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Aliases for CHCHD4 Gene

Aliases for CHCHD4 Gene

  • Coiled-Coil-Helix-Coiled-Coil-Helix Domain Containing 4 2 3 5
  • Coiled-Coil-Helix-Coiled-Coil-Helix Domain-Containing Protein 4 3 4
  • MIA40 3 4
  • Mitochondrial Intermembrane Space Import And Assembly 40 Homolog (S. Cerevisiae) 2
  • Translocase Of Inner Mitochondrial Membrane 40 Homolog (S. Cerevisiae) 2
  • Mitochondrial Intermembrane Space Import And Assembly Protein 40 3
  • Translocase Of Inner Mitochondrial Membrane 40 Homolog 3
  • TIMM40 3

External Ids for CHCHD4 Gene

Previous GeneCards Identifiers for CHCHD4 Gene

  • GC03M014128
  • GC03M014153

Summaries for CHCHD4 Gene

Entrez Gene Summary for CHCHD4 Gene

  • 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]

GeneCards Summary for CHCHD4 Gene

CHCHD4 (Coiled-Coil-Helix-Coiled-Coil-Helix Domain Containing 4) is a Protein Coding gene. Among its related pathways are Metabolism of proteins and Mitochondrial protein import. GO annotations related to this gene include protein disulfide oxidoreductase activity.

UniProtKB/Swiss-Prot for CHCHD4 Gene

  • Functions as chaperone and catalyzes the formation of disulfide bonds in substrate proteins, such as COX17 or MICU1 (PubMed:16185709, PubMed:26387864, PubMed:19182799, PubMed:21059946, PubMed:23186364). Required for the import and folding of small cysteine-containing proteins (small Tim) in the mitochondrial intermembrane space (IMS) (PubMed:16185709, PubMed:19182799, PubMed:21059946). Precursor proteins to be imported into the IMS are translocated in their reduced form into the mitochondria (PubMed:16185709, PubMed:19182799, PubMed:21059946). 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). 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).

No data available for CIViC summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for CHCHD4 Gene

Genomics for CHCHD4 Gene

Regulatory Elements for CHCHD4 Gene

Enhancers for CHCHD4 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH03G014122 1.8 FANTOM5 ENCODE dbSUPER 15.8 -0.4 -366 5.4 HDGF PKNOX1 FOXA2 CREB3L1 ARNT WRNIP1 ARID4B SIN3A FEZF1 DMAP1 CHCHD4 ENSG00000228242 XPC VN1R20P TMEM43 TPRXL ENSG00000268279
GH03G014177 1.1 ENCODE 21.4 -53.8 -53833 2.8 HDGF PKNOX1 FOXA2 MLX CREB3L1 ARNT ARID4B SIN3A FEZF1 DMAP1 CHCHD4 TMEM43 XPC LSM3
GH03G014118 1.3 ENCODE dbSUPER 15.8 +4.4 4443 4.1 ATF1 FOXA2 ARNT ARID4B E2F7 ZNF48 YY1 TCF12 SLC30A9 GATA2 CHCHD4 VN1R20P RBSN VN1R21P
GH03G013890 1.4 FANTOM5 Ensembl ENCODE 10.2 +233.8 233810 1.5 ATF1 CBX3 DEAF1 ZBTB40 YY1 ETS1 TCF12 ZNF766 ELK1 EGR1 LINC00620 TMEM43 CHCHD4 VN1R20P LOC105376957 WNT7A
GH03G014140 1.5 Ensembl ENCODE dbSUPER 9 -19.9 -19890 8.5 PKNOX1 FOXA2 ATF1 WRNIP1 ARID4B SIN3A FEZF1 YY1 GATA2 FOS XPC VN1R20P LSM3 CHCHD4 TMEM43 RBSN ENSG00000228242
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around CHCHD4 on UCSC Golden Path with GeneCards custom track

Promoters for CHCHD4 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000148875 -229 2201 HDGF PKNOX1 FOXA2 CREB3L1 ARNT WRNIP1 ARID4B SIN3A FEZF1 DMAP1

Genomic Location for CHCHD4 Gene

Chromosome:
3
Start:
14,112,077 bp from pter
End:
14,124,871 bp from pter
Size:
12,795 bases
Orientation:
Minus strand

Genomic View for CHCHD4 Gene

Genes around CHCHD4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CHCHD4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CHCHD4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for CHCHD4 Gene

Proteins for CHCHD4 Gene

  • Protein details for CHCHD4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q8N4Q1-MIA40_HUMAN
    Recommended name:
    Mitochondrial intermembrane space import and assembly protein 40
    Protein Accession:
    Q8N4Q1
    Secondary Accessions:
    • A8K3Z9
    • Q96AI2
    • Q96MY6

    Protein attributes for CHCHD4 Gene

    Size:
    142 amino acids
    Molecular mass:
    15996 Da
    Quaternary structure:
    • Monomer (PubMed:19182799). Can form homooligomers (PubMed:16185709). Interacts with GFER and forms transient disulfide bonds with GFER (PubMed:23186364). Interacts with MICU1 (PubMed:26387864).

