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    UGT1A4 UDP glucuronosyltransferase family 1 member A4 [ Homo sapiens (human) ]

    Gene ID: 54657, updated on 14-Nov-2024

    Summary

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    Official Symbol
    UGT1A4provided by HGNC
    Official Full Name
    UDP glucuronosyltransferase family 1 member A4provided by HGNC
    Primary source
    HGNC:HGNC:12536
    See related
    Ensembl:ENSG00000244474 MIM:606429; AllianceGenome:HGNC:12536
    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
    GNT1; UGT1; UDPGT; UGT1A; UGT1D; UGT-1A; UGT-1D; UGT1.1; UGT1.4; UGT1A1; HUG-BR2; UGT1-01; UGT1-04; UGT1A4S; hUG-BR1; UDPGT 1-4
    Summary
    This gene encodes a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids, bilirubin, hormones, and drugs, into water-soluble, excretable metabolites. This gene is part of a complex locus that encodes several UDP-glucuronosyltransferases. The locus includes thirteen unique alternate first exons followed by four common exons. Four of the alternate first exons are considered pseudogenes. Each of the remaining nine 5' exons may be spliced to the four common exons, resulting in nine proteins with different N-termini and identical C-termini. Each first exon encodes the substrate binding site, and is regulated by its own promoter. This enzyme has some glucuronidase activity towards bilirubin, although is is more active on amines, steroids, and sapogenins. [provided by RefSeq, Jul 2008]
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    Genomic context

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    See UGT1A4 in Genome Data Viewer
    Location:
    2q37.1
    Exon count:
    5
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (233718736..233773300)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (234207385..234261929)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (234627382..234681946)

    Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene UDP glucuronosyltransferase family 1 member A complex locus Neighboring gene UDP glucuronosyltransferase family 1 member A11, pseudogene Neighboring gene UDP glucuronosyltransferase family 1 member A8 Neighboring gene UDP glucuronosyltransferase family 1 member A10 Neighboring gene UDP glucuronosyltransferase family 1 member A13, pseudogene Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr2:234599674-234600281 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr2:234600282-234600888 Neighboring gene UDP glucuronosyltransferase family 1 member A9 Neighboring gene UDP glucuronosyltransferase family 1 member A7 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:234621256-234621756 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:234621757-234622257 Neighboring gene UDP glucuronosyltransferase family 1 member A6 Neighboring gene UDP glucuronosyltransferase family 1 member A5 Neighboring gene ribosomal protein L17 pseudogene 11 Neighboring gene UDP glucuronosyltransferase family 1 member A3 Neighboring gene DnaJ heat shock protein family (Hsp40) member B3 pseudogene Neighboring gene ReSE screen-validated silencer GRCh37_chr2:234668353-234668527 Neighboring gene DnaJ heat shock protein family (Hsp40) member B3 Neighboring gene UDP glucuronosyltransferase family 1 member A2, pseudogene Neighboring gene UDP glucuronosyltransferase family 1 member A1 Neighboring gene maestro heat like repeat family member 2A Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:234731477-234731977 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:234759038-234759538 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:234763063-234764055 Neighboring gene Holliday junction recognition protein

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues 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

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    Related articles in PubMed

    1. Frequencies of UGT1A4*2 (P24T) and *3 (L48V) and their effects on serum concentrations of lamotrigine. Reimers A, et al. Eur J Drug Metab Pharmacokinet, 2016 Apr. PMID 25492569
    2. UDP-glucuronosyltransferase 1A4 (UGT1A4) polymorphisms in a Jordanian population. Hakooz N, et al. Mol Biol Rep, 2012 Jul. PMID 22367373
    3. Characterization of nicotine and cotinine N-glucuronidations in human liver microsomes. Nakajima M, et al. Drug Metab Dispos, 2002 Dec. PMID 12433823
    4. Retigabine N-glucuronidation and its potential role in enterohepatic circulation. Hiller A, et al. Drug Metab Dispos, 1999 May. PMID 10220490
    5. UGT1A4*3 encodes significantly increased glucuronidation of olanzapine in patients on maintenance treatment and in recombinant systems. Haslemo T, et al. Clin Pharmacol Ther, 2012 Aug. PMID 22713701

