Trimethyllysine dioxygenase, mitochondrial is an enzyme that in humans is encoded by the TMLHE gene in chromosome X.^[4][5][6] Mutations in the TMLHE gene resulting in carnitine biosynthesis disruption have been associated with autism symptoms.^[7]

Quick Facts Identifiers, Aliases ...

TMLHE
Identifiers
Aliases	TMLHE, AUTSX6, BBOX2, TMLD, TMLH, TMLHED, XAP130, D430017M14Rik, trimethyllysine hydroxylase, epsilon
External IDs	OMIM: 300777 MGI: 2180203 HomoloGene: 21853 GeneCards: TMLHE
Gene location (Human) Chr. X chromosome (human)[1] Band Xq28 Start 155,489,011 bp[1] End 155,719,098 bp[1]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in skeletal muscle tissue gastrocnemius muscle blood left ventricle monocyte islet of Langerhans ganglionic eminence smooth muscle tissue right adrenal gland rectum n/a More reference expression data BioGPS n/a
Gene ontology Molecular function iron ion binding oxidoreductase activity oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen metal ion binding dioxygenase activity trimethyllysine dioxygenase activity protein binding Cellular component mitochondrial matrix mitochondrion Biological process negative regulation of oxidoreductase activity carnitine biosynthetic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 55217 192289 Ensembl ENSG00000185973 ENSMUSG00000079834 UniProt Q9NVH6 Q91ZE0 RefSeq (mRNA) NM_001184797 NM_018196 NM_138758 RefSeq (protein) NP_001171726 NP_060666 NP_620097 Location (UCSC) Chr X: 155.49 – 155.72 Mb n/a PubMed search [2] [3]
Wikidata
View/Edit Human View/Edit Mouse

Close

The TMHLE gene is located at the extreme end of the Xq28 region with high genomic instability,^[8] and encodes a protein trimethyllysine dioxygenase, a, Fe2+ and 2-oxoglytarate dependent non-heme-ferrous iron hydrolase localized to the mitochondrial matrix.^[9]

The trimethyllysine dioxygenase enzyme catalyzes the first step in the carnitine biosynthesis pathway,^[9] which is part of amine biosynthesis. Carnitine is a molecule that play an essential role in the transport of activated fatty acids across the inner mitochondrial membrane where they are metabolized. The encoded protein converts trimethyllysine into hydroxytrimethyllysine with the reaction (EC 1.14.11.8):

N₆,N₆,N(6)-trimethyl-L-lysine + 2-oxoglutarate + O₂ = 3-hydroxy-N₆,N₆,N(6)-trimethyl-L-lysine + succinate + CO₂.

and requires iron and L-ascorbate as co-factors.

Mutations in the TMLHE gene cause epsilon-trimethyllysine hydroxylase deficiency (TMLHED),^[10][11] an inborn error of metabolism in carnitine biosynthesis, which may increase the risks of developing neurodevelopmental disorders, autism-related behaviors, and autism spectrum disorders.^[12][7]

TMLHE has been shown to have 14 binary protein-protein interactions including 12 co-complex interactions. TMLHE appears to interact with SUGCT.^[13]