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Aliases for TMLHE Gene

Aliases for TMLHE Gene

  • Trimethyllysine Hydroxylase, Epsilon 2 3 5
  • Butyrobetaine (Gamma), 2-Oxoglutarate Dioxygenase (Gamma-Butyrobetaine Hydroxylase) 2 2 3
  • Epsilon-Trimethyllysine 2-Oxoglutarate Dioxygenase 3 4
  • Epsilon-Trimethyllysine Hydroxylase 3 4
  • TML-Alpha-Ketoglutarate Dioxygenase 3 4
  • TML Hydroxylase 3 4
  • EC 1.14.11.8 4 61
  • TMLD 3 4
  • TMLH 3 4
  • Trimethyllysine Dioxygenase, Mitochondrial 3
  • TML Dioxygenase 4
  • AUTSX6 3
  • TMLHED 3
  • XAP130 3
  • BBOX2 3

External Ids for TMLHE Gene

Previous GeneCards Identifiers for TMLHE Gene

  • GC0XM148537
  • GC0XM150855
  • GC0XP152095
  • GC0XM153151
  • GC0XM154283
  • GC0XM154372
  • GC0XM154719
  • GC0XP143121

Summaries for TMLHE Gene

Entrez Gene Summary for TMLHE 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]

GeneCards Summary for TMLHE Gene

TMLHE (Trimethyllysine Hydroxylase, Epsilon) is a Protein Coding gene. Diseases associated with TMLHE include Epsilon-Trimethyllysine Hydroxylase Deficiency and Pervasive Developmental Disorder. Among its related pathways are Valine, leucine and isoleucine degradation and Lysine degradation. GO annotations related to this gene include oxidoreductase activity and L-ascorbic acid binding. An important paralog of this gene is BBOX1.

UniProtKB/Swiss-Prot for TMLHE Gene

  • Converts trimethyllysine (TML) into hydroxytrimethyllysine (HTML) (PubMed:11431483, PubMed:23092983).

Gene Wiki entry for TMLHE Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for TMLHE Gene

Genomics for TMLHE Gene

Regulatory Elements for TMLHE Gene

Enhancers for TMLHE Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
- Elite enhancer/Elite enhancer-gene association

Enhancers around TMLHE on UCSC Golden Path with GeneCards custom track

Genomic Location for TMLHE Gene

Chromosome:
X
Start:
155,489,011 bp from pter
End:
155,669,944 bp from pter
Size:
180,934 bases
Orientation:
Minus strand

Genomic View for TMLHE Gene

Genes around TMLHE on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
TMLHE Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for TMLHE Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for TMLHE Gene

Proteins for TMLHE Gene

  • Protein details for TMLHE Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9NVH6-TMLH_HUMAN
    Recommended name:
    Trimethyllysine dioxygenase, mitochondrial
    Protein Accession:
    Q9NVH6
    Secondary Accessions:
    • A8K6M9
    • B4E3R3
    • Q5TZB5
    • Q6IA90
    • Q8TBT0

    Protein attributes for TMLHE Gene

    Size:
    421 amino acids
    Molecular mass:
    49518 Da
    Cofactor:
    Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
    Cofactor:
    Name=L-ascorbate; Xref=ChEBI:CHEBI:38290;
    Quaternary structure:
    • Homodimer.

    Alternative splice isoforms for TMLHE Gene

neXtProt entry for TMLHE Gene

Post-translational modifications for TMLHE Gene

  • Ubiquitination at Lys 135
  • Modification sites at PhosphoSitePlus

Other Protein References for TMLHE Gene

ENSEMBL proteins:
REFSEQ proteins:

Domains & Families for TMLHE Gene

Protein Domains for TMLHE Gene

Suggested Antigen Peptide Sequences for TMLHE Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q9NVH6

UniProtKB/Swiss-Prot:

