CMTRID

Genetic Context

HGNC-Approved Gene Symbol

COX6A1

Gene Full Name

Cytochrome C Oxidase Subunit 6a1

HGNC Gene Alias(es)

COX6AL

Chromosome

12p24.31

Zygosity of Responsible Variant

Homozygous

Mitochondrial Involvement

Yes

Variant Mechanism

Loss of Function (LoF)

Details

Mechanistic basis:
Biallelic

Confidence:
Medium

Prediction:
The literature predicts a biallelic loss-of-function mechanism for CMTRID: COX6A1 encodes a nuclear-encoded subunit of cytochrome c oxidase, and recessive splice-region and loss variants reduce or abolish functional subunit, causing complex IV assembly deficiency and reduced activity in patient fibroblasts. Because both alleles must be impaired and restored wild-type COX6A1 is predicted to restore complex IV, this is a recessive loss of function rather than a dominant-negative or gain-of-function effect.

Rationale:
Recessive COX6A1 splice and loss variants deplete a nuclear-encoded complex IV subunit, so restored wild-type is predicted to restore cytochrome c oxidase assembly and activity: a biallelic loss of function, with no dominant-negative or gain-of-function contribution.

ClinVar Pathogenic Variants

View CMTRID ClinVar Variants

CMTRID OMIM Entry

CMTRID OMIM

COX6A1 OMIM Entry

COX6A1 OMIM