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IEMbase 0731: COX6A1-related cytochrome c oxidase subunit 6A1 deficiency

Scope

Field Value
IEMbase ID 731
Nosology 7.4.05.02
Nosology code IEM0466
Gene COX6A1
External IDs OMIM:616039; ORPHA:435998
Generated mapping UNMAPPED; weak candidate COX6A2-Related_COX_Deficiency.yaml
Candidate DisMech targets No exact COX6A1/CMTD target identified
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents autosomal recessive COX6A1-related cytochrome c oxidase subunit 6A1 deficiency. The alternate-name field identifies recessive intermediate Charcot-Marie-Tooth disease type D. The cached rows are sparse but specific: adult hearing loss and polyneuropathy that begins in childhood and is strongest in adulthood.

DisMech phenotype coverage

No exact COX6A1 or recessive intermediate Charcot-Marie-Tooth disease type D local target was identified.

The generated COX6A2-Related_COX_Deficiency.yaml candidate is not exact coverage. COX6A2 is the striated-muscle isoform of cytochrome c oxidase subunit VIa and causes a muscle-specific complex IV deficiency with weakness, hypotonia, and sometimes cardiomyopathy. COX6A1 is a different isoform and the IEMbase record is a neuropathy/CMTD phenotype. Local Charcot-Marie-Tooth files provide broad neuropathy context only, not COX6A1-specific disease coverage.

Concordance and completeness

Judgement: true local COX6A1/CMTD gap. The COX6A2 candidate should be rejected as exact coverage.

The shared complex IV subunit-family language is not enough to map across COX6A1 and COX6A2. IEMbase points to a neuropathy-dominant CMTD entity, whereas the local COX6A2 entry is a muscle-specific COX deficiency.

Curation actions

  • Add a dedicated COX6A1/recessive intermediate Charcot-Marie-Tooth disease type D target if curated.
  • Reject COX6A2-Related_COX_Deficiency.yaml as exact coverage.
  • Preserve adult hearing loss and childhood-to-adult polyneuropathy.
  • Use generic CMT content only as broad context, not as a resolved exact target.