Trimethyllysine dioxygenase, mitochondrial (TMLHE)

Trimethyllysine dioxygenase, mitochondrial (TMLHE) is a non-heme iron-dependent enzyme located in the mitochondrial matrix, encoded by the TMLHE gene on chromosome Xq28[1][3]. It catalyzes the initial step in carnitine biosynthesis, converting trimethyllysine to hydroxytrimethyllysine using iron and 2-oxoglutarate as cofactors. Carnitine is essential for the transport of activated fatty acids into mitochondria for β-oxidation. Loss-of-function mutations in TMLHE disrupt carnitine biosynthesis and have been associated with increased risk for neurodevelopmental disorders, such as autism spectrum disorder, as well as the rare condition epsilon-trimethyllysine hydroxylase deficiency. TMLHE shows critical roles in neural stem cell maintenance, likely by supporting mitochondrial fatty acid oxidation and redox homeostasis[2][4]. No approved drugs directly target TMLHE, but carnitine supplementation is considered for individuals with deficiency syndromes.

Other names

Trimethyllysine hydroxylase, epsilonTMLHTML dioxygenaseTMLDFLJ10727BBOX2XAP130Epsilon-trimethyllysine 2-oxoglutarate dioxygenaseEpsilon-trimethyllysine hydroxylaseTML hydroxylaseTML-alpha-ketoglutarate dioxygenaseButyrobetaine (gamma), 2-oxoglutarate dioxygenase (gamma-butyrobetaine hydroxylase) 2AUTSX6TMLHED

not a drug target for direct-acting therapeutics; variants may be targeted indirectly through metabolic or dietary intervention