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mitochondrial complex IV deficiency, nuclear type 21 - Clinical Profile, Genes & Research | Kisho | Kisho

Rare Disease

mitochondrial complex IV deficiency, nuclear type 21

MONDO:0033656

Also known as:MC4DN21

Overview

Any mitochondrial complex IV deficiency in which the cause of the disease is a mutation in the COXFA4 gene.

GeneticsAutosomal recessive · COXFA4 (chr 7)

OnsetCONGENITAL

Clinical Presentation

Built from Human Phenotype Ontology (HPO) phenotype annotations and GeneReviews clinical descriptions. Features represent findings documented across known cases — not an exhaustive list of possible symptoms.

Features include always present findings: Delayed speech and language development, Increased CSF lactate, Increased intramyocellular lipid droplets, and Cytochrome C oxidase-negative muscle fibers and others; and common findings: Failure to thrive in infancy, Dystonia, Ataxia, and Motor delay. 18 total HPO annotations.

Organ System	Phenotype Count	Example Features
Brain and nerves	7	Bilateral tonic-clonic seizure, Spastic diplegia, Delayed speech and language development

Genetic Landscape

Assembled from HGNC gene records, ClinGen gene-disease validity evidence, and ClinVar pathogenic variant data. Validity classifications reflect the strength of published evidence linking each gene to this disease.

COXFA4 encodes cytochrome c oxidase associated subunit FA4 (81 aa). Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. Highest expression in Heart Atrial Appendage (366.6 TPM) and Heart Left Ventricle (353.9 TPM).

Mitochondrial complex IV deficiency, nuclear type 21 is associated with mutations in the COXFA4 gene on chromosome 7.

COXFA4 is classified as a druggable target with score 0.0.

Diagnosis

Genetic testing for COXFA4 is available. Testing is considered confirmatory for diagnosis.

Prognosis

Phenotype severity distribution: 5 always present features, 4 common features.

Data assembled from 4 of 12 sources · Last updated Sep 18, 2026, 1:48 AM UTC

MONDOHPOClinicalTrials.govFDAPubMedHGNCClinVarClinGenGeneReviewsOrphanetOMIMRUSP

Medical References

External Resources

OMIM

Online Mendelian Inheritance in Man

OMIM:619065

GARD

Genetic and Rare Diseases Info Center

GARD:16418

Questions for Your Care Team

→Should my partner and I meet with a genetic counselor to discuss carrier status and family planning?
→Are there specialists or centers of excellence for this condition in my area?
→Is there a patient registry I should consider joining?

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mitochondrial complex IV deficiency, nuclear type 21

Overview

Clinical Presentation

Genetic Landscape

Diagnosis

Prognosis

Medical References

External Resources

OMIM

GARD

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Questions for Your Care Team

Questions for Your Care Team

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