UGT1A1 (UDP-glucuronosyltransferase 1A1) variants and mutations
UGT1A1 (also known as UDP-glucuronosyltransferase 1A1) is a human protein-coding gene encoding an UDP-glucuronosyltransferase 1A1 protein. It conjugates bilirubin and many lipophilic compounds with glucuronic acid, enabling efficient elimination in bile or urine. Reduced activity causes Gilbert syndrome or Crigler-Najjar syndrome and can also increase toxicity from drugs such as irinotecan. This analysis covers 1,285 UGT1A1 variants and mutations. Of these, 85% have computational variant effect predictions. Disease context includes Crigler-Najjar syndrome type 1, Crigler-Najjar syndrome type 2, and Gilbert syndrome. Example UGT1A1 variants include M1R, A2G, and A2P.
Variant analysis overview
- Gene: UGT1A1
- Protein: UDP-glucuronosyltransferase 1A1
- UniProt accession: P22309
- Organism: Homo sapiens
- Variants analyzed: 1285
- Variant scope: all variants
- Completed: 2026-08-09
Variant and mutation evidence
- Variant composition: 947 unspecified-consequence records; 155 synonymous variants; 143 missense variants; 20 frameshift variants; 1 in-frame insertions; 6 stop-gained variants; 8 in-frame deletions; 3 splice-region variants; 2 substitution
- Prediction scores: 1,097 variants have prediction scores (85% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Crigler-Najjar syndrome type 1, Crigler-Najjar syndrome type 2, Gilbert syndrome, Crigler-Najjar syndrome, bilirubin metabolism disease, porphyrin metabolism disease, transient familial neonatal hyperbilirubinemia, Hyperbilirubinemia, hereditary disease, cholelithiasis, Jaundice, Cholecystitis.
Protein structure and variant hotspots
- Protein features: 1 transmembrane segments; 3 post-translational modification sites.
- Structural context: 20 variants have structural context.
- PTM context: 5 variants overlap post-translational modification sites.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.
Notable UGT1A1 variants
Examples include M1R, A2G, A2P, A2S, A2T, A2V, A2A, V3G. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1R (p.Met1Arg), rs2125981899, ClinGen CA2573135609, ClinVar RCV002226966, Likely pathogenic
- A2G (p.Ala2Gly), TOPMed rs1437444805, gnomAD rs1437444805, Uncertain significance, Hyperbilirubinemia
- A2P (p.Ala2Pro), Ensembl rs2125981972
- A2S (p.Ala2Ser), Ensembl rs2125981972
- A2T (p.Ala2Thr), Ensembl rs2125981972, SIFT 0.30
- A2V (p.Ala2Val), TOPMed rs1437444805, gnomAD rs1437444805, REVEL 0.04, CADD 13.80
- A2A (p.Ala2Ala), rs1359528738, gnomAD 2-233760293-T-A, CADD 0.83
- V3G (p.Val3Gly), Ensembl rs74720349
- V3L (p.Val3Leu), TOPMed rs1697387669, SIFT 0.49