TMLH_HUMAN :
  • Belongs to the gamma-BBH/TMLD family.
Family:
  • Belongs to the gamma-BBH/TMLD family.
genes like me logo Genes that share domains with TMLHE: view

No data available for Gene Families for TMLHE Gene

Function for TMLHE Gene

Molecular function for TMLHE Gene

UniProtKB/Swiss-Prot CatalyticActivity:
N(6),N(6),N(6)-trimethyl-L-lysine + 2-oxoglutarate + O(2) = 3-hydroxy-N(6),N(6),N(6)-trimethyl-L-lysine + succinate + CO(2).
UniProtKB/Swiss-Prot Function:
Converts trimethyllysine (TML) into hydroxytrimethyllysine (HTML) (PubMed:11431483, PubMed:23092983).

Enzyme Numbers (IUBMB) for TMLHE Gene

Gene Ontology (GO) - Molecular Function for TMLHE Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005506 iron ion binding IEA --
GO:0016702 oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen IEA --
GO:0031418 L-ascorbic acid binding IEA --
GO:0050353 trimethyllysine dioxygenase activity TAS --
genes like me logo Genes that share ontologies with TMLHE: view
genes like me logo Genes that share phenotypes with TMLHE: view

Human Phenotype Ontology for TMLHE Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Model Products

CRISPR Products

Inhibitory RNA Products

Clone Products

Flow Cytometry Products

No data available for Animal Models , Transcription Factor Targets and HOMER Transcription for TMLHE Gene

Localization for TMLHE Gene

Subcellular locations from UniProtKB/Swiss-Prot for TMLHE Gene

Mitochondrion matrix.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for TMLHE Gene COMPARTMENTS Subcellular localization image for TMLHE gene
Compartment Confidence
mitochondrion 5
cytosol 3
extracellular 1
peroxisome 1

Gene Ontology (GO) - Cellular Components for TMLHE Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005739 mitochondrion IDA --
GO:0005759 mitochondrial matrix TAS --
genes like me logo Genes that share ontologies with TMLHE: view

Pathways & Interactions for TMLHE Gene

genes like me logo Genes that share pathways with TMLHE: view

Pathways by source for TMLHE Gene

1 KEGG pathway for TMLHE Gene

UniProtKB/Swiss-Prot Q9NVH6-TMLH_HUMAN

  • Pathway: Amine and polyamine biosynthesis; carnitine biosynthesis.

Interacting Proteins for TMLHE Gene

STRING Interaction Network Preview (showing 3 interactants - click image to see details)
http://string-db.org/version_10/api/image/networkList?limit=0&targetmode=proteins&caller_identity=gene_cards&network_flavor=evidence&identifiers=9606.ENSP00000335261%0d%0a9606.ENSP00000272645%0d%0a9606.ENSP00000285896%0d%0a9606.ENSP00000355279%0d%0a
Selected Interacting proteins: ENSP00000335261 Q9NVH6-TMLH_HUMAN for TMLHE Gene via STRING IID

Gene Ontology (GO) - Biological Process for TMLHE Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0045329 carnitine biosynthetic process TAS --
GO:0055114 oxidation-reduction process IEA --
genes like me logo Genes that share ontologies with TMLHE: view

No data available for SIGNOR curated interactions for TMLHE Gene

Drugs & Compounds for TMLHE Gene

(9) Drugs for TMLHE Gene - From: DrugBank, ApexBio, and HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Succinic acid Approved Nutra Full agonist, Agonist, Target 0
Vitamin C Approved Nutra Target 488,488
Carbon dioxide Approved, Vet_approved Pharma 0
Oxygen Approved, Vet_approved Pharma 0
spermine Approved Nutra Full agonist, Agonist 0

