GeneBe

COQ5

protein-coding

coenzyme Q5, methyltransferase, the group of 7BS small molecule methyltransferases

Gene summary

Enables 2-methoxy-6-polyprenyl-1,4-benzoquinol methyltransferase activity. Involved in methylation and ubiquinone biosynthetic process. Located in mitochondrial inner membrane and mitochondrial matrix. Part of protein-containing complex. Implicated in primary coenzyme Q10 deficiency 9. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_032314.4

Inheritance

AR

ClinVar variants

P:2U:52B:15

Top phenotype

Coenzyme Q10 deficiency, primary, 1

gnomAD constraint

pLI —, LoF o/e 0.56

Max pathogenic AF

—

Genomic locus

chr12:120,503,279-120,534,434

External References & Databases

Ensembl (ENSG00000110871)NCBI Gene (84274)OMIM (616359)HGNC:28722GenCCUniProt (Q5HYK3)AlphaFoldClinVar (COQ5)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~31.2 kb
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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

mitochondrial diseaseMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0044970

Submitter: ClinGen

*COQ5* was first reported in relation to autosomal recessive coenzyme Q10 deficiency, a primary mitochondrial disease, in 2018 (Malicdan MCV, et al., PMID: 29044765). The *COQ5* gene encodes coenzyme Q5, methyltransferase which is involved in mitochondrial ubiquinone (coenzyme Q10, CoQ10) biosynthesis. Coenzyme Q10 is critical for many processes in the cell, including in the mitochondrial respiratory chain transferring electrons from complexes I and II to complex III. CoQ10 deficiency is a multisystem primary mitochondrial disease characterized by variable clinical manifestations that include encephalopathy, seizures, movement disorder, hypotonia, nephrotic syndrome, hypertrophic cardiomyopathy, muscle weakness, exercise intolerance, retinopathy and sensorineural hearing loss. Laboratory findings include reduced CoQ10 biosynthesis and reduced activity of mitochondrial complex I+II and I+III and II+III (PMID: 28125198). Three variants (1 large tandem duplication, 1 canonical splice-site, 1 missense) that have been reported in 2 probands in 2 publications (PMIDs: 29044765, 37599337) are included in this curation. The mechanism of pathogenicity appears to be loss of function. This gene-disease relationship is also supported by experimental evidence including the biochemical function of ubiquinone biosynthesis that is shared with other known genes in the disease of interest (PMIDs: 9083048, 33340416, 28125198), protein interaction with *COQ4* which is another ubiquinone biosynthesis gene that has a definitive classification for mitochondrial disease (PMID: 25152161), and a human rescue model where high-dose oral supplementation of CoQ10 was shown to improve the clinical manifestations and Q10 levels in patients with *COQ5*-related coenzyme Q10 deficiency (PMID: 29044765). In summary, there is moderate evidence to support this gene-disease relationship. While more evidence is needed to establish this relationship definitively, no convincing contradictory evidence has emerged. This classification was approved by the ClinGen Ataxia GCEP on the meeting date July 10, 2024 (SOP Version 10).

neurodevelopmental disorderLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0700092

Submitter: G2P

coenzyme q10 deficiency, primary, 9LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0033615

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Coenzyme Q10 deficiency, primary, 1AR

Manifestation: Biochemical; Neurologic

Intervention: Biochemical

Rationale: Treatment with coenzyme Q10 has been described as beneficial

Refs: 29044765Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to COQ5 variants in ClinVar

4 Conditions Cataloged
not specifiedTotal: 52
not providedTotal: 13
COQ5-related disorderTotal: 5
Coenzyme q10 deficiency, primary, 9Total: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_032314.4. 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.

EffectPLPVUSLBBSum
synonymous
7
clinvar
1
clinvar
 8
missense
1
clinvar
50
clinvar
7
clinvar
 58
nonsense
1
clinvar
 1
start loss
0
frameshift
2
clinvar
 2
splice donor/acceptor (+/-2bp)
0
Total025214169

Highest pathogenic variant AF is 0.000024172705

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 27 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_032314.4RefSeqNP_115690.37MANE Select
ENST00000288532.11EnsemblENSP00000288532.67MANE Select
ENST00000445328.6EnsemblENSP00000401798.26Standard
ENST00000445328.7EnsemblENSP00000401798.26Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Ubiquinone and other terpenoid-quinone biosynthesis - Homo sapiens (human)
  • Ubiquinone Biosynthesis
  • Metabolism
  • Ubiquinol biosynthesis
  • Metabolism of cofactors

Biological Process

  • ubiquinone biosynthetic process
  • methylation

Molecular Function

  • protein binding
  • 2-octaprenyl-6-methoxy-1,4-benzoquinone methylase activity
  • 2-decaprenyl-6-methoxy-1,4-benzoquinone methyltransferase activity

Cellular Component

  • mitochondrion
  • mitochondrial inner membrane
  • mitochondrial matrix
  • extrinsic component of mitochondrial inner membrane
  • protein-containing complex

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000288532
Coding exons
7
Length
31161
Individuals with no LoFs
125716
Homozygous LoFs
0
Heterozygous LoFs
32
Defined
125748
p
0.000127
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense-0.3631911771.080.000009652147
Missense (PolyPhen)7379.3240.92028956
Synonymous0.7266067.60.8880.00000351618
Loss of Function1.721017.80.5618.68e-7203

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000120.00012rare
Latino/Admixed American0.0000580.000058rare
Ashkenazi Jewish00.0absent
East Asian0.000490.00049rare
Finnish0.0000460.000046rare
European (Non-Finnish)0.000150.00015rare
South Asian0.0000330.000033rare
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Methyltransferase required for the conversion of 2- polyprenyl-6-methoxy-1,4-benzoquinol (DDMQH2) to 2-polyprenyl-3- methyl-6-methoxy-1,4-benzoquinol (DMQH2). {ECO:0000255|HAMAP- Rule:MF_03191}.;

Recessive Scores

pRec
0.173

Intolerance Scores

LoFtool
0.867
RVIS EVS
-0.09
RVIS percentile EVS
46.74

Essentials

Essential (CRISPR)
E
Essential (CRISPR2)
E
Essential (gene trap)
E
Indispensability pred.
N
Indispensability score
0.179

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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