    Three dimensional structures from OCA and Proteopedia for CHCHD4 Gene

    Alternative splice isoforms for CHCHD4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for CHCHD4 Gene

Post-translational modifications for CHCHD4 Gene

  • Forms intrachain disulfide bridges, but exists in different redox states.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for CHCHD4 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for CHCHD4 Gene

Domains & Families for CHCHD4 Gene

Protein Domains for CHCHD4 Gene

InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for CHCHD4 Gene

Graphical View of Domain Structure for InterPro Entry

Q8N4Q1

UniProtKB/Swiss-Prot:

MIA40_HUMAN :
  • The CHCH domain contains a conserved twin Cys-X(9)-Cys motif which is required for import and stability of MIA40 in mitochondria.
Domain:
  • The CHCH domain contains a conserved twin Cys-X(9)-Cys motif which is required for import and stability of MIA40 in mitochondria.
genes like me logo Genes that share domains with CHCHD4: view

Function for CHCHD4 Gene

Molecular function for CHCHD4 Gene

UniProtKB/Swiss-Prot Function:
Functions as chaperone and catalyzes the formation of disulfide bonds in substrate proteins, such as COX17 or MICU1 (PubMed:16185709, PubMed:26387864, PubMed:19182799, PubMed:21059946, PubMed:23186364). Required for the import and folding of small cysteine-containing proteins (small Tim) in the mitochondrial intermembrane space (IMS) (PubMed:16185709, PubMed:19182799, PubMed:21059946). Precursor proteins to be imported into the IMS are translocated in their reduced form into the mitochondria (PubMed:16185709, PubMed:19182799, PubMed:21059946). 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). 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).

Gene Ontology (GO) - Molecular Function for CHCHD4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 26387864
GO:0015035 protein disulfide oxidoreductase activity IMP 19182799
GO:0016491 oxidoreductase activity IEA --
genes like me logo Genes that share ontologies with CHCHD4: view

Phenotypes for CHCHD4 Gene

genes like me logo Genes that share phenotypes with CHCHD4: view

Animal Model Products

CRISPR Products

Inhibitory RNA Products

Clone Products

Flow Cytometry Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for CHCHD4 Gene

Localization for CHCHD4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for CHCHD4 Gene

Mitochondrion intermembrane space.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for CHCHD4 gene
Compartment Confidence
mitochondrion 5
cytosol 3
extracellular 2
plasma membrane 1
nucleus 1
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for CHCHD4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005739 mitochondrion IDA,IEA 24101517
GO:0005758 mitochondrial intermembrane space IEA,IDA 16185709
genes like me logo Genes that share ontologies with CHCHD4: view

Pathways & Interactions for CHCHD4 Gene

genes like me logo Genes that share pathways with CHCHD4: view

Pathways by source for CHCHD4 Gene

2 Reactome pathways for CHCHD4 Gene

Gene Ontology (GO) - Biological Process for CHCHD4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006810 transport IEA --
GO:0015031 protein transport IEA --
GO:0022417 protein maturation by protein folding IMP 21059946
GO:0045041 protein import into mitochondrial intermembrane space IMP 16185709
GO:0051084 de novo posttranslational protein folding IMP 21059946
genes like me logo Genes that share ontologies with CHCHD4: view

No data available for SIGNOR curated interactions for CHCHD4 Gene

Transcripts for CHCHD4 Gene

mRNA/cDNA for CHCHD4 Gene

Unigene Clusters for CHCHD4 Gene

Coiled-coil-helix-coiled-coil-helix domain containing 4:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

Clone Products

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for CHCHD4 Gene

ExUns: 1a · 1b · 1c ^ 2 ^ 3 ^ 4 ^ 5a · 5b · 5c
SP1:
SP2: -
SP3: - -

Relevant External Links for CHCHD4 Gene

GeneLoc Exon Structure for
CHCHD4
ECgene alternative splicing isoforms for
CHCHD4

Expression for CHCHD4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for CHCHD4 Gene

Protein differential expression in normal tissues from HIPED for CHCHD4 Gene

This gene is overexpressed in Adrenal (24.0) and Pancreas (9.3).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for CHCHD4 Gene



Protein tissue co-expression partners for CHCHD4 Gene

NURSA nuclear receptor signaling pathways regulating expression of CHCHD4 Gene:

CHCHD4

SOURCE GeneReport for Unigene cluster for CHCHD4 Gene:

Hs.517815

mRNA Expression by UniProt/SwissProt for CHCHD4 Gene:

Q8N4Q1-MIA40_HUMAN
Tissue specificity: Expressed in all tissues tested, suggesting an ubiquitous expression.

