UGT1A1

Chr 2ARAD

UDP glucuronosyltransferase family 1 member A1

Also known as: BILIQTL1, GNT1, HUG-BR1, UDPGT, UDPGT 1-1, UGT1, UGT1A

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 complex locus that encodes several UDP-glucuronosyltransferases. The locus includes thirteen unique alternate first exons followed by four common exons. Four of the alternate first exons are considered pseudogenes. Each of the remaining nine 5' exons may be spliced to the four common exons, resulting in nine proteins with different N-termini and identical C-termini. Each first exon encodes the substrate binding site, and is regulated by its own promoter. The preferred substrate of this enzyme is bilirubin, although it also has moderate activity with simple phenols, flavones, and C18 steroids. Mutations in this gene result in Crigler-Najjar syndromes types I and II and in Gilbert syndrome. [provided by RefSeq, Jul 2008]

OMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

[Bilirubin, serum level of, QTL1]MIM #601816
[Gilbert syndrome]MIM #143500
AR
Crigler-Najjar syndrome, type IMIM #218800
AR
Crigler-Najjar syndrome, type IIMIM #606785
AR
Hyperbilirubinemia, familial transient neonatalMIM #237900
ADAR
UniProtTransient familial neonatal hyperbilirubinemia

Clinical highlights

Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.
12
Active trials
268
Pubs (1 yr)
P/LP submissions
P/LP missense
1.33
LOEUF
LOF
Mechanism· G2P

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
1.33LOEUF
pLI 0.000
Z-score 0.52
OE 0.86 (0.581.33)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
-1.35Z-score
OE missense 1.22 (1.121.33)
360 obs / 294.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?0.86 (0.581.33)
00.351.4
Missense OE?1.22 (1.121.33)
00.61.4
Synonymous OE?1.33
01.21.6
LoF obs/exp: 15 / 17.4Missense obs/exp: 360 / 294.9Syn Z: -2.82

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

UGT1A1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Colorectal CancerPancreatic Cancer

GENOCARE: A Prospective, Randomized Clinical Trial of Genotype-Guided Dosing Versus Usual Care

RECRUITING
NCT05391126Phase NAReema A. PatelStarted 2022-09-28
Irinotecan
Advanced Solid TumorMetastatic Triple-Negative Breast CancerHR+/HER2- Metastatic Breast Cancer

Study of Sacituzumab Govitecan (SG) in Japanese Participants With Advanced Solid Tumors

ACTIVE NOT RECRUITING
NCT05101096Phase PHASE1, PHASE2Gilead SciencesStarted 2021-10-20
Sacituzumab Govitecan-hziy
Rectal Cancer

An Adaptive-design Prospective Cohort Study of Watch and Wait Strategy in Patients With Locally Advanced Rectal Cancer

NOT YET RECRUITING
NCT04443543Phase PHASE2Fudan UniversityStarted 2020-06-22
Capecitabine (Xeloda) Pharmacogenetic Test ReagentsirinotecanIMRT
Pancreatic AdenocarcinomaGastroesophageal Junction AdenocarcinomaAdenocarcinoma

Safety of Combining Irinotecan With 5-FU, Leucovorin/Folinic Acid, Oxaliplatin, and Docetaxel Chemotherapies

RECRUITING
NCT04361708Phase PHASE1University of ChicagoStarted 2020-05-08
OxaliplatinDocetaxelLeucovorin
Rectal Cancer Stage III

UGT1A1-Based Irinotecan Therapy for Locally Advanced Rectal Cancer

RECRUITING
NCT05148767Phase PHASE4Zhejiang Cancer HospitalStarted 2022-01-01
Neoadjuvant chemoradiotherapy based on irinotecan
Advanced Breast Cancer

Sacituzumab Govitecan Plus Bevacizumab in Metastatic TNBC

ENROLLING BY INVITATION
NCT07359404Phase PHASE2YING FANStarted 2024-04-01
Sacituzumab Govitecan (SG)Bevacizumab
Locally Recurrent Rectal Cancer

Hypofractionated Radiotherapy Combined With NALIRIF, PD-1 Antibody in Locally Recurrent Rectal Cancer(NOVELTY-R)

RECRUITING
NCT07183865Phase PHASE2Fudan UniversityStarted 2025-03-09
radiotherapyIrinotecan Hydrochloride Liposome5-FU
Pediatric Solid Tumor

UGT1A1 Genotype-drien Phase I Study of Irinotecan in VIT Regimen for the Treatment of Pediatric R/R Solid Tumors

RECRUITING
NCT06760117Phase PHASE1Sun Yat-sen UniversityStarted 2022-01-01
Irinotecan (CPT-11)Temozolomide (TMZ)Vincristine
Liver CirrhosisGall Stone

Genetic Variants Associated With the Risk of Gall Stones and Cirrhosis.

NOT YET RECRUITING
NCT06679738Institute of Liver and Biliary Sciences, IndiaStarted 2024-11-10
Colorectal Neoplasms

The Role of the Tumor Molecular Profile (CMS), UGT1A1 Genotype and Beta-glucuronidase Activity of the Intestinal Microbiota for Treatment Efficiency, Toxicity, Survival and Quality of Life in Patients With Metastatic or Unresectable Colorectal Cancer During Irinotecan-based Systemic Treatment

RECRUITING
NCT05655780Maastricht University Medical CenterStarted 2023-01-09
Gastric Cancer

Clinical Study of Irinotecan Liposome Combination Therapy for Advanced Gastric Cancer

NOT YET RECRUITING
NCT06499610Phase PHASE4First Affiliated Hospital Xi'an Jiaotong UniversityStarted 2024-07-15
Irinotecan Hydrochloride Liposome Injection
Colorectal Cancer Metastatic

Clinical Study of Irinotecan Liposome (II)-Based Combination Treatment for Irinotecan-resistant Colorectal Cancer.

RECRUITING
NCT07044921Phase PHASE2Chinese PLA General HospitalStarted 2024-09-01
Irinotecan Liposomes (II)+Cetuximab+Bevacizumabl