UGT1A1

Chr 2ARAD

UDP glucuronosyltransferase family 1 member A1

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

The protein is a UDP-glucuronosyltransferase that conjugates lipophilic substrates including bilirubin with glucuronic acid to facilitate their excretion, serving as essential for drug detoxification and elimination of endogenous compounds. Mutations cause Crigler-Najjar syndromes types I and II, Gilbert syndrome, and familial transient neonatal hyperbilirubinemia, with inheritance patterns that can be either autosomal recessive or autosomal dominant depending on the specific condition. The gene shows low constraint against loss-of-function variants (LOEUF 1.331), and these bilirubin metabolism disorders typically present in the neonatal period or early infancy.

Summary from RefSeq, OMIM, UniProt
Research Assistant →

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
12
Active trials
174
Pubs (1 yr)
0
P/LP submissions
P/LP missense
1.33
LOEUF
LOF
Mechanism· G2P
Clinical SummaryUGT1A1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
💊
Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available

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 OE0.86 (0.581.33)
00.351.4
Missense OE1.22 (1.121.33)
00.61.4
Synonymous OE1.33
01.21.6
LoF obs/exp: 15 / 17.4Missense obs/exp: 360 / 294.9Syn Z: -2.82
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveUGT1A1-related Crigler-Najjar syndromeLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.80top 25%
GOF
0.72top 25%
LOF
0.1796th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Literature Evidence

DNClinical observations indicate that some mutant forms of human UGT1A1 (hUGT1A1) may be dominant-negative, suggesting their interaction with the wild-type enzyme.PMID:11546782

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

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

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
Crigler-Najjar Syndrome

Gene Therapy for Severe Crigler Najjar Syndrome

RECRUITING
NCT03466463Phase NAGenethonStarted 2018-03-19
GNT0003
Advanced Pancreatic Cancer

A Real-world Study of Liposomal Irinotecan (Onivyde)-Based Therapy in Patients With Locally Advanced/Metastatic Pancreatic Cancer in China

NOT YET RECRUITING
NCT07026123RenJi HospitalStarted 2025-07-01
Nal-IRI (Onivyde®)-based treatmentOther second-line treatment
Epilepsy

Precision Medicine in the Treatment of Epilepsy

RECRUITING
NCT05450822Gitte Moos KnudsenStarted 2022-02-18
LevetiracetamLevetiracetam TabletsLamotrigine tablet
Locally-advanced Rectal Cancer

Preoperative Radiotherapy And ASTX660 in Rectum Cancer

RECRUITING
NCT05912075Phase PHASE1Gustave Roussy, Cancer Campus, Grand ParisStarted 2023-12-19
mFOLFIRINOXPelvic radiotherapy LCRTCapecitabine
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
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
Mental DisorderPharmacogeneticsAdverse Drug Reaction (ADR)

Pharmacogenomics-Supported Psychotropic Prescribing Trial

RECRUITING
NCT06929533Phase NAUniversity of ManitobaStarted 2025-07-01
Pharmacogenetic Testing
Advanced Breast Cancer

Sacituzumab Govitecan Plus Bevacizumab in Metastatic TNBC

ENROLLING BY INVITATION
NCT07359404Phase PHASE2YING FANStarted 2024-04-01
Sacituzumab Govitecan (SG)Bevacizumab
Metastatic Pancreatic Ductal Adenocarcinoma

A Study Evaluating the Efficacy of 5-FU + NALIRI and 5-FU + NALIRINOX for PDAC (NALPAC)

RECRUITING
NCT05472259Phase PHASE2Belgian Group of Digestive OncologyStarted 2022-05-25
Nanoliposomal irinotecan5 FULeucovorin
Risk FactorsPolypharmacyDrug Interactions

Telecommunication Technology-based Online Survey

RECRUITING
NCT06159699Tomsk National Research Medical Center of the Russian Academy of SciencesStarted 2022-12-02
Online SurveyGenetic Testing
HIV-1-infection

DORAvirine Versus DOlutegravir Based Antiretroviral Regimens in Treatment-naïve People Living With HIV-1 Infection

RECRUITING
NCT06203132Phase PHASE3ANRS, Emerging Infectious DiseasesStarted 2025-01-27
Doravirine + tenofovir DF + lamivudineDolutegravir + tenofovir DF + lamivudine or emtricitabine
Clinical Literature
Open Research Assistant →