-terminus, compared to isoform 1.

Source sequence(s)

AK056271, BC017082, DB452249

Consensus CDS

CCDS2617.1

Related

ENSP00000295767.5, ENST00000295767.9

Conserved Domains (1) summary

pfam06747
Location:77 → 113

CHCH; CHCH domain