- V3M (p.Val3Met), TOPMed rs1697387669, REVEL 0.05, CADD 2.24
- E4D (p.Glu4Asp), ExAC rs781590934, gnomAD rs781590934, REVEL 0.07, CADD 0.48
- E4G (p.Glu4Gly), TOPMed rs1697389087
- E4K (p.Glu4Lys), Ensembl rs2125982051
- E4Q (p.Glu4Gln), Ensembl rs2125982051
- E4V (p.Glu4Val), TOPMed rs1697389087, SIFT 0.24
- E4E (p.Glu4Glu), rs781590934, gnomAD 2-233760299-G-A, CADD 0.80
- S5A (p.Ser5Ala), gnomAD rs1271688129, REVEL 0.07, CADD 1.96
- S5C (p.Ser5Cys), TOPMed rs1697391714, REVEL 0.03, CADD 0.97
- S5T (p.Ser5Thr), gnomAD rs1271688129
- S5Y (p.Ser5Tyr), TOPMed rs1697391714, REVEL 0.03, CADD 0.06
- S5F (p.Ser5Phe), gnomAD 2-233760301-C-T, REVEL 0.03, CADD 0.26
- Q6* (p.Gln6Ter), Ensembl rs2125982207, CADD 28.30, Likely pathogenic
- Q6E (p.Gln6Glu), Ensembl rs2125982207, Likely pathogenic
- Q6H (p.Gln6His), cosmic curated COSV10963, ExAC rs745957787, TOPMed rs745957787, gnomAD rs745957787, REVEL 0.06, CADD 4.98
- Q6K (p.Gln6Lys), Ensembl rs2125982207, Likely pathogenic
- Q6L (p.Gln6Leu), Ensembl rs2125982244
- Q6P (p.Gln6Pro), Ensembl rs2125982244
- Q6R (p.Gln6Arg), Ensembl rs2125982244, SIFT 0.38
- Q6Q (p.Gln6Gln), rs745957787, gnomAD 2-233760305-G-A, CADD 1.33
- G7A (p.Gly7Ala), Ensembl rs2125982302
- G7D (p.Gly7Asp), Ensembl rs2125982302
- G7R (p.Gly7Arg), TOPMed rs1006073064, gnomAD rs1006073064, Uncertain significance
- G7S (p.Gly7Ser), rs1006073064, ClinGen CA67589465, ClinVar RCV000592885, TOPMed rs1006073064, AlphaMissense 0.12, MetaLR 0.14, Uncertain significance, not provided
- G7G (p.Gly7Gly), rs780253764, gnomAD 2-233760308-C-T, CADD 2.56
- G8* (p.Gly8Ter), ExAC rs749552053, TOPMed rs749552053, gnomAD rs749552053, Likely benign
- G8A (p.Gly8Ala), ExAC rs768521253, gnomAD rs768521253
- G8E (p.Gly8Glu), ExAC rs768521253, gnomAD rs768521253, SIFT 0.51
- G8R (p.Gly8Arg), rs749552053, ClinGen CA2179759, cosmic curated COSV10736, ClinVar RCV000733748, REVEL 0.05, CADD 0.14, Conflicting interpretations, not provided; Inborn genetic diseases
- G8V (p.Gly8Val), rs768521253, ExAC rs768521253, gnomAD rs768521253, REVEL 0.09, CADD 0.62, Variant assessed as somatic; moderate impact.
- R9C (p.Arg9Cys), rs370790922, ClinGen CA2179761, cosmic curated COSV59389, ClinVar RCV001137542, REVEL 0.09, CADD 5.26, Uncertain significance, Crigler-Najjar syndrome; Lucey-Driscoll syndrome; Gilbert syndrome
- R9G (p.Arg9Gly), ESP rs370790922, ExAC rs370790922, TOPMed rs370790922, gnomAD rs370790922, REVEL 0.09, CADD 1.41, Uncertain significance
- R9H (p.Arg9His), rs761736540, NCI-TCGA Cosmic COSV5938, cosmic curated COSV59384, ExAC rs761736540, REVEL 0.03, CADD 0.08, Variant assessed as somatic; moderate impact.
