UGT1A4 (UDP glucuronosyltransferase family 1 member A4)

Gene

• Entrez ID: 54657
• Gene name: UDP glucuronosyltransferase family 1 member A4
• Gene symbol: UGT1A4
• Synonyms (NCBI Gene): GNT1, HUG-BR2, UDPGT, UDPGT 1-4, UGT-1A, UGT-1D, UGT1, UGT1-01, UGT1-04, UGT1.1, UGT1.4, UGT1A, UGT1A1, UGT1A4S, UGT1D, hUG-BR1
• Chromosome: 2
• Chromosome location: 2q37.1
• 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 comp

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT1473389	hsa-miR-1202	CLIP-seq
MIRT1473390	hsa-miR-136	CLIP-seq
MIRT1473391	hsa-miR-3120-5p	CLIP-seq
MIRT1473392	hsa-miR-3130-3p	CLIP-seq
MIRT1473393	hsa-miR-3194-5p	CLIP-seq
MIRT1473394	hsa-miR-346	CLIP-seq
MIRT1473395	hsa-miR-3909	CLIP-seq
MIRT1473396	hsa-miR-3940-5p	CLIP-seq
MIRT1473397	hsa-miR-3972	CLIP-seq
MIRT1473398	hsa-miR-4288	CLIP-seq
MIRT1473399	hsa-miR-4421	CLIP-seq
MIRT1473400	hsa-miR-4507	CLIP-seq
MIRT1473401	hsa-miR-4766-5p	CLIP-seq
MIRT1473402	hsa-miR-4793-3p	CLIP-seq
MIRT1473403	hsa-miR-489	CLIP-seq
MIRT1473404	hsa-miR-514	CLIP-seq
MIRT1473405	hsa-miR-514b-3p	CLIP-seq
MIRT1473406	hsa-miR-548a-5p	CLIP-seq
MIRT1473407	hsa-miR-548ab	CLIP-seq
MIRT1473408	hsa-miR-548ak	CLIP-seq
MIRT1473409	hsa-miR-548b-5p	CLIP-seq
MIRT1473410	hsa-miR-548c-5p	CLIP-seq
MIRT1473411	hsa-miR-548d-5p	CLIP-seq
MIRT1473412	hsa-miR-548h	CLIP-seq
MIRT1473413	hsa-miR-548i	CLIP-seq
MIRT1473414	hsa-miR-548j	CLIP-seq
MIRT1473415	hsa-miR-548n	CLIP-seq
MIRT1473416	hsa-miR-548w	CLIP-seq
MIRT1473417	hsa-miR-548y	CLIP-seq
MIRT1473418	hsa-miR-559	CLIP-seq
MIRT1473419	hsa-miR-629	CLIP-seq
MIRT1473420	hsa-miR-632	CLIP-seq
MIRT2142602	hsa-miR-579	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
ESR1	Activation	19546240
SP1	Activation	19546240

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001972	Function	Retinoic acid binding	IDA	20308471
GO:0004857	Function	Enzyme inhibitor activity	ISS	20610558
GO:0005783	Component	Endoplasmic reticulum	IBA
GO:0005783	Component	Endoplasmic reticulum	IDA	17179145
GO:0005783	Component	Endoplasmic reticulum	IEA
GO:0005783	Component	Endoplasmic reticulum	NAS	20610558
GO:0005789	Component	Endoplasmic reticulum membrane	IEA
GO:0005789	Component	Endoplasmic reticulum membrane	IKR	20610558
GO:0005789	Component	Endoplasmic reticulum membrane	NAS	20610558
GO:0005789	Component	Endoplasmic reticulum membrane	TAS
GO:0006629	Process	Lipid metabolic process	IEA
GO:0006789	Process	Bilirubin conjugation	TAS
GO:0006805	Process	Xenobiotic metabolic process	IKR	20610558
GO:0008194	Function	UDP-glycosyltransferase activity	IEA
GO:0008202	Process	Steroid metabolic process	IEA
GO:0015020	Function	Glucuronosyltransferase activity	IDA	1898728, 15231852, 18177842, 22579593, 24641623
GO:0015020	Function	Glucuronosyltransferase activity	IEA
GO:0015020	Function	Glucuronosyltransferase activity	IKR	20610558
GO:0015020	Function	Glucuronosyltransferase activity	ISS	20610558
GO:0015020	Function	Glucuronosyltransferase activity	TAS
GO:0016020	Component	Membrane	IEA
GO:0016740	Function	Transferase activity	IEA
GO:0016757	Function	Glycosyltransferase activity	IEA
GO:0019899	Function	Enzyme binding	IBA
GO:0019899	Function	Enzyme binding	IEA
GO:0019899	Function	Enzyme binding	IPI	17179145, 20610558
GO:0042167	Process	Heme catabolic process	TAS
GO:0042803	Function	Protein homodimerization activity	IDA	17179145
GO:0042803	Function	Protein homodimerization activity	IEA
GO:0045922	Process	Negative regulation of fatty acid metabolic process	ISS	20610558
GO:0046982	Function	Protein heterodimerization activity	IEA
GO:0046982	Function	Protein heterodimerization activity	IPI	20610558
GO:0070640	Process	Vitamin D3 metabolic process	IDA	18177842, 24641623