    See all (91) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Impact of UGT1A4 and UGT2B7 polymorphisms on lamotrigine plasma concentration in patients with bipolar disorder.
      Title: Impact of UGT1A4 and UGT2B7 polymorphisms on lamotrigine plasma concentration in patients with bipolar disorder.
    2. Bearing variant alleles at uridine glucuronosyltransferase polymorphisms UGT2B7 -161C > T (rs7668258) or UGT1A4*3 c.142 T > G (rs2011425) has no relevant consequences for lamotrigine troughs in adults with epilepsy.
      Title: Bearing variant alleles at uridine glucuronosyltransferase polymorphisms UGT2B7 -161C > T (rs7668258) or UGT1A4*3 c.142 T > G (rs2011425) has no relevant consequences for lamotrigine troughs in adults with epilepsy.
    3. Hepatotoxicity with High-Dose Green Tea Extract: Effect of Catechol-O-Methyltransferase and Uridine 5'-Diphospho-glucuronosyltransferase 1A4 Genotypes.
      Title: Hepatotoxicity with High-Dose Green Tea Extract: Effect of Catechol-O-Methyltransferase and Uridine 5'-Diphospho-glucuronosyltransferase 1A4 Genotypes.
    4. A validation study of the UGT1A4 rs2011404 variant and the risk of anti-tuberculosis drug-induced hepatotoxicity in an Eastern Chinese Han population.
      Title: A validation study of the UGT1A4 rs2011404 variant and the risk of anti-tuberculosis drug-induced hepatotoxicity in an Eastern Chinese Han population.
    5. The association of genetic polymorphisms in CYP1A2, UGT1A4, and ABCB1 with autonomic nervous system dysfunction in schizophrenia patients treated with olanzapine.
      Title: The association of genetic polymorphisms in CYP1A2, UGT1A4, and ABCB1 with autonomic nervous system dysfunction in schizophrenia patients treated with olanzapine.
    6. Representation of CYP3A4, CYP3A5 and UGT1A4 Polymorphisms within Croatian Breast Cancer Patients' Population.
      Title: Representation of CYP3A4, CYP3A5 and UGT1A4 Polymorphisms within Croatian Breast Cancer Patients' Population.
    7. Association of CYP2C19 and UGT1A4 polymorphisms with voriconazole-induced liver injury.
      Title: Association of CYP2C19 and UGT1A4 polymorphisms with voriconazole-induced liver injury.
    8. Chinese patients with A/A or G/A genotype in the promoter region of bilirubin glucuronoside glucuronosyltransferase (UGT1A4) have a lower 5-year disease-free survival (DFS) rate than those with the wild-type G/G genotype when treated with adjuvant tamoxifen. The rs869283 genotype remains an independent prognostic marker for DFS in multivariate analysis.
      Title: The Effect of Polymorphism in UGT1A4 on Clinical Outcomes of Adjuvant Tamoxifen Therapy for Patients With Breast Cancer in China.
    9. Genetic polymorphism in UGT1A4 and UGT2B7 may play a modest role in lamotrigine clearance changes during pregnancy. In addition, study indicates that the sex of the foetus influenced significantly the change in LTG clearance.
      Title: UGT polymorphisms and lamotrigine clearance during pregnancy.
    10. Plant steroids competitively inhibited the UGT1A4-catalyzed trifluoperazine glucuronidation reaction suggesting potential for herb-drug interactions to occur.
      Title: Drug interaction study of natural steroids from herbs specifically toward human UDP-glucuronosyltransferase (UGT) 1A4 and their quantitative structure activity relationship (QSAR) analysis for prediction.
    Submit: New GeneRIF Correction See all GeneRIFs (37)

