U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

TMLHE trimethyllysine hydroxylase, epsilon [ Homo sapiens (human) ]

Gene ID: 55217, updated on 5-Mar-2024

Summary

Go to the top of the page Help
Official Symbol
TMLHEprovided by HGNC
Official Full Name
trimethyllysine hydroxylase, epsilonprovided by HGNC
Primary source
HGNC:HGNC:18308
See related
Ensembl:ENSG00000185973 MIM:300777; AllianceGenome:HGNC:18308
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
TMLD; TMLH; BBOX2; AUTSX6; TMLHED; XAP130
Summary
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]
Expression
Ubiquitous expression in heart (RPKM 6.4), fat (RPKM 5.3) and 25 other tissues See more
Orthologs
mouse all
NEW
Try the new Gene table
Try the new Transcript table

Genomic context

Go to the top of the page Help
See TMLHE in Genome Data Viewer
Location:
Xq28
Exon count:
13
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) X NC_000023.11 (155489011..155612952, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) X NC_060947.1 (153718334..153838175, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) X NC_000023.10 (154718672..154842613, complement)

Chromosome X - NC_000023.11Genomic Context describing neighboring genes Neighboring gene int22h-3 recombination region Neighboring gene microRNA 1184-3 Neighboring gene TMLHE antisense RNA 1 Neighboring gene H2A.B variant histone 3 Neighboring gene coagulation factor VIII associated 3 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 30078 Neighboring gene sprouty RTK signaling antagonist 3 Neighboring gene meiotic recombination hotspot PAR2A Neighboring gene meiotic recombination hotspot PAR2 Neighboring gene adenosylmethionine decarboxylase 1 pseudogene 2 Neighboring gene diphthamide biosynthesis 3 pseudogene 2

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help
  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

Go to the top of the pageHelp

Related articles in PubMed

  1. Investigating the active site of human trimethyllysine hydroxylase. Wang Y, et al. Biochem J, 2019 Apr 10. PMID 30898847
  2. A common X-linked inborn error of carnitine biosynthesis may be a risk factor for nondysmorphic autism. Celestino-Soper PB, et al. Proc Natl Acad Sci U S A, 2012 May 22. PMID 22566635, Free PMC Article
  3. Use of array CGH to detect exonic copy number variants throughout the genome in autism families detects a novel deletion in TMLHE. Celestino-Soper PB, et al. Hum Mol Genet, 2011 Nov 15. PMID 21865298, Free PMC Article
  4. Complex recombination with deletion in the F8 and duplication in the TMLHE mediated by int22h copies during early embryogenesis. Chen C, et al. Thromb Haemost, 2017 Jul 26. PMID 28492696
  5. Analysis of the chromosome X exome in patients with autism spectrum disorders identified novel candidate genes, including TMLHE. Nava C, et al. Transl Psychiatry, 2012 Oct 23. PMID 23092983, Free PMC Article

See all (34) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. This work demonstrates the importance of the recognition sites that contribute to the enzymatic activity of TMLH: the Fe(II)-binding H242-D244-H389 residues, R391-R398 involved in 2OG binding and several residues (D231, N334 and the aromatic cage comprised of W221, Y217 and Y234) associated with binding of (2S)-N (epsilon)-trimethyllysine.
    Title: Investigating the active site of human trimethyllysine hydroxylase.
  2. Case Report: complex recombination with deletion in the F8 and duplication in the TMLHE mediated by int22h copies during early embryogenesis in proband's mother.
    Title: Complex recombination with deletion in the F8 and duplication in the TMLHE mediated by int22h copies during early embryogenesis.
  3. Study found 3 mutations in TMLHE to be associated with autism spectrum disorder, c.229C>T/p.Arg77X, c.730G>C/p.Asp244His, and c.1107G>T/p.Glu369Asp.
    Title: Analysis of the chromosome X exome in patients with autism spectrum disorders identified novel candidate genes, including TMLHE.
  4. TMLHE deficiency is common in control males and was not significantly increased in frequency in probands from simplex autism families, however, it was 2.82-fold more frequent in probands from male-male multiplex autism families.
    Title: A common X-linked inborn error of carnitine biosynthesis may be a risk factor for nondysmorphic autism.
  5. Use of array CGH to detect exonic copy number variants throughout the genome in autism families detects a novel deletion in TMLHE.
    Title: Use of array CGH to detect exonic copy number variants throughout the genome in autism families detects a novel deletion in TMLHE.
  6. By 5' and 3' RACE, we identified and mapped two alternative 5' TMLH first exons and seven alternative 3'-splice variants.
    Title: Functional characterization of the TMLH gene: promoter analysis, in situ hybridization, identification and mapping of alternative splicing variants.
  7. C-terminal region of trimethyllysine hydroxylase, epsilon contains the main determinants for its enzymatic activity including a key H389 residue
    Title: Functional analysis of TMLH variants and definition of domains required for catalytic activity and mitochondrial targeting.
Submit: New GeneRIF Correction

Phenotypes

Go to the top of the page Help

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Epsilon-trimethyllysine hydroxylase deficiency
MedGen: C3550875 OMIM: 300872 GeneReviews: Not available
Compare labs

Copy number response

Description
Copy number response
Triplosensitivity

No evidence available (Last evaluated 2013-08-01)

ClinGen Genome Curation Page
Haploinsufficency

Little evidence for dosage pathogenicity (Last evaluated 2013-08-01)