(6) Additional Compounds for TMLHE Gene - From: HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
3-Hydroxy-N6,N6,N6-trimethyl-L-lysine
  • 3-Hydroxy-N(6),N(6),N(6)-trimethyl-L-lysine
  • 3-Hydroxy-N(6),N(6),N(6)-trimethyllysine
  • 3-Hydroxy-N6,N6,N6-trimethyl-L-lysin-N6-ium
  • 3-Hydroxy-N6,N6,N6-trimethyl-L-lysine
Fe2+
  • Armco iron
  • Carbonyl iron
  • FE
  • Ferrovac e
  • Hematite
15438-31-0
N1-acetylspermine
  • N'-Acetylspermine
  • N'-Monoacetylspermine
  • N(1)-Acetylspermine
  • N-(3-((4-((3-Aminopropyl)amino)butyl)amino)propyl)-Acetamide
  • N-Acetylspermine
25593-72-0
N6,N6,N6-Trimethyl-L-lysine
  • (S)-2-amino-6-(trimethylammonio)hexanoate
  • (S)-2-amino-6-(trimethylammonio)hexanoic acid
  • delta-Trimethyllysine
  • epsilon-N-Trimethyl-L-lysine
  • epsilon-Trimethyl-L-lysine
19253-88-4
Norspermidine
  • -1,3-propanediamine
  • 1,7-Diamino-4-azaheptane
  • 3, 3'-Diaminodipropylamine
  • 3, {3'-Iminobis[propylamine]}
  • 3,3'-Diamino-Dipropylamine
56-18-8

(1) ApexBio Compounds for TMLHE Gene

Compound Action Cas Number
WWL 70 α/β-hydrolase domain 6 inhibitor 947669-91-2
genes like me logo Genes that share compounds with TMLHE: view

Transcripts for TMLHE Gene

Unigene Clusters for TMLHE Gene

Trimethyllysine hydroxylase, epsilon:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

Clone Products

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for TMLHE Gene

No ASD Table

Relevant External Links for TMLHE Gene

GeneLoc Exon Structure for
TMLHE
ECgene alternative splicing isoforms for
TMLHE

Expression for TMLHE Gene

mRNA expression in normal human tissues for TMLHE Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for TMLHE Gene

This gene is overexpressed in Bone (13.3), Stomach (7.1), and Salivary gland (6.7).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for TMLHE Gene



Protein tissue co-expression partners for TMLHE Gene

NURSA nuclear receptor signaling pathways regulating expression of TMLHE Gene:

TMLHE

SOURCE GeneReport for Unigene cluster for TMLHE Gene:

Hs.133321

mRNA Expression by UniProt/SwissProt for TMLHE Gene:

Q9NVH6-TMLH_HUMAN
Tissue specificity: All isoforms, but isoform 8, are widely expressed in adult and fetal tissues. Isoform 8 is restricted to heart and skeletal muscle.
genes like me logo Genes that share expression patterns with TMLHE: view

Primer Products

No data available for mRNA differential expression in normal tissues for TMLHE Gene

Orthologs for TMLHE Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for TMLHE Gene

