Human Disease Model Report: coenzyme Q10 deficiency, primary, 4

General Information

Name

coenzyme Q10 deficiency, primary, 4

FlyBase ID

FBhh0001447

Disease Ontology Term

primary coenzyme Q10 deficiency 4

Parent Disease

coenzyme Q10 deficiency, primary

OMIM

COENZYME Q10 DEFICIENCY, PRIMARY, 4; COQ10D4

Overview

This report describes coenzyme Q10 deficiency, primary, 4 (COQ10D4); COQ10D4 exhibits autosomal recessive inheritance. The human gene implicated in this disease is COQ8A, which encodes a mitochondrial protein involved in the biosynthesis of coenzyme Q (ubiquinone). There is a single orthologous gene in Drosophila, Dmel\Coq8, for which missense alleles and RNAi-targeting constructs have been generated. Dmel\Coq8 is also orthologous to the human gene COQ8B; COQ8B is implicated in nephrotic syndrome, type 9 (MIM:615573, FBhh0000621).

A wild-type UAS construct of the human Hsap\COQ8A gene has been introduced into flies. Expression of the human gene results in dominant negative phenotypes, preventing assessment of functional complementation. Since Coq8 functions as a dimer, it is possible that Hsap\COQ8A interferes with Coq8 function.

Pan-neuronal RNAi knockdown of Dmel\Coq8 is semi-lethal, with escapers exhibiting severe locomotor deficits. Knockdown of Coq8 in the eye results in degeneration of photoreceptors, progressive necrosis and increased generation of reactive oxygen species. Mutations in the fly gene analogous to variants implicated in human disease have been characterized; see the 'Disease-Implicated Variants' table below.

[updated Apr. 2022 by FlyBase; FBrf0222196]

Disease Summary Information

Parent Disease Summary: coenzyme Q10 deficiency, primary

Symptoms and phenotype

Specific Disease Summary: coenzyme Q10 deficiency, primary, 4

OMIM report

[COENZYME Q10 DEFICIENCY, PRIMARY, 4; COQ10D4](https://omim.org/entry/612016)

Human gene(s) implicated

[COENZYME Q8A; COQ8A](https://omim.org/entry/606980)

Symptoms and phenotype

Primary coenzyme Q10 deficiency-4 (COQ10D4) is an autosomal recessive disorder characterized by childhood-onset of cerebellar ataxia and exercise intolerance. Some affected individuals develop seizures and have mild mental impairment, indicating variable severity (summary by Mollet et al., 2008, pubmed:18319072; Lagier-Tourenne et al., 2008, pubmed:18319074). [from MIM:612016; 2022.04.04]

(OMIM, 2013-)

Genetics

Primary coenzyme Q10 deficiency-4 (COQ10D4) is caused by homozygous or compound heterozygous mutation in the COQ8A gene (previously designated ADCK3). [from MIM:612016; 2022.04.04]

(OMIM, 2013-)

Cellular phenotype and pathology

Molecular information

COQ8A encodes a mitochondrial protein involved in the biosynthesis of coenzyme Q (ubiquinone), an essential lipid-soluble electron transporter for aerobic cellular respiration. [Gene Cards, COQ8A; 2022.04.04]

(FlyBase Curators, 2013-)

Oral coenzyme Q10 supplementation does not result in significant improvement of neurologic symptoms. [from MIM:612016; 2022.04.04]

(OMIM, 2013-)

External links

Gene2Function (human gene): COQ8A
Gene Cards: COQ8A
GeneReviews, NCBI Bookshelf: Primary Coenzyme Q10 Deficiency
MedlinePlus (condition): Primary coenzyme Q10 deficiency
MedlinePlus (gene): COQ8A
MARRVEL (human gene): COQ8A
NCBI MedGen: Coenzyme Q10 deficiency, primary, 4 (COQ10D4)
NCBI (Entrez) gene: COQ8A; coenzyme Q8A

Disease synonyms

autosomal recessive spinocerebellar ataxia-9

COQ10D4

SCAR9

Related Diseases

Related human health report(s)

nephrotic syndrome related to coenzyme Q deficiency

Related Specific Diseases

OMIM phenotypic series

Coenzyme Q10 deficiency, primary

Disease

Associated Human gene(s)

Drosophila model

Human transgene in Drosophila

[COQ10D1](https://omim.org/entry/607426)

[COQ2](https://omim.org/entry/609825)

nephrotic syndrome related to coenzyme Q deficiency

[COQ10D4](https://omim.org/entry/612016)

[COQ8A](https://omim.org/entry/606980)

coenzyme Q10 deficiency, primary, 4

Ortholog Information

Human gene(s) in FlyBase

Hsap\COQ8A

Human gene (HGNC)

Symbol / Name

COQ8A; coenzyme Q8A

D. melanogaster ortholog (based on DIOPT)

Dmel\Coq8

(DIOPT, 2013-)

Comments on ortholog(s)

Many to one: 2 human genes to 1 Drosophila gene.