Evidence on tissue expression from TISSUES for CHCHD4 Gene

  • Liver(4.3)
  • Intestine(4.2)
  • Nervous system(2)
genes like me logo Genes that share expression patterns with CHCHD4: view

Primer Products

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for CHCHD4 Gene

Orthologs for CHCHD4 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for CHCHD4 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia CHCHD4 34 35
  • 99.53 (n)
dog
(Canis familiaris)
Mammalia CHCHD4 34 35
  • 90 (n)
rat
(Rattus norvegicus)
Mammalia Chchd4 34
  • 86.33 (n)
cow
(Bos Taurus)
Mammalia CHCHD4 34 35
  • 83.94 (n)
mouse
(Mus musculus)
Mammalia Chchd4 34 16
  • 83.69 (n)
AU015836 35
  • 35 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia CHCHD4 35
  • 79 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia -- 35
  • 77 (a)
OneToMany
-- 35
  • 75 (a)
OneToMany
chicken
(Gallus gallus)
Aves CHCHD4 34 35
  • 76.09 (n)
lizard
(Anolis carolinensis)
Reptilia CHCHD4 35
  • 76 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia chchd4 34
  • 75.54 (n)
MGC76323 34
African clawed frog
(Xenopus laevis)
Amphibia Xl.29530 34
zebrafish
(Danio rerio)
Actinopterygii chchd4 34 35
  • 77.57 (n)
CHCHD4 (2 of 2) 35
  • 44 (a)
OneToMany
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.6483 34
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP002940 34
  • 62.75 (n)
fruit fly
(Drosophila melanogaster)
Insecta CG7950 34 35
  • 61 (n)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes MIA40 35 37
  • 13 (a)
OneToOne
sea squirt
(Ciona savignyi)
Ascidiacea CSA.10518 35
  • 34 (a)
OneToOne
Species where no ortholog for CHCHD4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for CHCHD4 Gene

ENSEMBL:
Gene Tree for CHCHD4 (if available)
TreeFam:
Gene Tree for CHCHD4 (if available)

Paralogs for CHCHD4 Gene

Pseudogenes.org Pseudogenes for CHCHD4 Gene

genes like me logo Genes that share paralogs with CHCHD4: view

No data available for Paralogs for CHCHD4 Gene

Variants for CHCHD4 Gene

Sequence variations from dbSNP and Humsavar for CHCHD4 Gene

SNP ID Clin Chr 03 pos Sequence Context AA Info Type
rs17038940 Likely benign 14,125,052(+) TAACT(A/G)CAGTA upstream-variant-2KB, utr-variant-5-prime
rs760598925 Uncertain significance 14,125,190(+) GGTCC(C/T)ACCAT upstream-variant-2KB, utr-variant-5-prime
rs886058025 Uncertain significance 14,124,990(+) CCGTA(C/T)AGTTT upstream-variant-2KB, utr-variant-5-prime
rs886058026 Uncertain significance 14,125,004(+) GGACG(C/T)CTCGC upstream-variant-2KB, utr-variant-5-prime
rs886058027 Uncertain significance 14,125,019(+) CGCAT(A/G)CGCAG upstream-variant-2KB, utr-variant-5-prime

Structural Variations from Database of Genomic Variants (DGV) for CHCHD4 Gene

Variant ID Type Subtype PubMed ID
esv2724945 CNV deletion 23290073
esv2724947 CNV deletion 23290073
esv34163 CNV loss 18971310
esv3573 CNV loss 18987735
nsv1011766 CNV gain 25217958

Variation tolerance for CHCHD4 Gene

Residual Variation Intolerance Score: 44.3% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.80; 16.80% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for CHCHD4 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
CHCHD4

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for CHCHD4 Gene

Disorders for CHCHD4 Gene

Relevant External Links for CHCHD4

Genetic Association Database (GAD)
CHCHD4
Human Genome Epidemiology (HuGE) Navigator
CHCHD4
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
CHCHD4

No disorders were found for CHCHD4 Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for CHCHD4 Gene

Publications for CHCHD4 Gene

  1. The Ca(2+)-dependent release of the Mia40-induced MICU1-MICU2 dimer from MCU regulates mitochondrial Ca(2+) uptake. (PMID: 26387864) Petrungaro C. … Riemer J. (Cell Metab. 2015) 3 4 64
  2. Disulfide bond formation: sulfhydryl oxidase ALR controls mitochondrial biogenesis of human MIA40. (PMID: 23186364) Sztolsztener M.E. … Chacinska A. (Traffic 2013) 3 4 64
  3. Human CHCHD4 mitochondrial proteins regulate cellular oxygen consumption rate and metabolism and provide a critical role in hypoxia signaling and tumor progression. (PMID: 22214851) Yang J. … Ashcroft M. (J. Clin. Invest. 2012) 2 3 64
  4. Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression. (PMID: 20877624) Hendrickson S.L. … O'Brien S.J. (PLoS ONE 2010) 3 46 64
  5. Molecular chaperone function of Mia40 triggers consecutive induced folding steps of the substrate in mitochondrial protein import. (PMID: 21059946) Banci L. … Tokatlidis K. (Proc. Natl. Acad. Sci. U.S.A. 2010) 3 4 64

Products for CHCHD4 Gene

Sources for CHCHD4 Gene

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