Organism Taxonomy Gene Similarity Type Details
cow
(Bos Taurus)
Mammalia TMLHE 34
  • 92.72 (n)
  • 91.69 (a)
TMLHE 35
  • 95 (a)
OneToOne
dog
(Canis familiaris)
Mammalia TMLHE 34
  • 93.35 (n)
  • 94.06 (a)
TMLHE 35
  • 94 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Tmlhe 34
  • 87.41 (n)
  • 88.12 (a)
Tmlhe 16
Tmlhe 35
  • 88 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia TMLHE 34
  • 99.53 (n)
  • 99.53 (a)
TMLHE 35
  • 99 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Tmlhe 34
  • 85.11 (n)
  • 86.46 (a)
oppossum
(Monodelphis domestica)
Mammalia TMLHE 35
  • 82 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia TMLHE 35
  • 83 (a)
OneToOne
chicken
(Gallus gallus)
Aves TMLHE 34
  • 74.88 (n)
  • 82.06 (a)
TMLHE 35
  • 82 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia TMLHE 35
  • 88 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia tmlhe 34
  • 66.75 (n)
  • 70.24 (a)
African clawed frog
(Xenopus laevis)
Amphibia MGC68497 34
zebrafish
(Danio rerio)
Actinopterygii tmlhe 34
  • 66.41 (n)
  • 71.87 (a)
tmlhe 35
  • 69 (a)
OneToOne
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.9575 34
fruit fly
(Drosophila melanogaster)
Insecta CG4335 36
  • 35 (a)
CG4335 34
  • 46.75 (n)
  • 36.98 (a)
CG4335 35
  • 34 (a)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP005447 34
  • 48.1 (n)
  • 38.48 (a)
worm
(Caenorhabditis elegans)
Secernentea gbh-2 36
  • 34 (a)
gbh-2 34
  • 47.71 (n)
  • 37.14 (a)
gbh-2 35
  • 30 (a)
OneToOne
A. gosspyii yeast
(Ashbya gossypii)
Saccharomycetes AGOS_AEL035W 34
  • 45.05 (n)
  • 35.99 (a)
K. lactis yeast
(Kluyveromyces lactis)
Saccharomycetes KLLA0A10945g 34
  • 46.63 (n)
  • 34.55 (a)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes AIM17 35
  • 17 (a)
OneToMany
AIM17 37
bread mold
(Neurospora crassa)
Ascomycetes NCU03802 34
  • 47.09 (n)
  • 39.45 (a)
Species where no ortholog for TMLHE was found in the sources mined by GeneCards:
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for TMLHE Gene

ENSEMBL:
Gene Tree for TMLHE (if available)
TreeFam:
Gene Tree for TMLHE (if available)

Paralogs for TMLHE Gene

Paralogs for TMLHE Gene

(1) SIMAP similar genes for TMLHE Gene using alignment to 1 proteins:

Pseudogenes.org Pseudogenes for TMLHE Gene

genes like me logo Genes that share paralogs with TMLHE: view

Variants for TMLHE Gene

Sequence variations from dbSNP and Humsavar for TMLHE Gene

SNP ID Clin Chr 0X pos Sequence Context AA Info Type
rs380439 -- 155,499,233(+) GGGAA(A/G)GTTAG intron-variant
rs395414 -- 155,499,650(-) ctttt(A/T)tggtt intron-variant
rs473579 -- 155,607,367(-) tgctg(A/C/G/T)aattt intron-variant
rs518178 -- 155,603,373(-) ctttc(A/T)ttcat intron-variant
rs546070 -- 155,494,878(+) CTCCT(C/T)TTACA intron-variant

Structural Variations from Database of Genomic Variants (DGV) for TMLHE Gene

Variant ID Type Subtype PubMed ID
dgv2549e212 CNV gain 25503493
dgv2550e212 CNV loss 25503493
dgv2551e212 CNV loss 25503493
esv1007887 CNV deletion 20482838
esv24743 CNV loss 19812545
esv24821 CNV gain+loss 19812545
esv2659146 CNV deletion 23128226
esv2660855 CNV deletion 23128226
esv2665236 CNV deletion 23128226
esv2669858 CNV deletion 23128226
esv2670601 CNV deletion 23128226
esv2671097 CNV deletion 23128226
esv2675898 CNV deletion 23128226
esv2994901 CNV deletion 24192839
esv29972 CNV gain 17803354
esv33784 CNV gain+loss 17666407
esv3381803 CNV insertion 20981092
esv3559517 CNV deletion 23714750
esv3559518 CNV deletion 23714750
esv3559519 CNV deletion 23714750
esv3559520 CNV deletion 23714750
esv3575071 CNV loss 25503493
esv3575074 CNV loss 25503493
esv3575076 CNV loss 25503493
esv3575078 CNV loss 25503493
esv3575079 CNV loss 25503493
esv992364 CNV loss 20482838
nsv1078693 CNV duplication 25765185
nsv1119373 CNV duplication 24896259
nsv1128558 CNV deletion 24896259
nsv1137701 CNV deletion 24896259
nsv1137702 CNV deletion 24896259
nsv1146049 CNV duplication 26484159
nsv438162 CNV loss 16468122
nsv499361 OTHER inversion 21111241
nsv499386 CNV loss 21111241
nsv510869 CNV deletion 20534489
nsv511652 CNV loss 21212237
nsv512705 CNV loss 21212237
nsv515187 CNV loss 21397061
nsv519485 CNV loss 19592680
nsv520699 CNV gain 19592680
nsv7162 CNV deletion 18451855
nsv7163 CNV insertion 18451855
nsv7470 OTHER inversion 18451855
nsv818043 CNV gain 17921354
nsv820472 CNV deletion 20802225
nsv829418 CNV loss 20364138
nsv829420 CNV loss 20364138
nsv953711 CNV deletion 24416366