Other mammalian ortholog(s) used

D. melanogaster Gene Information (1)

Dmel\Coq8

Gene Snapshot

Contributions welcome

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

Comments on ortholog(s)

High-scoring ortholog of human COQ8B and COQ8A (1 Drosophila to 2 human).

Orthologs and Alignments from DRSC

DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans

H. sapiens (Human)

Other Genes Used: Viral, Bacterial, Synthetic (0)

Summary of Physical Interactions (0 groups)

Coq8

Alleles Reported to Model Human Disease (Disease Ontology) (8 alleles)

Coq8

Models Based on Experimental Evidence ( 7 )

Allele

Disease

Evidence

References

Coq8^GL01574

model of primary coenzyme Q10 deficiency 4

CEC

(Zhu et al., 2017)

model of nephrotic syndrome

CEA

(Zhu et al., 2017)

Coq8^GL00260

model of primary coenzyme Q10 deficiency 4

CEC

(Zhu et al., 2017)

model of nephrotic syndrome

CEA

(Zhu et al., 2017)

Coq8^KK107966

model of coenzyme Q10 deficiency disease

CEA

(Hura et al., 2022)

Coq8^HMS04484

model of primary coenzyme Q10 deficiency 4

CEC

(Zhu et al., 2017)

model of nephrotic syndrome

CEA

(Zhu et al., 2017)

Coq8^RNAi.UAS.cUa

model of nephrotic syndrome type 9

CEA

(Ashraf et al., 2013)

Coq8^{I295P.UAS.Tag:MYC}

model of coenzyme Q10 deficiency disease

CEA

(Hura et al., 2022)

Coq8^{L520.UAS.Tag:MYC}

model of coenzyme Q10 deficiency disease

CEA

(Hura et al., 2022)

Modifiers Based on Experimental Evidence ( 1 )

Allele

Disease

Interaction

References

Coq8^KK107966

model of coenzyme Q10 deficiency disease

is exacerbated by Hsap\COQ8A^UAS.cHa

(Hura et al., 2022)

Hsap\COQ8A

Models Based on Experimental Evidence ( 0 )

Allele

Disease

Evidence

References

Modifiers Based on Experimental Evidence ( 1 )

Allele

Disease

Interaction

References

Hsap\COQ8A^UAS.cHa

exacerbates coenzyme Q10 deficiency disease

modeled by Coq8^KK107966

(Hura et al., 2022)

Alleles Representing Disease-Implicated Variants

Genetic Tools, Stocks and Reagents

Sources of Stocks

Contact lab of origin for a reagent not available from a public stock center.

Bloomington Stock Center Disease Page

Related mammalian, viral, bacterial, or synthetic transgenes

Allele

Transgene

Publicly Available Stocks

Hsap\COQ8A^UAS.Tag:HA

PBac{UAS-hCOQ8A.HA}

y¹ w^*; PBac{UAS-hCOQ8A.HA}VK00037

Hsap\COQ8A^UAS.cHa

PBac{UAS-hCOQ8A.H}

Selected Drosophila transgenes

Allele

Transgene

Publicly Available Stocks

Coq8^{I295P.UAS.Tag:MYC}

PBac{UAS-Coq8.I295P.MYC}

Coq8^{L520.UAS.Tag:MYC}

PBac{UAS-Coq8.L520.MYC}

RNAi constructs available

Allele

Transgene

Publicly Available Stocks

w¹¹¹⁸; P{GD11306}v26536

Coq8^GL00260

P{TRiP.GL00260}

y¹ sc^* v¹ sev²¹; P{TRiP.GL00260}attP2

Coq8^GL01574

P{TRiP.GL01574}

y¹ sc^* v¹ sev²¹; P{TRiP.GL01574}attP2

Coq8^HMS04484

P{TRiP.HMS04484}

y¹ sc^* v¹ sev²¹; P{TRiP.HMS04484}attP40

Coq8^KK107966

P{KK107966}

P{KK107966}VIE-260B

Selected Drosophila classical alleles

Allele

Allele class

Mutagen

Publicly Available Stocks

References (5)

Report Sections

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