Genetic Epilepsy
Gene: COQ5 Green List (high evidence)Green List (high evidence)
PMID: 29044765 3 siblings with cerebellar ataxia, encephalopathy, seizures, developmental delay, and oculomotor apraxia or nystagmus.. All homozygous for a tandem duplication of 9.59kb encompassing the last 4 exons. Parents both shown to be carriers and 3 siblings were either het or did not have the dup. qRT-PCR in patient fibroblasts showed COQ5 mRNA levels were at 2-4% compared to controls. Reduced COQ5 protein was also shown on western blots.
PMID: 37599337 1 patient compound heterozygous for c.681+1G>A and Gly118Ser. Cerebellar ataxia, encephalopathy, developmental delay, short stature, and microcephaly. COQ5 mRNA levels were markedly diminished in patient cells, and different mis-splicing events were seen on both alleles (confirmed in carrier parents). This paper also referenced another patient in PMID: 21937992, a large ID cohort with limited phenotypic information who was homozygous for the same missense variant in their patient Gly118Ser.
PMID: 41199775 2 siblings with a different missense at the recurring amino acid Gly118, Gly118Asp, in trans with an NMD predicted frameshift. Both siblings had severe developmental delay, microcephaly, spasticity, ataxia, seizures, and feeding difficulties. Recurrent strokes and other brain anomalies commonly seen in mitochondrial disorders were seen on brain MRI, but there was no cerebellar atrophy. 1 sibling also had retinitis pigmentosa. Yeast modelling of this missense variant showed yeast harboring p.Gly118Asp (yeast equivalent) had decreased CoQ6 levels and an accumulation of the COQ5 yeast-equivalent substrate, DDMQ suggesting LOF.
PMID: 36266294 2 probands with retinitis pigmentosa from 2 families, 1 individual had symptoms onset at 49 years old with no other features while the 2nd had onset at 5 years old and also had muscular weakness and hypertelorism. Both patients had COQ5 c.682-7T>G which has 285 hets but no homs in gnomad v4. RT-PCR on patient cells showed majority exon 5 skipping, and minor exon 4+5 skipping, both out of frame and predicted to cause NMD. The major splicing event was seen in 56% of transcripts for that allele, so normal splicing is still occurring and its not a complete LOF allele. Both patients had different 2nd hits, Tyr311* and Arg123Trp.
The two patients in PMID: 36266294 are phenotypic outliers, PMID: 41199775 suggests you need a mutation affecting Gly118 to cause severe multisystem disease. Gly118 is in a might conserved DVAGGSG motif which is essential for binding S-adenosylmethionine. All other cases have a missense at this residue except for the family with the large duplication.Created: 26 Nov 2025, 2:31 p.m. | Last Modified: 26 Nov 2025, 2:31 p.m.
Panel Version: 1.3660
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Coenzyme Q10 deficiency, primary, 9 MIM#619028
Publications
Gene: coq5 has been classified as Green List (High Evidence).
gene: COQ5 was added gene: COQ5 was added to Genetic Epilepsy. Sources: Expert Review Green,Expert list,Victorian Clinical Genetics Services Mode of inheritance for gene: COQ5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: COQ5 were set to 29044765; 37599337; 21937992; 41199775; 36266294 Phenotypes for gene: COQ5 were set to Coenzyme Q10 deficiency, primary 9, MIM#619028
If promoting or demoting a gene, please provide comments to justify a decision to move it.
Genes included in a Genomics England gene panel for a rare disease category (green list) should fit the criteria A-E outlined below.
These guidelines were developed as a combination of the ClinGen DEFINITIVE evidence for a causal role of the gene in the disease(a), and the Developmental Disorder Genotype-Phenotype (DDG2P) CONFIRMED DD Gene evidence level(b) (please see the original references provided below for full details). These help provide a guideline for expert reviewers when assessing whether a gene should be on the green or the red list of a panel.
A. There are plausible disease-causing mutations(i) within, affecting or encompassing an interpretable functional region(ii) of this gene identified in multiple (>3) unrelated cases/families with the phenotype(iii).