Other IDs

• MIM: 606429
• HGNC: 12536
• e!Ensembl: ENSG00000244474

Protein

• UniProt ID: P22310
• Protein name: UDP-glucuronosyltransferase 1A4 (UGT1A4) (EC 2.4.1.17) (Bilirubin-specific UDPGT isozyme 2) (hUG-BR2) (UDP-glucuronosyltransferase 1-4) (UDPGT 1-4) (UGT1*4) (UGT1-04) (UGT1.4) (UDP-glucuronosyltransferase 1-D) (UGT-1D) (UGT1D)
• Protein function: [Isoform 1]: UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion i
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00201	UDPGT	29 → 525	UDP-glucoronosyl and UDP-glucosyl transferase	Family

• Tissue specificity: TISSUE SPECIFICITY: [Isoform 1]: Expressed in liver (PubMed:1339448, PubMed:18004212). Expressed in kidney, colon and small intestine (PubMed:18004212). Not expressed in esophagus (PubMed:18004212). Not expressed in skin (PubMed:1339448). {ECO:0000269|Pub
• Sequence:

  MARGLQVPLPRLATGLLLLLSVQPWAESGKVLVVPTDGSPWLSMREALRELHARGHQAVV
  LTPEVNMHIKEEKFFTLTAYAVPWTQKEFDRVTLGYTQGFFETEHLLKRYSRSMAIMNNV
  SLALHRCCVELLHNEALIRHLNATSFDVVLTDPVNLCGAVLAKYLSIPAVFFWRYIPCDL
  DFKGTQCPNPSSYIPKLLTTNSDHMTFLQRVKNMLYPLALSYICHTFSAPYASLASELFQ
  REVSVVDLVSYASVWLFRGDFVMDYPRPIMPNMVFIGGINCANGKPLSQEFEAYINASGE
  HGIVVFSLGSMVSEIPEKKAMAIADALGKIPQTVLWRYTGTRPSNLANNTILVKWLPQND
  LLGHPMTRAFITHAGSHGVYESICNGVPMVMMPLFGDQMDNAKRMETKGAGVTLNVLEMT
  SEDLENALKAVINDKSYKENIMRLSSLHKDRPVEPLDLAVFWVEFVMRHKGAPHLRPAAH
  DLTWYQYHSLDVIGFLLAVVLTVAFITFKCCAYGYRKCLGKKGRVKKAHKSKTH

• Sequence length: 534

Pathways

KEGG:

Pentose and glucuronate interconversions
Ascorbate and aldarate metabolism
Steroid hormone biosynthesis
Retinol metabolism
Porphyrin metabolism
Metabolism of xenobiotics by cytochrome P450
Drug metabolism - cytochrome P450
Drug metabolism - other enzymes
Metabolic pathways
Biosynthesis of cofactors
Bile secretion
Chemical carcinogenesis - DNA adducts
Chemical carcinogenesis - receptor activation

Reactome:

