UGT1A8

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

Basic information

Region (hg38): 2:233617633-233773300

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_specified (317 variants)
• not_provided (294 variants)
• UGT1A1-related_disorder (91 variants)
• Gilbert_syndrome (91 variants)
• Lucey-Driscoll_syndrome (75 variants)
• Crigler-Najjar_syndrome_type_1 (64 variants)
• Crigler-Najjar_syndrome,_type_II (56 variants)
• Crigler-Najjar_syndrome (39 variants)
• BILIRUBIN,_SERUM_LEVEL_OF,_QUANTITATIVE_TRAIT_LOCUS_1 (38 variants)
• Inborn_genetic_diseases (23 variants)
• Hyperbilirubinemia (16 variants)
• UGT1A9-related_disorder (11 variants)
• Irinotecan_response (3 variants)
• UGT1A4-related_disorder (2 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. These statistics are base on transcript: NM_000019076.5. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	29		32
missense	5	17	104	4		130
nonsense	4	3	1			8
start loss						0
frameshift	6	5				11
splice donor/acceptor (+/-2bp)	2	4				6
Total	17	29	108	33	0

Highest pathogenic variant AF is 0.00048507

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