COQ2

coenzyme Q2, polyprenyltransferase

Basic information

Region (hg38): 4:83261536-83284914

Links

ENSG00000173085 ∙ NCBI:27235 ∙ OMIM:609825 ∙ HGNC:25223 ∙ Uniprot:Q96H96 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• coenzyme Q10 deficiency, primary, 1 (Definitive), mode of inheritance: AR
• multiple system atrophy (Moderate), mode of inheritance: AR
• Leigh syndrome with nephrotic syndrome (Supportive), mode of inheritance: AR
• coenzyme Q10 deficiency, primary, 1 (Strong), mode of inheritance: AR
• mitochondrial disease (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Coenzyme Q10 deficiency, primary, 1	AR	Biochemical	Treatment with coenzyme Q10 has been described as beneficial	Biochemical; Musculoskeletal; Neurologic; Renal	16116126; 17855635; 17374725; 17332895; 17420317; 23758206; 24988567; 24988570
A heterogenous group of disorders has been described, but the molecular etiologies of some are unclear; Variants may contribute to Multiple system atrophy, susceptibility to 1 (AR)

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the COQ2 gene.

• not provided (6 variants)
• Coenzyme Q10 deficiency, primary, 1;Multiple system atrophy 1, susceptibility to (1 variants)
• Multiple system atrophy (1 variants)
• Coenzyme Q10 deficiency, primary, 1 (1 variants)
• Coenzyme Q10 deficiency (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the COQ2 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				86	2	88
missense	1	4	128	5	3	141
nonsense	2	4	1	1		8
start loss			2			2
frameshift	5	2	4			11
inframe indel			2			2
splice donor/acceptor (+/-2bp)		5	2			7
splice region			5	7		12
non coding		1	2	38	17	58
Total	8	16	141	130	22

Highest pathogenic variant AF is 0.0000197

Variants in COQ2

This is a list of pathogenic ClinVar variants found in the COQ2 region.

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

Position	Type	Phenotype	Significance	ClinVar
4-83263850-T-TA		Coenzyme Q10 deficiency	Uncertain significance (Jun 14, 2016)
4-83263930-C-T			Likely benign (Feb 21, 2019)
4-83263942-A-G		Coenzyme Q10 deficiency	Uncertain significance (Jun 14, 2016)
4-83264146-C-T			Likely benign (Jun 26, 2018)
4-83264190-TTTCA-T		COQ2-related disorder	Likely benign (Aug 10, 2024)
4-83264191-T-C		COQ2-related disorder	Likely benign (Dec 19, 2022)
4-83264206-T-C		COQ2-related disorder	Uncertain significance (Oct 04, 2022)
4-83264215-T-C		not specified	Conflicting classifications of pathogenicity (Dec 11, 2023)
4-83264222-T-A			Uncertain significance (Jan 07, 2022)
4-83264242-GTCT-G		Coenzyme Q10 deficiency, primary, 1 • Coenzyme Q10 deficiency, primary, 1;Multiple system atrophy 1, susceptibility to	Uncertain significance (Jul 21, 2021)
4-83264259-C-T			Likely benign (Aug 22, 2022)
4-83264267-CA-C		Coenzyme Q10 deficiency, primary, 1 • Coenzyme Q10 deficiency	Likely pathogenic (Jan 23, 2024)
4-83264271-G-A		Coenzyme Q10 deficiency, primary, 1;Multiple system atrophy 1, susceptibility to • COQ2-related disorder	Likely benign (Jan 11, 2024)
4-83264275-A-G		Inborn genetic diseases	Uncertain significance (Mar 15, 2024)
4-83264277-C-A			Likely benign (Oct 13, 2023)
4-83264280-T-TA			Pathogenic (Oct 10, 2022)
4-83264281-A-G		Inborn genetic diseases	Uncertain significance (Jul 25, 2023)
4-83264287-A-G		not specified	Benign/Likely benign (Jan 21, 2024)
4-83264296-C-G			Uncertain significance (Mar 18, 2022)
4-83264303-T-C		Inborn genetic diseases	Uncertain significance (Dec 28, 2023)
4-83264305-C-T		Multiple system atrophy	Uncertain significance (Sep 19, 2022)
4-83264306-G-A		Multiple system atrophy • Coenzyme Q10 deficiency	risk factor (Jul 18, 2013)
4-83264308-T-C			Uncertain significance (Nov 27, 2021)
4-83264315-T-A			Uncertain significance (Jul 20, 2023)
4-83264315-T-C			Uncertain significance (Feb 28, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
COQ2	protein_coding	protein_coding	ENST00000311469	7	23379

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00134	0.966	124622	0	25	124647	0.000100

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0284	194	193	1.01	0.00000936	2592
Missense in Polyphen		35	46.649	0.75029		602
Synonymous	-1.21	88	74.7	1.18	0.00000384	887
Loss of Function	1.88	7	14.8	0.472	6.32e-7	199

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000648	0.0000646
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000575	0.0000556
Finnish	0.000142	0.000139
European (Non-Finnish)	0.000132	0.000124
Middle Eastern	0.0000575	0.0000556
South Asian	0.000187	0.000163
Other	0.000167	0.000165

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the prenylation of para-hydroxybenzoate (PHB) with an all-trans polyprenyl group. Mediates the second step in the final reaction sequence of coenzyme Q (CoQ) biosynthesis, which is the condensation of the polyisoprenoid side chain with PHB, generating the first membrane-bound Q intermediate. {ECO:0000255|HAMAP-Rule:MF_03189, ECO:0000269|PubMed:15153069, ECO:0000269|PubMed:16400613, ECO:0000269|PubMed:17374725, ECO:0000269|PubMed:27493029}.
• Disease: DISEASE: Multiple system atrophy 1 (MSA1) [MIM:146500]: A progressive neurodegenerative disorder clinically characterized by parkinsonism, cerebellar ataxia, and autonomic, urogenital, and pyramidal dysfunction in various combinations. Pathologically, it is characterized by degeneration of striatonigral and olivopontocerebellar structures, and glial cytoplasmic inclusions that consist of abnormally phosphorylated alpha-synuclein or tau. {ECO:0000269|PubMed:23758206}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
• Pathway: Ubiquinone and other terpenoid-quinone biosynthesis - Homo sapiens (human);Ubiquinone Biosynthesis;Metabolism of proteins;Metabolism;Ubiquinol biosynthesis;Metabolism of cofactors;Metabolism of vitamins and cofactors;ubiquinol-10 biosynthesis;Mitochondrial protein import (Consensus)

Recessive Scores

• pRec: 0.130

Intolerance Scores

• loftool: 0.523
• rvis_EVS: 0.15
• rvis_percentile_EVS: 64.32

Haploinsufficiency Scores

• pHI: 0.107
• hipred: N
• hipred_score: 0.170
• ghis: 0.419

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: K
• gene_indispensability_pred: N
• gene_indispensability_score: 0.330

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Coq2
• Phenotype: adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); 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); skeleton phenotype

Zebrafish Information Network

• Gene name: coq2
• Affected structure: yolk
• Phenotype tag: abnormal
• Phenotype quality: morphology

Gene ontology

• Biological process: glycerol metabolic process;ubiquinone biosynthetic process;isoprenoid biosynthetic process
• Cellular component: mitochondrion;mitochondrial inner membrane;integral component of mitochondrial inner membrane
• Molecular function: 4-hydroxybenzoate decaprenyltransferase activity;transferase activity, transferring alkyl or aryl (other than methyl) groups;4-hydroxybenzoate nonaprenyltransferase activity