Glucuronidation
Heme degradation
Defective UGT1A4 causes hyperbilirubinemia

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
BILIRUBIN METABOLISM DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CELIAC DISEASE	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHOLELITHIASIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CRIGLER NAJJAR SYNDROME, TYPE 1	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CRIGLER NAJJAR SYNDROME, TYPE 2	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CRIGLER-NAJJAR SYNDROME	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GALLSTONES	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GILBERT DISEASE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
INSOMNIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LIVER DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LUCEY-DRISCOLL SYNDROME	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NON-ALCOHOLIC FATTY LIVER DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PERINATAL DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
UGT1A4-related disorder	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
alpha-Thalassemia	alpha Thalassemia	BEFREE	27557546		★☆☆☆☆ Found in Text Mining only
alpha^+^ Thalassemia	alpha Thalassemia	BEFREE	27557546		★☆☆☆☆ Found in Text Mining only
Anemia, Sickle Cell	Anemia	BEFREE	12850481, 18392554		★☆☆☆☆ Found in Text Mining only
Anemia, Sickle Cell	Anemia	GWASCAT_DG	22558097		★☆☆☆☆ Found in Text Mining only
Benign Prostatic Hyperplasia	Benign Prostatic Hyperplasia	BEFREE	24057187		★☆☆☆☆ Found in Text Mining only
beta Thalassemia	beta Thalassemia	BEFREE	18081723, 19021734, 9375768		★☆☆☆☆ Found in Text Mining only
beta^+^ Thalassemia	beta Thalassemia	BEFREE	18081723, 9375768		★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	30630678		★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	32456253, 34886806	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma	Carcinoma	BEFREE	27690298		★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	25288013, 26010150	Associate	★☆☆☆☆ Found in Text Mining only
Celiac Disease	Celiac disease	CTD_human_DG	30097691		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cholecystolithiasis	Cholecystolithiasis	BEFREE	11425418, 11843828, 14555305, 21319362		★☆☆☆☆ Found in Text Mining only
Cholelithiasis	Cholelithiasis	BEFREE	11425418, 11843828, 14555305, 16237771, 18081723, 19021734, 21319362, 24204915		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cholelithiasis	Cholelithiasis	GWASCAT_DG	22558097		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cholelithiasis	Cholelithiasis	GWASDB_DG	22558097		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cholestasis	Cholestasis	BEFREE	29867509		★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	BEFREE	20965940, 21310730, 26710796		★☆☆☆☆ Found in Text Mining only
Crigler Najjar syndrome, type 1	Crigler-Najjar syndrome	BEFREE	11013440, 12378576, 18180294, 19845429, 23403257, 7614251, 7906695, 7936809, 7989045, 9039987, 9156798, 9435989		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Crigler Najjar syndrome, type 1	Crigler-Najjar syndrome	CLINVAR_DG	11182932, 15712364, 26697581		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Crigler Najjar syndrome, type 2	Crigler-Najjar syndrome	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Deficiency of glucose-6-phosphate dehydrogenase	Deficiency Of Glucose-6-Phosphate Dehydrogenase	BEFREE	10541948, 27557546		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus, Non-Insulin-Dependent	Diabetes Mellitus	BEFREE	26628212		★☆☆☆☆ Found in Text Mining only
Differentiated Thyroid Gland Carcinoma	Thyroid Carcinoma	BEFREE	21317830		★☆☆☆☆ Found in Text Mining only
Epilepsy	Epilepsy	BEFREE	21601426, 23865846, 24820767, 25922177		★☆☆☆☆ Found in Text Mining only
