COX17
protein-codingcytochrome c oxidase copper chaperone COX17, the group of Mitochondrial respiratory chain complex assembly factors
Gene summary
Cytochrome c oxidase (COX), the terminal component of the mitochondrial respiratory chain, catalyzes the electron transfer from reduced cytochrome c to oxygen. This component is a heteromeric complex consisting of 3 catalytic subunits encoded by mitochondrial genes and multiple structural subunits encoded by nuclear genes. The mitochondrially-encoded subunits function in electron transfer, and the nuclear-encoded subunits may function in the regulation and assembly of the complex. This nuclear gene encodes a protein which is not a structural subunit, but may be involved in the recruitment of copper to mitochondria for incorporation into the COX apoenzyme. This protein shares 92% amino acid sequence identity with mouse and rat Cox17 proteins. This gene is no longer considered to be a candidate gene for COX deficiency. A pseudogene COX17P has been found on chromosome 13. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~22.9 kbGenCC 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 COX17 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005694.2. 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 | 0 | |||||
| missense | 8 | 8 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 8 | 0 | 0 | 8 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005685.1 | 2 | MANE Select | |
| Ensembl | ENSP00000261070.2 | 2 | MANE Select | |
| RefSeq | NP_001368931.1 | 3 | Standard | |
| RefSeq | NP_001368932.1 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Thermogenesis - Homo sapiens (human)
- Oxidative phosphorylation - Homo sapiens (human)
- Electron Transport Chain
- Copper homeostasis
- Metabolism of proteins
Biological Process
- generation of precursor metabolites and energy
- copper ion transport
- brain development
- heart development
- positive regulation of cell population proliferation
Molecular Function
- copper ion binding
- protein binding
- copper chaperone activity
- cuprous ion binding
Cellular Component
- cytoplasm
- mitochondrial intermembrane space
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000261070
- Coding exons
- 2
- Length
- 22942
- Individuals with no LoFs
- 124006
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 1
- Defined
- 124007
- p
- 0.00000403
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.229 | 32 | 35.9 | 0.892 | 0.00000161 | 401 |
| Missense (PolyPhen) | 13 | 14.28 | 0.91036 | 172 | ||
| Synonymous | -0.0797 | 15 | 14.6 | 1.03 | 7.01e-7 | 117 |
| Loss of Function | 0.980 | 1 | 2.76 | 0.363 | 1.14e-7 | 41 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000047 | 0.000047 | rare |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Copper metallochaperone essential for the assembly of the mitochondrial respiratory chain complex IV (CIV), also known as cytochrome c oxidase. Binds two copper ions and delivers them to the metallochaperone SCO1 which transports the copper ions to the Cu(A) site on the cytochrome c oxidase subunit II (MT- CO2/COX2). {ECO:0000269|PubMed:19393246}.;
Recessive Scores
- pRec
- 0.194
Intolerance Scores
- LoFtool
- 0.345
- RVIS EVS
- 0.1
- RVIS percentile EVS
- 60.96
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- N
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.970
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |