COQ6

coenzyme Q6, monooxygenase

Basic information

Region (hg38): 14:73949926-73963670

Links

ENSG00000119723 ∙ NCBI:51004 ∙ OMIM:614647 ∙ HGNC:20233 ∙ Uniprot:Q9Y2Z9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• familial steroid-resistant nephrotic syndrome with sensorineural deafness (Moderate), mode of inheritance: AR
• familial steroid-resistant nephrotic syndrome with sensorineural deafness (Supportive), mode of inheritance: AR
• familial steroid-resistant nephrotic syndrome with sensorineural deafness (Strong), mode of inheritance: AR
• SMARCB1-related schwannomatosis (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Coenzyme Q10 deficiency, primary 6	AR	Biochemical	Some patients have been reported as showing a favorable response to oral Coenzyme Q supplementation	Biochemical; Musculoskeletal; Neurologic; Renal	21540551

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the COQ6 gene.

• not provided (7 variants)
• Familial steroid-resistant nephrotic syndrome with sensorineural deafness (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the COQ6 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				52	2	54
missense		2	89	2	5	98
nonsense	3	2	1			6
start loss						0
frameshift	8	1	1			10
inframe indel		1	1			2
splice donor/acceptor (+/-2bp)		2				2
splice region			4	10	1	15
non coding			10	40	33	83
Total	11	8	102	94	40

Highest pathogenic variant AF is 0.0000132

Variants in COQ6

This is a list of pathogenic ClinVar variants found in the COQ6 region.

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

Position	Type	Phenotype	Significance	ClinVar
14-73949943-T-G			Benign (Jul 15, 2018)
14-73949962-T-C			Benign (Jun 23, 2018)
14-73949993-C-T		not specified	Uncertain significance (Feb 14, 2023)
14-73949995-C-G			Benign (Jun 28, 2018)
14-73950026-T-C		not specified	Uncertain significance (Mar 02, 2023)
14-73950052-C-CAGTGACAGCGAT		not specified	Likely benign (Dec 21, 2015)
14-73950062-G-T		not specified	Uncertain significance (Aug 17, 2021)
14-73950073-C-T		not specified	Uncertain significance (May 04, 2022)
14-73950079-T-G		not specified	Benign (Dec 09, 2013)
14-73950095-G-A		not specified	Uncertain significance (May 24, 2023)
14-73950113-C-G		not specified	Uncertain significance (Jan 08, 2024)
14-73950129-G-T		not specified	Benign (Apr 23, 2014)
14-73950133-G-A		not specified • Familial steroid-resistant nephrotic syndrome with sensorineural deafness • COQ6-related disorder	Benign (Jan 02, 2020)
14-73950154-C-T			Likely benign (Mar 03, 2021)
14-73950161-A-G		COQ6-related disorder	Likely benign (Dec 07, 2019)
14-73950161-A-T		not specified	Uncertain significance (Apr 24, 2024)
14-73950184-C-G		not specified	Uncertain significance (Nov 26, 2024)
14-73950234-G-C			Benign (Jul 15, 2018)
14-73950242-G-C		not specified	Benign (Jul 15, 2024)
14-73950293-G-T		not specified	Benign (Dec 09, 2013)
14-73950333-A-G		Familial steroid-resistant nephrotic syndrome with sensorineural deafness	Uncertain significance (Feb 07, 2024)
14-73950337-C-A			Uncertain significance (Jun 15, 2022)
14-73950337-C-T			Uncertain significance (Jun 04, 2022)
14-73950339-G-A		Familial steroid-resistant nephrotic syndrome with sensorineural deafness	Uncertain significance (Mar 28, 2024)
14-73950342-C-A			Likely benign (Sep 13, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
COQ6	protein_coding	protein_coding	ENST00000334571	12	13745

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.33e-15	0.0238	125677	0	71	125748	0.000282

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.618	232	260	0.892	0.0000149	3041
Missense in Polyphen		79	93.187	0.84776		1117
Synonymous	1.25	89	105	0.845	0.00000673	952
Loss of Function	0.286	23	24.5	0.938	0.00000135	270

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000231	0.000231
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000272	0.000272
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000267	0.000264
Middle Eastern	0.000272	0.000272
South Asian	0.000751	0.000752
Other	0.000489	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: FAD-dependent monooxygenase required for the C5-ring hydroxylation during ubiquinone biosynthesis. Catalyzes the hydroxylation of 3-polyprenyl-4-hydroxybenzoic acid to 3- polyprenyl-4,5-dihydroxybenzoic acid. The electrons required for the hydroxylation reaction may be funneled indirectly from NADPH via a ferredoxin/ferredoxin reductase system to COQ6. {ECO:0000255|HAMAP-Rule:MF_03193}.
• Disease: DISEASE: Note=Mutations in COQ6 may play a role in susceptibility to Schwannomatosis, a cancer predisposition syndrome in which patients develop multiple non-vestibular schwannomas, benign neoplasms that arise from Schwann cells of the cranial, peripheral, and autonomic nerves. {ECO:0000269|PubMed:24763291}.
• Pathway: Ubiquinone and other terpenoid-quinone biosynthesis - Homo sapiens (human);Ubiquinone Biosynthesis;Metabolism;Ubiquinol biosynthesis;Metabolism of cofactors;Metabolism of vitamins and cofactors;ubiquinol-10 biosynthesis (Consensus)

Recessive Scores

• pRec: 0.220

Intolerance Scores

• loftool: 0.849
• rvis_EVS: 0.71
• rvis_percentile_EVS: 85.68

Haploinsufficiency Scores

• pHI: 0.159
• hipred: N
• hipred_score: 0.248
• ghis: 0.454

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.892

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	Medium	Medium
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Coq6
• Phenotype: homeostasis/metabolism phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); growth/size/body region phenotype; vision/eye phenotype; limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); embryo phenotype

Zebrafish Information Network

• Gene name: coq6
• Affected structure: apoptotic process
• Phenotype tag: abnormal
• Phenotype quality: increased occurrence

Gene ontology

• Biological process: ubiquinone biosynthetic process;oxidation-reduction process
• Cellular component: mitochondrion;Golgi apparatus;extrinsic component of mitochondrial inner membrane;cell projection
• Molecular function: protein binding;oxidoreductase activity;oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD(P)H as one donor, and incorporation of one atom of oxygen;oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen;FAD binding