- R9L (p.Arg9Leu), ExAC rs761736540, gnomAD rs761736540, REVEL 0.03, CADD 0.05
- R9P (p.Arg9Pro), ExAC rs761736540, gnomAD rs761736540
- R9S (p.Arg9Ser), ESP rs370790922, ExAC rs370790922, TOPMed rs370790922, gnomAD rs370790922, REVEL 0.09, CADD 0.70, Uncertain significance
- R9V (p.Arg9Val), Ensembl rs386656374, SIFT 0.34
- R9R (p.Arg9Arg), rs2125982476, gnomAD 2-233760314-C-T, CADD 0.21
- P10A (p.Pro10Ala), Ensembl rs2125982493
- P10Q (p.Pro10Gln), Ensembl rs2125982506, SIFT 0.20
- P10L (p.Pro10Leu), gnomAD 2-233760316-C-T, REVEL 0.02, CADD 0.28
- P10P (p.Pro10Pro), gnomAD 2-233760317-A-T, CADD 0.96
- L11H (p.Leu11His), 1000Genomes rs201984525, ExAC rs201984525, gnomAD rs201984525, REVEL 0.30, CADD 21.80
- L11P (p.Leu11Pro), 1000Genomes rs201984525, ExAC rs201984525, gnomAD rs201984525, REVEL 0.15, CADD 14.60
- L11V (p.Leu11Val), Ensembl rs2125982543, SIFT 0.31
- V12D (p.Val12Asp), Ensembl rs2125982587
- V12G (p.Val12Gly), Ensembl rs2125982587
- V12L (p.Val12Leu), Ensembl rs2125982570, SIFT 1.00
- V12I (p.Val12Ile), gnomAD 2-233760321-G-A, REVEL 0.22, CADD 0.00
- V12V (p.Val12Val), rs760176104, gnomAD 2-233760323-C-G, CADD 3.14
- L13M (p.Leu13Met), Ensembl rs2125982623
- L13V (p.Leu13Val), Ensembl rs2125982623, SIFT 0.37
- L13L (p.Leu13Leu), gnomAD 2-233760326-G-T, CADD 6.02
- G14A (p.Gly14Ala), Ensembl rs1559406694
- G14D (p.Gly14Asp), Ensembl rs1559406694
- G14R (p.Gly14Arg), Ensembl rs2125982664, SIFT 0.21
- G14G (p.Gly14Gly), rs765814343, gnomAD 2-233760329-C-A, CADD 7.31
- L15P (p.Leu15Pro), Ensembl rs111033541, SIFT 0.02, Pathogenic, in CN2
- L15R (p.Leu15Arg), rs111033541, ClinGen CA122115, ClinVar RCV000013081, ClinVar RCV001529911, REVEL 0.42, CADD 23.40, Likely pathogenic, Gilbert syndrome; Crigler-Najjar syndrome type 1; Lucey-Driscoll syndrome
- L15V (p.Leu15Val), Ensembl rs2125982719, REVEL 0.17, CADD 14.90
- L15L (p.Leu15Leu), rs1697406226, gnomAD 2-233760332-G-C, CADD 6.31
- L16M (p.Leu16Met), Ensembl rs1559406714
- L16Q (p.Leu16Gln), Ensembl rs1575771125
- L16V (p.Leu16Val), Ensembl rs1559406714, SIFT 0.18
- L16L (p.Leu16Leu), rs1559406714, gnomAD 2-233760333-C-T, CADD 8.49
- L17M (p.Leu17Met), gnomAD rs1472715638, REVEL 0.29, CADD 21.30
- L17L (p.Leu17Leu), rs753493472, gnomAD 2-233760338-G-C, CADD 4.97
- C18R (p.Cys18Arg), Ensembl rs2125982853
- C18W (p.Cys18Trp), Ensembl rs2125982885
- C18Y (p.Cys18Tyr), Ensembl rs2125982870, SIFT 0.08
- V19E (p.Val19Glu), Ensembl rs2125982923
- V19G (p.Val19Gly), Ensembl rs2125982923
- V19L (p.Val19Leu), Ensembl rs2125982896, REVEL 0.13, CADD 1.35
- V19M (p.Val19Met), Ensembl rs2125982896, SIFT 0.28
- V19V (p.Val19Val), rs897355036, gnomAD 2-233760344-G-C, CADD 0.41
- L20M (p.Leu20Met), Ensembl rs2125982956
- L20V (p.Leu20Val), Ensembl rs2125982956, SIFT 0.16
- L20L (p.Leu20Leu), rs1239455417, gnomAD 2-233760347-G-A, CADD 0.17
- G21S (p.Gly21Ser), ExAC rs759212811, gnomAD rs759212811, REVEL 0.04, CADD 0.31
- G21A (p.Gly21Ala), gnomAD 2-233760349-G-C, REVEL 0.06, CADD 5.78
- G21G (p.Gly21Gly), rs1374994213, gnomAD 2-233760350-C-T, CADD 0.94
- V23V (p.Val23Val), rs1414123680, gnomAD 2-233760356-G-A, CADD 0.06
- V24M (p.Val24Met), NCI-TCGA Cosmic COSV5939, cosmic curated COSV59393, TOPMed rs1697415689, gnomAD rs1697415689, REVEL 0.04, CADD 4.42, Variant assessed as somatic; moderate impact.
