U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

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

Gene ID: 54657, updated on 27-Nov-2024

Summary

Go to the top of the page Help
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]
NEW
Try the new Gene table
Try the new Transcript table

Genomic context

Go to the top of the page Help
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

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. 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

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

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

Go to the top of the page Help

See Variation Viewer (GRCh37.p13)

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

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

Go to the top of the page Help
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)

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_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
Molecular Biology Databases
Research Materials
Tools
Miscellaneous