UGT1A4

UDP glucuronosyltransferase family 1 member A4, the group of UDP glucuronosyltransferases

Basic information

Region (hg38): 2:233718735-233773300

Links

ENSG00000244474 ∙ NCBI:54657 ∙ OMIM:606429 ∙ HGNC:12536 ∙ Uniprot:P22310 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the UGT1A4 gene.

• not provided (213 variants)
• Gilbert syndrome (60 variants)
• Crigler-Najjar syndrome (49 variants)
• Lucey-Driscoll syndrome (45 variants)
• Inborn genetic diseases (41 variants)
• UGT1A1-related condition (20 variants)
• Crigler-Najjar syndrome, type II (17 variants)
• Hyperbilirubinemia (16 variants)
• Crigler-Najjar syndrome type 1 (14 variants)
• not specified (13 variants)
• Irinotecan response (5 variants)
• UGT1A1-Related Disorders (4 variants)
• Bilirubin, serum level of, quantitative trait locus 1 (2 variants)
• Gilbert syndrome;Crigler-Najjar syndrome type 1;Crigler-Najjar syndrome, type II;Bilirubin, serum level of, quantitative trait locus 1;Lucey-Driscoll syndrome (2 variants)
• Bilirubin, serum level of, quantitative trait locus 1;Crigler-Najjar syndrome type 1;Lucey-Driscoll syndrome;Crigler-Najjar syndrome, type II;Gilbert syndrome (2 variants)
• irinotecan response - Toxicity (1 variants)
• UGT1A1-related disorder (1 variants)
• Lucey-Driscoll syndrome;Crigler-Najjar syndrome, type II;Gilbert syndrome;Crigler-Najjar syndrome type 1;Bilirubin, serum level of, quantitative trait locus 1 (1 variants)
• Bilirubin, serum level of, quantitative trait locus 1;Crigler-Najjar syndrome type 1;Crigler-Najjar syndrome, type II;Lucey-Driscoll syndrome;Gilbert syndrome (1 variants)
• Crigler-Najjar syndrome, type II;Lucey-Driscoll syndrome;Crigler-Najjar syndrome type 1;Bilirubin, serum level of, quantitative trait locus 1;Gilbert syndrome (1 variants)
• Gilbert syndrome, susceptibility to (1 variants)
• Bilirubin, serum level of, quantitative trait locus 1;Lucey-Driscoll syndrome;Crigler-Najjar syndrome, type II;Gilbert syndrome;Crigler-Najjar syndrome type 1 (1 variants)
• Lucey-Driscoll syndrome;Crigler-Najjar syndrome, type II;Bilirubin, serum level of, quantitative trait locus 1;Gilbert syndrome;Crigler-Najjar syndrome type 1 (1 variants)
• Crigler-Najjar syndrome type 1;Gilbert syndrome;Crigler-Najjar syndrome, type II;Lucey-Driscoll syndrome (1 variants)
• Crigler-Najjar syndrome, type II;Gilbert syndrome;Lucey-Driscoll syndrome;Crigler-Najjar syndrome type 1;Bilirubin, serum level of, quantitative trait locus 1 (1 variants)
• Gilbert syndrome;Bilirubin, serum level of, quantitative trait locus 1;Crigler-Najjar syndrome type 1;Lucey-Driscoll syndrome;Crigler-Najjar syndrome, type II (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the UGT1A4 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			7	11		18
missense	3	8	63	5		79
nonsense	4		2			6
start loss						0
frameshift	4					4
inframe indel			2			2
splice donor/acceptor (+/-2bp)	1	3				4
splice region			2	1		3
non coding	15	10	95	17	13	150
Total	27	21	169	33	13

Highest pathogenic variant AF is 0.0000919

Variants in UGT1A4

This is a list of pathogenic ClinVar variants found in the UGT1A4 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-233718831-G-A		not specified	Uncertain significance (May 26, 2023)
2-233718852-G-A		not specified	Likely benign (Mar 01, 2023)
2-233718862-A-G			Likely benign (Mar 01, 2023)
2-233718864-G-T		not specified	Uncertain significance (Feb 05, 2024)
2-233718873-T-A		not specified	Uncertain significance (Dec 27, 2022)
2-233718885-T-C		not specified	Uncertain significance (Jan 04, 2024)
2-233718960-C-T		not specified	Likely benign (Nov 07, 2022)
2-233718970-G-C			Likely benign (Feb 01, 2024)
2-233718977-G-T		not specified	Uncertain significance (Nov 14, 2023)
2-233718978-C-G		not specified	Uncertain significance (Jun 27, 2022)
2-233718987-A-G		not specified	Uncertain significance (Oct 10, 2023)
2-233719077-A-G		not specified	Uncertain significance (Feb 22, 2023)
2-233719094-G-A		not specified	Uncertain significance (Feb 28, 2023)
2-233719115-G-C		not specified	Uncertain significance (Feb 14, 2023)
2-233719154-A-G		not specified	Uncertain significance (Feb 23, 2023)
2-233719168-T-G		not specified	Uncertain significance (Mar 14, 2023)
2-233719280-G-T		not specified	Uncertain significance (Nov 09, 2022)
2-233719296-C-T		not specified	Uncertain significance (Nov 01, 2022)
2-233719505-G-T		not specified	Uncertain significance (Aug 30, 2022)
2-233719519-T-C			Likely benign (Apr 01, 2023)
2-233719531-G-C		not specified	Uncertain significance (Jan 24, 2024)
2-233719565-G-C		not specified	Likely benign (Jan 20, 2023)
2-233719571-T-C		not specified	Likely benign (Jan 20, 2023)
2-233719623-C-T		not specified	Uncertain significance (Oct 25, 2023)
2-233719682-T-C		not specified	Uncertain significance (Jan 23, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
UGT1A4	protein_coding	protein_coding	ENST00000373409	5	54522

