COQ8A

coenzyme Q8A

Basic information

Region (hg38): 1:226940285-226987544

Previous symbols: [ "CABC1", "ADCK3" ]

Links

ENSG00000163050 ∙ NCBI:56997 ∙ OMIM:606980 ∙ HGNC:16812 ∙ Uniprot:Q8NI60 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• coenzyme Q10 deficiency (Definitive), mode of inheritance: AR
• autosomal recessive ataxia due to ubiquinone deficiency (Supportive), mode of inheritance: AR
• coenzyme Q10 deficiency, primary, 1 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Coenzyme Q10 deficiency, primary 4	AR	Biochemical	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	Biochemical; Neurologic	12682339; 15326254; 18319074; 18319072; 20580948; 22036850; 22231380; 32337771

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the COQ8A gene.

• not provided (568 variants)
• Autosomal recessive ataxia due to ubiquinone deficiency (151 variants)
• not specified (85 variants)
• Autosomal recessive cerebellar ataxia (30 variants)
• Coenzyme Q10 deficiency, Spinocerebellar Ataxia Type (28 variants)
• Inborn genetic diseases (22 variants)
• See cases (4 variants)
• COQ8A-related condition (3 variants)
• Mitochondrial disease (3 variants)
• ADCK3-Related Disorders (2 variants)
• Global developmental delay (1 variants)
• Coenzyme Q10 deficiency, primary, 1 (1 variants)
• Abnormality of the nervous system (1 variants)
• Joubert syndrome 17 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the COQ8A 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			6	97	6	109
missense	4	19	207	11		241
nonsense	8	3				11
start loss						0
frameshift	18	8	1			27
inframe indel		1	6			7
splice donor/acceptor (+/-2bp)	2	7				9
splice region	1		16	20		37
non coding			23	79	33	135
Total	32	38	243	187	39

Highest pathogenic variant AF is 0.0000526

Variants in COQ8A

This is a list of pathogenic ClinVar variants found in the COQ8A region.

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

Position	Type	Phenotype	Significance	ClinVar
1-226940296-A-G		Autosomal recessive cerebellar ataxia • Autosomal recessive ataxia due to ubiquinone deficiency	Uncertain significance (Jan 13, 2018)
1-226940334-C-T		Coenzyme Q10 deficiency, Spinocerebellar Ataxia Type • Autosomal recessive ataxia due to ubiquinone deficiency	Uncertain significance (Jan 13, 2018)
1-226940407-T-C		not specified • Autosomal recessive cerebellar ataxia • Autosomal recessive ataxia due to ubiquinone deficiency	Benign/Likely benign (Jan 12, 2018)
1-226961395-A-G			Uncertain significance (May 05, 2022)
1-226961396-T-A			Uncertain significance (Oct 21, 2022)
1-226961398-T-C			Likely benign (Aug 06, 2018)
1-226961410-A-G			Likely benign (Mar 27, 2023)
1-226961416-GT-G		Autosomal recessive ataxia due to ubiquinone deficiency	Likely pathogenic (Nov 07, 2023)
1-226961435-A-G		not specified	Uncertain significance (Dec 28, 2016)
1-226961439-G-T			Likely benign (Jun 29, 2023)
1-226961441-C-T			Likely benign (Jan 16, 2024)
1-226961442-C-G			Likely benign (Sep 03, 2023)
1-226961442-C-T			Likely benign (Mar 29, 2018)
1-226961447-C-A			Uncertain significance (Mar 03, 2023)
1-226961447-C-T		not specified	Conflicting classifications of pathogenicity (Jan 30, 2024)
1-226961448-G-A		not specified • Coenzyme Q10 deficiency, Spinocerebellar Ataxia Type • Autosomal recessive ataxia due to ubiquinone deficiency	Conflicting classifications of pathogenicity (Jan 31, 2024)
1-226961452-G-A		not specified • Autosomal recessive ataxia due to ubiquinone deficiency • Inborn genetic diseases	Conflicting classifications of pathogenicity (Jan 18, 2024)
1-226961453-T-C			Uncertain significance (Jul 07, 2022)
1-226961454-G-A			Likely benign (Oct 07, 2022)
1-226961463-C-T		not specified	Benign (Jan 31, 2024)
1-226961472-C-G			Uncertain significance (Jul 20, 2022)
1-226961481-C-T			Likely benign (Jan 22, 2024)
1-226961482-G-A			Uncertain significance (Sep 07, 2023)
1-226961484-A-C			Likely benign (Dec 01, 2021)
1-226961501-C-T		Autosomal recessive ataxia due to ubiquinone deficiency	Uncertain significance (May 27, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
COQ8A	protein_coding	protein_coding	ENST00000366779	14	90010

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
9.29e-11	0.716	125617	0	131	125748	0.000521

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.872	448	399	1.12	0.0000270	4255
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000819	0.000811
Ashkenazi Jewish	0.00	0.00
East Asian	0.000658	0.000653
Finnish	0.000464	0.000462
European (Non-Finnish)	0.000602	0.000589
Middle Eastern	0.000658	0.000653
South Asian	0.000523	0.000523
Other	0.000818	0.000815

dbNSFP

Source: dbNSFP

• 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

Haploinsufficiency Scores

• pHI: 0.125
• hipred: N
• hipred_score: 0.394
• ghis: 0.584

Essentials

• essential_gene_gene_trap: N

Mouse Genome Informatics

• Gene name: Coq8a

Gene ontology

• Biological process: protein phosphorylation;ubiquinone biosynthetic process;phosphorylation
• Cellular component: mitochondrion;integral component of membrane;extrinsic component of mitochondrial inner membrane
• Molecular function: protein kinase activity;protein binding;ATP binding;kinase activity;ADP binding