DHTKD1

Chr 10

dehydrogenase E1 and transketolase domain containing 1

Also known as: AAKAD, AMOXAD, CMT2Q, E1a, OADC-E1, OADH-E1

NCBI Gene: 55526 ENSG00000181192 UniProt: Q96HY7

The protein functions as the 2-oxoadipate dehydrogenase component of the mitochondrial 2-oxoadipate dehydrogenase complex, catalyzing the rate-limiting decarboxylation of 2-oxoadipate in the final degradation pathway of lysine, hydroxylysine, and tryptophan. Mutations cause either alpha-aminoadipic and alpha-ketoadipic aciduria (a metabolic disorder) or Charcot-Marie-Tooth disease type 2Q (an axonal peripheral neuropathy), with both autosomal dominant and autosomal recessive inheritance patterns reported. The gene shows relatively low constraint against loss-of-function variants, which may explain the variable clinical presentations and inheritance patterns.

ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a component of a mitochondrial 2-oxoglutarate-dehydrogenase-complex-like protein involved in the degradation pathways of several amino acids, including lysine. Mutations in this gene are associated with 2-aminoadipic 2-oxoadipic aciduria and Charcot-Marie-Tooth Disease Type 2Q. [provided by RefSeq, May 2013]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtCharcot-Marie-Tooth disease, axonal, type 2Q

UniProtAlpha-aminoadipic and alpha-ketoadipic aciduria

Clinical highlights

Gene-disease validity (ClinGen)

2-aminoadipic 2-oxoadipic aciduria · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.25

LOEUF

LOF

Mechanism· G2P

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429