COQ8A
protein-codingcoenzyme Q8A
Gene summary
This gene encodes a mitochondrial protein similar to yeast ABC1, which functions in an electron-transferring membrane protein complex in the respiratory chain. It is not related to the family of ABC transporter proteins. Expression of this gene is induced by the tumor suppressor p53 and in response to DNA damage, and inhibiting its expression partially suppresses p53-induced apoptosis. Alternatively spliced transcript variants have been found; however, their full-length nature has not been determined. [provided by RefSeq, Jul 2008]
- CABC1
- ADCK3
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~47.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0012784
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0012784
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0018151
Submitter: Illumina
Clinical Genomic Database (CGD)
Manifestation: Biochemical; Neurologic
Intervention: Biochemical
Rationale: Treatment with coenzyme Q10 may have some benefit in some individuals, though some features may not be affected, and some invidiuals may not derive benefit
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to COQ8A variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_020247.5. 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 | 7 | 170 | 2 | 179 | ||
| missense | 8 | 35 | 246 | 30 | 319 | |
| nonsense | 8 | 7 | 2 | 17 | ||
| start loss | 0 | |||||
| frameshift | 23 | 22 | 2 | 47 | ||
| splice donor/acceptor (+/-2bp) | 3 | 16 | 5 | 24 | ||
| Total | 42 | 80 | 262 | 200 | 2 | 586 |
Highest pathogenic variant AF is 0.000084975676
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_064632.2 | 14 | MANE Select | |
| Ensembl | ENSP00000355739.3 | 14 | MANE Select | |
| Ensembl | ENSP00000355740.1 | 14 | Standard | |
| Ensembl | ENSP00000355740.1 | 14 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- protein phosphorylation
- ubiquinone biosynthetic process
- phosphorylation
Molecular Function
- protein kinase activity
- protein binding
- ATP binding
- kinase activity
- ADP binding
Cellular Component
- mitochondrion
- integral component of membrane
- extrinsic component of mitochondrial inner membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000366779
- Coding exons
- 14
- Length
- 90010
- Individuals with no LoFs
- 125617
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 131
- Defined
- 125748
- p
- 0.000521
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.872 | 448 | 399 | 1.12 | 0.0000270 | 4255 |
| Missense (PolyPhen) | 108 | 100.79 | 1.0716 | 1032 | ||
| Synonymous | -2.76 | 216 | 170 | 1.27 | 0.0000125 | 1278 |
| Loss of Function | 1.53 | 20 | 28.9 | 0.693 | 0.00000153 | 324 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00038 | 0.00037 | rare |
| Latino/Admixed American | 0.00044 | 0.00043 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00066 | 0.00065 | rare |
| Finnish | 0.00046 | 0.00046 | rare |
| European (Non-Finnish) | 0.00060 | 0.00059 | rare |
| South Asian | 0.00052 | 0.00052 | rare |
| Other | 0.00082 | 0.00081 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Atypical kinase involved in the biosynthesis of coenzyme Q, also named ubiquinone, an essential lipid-soluble electron transporter for aerobic cellular respiration (PubMed:25498144, PubMed:21296186, PubMed:25540914, PubMed:27499294). Its substrate specificity is unclear: does not show any protein kinase activity (PubMed:25498144, PubMed:27499294). Probably acts as a small molecule kinase, possibly a lipid kinase that phosphorylates a prenyl lipid in the ubiquinone biosynthesis pathway, as suggested by its ability to bind coenzyme Q lipid intermediates (PubMed:25498144, PubMed:27499294). Shows an unusual selectivity for binding ADP over ATP (PubMed:25498144). {ECO:0000269|PubMed:25498144, ECO:0000269|PubMed:27499294, ECO:0000305|PubMed:21296186, ECO:0000305|PubMed:25540914}.;
- Disease
- DISEASE: Coenzyme Q10 deficiency, primary, 4 (COQ10D4) [MIM:612016]: An autosomal recessive disorder characterized by childhood-onset of cerebellar ataxia and exercise intolerance. Patient manifest gait ataxia and cerebellar atrophy with slow progression. Additional features include brisk tendon reflexes and Hoffmann sign, variable psychomotor retardation and variable seizures. {ECO:0000269|PubMed:18319072, ECO:0000269|PubMed:18319074, ECO:0000269|PubMed:20580948, ECO:0000269|PubMed:22036850, ECO:0000269|PubMed:24048965, ECO:0000269|PubMed:24218524, ECO:0000269|PubMed:25498144, ECO:0000269|PubMed:26818466, ECO:0000269|PubMed:27106809}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.172
Intolerance Scores
- RVIS EVS
- -1.7
- RVIS percentile EVS
- 2.55
Essentials
- Essential (gene trap)
- N