CMT2Q

Genetic Context

HGNC-Approved Gene Symbol

DHTKD1

Gene Full Name

dehydrogenase E1 and transketolase domain containing 1

HGNC Gene Alias(es)

KIAA1630, MGC3090, DKFZP762M115, OADH-E1, OADC-E1, E1a

Chromosome

10p14

Zygosity of Responsible Variant

Heterozygous

Mitochondrial Involvement

Yes

Variant Mechanism

Loss of Function (LoF)

Details

Mechanistic basis:
Haploinsufficiency

Confidence:
Medium

Prediction:
DHTKD1 encodes the E1 component of the 2-oxoadipate dehydrogenase complex in the lysine degradation pathway. For CMT2Q the literature predicts haploinsufficiency as the route to loss of function: the heterozygous nonsense allele p.Y486* reported by Xu et al. (2012) lowered DHTKD1 transcript and protein in patient cells, with reduced ATP production and elevated reactive oxygen species. Because no truncated product is retained, added wild-type protein is predicted to rescue.

Rationale:
Nonsense-mediated decay of the p.Y486* transcript removes the message rather than delivering a truncated enzyme into the complex, so the deficit reads as dosage. Two things temper the evidence: only one dominant family has been described, and complete biallelic DHTKD1 loss causes a separate recessive disease, 2-aminoadipic 2-oxoadipic aciduria (AMOXAD), leaving it unsettled whether one lost copy suffices for dominant CMT. Confidence sits at medium.

ClinVar Pathogenic Variants

View DHTKD1 ClinVar Variants

CMT2Q OMIM Entry

CMT2Q OMIM

DHTKD1 OMIM Entry

DHTKD1 OMIM