    Phenotypes

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

    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    A genome-wide assessment of variability in human serum metabolism.
    EBI GWAS Catalog
    A genome-wide association study for serum bilirubin levels and gene-environment interaction in a Chinese population.
    EBI GWAS Catalog
    A genome-wide association study identifies UGT1A1 as a regulator of serum cell-free DNA in young adults: The Cardiovascular Risk in Young Finns Study.
    EBI GWAS Catalog
    A genome-wide association study of total bilirubin and cholelithiasis risk in sickle cell anemia.
    EBI GWAS Catalog
    An atlas of genetic influences on human blood metabolites.
    EBI GWAS Catalog
    Association of SNPs in the UGT1A gene cluster with total bilirubin and mortality in the Diabetes Heart Study.
    EBI GWAS Catalog
    Common variants in the SLCO1B3 locus are associated with bilirubin levels and unconjugated hyperbilirubinemia.
    EBI GWAS Catalog
    Discovery and refinement of loci associated with lipid levels.
    EBI GWAS Catalog
    Genetic determinants influencing human serum metabolome among African Americans.
    EBI GWAS Catalog
    Genome-wide analysis of hepatic lipid content in extreme obesity.
    EBI GWAS Catalog
    Genome-wide association meta-analysis for total serum bilirubin levels.
    EBI GWAS Catalog
    Genome-wide association of serum bilirubin levels in Korean population.
    EBI GWAS Catalog
    Human metabolic individuality in biomedical and pharmaceutical research.
    EBI GWAS Catalog
    Mayo Genome Consortia: a genotype-phenotype resource for genome-wide association studies with an application to the analysis of circulating bilirubin levels.
    EBI GWAS Catalog
    UGT1A1 is a major locus influencing bilirubin levels in African Americans.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables enzyme binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables enzyme binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables enzyme inhibitor activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		 PubMed 
    enables glucuronosyltransferase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    NOT enables glucuronosyltransferase activity IKR
    Inferred from Key Residues
    more info
    		 PubMed 
    enables glucuronosyltransferase activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		 PubMed 
    enables glucuronosyltransferase activity TAS
    Traceable Author Statement
    more info
    		  
    enables protein heterodimerization activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein heterodimerization activity IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein homodimerization activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    NOT enables retinoic acid binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in bilirubin conjugation TAS
    Traceable Author Statement
    more info
    		  
    involved_in cellular glucuronidation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in cellular glucuronidation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in cellular glucuronidation ISS
    Inferred from Sequence or Structural Similarity
    more info
    		 PubMed 
    involved_in cellular glucuronidation TAS
    Traceable Author Statement
    more info
    		  
    involved_in heme catabolic process TAS
    Traceable Author Statement
    more info
    		  
    involved_in negative regulation of cellular glucuronidation ISS
    Inferred from Sequence or Structural Similarity
    more info
    		 PubMed 
    involved_in negative regulation of fatty acid metabolic process ISS
    Inferred from Sequence or Structural Similarity
    more info
    		 PubMed 
    involved_in vitamin D3 metabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    NOT involved_in xenobiotic metabolic process IKR
    Inferred from Key Residues
    more info
    		 PubMed 
    Component Evidence Code Pubs
    is_active_in endoplasmic reticulum IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in endoplasmic reticulum IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in endoplasmic reticulum NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    NOT located_in endoplasmic reticulum membrane IKR
    Inferred from Key Residues
    more info
    		 PubMed 
    located_in endoplasmic reticulum membrane NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    located_in endoplasmic reticulum membrane TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    UDP-glucuronosyltransferase 1A4
    Names
    Bilirubin-specific UDPGT isozyme 1
    UDP glucuronosyltransferase 1 family, polypeptide A4
    UDP glycosyltransferase 1 family, polypeptide A4
    UDP-glucuronosyltransferase 1 family polypeptide A4s
    UDP-glucuronosyltransferase 1-1
    UDP-glucuronosyltransferase 1-4
    UDP-glucuronosyltransferase 1-A
    UDP-glucuronosyltransferase 1-D
    UDP-glucuronosyltransferase 1A1
    UDPGT 1-1
    bilirubin UDP-glucuronosyltransferase isozyme 2
    bilirubin-specific UDPGT isozyme 2
    NP_009051.1

    NCBI Reference Sequences (RefSeq)

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    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_002601.2 RefSeqGene

      Range
      134049..188556
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_007120.3 → NP_009051.1  UDP-glucuronosyltransferase 1A4 precursor

      See identical proteins and their annotated locations for NP_009051.1

      Status: REVIEWED

      Source sequence(s)
      AC006985, AC114812, AY435139, M57951
      Consensus CDS
      CCDS33405.1
      UniProtKB/Swiss-Prot
      B2R937, B8K288, P22310, Q5DT00
      UniProtKB/TrEMBL
      A3KME6
      Related
      ENSP00000362508.4, ENST00000373409.8
      Conserved Domains (1) summary
      pfam00201
      Location:29 → 525
      UDPGT; UDP-glucoronosyl and UDP-glucosyl transferase

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000002.12 Reference GRCh38.p14 Primary Assembly

      Range
      233718736..233773300
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060926.1 Alternate T2T-CHM13v2.0

      Range
      234207385..234261929
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P22310.1 GenPept UniProtKB/Swiss-Prot:P22310

    Gene LinkOut

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

    Chemical Information
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