Variation tolerance for TMLHE Gene

Residual Variation Intolerance Score: 38.6% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.61; 13.01% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for TMLHE Gene

Human Gene Mutation Database (HGMD)
TMLHE
SNPedia medical, phenotypic, and genealogical associations of SNPs for
TMLHE

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for TMLHE Gene

Disorders for TMLHE Gene

MalaCards: The human disease database

(4) MalaCards diseases for TMLHE Gene - From: OMIM, ClinVar, GeneTests, Swiss-Prot, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
epsilon-trimethyllysine hydroxylase deficiency
  • autism, x-linked 6
pervasive developmental disorder
  • pervasive development disorder
incontinentia pigmenti
  • bloch-sulzberger syndrome
opitz-gbbb syndrome
  • opitz g/bbb syndrome
- elite association - COSMIC cancer census association via MalaCards
Search TMLHE in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

TMLH_HUMAN
  • Autism, X-linked 6 (AUTSX6) [MIM:300872]: A form of autism, a complex multifactorial, pervasive developmental disorder characterized by impairments in reciprocal social interaction and communication, restricted and stereotyped patterns of interests and activities, and the presence of developmental abnormalities by 3 years of age. Most individuals with autism also manifest moderate mental retardation. AUTSX6 patients may respond favorably to carnitine supplementation. {ECO:0000269 PubMed:21865298, ECO:0000269 PubMed:23092983}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Relevant External Links for TMLHE

Atlas of Genetics and Cytogenetics in Oncology and Haematology:
TMLHE
genes like me logo Genes that share disorders with TMLHE: view

No data available for Genatlas for TMLHE Gene

Publications for TMLHE Gene

  1. Functional analysis of TMLH variants and definition of domains required for catalytic activity and mitochondrial targeting. (PMID: 15754339) Monfregola J. … Ursini M.V. (J. Cell. Physiol. 2005) 3 4 22 65
  2. Molecular and biochemical characterization of rat epsilon-N- trimethyllysine hydroxylase, the first enzyme of carnitine biosynthesis. (PMID: 11431483) Vaz F.M. … Wanders R.J.A. (J. Biol. Chem. 2001) 2 3 4 65
  3. Analysis of the chromosome X exome in patients with autism spectrum disorders identified novel candidate genes, including TMLHE. (PMID: 23092983) Nava C. … Depienne C. (Transl Psychiatry 2012) 3 4 65
  4. Use of array CGH to detect exonic copy number variants throughout the genome in autism families detects a novel deletion in TMLHE. (PMID: 21865298) Celestino-Soper P.B. … Beaudet A.L. (Hum. Mol. Genet. 2011) 3 4 65
  5. Functional characterization of the TMLH gene: promoter analysis, in situ hybridization, identification and mapping of alternative splicing variants. (PMID: 17408883) Monfregola J. … Ursini M.V. (Gene 2007) 3 4 65

Products for TMLHE Gene

Sources for TMLHE Gene

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