OR
B. There are plausible disease-causing mutations(i) within, affecting or encompassing cis-regulatory elements convincingly affecting the expression of a single gene identified in multiple (>3) unrelated cases/families with the phenotype(iii).
OR
C. As definitions A or B but in 2 or 3 unrelated cases/families with the phenotype, with the addition of convincing bioinformatic or functional evidence of causation e.g. known inborn error of metabolism with mutation in orthologous gene which is known to have the relevant deficient enzymatic activity in other species; existence of an animal model which recapitulates the human phenotype.
AND
D. Evidence indicates that disease-causing mutations follow a Mendelian pattern of causation appropriate for reporting in a diagnostic setting(iv).
AND
E. No convincing evidence exists or has emerged that contradicts the role of the gene in the specified phenotype.
(i)Plausible disease-causing mutations: Recurrent de novo mutations convincingly affecting gene function. Rare, fully-penetrant mutations - relevant genotype never, or very rarely, seen in controls. (ii) Interpretable functional region: ORF in protein coding genes miRNA stem or loop. (iii) Phenotype: the rare disease category, as described in the eligibility statement. (iv) Intermediate penetrance genes should not be included.
It’s assumed that loss-of-function variants in this gene can cause the disease/phenotype unless an exception to this rule is known. We would like to collect information regarding exceptions. An example exception is the PCSK9 gene, where loss-of-function variants are not relevant for a hypercholesterolemia phenotype as they are associated with increased LDL-cholesterol uptake via LDLR (PMID: 25911073).
If a curated set of known-pathogenic variants is available for this gene-phenotype, please contact us at panelapp@genomicsengland.co.uk
We classify loss-of-function variants as those with the following Sequence Ontology (SO) terms:
Term descriptions can be found on the PanelApp homepage and Ensembl.
If you are submitting this evaluation on behalf of a clinical laboratory please indicate whether you report variants in this gene as part of your current diagnostic practice by checking the box
Standardised terms were used to represent the gene-disease mode of inheritance, and were mapped to commonly used terms from the different sources. Below each of the terms is described, along with the equivalent commonly-used terms.
A variant on one allele of this gene can cause the disease, and imprinting has not been implicated.
A variant on the paternally-inherited allele of this gene can cause the disease, if the alternate allele is imprinted (function muted).
A variant on the maternally-inherited allele of this gene can cause the disease, if the alternate allele is imprinted (function muted).
A variant on one allele of this gene can cause the disease. This is the default used for autosomal dominant mode of inheritance where no knowledge of the imprinting status of the gene required to cause the disease is known. Mapped to the following commonly used terms from different sources: autosomal dominant, dominant, AD, DOMINANT.
A variant on both alleles of this gene is required to cause the disease. Mapped to the following commonly used terms from different sources: autosomal recessive, recessive, AR, RECESSIVE.
The disease can be caused by a variant on one or both alleles of this gene. Mapped to the following commonly used terms from different sources: autosomal recessive or autosomal dominant, recessive or dominant, AR/AD, AD/AR, DOMINANT/RECESSIVE, RECESSIVE/DOMINANT.
A variant on one allele of this gene can cause the disease, however a variant on both alleles of this gene can result in a more severe form of the disease/phenotype.
A variant in this gene can cause the disease in males as they have one X-chromosome allele, whereas a variant on both X-chromosome alleles is required to cause the disease in females. Mapped to the following commonly used term from different sources: X-linked recessive.
A variant in this gene can cause the disease in males as they have one X-chromosome allele. A variant on one allele of this gene may also cause the disease in females, though the disease/phenotype may be less severe and may have a later-onset than is seen in males. X-linked inactivation and mosaicism in different tissues complicate whether a female presents with the disease, and can change over their lifetime. This term is the default setting used for X-linked genes, where it is not known definitately whether females require a variant on each allele of this gene in order to be affected. Mapped to the following commonly used terms from different sources: X-linked dominant, x-linked, X-LINKED, X-linked.
The gene is in the mitochondrial genome and variants within this can cause this disease, maternally inherited. Mapped to the following commonly used term from different sources: Mitochondrial.
Mapped to the following commonly used terms from different sources: Unknown, NA, information not provided.
For example, if the mode of inheritance is digenic, please indicate this in the comments and which other gene is involved.