- V24L (p.Val24Leu), gnomAD 2-233760357-G-T, REVEL 0.04, CADD 0.43
- V24V (p.Val24Val), rs764918207, gnomAD 2-233760359-G-A, CADD 2.46
- S25T (p.Ser25Thr), ExAC rs751894919, gnomAD rs751894919, REVEL 0.11, CADD 3.63
- S25F (p.Ser25Phe), gnomAD 2-233760361-C-T, REVEL 0.23, CADD 17.10
- H26N (p.His26Asn), gnomAD rs1400895192, REVEL 0.16, CADD 13.90
- H26R (p.His26Arg), gnomAD rs1697418455, REVEL 0.10, CADD 9.78
- H26H (p.His26His), rs994298046, gnomAD 2-233760365-T-C, CADD 5.50
- A27D (p.Ala27Asp), NCI-TCGA Cosmic COSV5938, cosmic curated COSV59386, Variant assessed as somatic; moderate impact.
- A27T (p.Ala27Thr), gnomAD rs1447031389, SIFT 0.01
- A27V (p.Ala27Val), rs775463336, gnomAD 2-233760364-ATGCT, CADD 25.80
- G28A (p.Gly28Ala), gnomAD rs1337235315, REVEL 0.30, CADD 23.00
- G28E (p.Gly28Glu), gnomAD 2-233760370-G-A, REVEL 0.30, CADD 22.40
- G28G (p.Gly28Gly), rs995864584, gnomAD 2-233760371-G-C, CADD 7.82
- K29N (p.Lys29Asn), NCI-TCGA TCGA novel, SIFT 0.04, Variant assessed as somatic; moderate impact.
- K29K (p.Lys29Lys), gnomAD 2-233760374-G-A, CADD 7.66
- I30L (p.Ile30Leu), TOPMed rs1032753915, gnomAD rs1032753915, REVEL 0.16, CADD 1.45
- I30M (p.Ile30Met), TOPMed rs1697424081, REVEL 0.17, CADD 5.72
- I30T (p.Ile30Thr), rs375204962, ClinGen CA2179772, cosmic curated COSV10053, NCI-TCGA Cosmic COSV5938, REVEL 0.46, CADD 22.80, Uncertain significance, not provided
- L31R (p.Leu31Arg), rs2472933388, ClinGen CA351065551, ClinVar RCV004547369, REVEL 0.90, CADD 25.10, Uncertain significance, Crigler-Najjar syndrome type 1
- L31L (p.Leu31Leu), gnomAD 2-233760378-C-T, CADD 1.02
- L32F (p.Leu32Phe), gnomAD rs1029837369
- L32W (p.Leu32Trp), cosmic curated COSV10881, gnomAD rs1697426202, REVEL 0.45, CADD 25.50
- L32* (p.Leu32Ter), rs1308601724, gnomAD 2-233760379-TG-T, CADD 22.90
- L32L (p.Leu32Leu), rs1029837369, gnomAD 2-233760383-G-A, CADD 7.78
- I33N (p.Ile33Asn), ESP rs368348566, ExAC rs368348566, TOPMed rs368348566, gnomAD rs368348566, REVEL 0.49, CADD 25.70
- I33T (p.Ile33Thr), ESP rs368348566, ExAC rs368348566, TOPMed rs368348566, gnomAD rs368348566, SIFT 0.01
- I33I (p.Ile33Ile), gnomAD 2-233760386-C-A, CADD 7.41
- P34Q (p.Pro34Gln), UniProt VAR 026134, SIFT 0.00, Pathogenic, in CN2
- P34S (p.Pro34Ser), ExAC rs756175438, gnomAD rs756175438, REVEL 0.50, CADD 24.60
- D36A (p.Asp36Ala), TOPMed rs1244863017, gnomAD rs1244863017, Uncertain significance, in CN1
