UGT1A4
Basic information
Region (hg38): 2:233718736-233773300
Links
Phenotypes
GenCC
Source:
ClinVar
This is a list of variants' phenotypes submitted to
- not_provided (243 variants)
- not_specified (107 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 (5 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 UGT1A4 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000007120.3. 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 | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
---|---|---|---|---|---|---|
synonymous | 31 | 34 | ||||
missense | 17 | 107 | 137 | |||
nonsense | 8 | |||||
start loss | 0 | |||||
frameshift | 11 | |||||
splice donor/acceptor (+/-2bp) | 6 | |||||
Total | 17 | 29 | 111 | 39 | 0 |
Highest pathogenic variant AF is 0.00048507
GnomAD
Source:
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:
- 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
- pHI
- hipred
- N
- hipred_score
- 0.112
- ghis
- 0.396
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- 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
- Phenotype
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