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.98e-7	0.688	125577	0	171	125748	0.000680

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.65	378	298	1.27	0.0000178	3483
Missense in Polyphen		172	148.57	1.1577		1753
Synonymous	-3.49	169	120	1.40	0.00000764	1085
Loss of Function	1.15	12	17.1	0.700	9.29e-7	209

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000572	0.000572
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.00272	0.00272
Finnish	0.000185	0.000185
European (Non-Finnish)	0.000618	0.000615
Middle Eastern	0.00272	0.00272
South Asian	0.000915	0.000915
Other	0.000815	0.000815

dbNSFP

Source: dbNSFP

• Function: FUNCTION: UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX- alpha to form both the IX-alpha-C8 and IX-alpha-C12 monoconjugates and diconjugate. Isoform 2 lacks transferase activity but acts as a negative regulator of isoform 1 (By similarity). {ECO:0000250}.
• Disease: DISEASE: Gilbert syndrome (GILBS) [MIM:143500]: Occurs as a consequence of reduced bilirubin transferase activity and is often detected in young adults with vague non-specific complaints. {ECO:0000269|PubMed:17496722}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Crigler-Najjar syndrome 1 (CN1) [MIM:218800]: Patients have severe hyperbilirubinemia and usually die of kernicterus (bilirubin accumulation in the basal ganglia and brainstem nuclei) within the first year of life. CN1 inheritance is autosomal recessive. {ECO:0000269|PubMed:1634050}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Crigler-Najjar syndrome 2 (CN2) [MIM:606785]: Patients have less severe hyperbilirubinemia and usually survive into adulthood without neurologic damage. Phenobarbital, which induces the partially deficient glucuronyl transferase, can diminish the jaundice. CN2 inheritance is autosomal dominant. {ECO:0000269|PubMed:8276413, ECO:0000269|PubMed:8280139}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Benzodiazepine Pathway, Pharmacokinetics;Retinol metabolism - Homo sapiens (human);Steroid hormone biosynthesis - Homo sapiens (human);nicotine degradation III;Metabolism of xenobiotics by cytochrome P450 - Homo sapiens (human);Drug metabolism - other enzymes - Homo sapiens (human);Drug metabolism - cytochrome P450 - Homo sapiens (human);Porphyrin and chlorophyll metabolism - Homo sapiens (human);Chemical carcinogenesis - Homo sapiens (human);Ascorbate and aldarate metabolism - Homo sapiens (human);Pentose and glucuronate interconversions - Homo sapiens (human);Phenytoin Pathway, Pharmacokinetics;Estrogen Metabolism Pathway;Tamoxifen Pathway, Pharmacokinetics;Valproic Acid Pathway, Pharmacokinetics;Nicotine Pathway, Pharmacokinetics;Irinotecan Pathway, Pharmacodynamics;Phenytoin (Antiarrhythmic) Action Pathway;Nicotine Metabolism Pathway;Nicotine Action Pathway;Tamoxifen Action Pathway;Tamoxifen Metabolism Pathway;Nicotine Metabolism;Aryl Hydrocarbon Receptor Pathway;Constitutive Androstane Receptor Pathway;Pregnane X Receptor pathway;Nuclear Receptors Meta-Pathway;NRF2 pathway;Liver steatosis AOP;Tamoxifen metabolism;Arylamine metabolism;Glucuronidation;Metapathway biotransformation Phase I and II;Glucuronidation;Phase II - Conjugation of compounds;Heme degradation;Metabolism of porphyrins;Tyrosine metabolism;Androgen and estrogen biosynthesis and metabolism;Biological oxidations;Metabolism;Linoleate metabolism;Vitamin A (retinol) metabolism;Xenobiotics metabolism;Porphyrin metabolism;nicotine degradation IV (Consensus)

Recessive Scores

• pRec: 0.581

Intolerance Scores

• loftool: 0.938
• rvis_EVS: 0.18
• rvis_percentile_EVS: 66.24

Haploinsufficiency Scores

• hipred: N
• hipred_score: 0.112
• ghis: 0.396

Essentials

• essential_gene_CRISPR: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0826

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Ugt1a5

Gene ontology

• Biological process: bilirubin conjugation;heme catabolic process;cellular glucuronidation;flavonoid glucuronidation;xenobiotic glucuronidation
• Cellular component: endoplasmic reticulum;endoplasmic reticulum membrane;integral component of membrane;intracellular membrane-bounded organelle
• Molecular function: retinoic acid binding;UDP-glycosyltransferase activity;glucuronosyltransferase activity;protein homodimerization activity;protein heterodimerization activity