ClinGen Genome Curation PagePubMed

Variation

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

Go to the top of the page

Interactions

Go to the top of the page Help
Products Interactant Other Gene Complex Source Pubs Description

General gene information

Go to the top of the page Help

Markers

Homology

Clone Names

  • FLJ10727

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables iron ion binding IEA
Inferred from Electronic Annotation
more info
  
enables trimethyllysine dioxygenase activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Process Evidence Code Pubs
involved_in carnitine biosynthetic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in carnitine biosynthetic process IEA
Inferred from Electronic Annotation
more info
  
involved_in carnitine biosynthetic process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Component Evidence Code Pubs
located_in mitochondrial matrix TAS
Traceable Author Statement
more info
  
is_active_in mitochondrion IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in mitochondrion IDA
Inferred from Direct Assay
more info
  

General protein information

Go to the top of the page Help
Preferred Names
trimethyllysine dioxygenase, mitochondrial
Names
TML hydroxylase
TML-alpha-ketoglutarate dioxygenase
butyrobetaine (gamma), 2-oxoglutarate dioxygenase (gamma-butyrobetaine hydroxylase) 2
epsilon-trimethyllysine 2-oxoglutarate dioxygenase
epsilon-trimethyllysine hydroxylase
NP_001171726.1
NP_060666.1
XP_011529484.1
XP_016885109.1
XP_047298190.1
XP_047298191.1
XP_047298192.1
XP_054183321.1
XP_054183322.1
XP_054183323.1
XP_054183324.1
XP_054183325.1

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

NEW Try the new Transcript table

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_021318.1 RefSeqGene

    Range
    5010..128951
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001184797.2 → NP_001171726.1  trimethyllysine dioxygenase, mitochondrial isoform 2 precursor

    See identical proteins and their annotated locations for NP_001171726.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the 3' UTR and coding region differences, compared to variant 1. The resulting protein (isoform 2) has a distinct C-terminus and is shorter than isoform 1.
    Source sequence(s)
    BC025269, DA323339, DB174485
    Consensus CDS
    CCDS55547.1
    UniProtKB/Swiss-Prot
    Q9NVH6
    Related
    ENSP00000358447.4, ENST00000369439.4
    Conserved Domains (1) summary
    cl26676
    Location:70 → 332
    TauD; Taurine dioxygenase, alpha-ketoglutarate-dependent [Secondary metabolites biosynthesis, transport and catabolism]

  2. NM_018196.4 → NP_060666.1  trimethyllysine dioxygenase, mitochondrial isoform 1 precursor

    See identical proteins and their annotated locations for NP_060666.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
    Source sequence(s)
    AK001589, BX571846, DB174485
    Consensus CDS
    CCDS14768.1
    UniProtKB/Swiss-Prot
    A8K6M9, B4E3R3, Q5TZB5, Q6IA90, Q8TBT0, Q9NVH6
    Related
    ENSP00000335261.3, ENST00000334398.8
    Conserved Domains (1) summary
    TIGR02410
    Location:70 → 419
    carnitine_TMLD; trimethyllysine dioxygenase

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000023.11 Reference GRCh38.p14 Primary Assembly

    Range
    155489011..155612952 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047442235.1 → XP_047298191.1  trimethyllysine dioxygenase, mitochondrial isoform X2

  2. XM_047442234.1 → XP_047298190.1  trimethyllysine dioxygenase, mitochondrial isoform X1

  3. XM_011531182.4 → XP_011529484.1  trimethyllysine dioxygenase, mitochondrial isoform X1

    Conserved Domains (3) summary
    cd00250
    Location:91 → 357
    CAS_like; Clavaminic acid synthetase (CAS) -like; CAS is a trifunctional Fe(II)/ 2-oxoglutarate (2OG) oxygenase carrying out three reactions in the biosynthesis of clavulanic acid, an inhibitor of class A serine beta-lactamases. In general, Fe(II)-2OG oxygenases ...
    TIGR02410
    Location:19 → 368
    carnitine_TMLD; trimethyllysine dioxygenase
    cl01414
    Location:10 → 82
    DUF971; Protein of unknown function (DUF971)

  4. XM_047442236.1 → XP_047298192.1  trimethyllysine dioxygenase, mitochondrial isoform X2

  5. XM_017029620.3 → XP_016885109.1  trimethyllysine dioxygenase, mitochondrial isoform X3

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060947.1 Alternate T2T-CHM13v2.0

    Range
    153718334..153838175 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054327348.1 → XP_054183323.1  trimethyllysine dioxygenase, mitochondrial isoform X2

  2. XM_054327346.1 → XP_054183321.1  trimethyllysine dioxygenase, mitochondrial isoform X4

    UniProtKB/Swiss-Prot
    A8K6M9, B4E3R3, Q5TZB5, Q6IA90, Q8TBT0, Q9NVH6

  3. XM_054327347.1 → XP_054183322.1  trimethyllysine dioxygenase, mitochondrial isoform X1

  4. XM_054327349.1 → XP_054183324.1  trimethyllysine dioxygenase, mitochondrial isoform X2

  5. XM_054327350.1 → XP_054183325.1  trimethyllysine dioxygenase, mitochondrial isoform X3

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9NVH6.1 GenPept UniProtKB/Swiss-Prot:Q9NVH6

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

Chemical Information
Molecular Biology Databases
Research Materials
Tools
Miscellaneous