- D36E (p.Asp36Glu), TOPMed rs1697431093
- D36G (p.Asp36Gly), rs1244863017, ClinGen CA351065635, ClinVar RCV003120145, TOPMed rs1244863017, REVEL 0.47, CADD 25.30, Uncertain significance, not provided
- D36H (p.Asp36His), Ensembl rs1697429657
- D36N (p.Asp36Asn), rs1697429657, UniProt VAR 071402, Ensembl rs1697429657, REVEL 0.53, CADD 27.50, Pathogenic, in CN1
- D36V (p.Asp36Val), TOPMed rs1244863017, gnomAD rs1244863017, SIFT 0.01, Uncertain significance, in CN1
- G37A (p.Gly37Ala), ExAC rs780016114, TOPMed rs780016114, gnomAD rs780016114, Uncertain significance
- G37D (p.Gly37Asp), rs780016114, ClinGen CA351065654, ClinVar RCV003443186, ExAC rs780016114, AlphaMissense 0.57, MetaLR 0.41, Uncertain significance, Crigler-Najjar syndrome, type II
- G37S (p.Gly37Ser), TOPMed rs1697431780, gnomAD rs1697431780, REVEL 0.46, CADD 25.80
- G37V (p.Gly37Val), rs780016114, ClinGen CA2179776, ClinVar RCV003555021, ExAC rs780016114, REVEL 0.56, AlphaMissense 0.57, Uncertain significance, not provided
- G37G (p.Gly37Gly), rs1018382617, gnomAD 2-233760398-C-T, CADD 6.91
- S38I (p.Ser38Ile), Ensembl rs2125983475
- S38N (p.Ser38Asn), Ensembl rs2125983475
- S38R (p.Ser38Arg), Ensembl rs2125983506
- S38T (p.Ser38Thr), Ensembl rs2125983475, SIFT 0.00
- S38S (p.Ser38Ser), rs2125983506, gnomAD 2-233760401-C-T, CADD 9.98
- H39D (p.His39Asp), rs72551339, UniProt VAR 026135, Ensembl rs72551339, AlphaMissense 0.92, MetaLR 0.73, Pathogenic, in CN1
- H39L (p.His39Leu), Ensembl rs2125983562, REVEL 0.72, CADD 24.60
- H39N (p.His39Asn), Ensembl rs72551339
- H39P (p.His39Pro), Ensembl rs2125983562
- H39Q (p.His39Gln), gnomAD rs1211296854, Uncertain significance, not provided
- H39Y (p.His39Tyr), cosmic curated COSV10517, Ensembl rs72551339, SIFT 0.00
- H39R (p.His39Arg), gnomAD 2-233760403-A-G, REVEL 0.75, CADD 24.00
- H39H (p.His39His), rs1211296854, gnomAD 2-233760404-C-T, CADD 4.62
- W40* (p.Trp40Ter), ExAC rs749423657, TOPMed rs749423657, gnomAD rs749423657, CADD 38.00
- W40L (p.Trp40Leu), Ensembl rs2125983610, SIFT 0.00
- W40R (p.Trp40Arg), rs1183811071, ClinGen CA351065698, ClinVar RCV003555022, TOPMed rs1183811071, REVEL 0.77, CADD 28.00, Conflicting interpretations, not provided
- L41M (p.Leu41Met), Ensembl rs2125983643
- L41V (p.Leu41Val), NCI-TCGA TCGA novel, SIFT 0.00, Variant assessed as somatic; moderate impact.