Epilepsy	Epilepsy	Pubtator	23865846	Associate	★☆☆☆☆ Found in Text Mining only
Fleck corneal dystrophy	Fleck Corneal Dystrophy	BEFREE	28273590		★☆☆☆☆ Found in Text Mining only
Gastroschisis	Gastroschisis	Pubtator	31075877	Associate	★☆☆☆☆ Found in Text Mining only
Gaucher Disease	Gaucher Disease	BEFREE	30822514		★☆☆☆☆ Found in Text Mining only
Generalized glycogen storage disease of infants	Glycogen Storage Disease	BEFREE	28363873		★☆☆☆☆ Found in Text Mining only
Gilbert Disease (disorder)	Gilbert Disease	BEFREE	10541948, 10583252, 11843828, 11915038, 12012638, 12068798, 14663278, 15858133, 17496722, 19021734, 19845429, 19932091, 20177420, 20194756, 21309756, 21319362, 22160004, 22398043, 24785582, 26781906, 31017737, 8596320, 9375768		★☆☆☆☆ Found in Text Mining only
Gilbert Disease (disorder)	Gilbert Disease	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Glycogen storage disease type II	Glycogen Storage Disease	BEFREE	28363873		★☆☆☆☆ Found in Text Mining only
Hematologic Neoplasms	Hematologic Neoplasms	BEFREE	29661871		★☆☆☆☆ Found in Text Mining only
Hematologic Neoplasms	Hematologic neoplasm	Pubtator	29661871	Associate	★☆☆☆☆ Found in Text Mining only
Hereditary spherocytosis	Hereditary Spherocytosis	BEFREE	14663278, 21319362		★☆☆☆☆ Found in Text Mining only
Hyperbilirubinemia	Hyperbilirubinemia	BEFREE	10541948, 15319464, 16609363, 18043502, 20194756, 20504240, 20890421, 21309756, 21592495, 21983082, 21993917, 23130636, 23609856, 24204915, 24785582, 26480925, 26859599, 9156798, 9748558		★☆☆☆☆ Found in Text Mining only
Hyperbilirubinemia, Neonatal	Hyperbilirubinemia	BEFREE	10541948, 21983082, 24104695, 26342858, 28025333, 28340583		★☆☆☆☆ Found in Text Mining only
Kernicterus	Kernicterus	BEFREE	28167773		★☆☆☆☆ Found in Text Mining only
Leukopenia	Leukopenia	BEFREE	15007088, 20653675, 25778466, 26352872, 26710796		★☆☆☆☆ Found in Text Mining only
Liver Cirrhosis Alcoholic	Liver cirrhosis	Pubtator	29695616	Associate	★☆☆☆☆ Found in Text Mining only
Lucey-Driscoll syndrome (disorder)	Lucey-Driscoll syndrome	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	30630678		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of prostate	Prostate cancer	BEFREE	20308029, 25452636		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of stomach	Stomach Neoplasms	BEFREE	23303296		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	11170257, 30307765, 30724669		★☆☆☆☆ Found in Text Mining only
Metabolic Syndrome X	Metabolic Syndrome	BEFREE	18180294		★☆☆☆☆ Found in Text Mining only
Metabolic Syndrome X	Metabolic Syndrome	GWASCAT_DG	30621171		★☆☆☆☆ Found in Text Mining only
Myeloid Leukemia, Chronic	Myeloid Leukemia	BEFREE	23609856		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	15318931, 26010150, 9230212		★☆☆☆☆ Found in Text Mining only
Neutropenia	Neutropenia	BEFREE	15007088, 20653675, 25778466, 26352872, 26710796		★☆☆☆☆ Found in Text Mining only
Non-alcoholic Fatty Liver Disease	Non-Alcoholic Fatty Liver Disease	BEFREE	28098838		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Obesity	Obesity	GWASCAT_DG	25246029		★☆☆☆☆ Found in Text Mining only
Prostate carcinoma	Prostate cancer	BEFREE	20308029, 25452636		★☆☆☆☆ Found in Text Mining only
Rheumatoid Arthritis	Rheumatoid arthritis	BEFREE	21993917		★☆☆☆☆ Found in Text Mining only
Secondary malignant neoplasm of colon and/or rectum	Colorectal Neoplasms	BEFREE	20096102, 25778466, 28474802		★☆☆☆☆ Found in Text Mining only
Stomach Carcinoma	Stomach Carcinoma	BEFREE	23303296		★☆☆☆☆ Found in Text Mining only
Thalassemia Intermedia	Thalassemia	BEFREE	12850481		★☆☆☆☆ Found in Text Mining only
Unconjugated hyperbilirubinemia	Hyperbilirubinemia	BEFREE	12439228, 15864125, 15965581, 18781851, 26781906, 9435989		★☆☆☆☆ Found in Text Mining only
Xeroderma Pigmentosum, Complementation Group D	Xeroderma Pigmentosum	BEFREE	17549067		★☆☆☆☆ Found in Text Mining only