TMLHE

Protein identityUniProt · HPA

UniProt accession

Q9NVH6

Gene

TMLHE

Ensembl

ENSG00000185973

Chromosome

X

Canonical length

421 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Mitochondria

Quaternary structure

Homodimer

OverviewNCBI Gene

This gene encodes the protein trimethyllysine dioxygenase which is the first enzyme in the carnitine biosynthesis pathway. Carnitine play an essential role in the transport of activated fatty acids across the inner mitochondrial membrane. The encoded protein converts trimethyllysine into hydroxytrimethyllysine. A pseudogene of this gene is found on chromosome X. Alternate splicing results in multiple transcript variants.[provided by RefSeq, May 2010]

Canonical amino-acid sequenceUniProt

421 residues, UniProt reviewed canonical sequence.

>Q9NVH6|TMLHE
     1  MWYHRLSHLH SRLQDLLKGG VIYPALPQPN FKSLLPLAVH WHHTASKSLT CAWQQHEDHF
    61  ELKYANTVMR FDYVWLRDHC RSASCYNSKT HQRSLDTASV DLCIKPKTIR LDETTLFFTW
   121  PDGHVTKYDL NWLVKNSYEG QKQKVIQPRI LWNAEIYQQA QVPSVDCQSF LETNEGLKKF
   181  LQNFLLYGIA FVENVPPTQE HTEKLAERIS LIRETIYGRM WYFTSDFSRG DTAYTKLALD
   241  RHTDTTYFQE PCGIQVFHCL KHEGTGGRTL LVDGFYAAEQ VLQKAPEEFE LLSKVPLKHE
   301  YIEDVGECHN HMIGIGPVLN IYPWNKELYL IRYNNYDRAV INTVPYDVVH RWYTAHRTLT
   361  IELRRPENEF WVKLKPGRVL FIDNWRVLHG RECFTGYRQL CGCYLTRDDV LNTARLLGLQ
   421  A

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against TMLHE can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.31

Highest tissue expression

31 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about TMLHE.

Disease | AllUniProt

Conditions TMLHE is implicated in, by any mechanism.

• Autism, X-linked 6 (AUTSX6) MIM:300872

Disease | GeneticClinVar

6 pathogenic / likely-pathogenic of 149 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Epsilon-trimethyllysine hydroxylase deficiency
• Schizophrenia
• Cerebellar vermis hypoplasia
• Corpus callosum, agenesis of
• Congenital cerebellar hypoplasia

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.18

gnomAD pLI

0

gnomAD missense Z

0.64

DepMap mean gene effect

0.12

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• carnitine biosynthetic process

Molecular functions

• iron ion binding
• trimethyllysine dioxygenase activity

Cellular components

• mitochondrial matrix
• mitochondrion

Protein domainsUniProt · Pfam · InterPro

• TauD/TfdA-like domain
• Gamma-butyrobetaine hydroxylase-like, N-terminal
• GBBH-like, N-terminal domain superfamily
• Glutarate 2-hydroxylase superfamily
• Alpha-ketoglutarate-dependent hydroxylases
• Taurine catabolism dioxygenase TauD, TfdA family
• Gamma-butyrobetaine hydroxylase-like, N-terminal
• Trimethyllysine dioxygenase

KeywordsUniProt

• Acetylation
• Alternative promoter usage
• Autism
• Autism spectrum disorder
• Carnitine biosynthesis
• Dioxygenase
• Iron
• Metal-binding
• Mitochondrion
• Oxidoreductase
• Transit peptide