UGT1A8

UDP glucuronosyltransferase family 1 member A8, the group of UDP glucuronosyltransferases

Basic information

Region (hg38): 2:233617632-233773300

Links

ENSG00000242366 ∙ NCBI:54576 ∙ OMIM:606433 ∙ HGNC:12540 ∙ Uniprot:Q9HAW9 ∙ 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 UGT1A8 gene.

• not provided (271 variants)
• Inborn genetic diseases (115 variants)
• Gilbert syndrome (60 variants)
• Crigler-Najjar syndrome (49 variants)
• Lucey-Driscoll syndrome (45 variants)
• UGT1A1-related condition (20 variants)
• not specified (17 variants)
• Crigler-Najjar syndrome, type II (17 variants)
• Hyperbilirubinemia (16 variants)
• Crigler-Najjar syndrome type 1 (14 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 UGT1A8 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	10		17
missense	3	8	66	1		78
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	189	35	35	284
Total	27	21	266	46	35

Highest pathogenic variant AF is 0.0000919

Variants in UGT1A8

This is a list of pathogenic ClinVar variants found in the UGT1A8 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-233617808-A-T		not specified	Uncertain significance (Apr 13, 2022)
2-233617849-C-T		not specified	Uncertain significance (Jan 24, 2023)
2-233617967-A-T		not specified	Uncertain significance (Feb 05, 2024)
2-233617969-C-T		not specified	Uncertain significance (Jul 25, 2023)
2-233617970-G-A		not specified	Uncertain significance (May 05, 2023)
2-233617987-G-A		not specified	Uncertain significance (Oct 10, 2023)
2-233618001-G-C		not specified	Uncertain significance (Oct 20, 2023)
2-233618011-G-A		not specified	Likely benign (Feb 15, 2023)
2-233618045-C-A		not specified	Uncertain significance (Apr 19, 2023)
2-233618045-C-T		not specified	Uncertain significance (Jul 19, 2023)
2-233618048-A-G		not specified	Uncertain significance (Jun 26, 2023)
2-233618066-T-C		not specified	Uncertain significance (Jan 09, 2024)
2-233618158-G-A		not specified	Uncertain significance (Dec 27, 2022)
2-233618177-T-A		not specified	Uncertain significance (Nov 08, 2022)
2-233618198-C-T		not specified	Uncertain significance (Oct 12, 2021)
2-233618233-T-C		not specified	Uncertain significance (Feb 22, 2023)
2-233618320-G-A		not specified	Uncertain significance (Feb 12, 2024)
2-233618330-G-A		not specified	Uncertain significance (Sep 29, 2023)
2-233618428-G-A		not specified	Uncertain significance (Oct 12, 2022)
2-233618463-G-T		not specified	Uncertain significance (Jan 30, 2024)
2-233618472-A-G			Likely benign (Dec 31, 2019)
2-233618487-C-G		not specified	Uncertain significance (Feb 13, 2024)
2-233618528-G-C		not specified	Uncertain significance (Aug 10, 2021)
2-233636550-G-A		not specified	Uncertain significance (Jul 14, 2021)
2-233636553-C-G		not specified	Uncertain significance (Oct 26, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
UGT1A8	protein_coding	protein_coding	ENST00000305208	5	13052

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000326	0.803	125699	0	49	125748	0.000195

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.247	309	297	1.04	0.0000175	3498
Missense in Polyphen		131	129.52	1.0114		1493
Synonymous	-0.219	126	123	1.03	0.00000800	1084
Loss of Function	1.32	11	16.9	0.653	8.19e-7	203

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000370	0.000369
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.000206	0.000202
Middle Eastern	0.000109	0.000109
South Asian	0.000555	0.000555
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. Isoform 2 lacks transferase activity but acts as a negative regulator of isoform 1. {ECO:0000269|PubMed:19545173}.
• Pathway: Retinol metabolism - Homo sapiens (human);Steroid hormone biosynthesis - Homo sapiens (human);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);Estrogen Metabolism Pathway;Tamoxifen Pathway, Pharmacokinetics;Tramadol Pharmacokinetics;Valproic Acid Pathway, Pharmacokinetics;Mycophenolic acid Pathway, Pharmacokinetics;Mycophenolic acid Pathway, Pharmacokinetics/Pharmacodynamics;Irinotecan Pathway, Pharmacodynamics;Mycophenolic Acid Metabolism Pathway;Morphine Metabolism Pathway;Morphine Action Pathway;Tramadol Metabolism Pathway;Codeine and Morphine Metabolism;Tamoxifen metabolism;Glucuronidation;Glucuronidation;Phase II - Conjugation of compounds;Biological oxidations;Metabolism;thyroid hormone metabolism II (via conjugation and/or degradation) (Consensus)

Recessive Scores

• pRec: 0.581

Intolerance Scores

• rvis_EVS: -0.42
• rvis_percentile_EVS: 25.73

Haploinsufficiency Scores

• hipred: N
• hipred_score: 0.112
• ghis: 0.420

Essentials

• essential_gene_CRISPR: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0701

Mouse Genome Informatics

• Gene name: Ugt1a9

Gene ontology

• Biological process: fatty acid metabolic process;steroid metabolic process;coumarin metabolic process;retinoic acid metabolic process;negative regulation of catalytic activity;negative regulation of fatty acid metabolic process;negative regulation of steroid metabolic process;flavone metabolic process;flavonoid glucuronidation;xenobiotic glucuronidation
• Cellular component: endoplasmic reticulum;endoplasmic reticulum membrane;integral component of membrane;intracellular membrane-bounded organelle
• Molecular function: retinoic acid binding;enzyme inhibitor activity;steroid binding;fatty acid binding;UDP-glycosyltransferase activity;glucuronosyltransferase activity;protein homodimerization activity;protein heterodimerization activity