- S42C (p.Ser42Cys), Ensembl rs1575771994
- S42G (p.Ser42Gly), Ensembl rs1575771994, REVEL 0.27, CADD 18.80
- S42N (p.Ser42Asn), rs533404227, ClinGen CA2179778, ClinVar RCV004539526, 1000Genomes rs533404227, REVEL 0.23, CADD 22.90, Uncertain significance, UGT1A1-related disorder
- S42R (p.Ser42Arg), Ensembl rs2125983699
- S42T (p.Ser42Thr), 1000Genomes rs533404227, ExAC rs533404227, TOPMed rs533404227, gnomAD rs533404227, SIFT 0.17, Uncertain significance
- M43I (p.Met43Ile), Ensembl rs1575772039, REVEL 0.29, CADD 15.10
- M43K (p.Met43Lys), Ensembl rs2125983730, REVEL 0.49, CADD 22.10
- M43L (p.Met43Leu), Ensembl rs2125983714, SIFT 0.11
- M43S (p.Met43Ser), gnomAD 2-233760414-AT-A, CADD 20.90
- M43T (p.Met43Thr), gnomAD 2-233760415-T-C, REVEL 0.28, CADD 16.40
- L44F (p.Leu44Phe), Ensembl rs2125983770
- L44H (p.Leu44His), rs1178608845, ClinGen CA351065795, ClinVar RCV001811920, TOPMed rs1178608845, REVEL 0.10, CADD 7.22, Uncertain significance, not provided
- L44I (p.Leu44Ile), Ensembl rs2125983770
- L44V (p.Leu44Val), Ensembl rs2125983770, SIFT 0.20
- G45E (p.Gly45Glu), Ensembl rs2125983841
- G45R (p.Gly45Arg), Ensembl rs1697440373
- G45V (p.Gly45Val), Ensembl rs2125983841
- G45W (p.Gly45Trp), Ensembl rs1697440373, SIFT 0.01
- A46D (p.Ala46Asp), TOPMed rs886044683, gnomAD rs886044683, Uncertain significance
- A46G (p.Ala46Gly), TOPMed rs886044683, gnomAD rs886044683, SIFT 0.01, Uncertain significance
- A46V (p.Ala46Val), rs886044683, ClinGen CA10607055, ClinVar RCV000386459, ClinVar RCV002504027, REVEL 0.09, CADD 0.83, Uncertain significance, BILIRUBIN, SERUM LEVEL OF, QUANTITATIVE TRAIT LOCUS 1; Crigler-Najjar syndrome t
- I47F (p.Ile47Phe), Ensembl rs2125983914
- I47L (p.Ile47Leu), Ensembl rs2125983914, SIFT 0.73
- I47I (p.Ile47Ile), rs34526305, gnomAD 2-233760428-C-T, CADD 7.94
- Q48* (p.Gln48Ter), cosmic curated COSV10518, ExAC rs747942373, TOPMed rs747942373, gnomAD rs747942373, Uncertain significance
- Q48E (p.Gln48Glu), rs747942373, ClinGen CA2179779, ClinVar RCV000733745, ClinVar RCV001139761, REVEL 0.15, CADD 5.96, Uncertain significance, Gilbert syndrome; Lucey-Driscoll syndrome; not provided
- Q48H (p.Gln48His), Ensembl rs2125983968, SIFT 0.05
- Q49* (p.Gln49Ter), rs587776765, ClinGen CA122074, ClinVar RCV000013069, ClinVar RCV005025048, AlphaMissense 0.08, MetaLR 0.04, Pathogenic
- Q49E (p.Gln49Glu), TOPMed rs587776765, Pathogenic
- Q49K (p.Gln49Lys), TOPMed rs587776765, Pathogenic
Public UGT1A1 analysis runs
- UGT1A1 analysis run — UGT1A1 (1,285 variants) — completed 2026-08-09