{"gene":{"symbol":"UGT1A1","name":"UDP Glucuronosyltransferase Family 1 Member A1","protein":"UDP-glucuronosyltransferase 1A1","ncbi_gene_id":"54658","locus":"2q37","summary":"UGT1A1 encodes the only enzyme that conjugates bilirubin for excretion. The reduced-function promoter variant UGT1A1*28 causes Gilbert syndrome, a common and benign cause of mild unconjugated hyperbilirubinemia that often shows up unexpectedly on a routine blood test. The same variant slows the breakdown of a few drugs, most importantly the chemotherapy agent irinotecan, where it changes the safe dose.","function":"When old red blood cells are recycled, their hemoglobin breaks down into bilirubin, which is fat-soluble and toxic if it accumulates. UGT1A1 attaches a sugar group (glucuronidation) to bilirubin, making it water-soluble so the liver can excrete it in bile; it is essentially the body's only enzyme for this job, so its activity sets baseline bilirubin. When activity is reduced, unconjugated bilirubin rises, usually mildly and harmlessly, climbing further during fasting, illness, dehydration or physical stress; Gilbert syndrome is benign and needs no treatment, and the main value of recognising it is to avoid an unnecessary workup for liver disease. UGT1A1 also glucuronidates several drugs: irinotecan's active metabolite SN-38 is cleared by UGT1A1, so low activity means higher SN-38 exposure and more toxicity; the HIV drug atazanavir causes visible but benign jaundice in people with reduced activity.","category":"pharmacogene","key_variants":[{"rsid":null,"name":"*1 ((TA)6 promoter, reference)","alleles":"Six TA repeats in the promoter","effect":"Normal transcription and normal bilirubin handling.","frequency_note":null},{"rsid":"rs887829","name":"*28 ((TA)7 promoter; rs887829 is the tag SNP)","alleles":"Plus strand, GRCh37 (as in 23andMe raw data): C reference, T variant (c.-364C>T), named UGT1A1*80. T usually travels with the *28 promoter repeat, but how closely depends on ancestry; it is not the repeat itself.","effect":"An extra TA repeat lowers UGT1A1 transcription; *28/*28 (Gilbert syndrome) gives roughly 30% of normal bilirubin-UGT function.","frequency_note":"T about 35% pooled in 1000 Genomes: ~49% African, ~30% European, ~38% Admixed American, ~13% East Asian, ~44% South Asian (Ensembl)."},{"rsid":"rs4148323","name":"*6 (G71R)","alleles":"Plus strand, GRCh37 (as in 23andMe raw data): G reference, A variant (Gly71Arg), which defines *6.","effect":"Reduced activity coding variant; the main Gilbert and irinotecan-risk allele in East Asian populations, where *28 is less common.","frequency_note":"Main reduced-function allele in East Asian ancestry."},{"rsid":null,"name":"Severe loss-of-function (rare coding variants)","alleles":null,"effect":"Rare two-hit loss of function causes Crigler-Najjar syndrome, a serious condition very different from benign Gilbert syndrome.","frequency_note":"Rare."}],"phenotypes":["Normal metabolizer","Intermediate metabolizer (one reduced allele)","Poor metabolizer (*28/*28 or equivalent, e.g. *6/*6)"],"clinical_relevance":"UGT1A1 genotype has clinical guidance from CPIC and DPWG and appears on FDA drug labels. Gilbert syndrome is benign; the practical value of a UGT1A1 result is reassurance and avoiding repeat liver investigations when mildly raised bilirubin is the only abnormality. Irinotecan (colorectal and other cancers): the FDA label notes a higher risk of severe neutropenia with *28/*28, *6/*6 or *6/*28 and advises considering a reduced starting dose, and DPWG recommends 70% of the standard starting dose for poor metabolizers (and no reduction for intermediate metabolizers), one of the clearest oncology pharmacogenomic actions. Atazanavir (HIV): CPIC reports a high likelihood of jaundice-related discontinuation in poor metabolizers (two decreased-function alleles) and suggests considering an alternative where jaundice would be a concern; for intermediate metabolizers the likelihood is low.","consumer_array_caveat":"The classic *28 variant is a TA-repeat length change that SNP arrays cannot measure directly, but the marker rs887829 (UGT1A1*80), which usually travels with *28 though how closely depends on ancestry, is commonly genotyped: its T is a hint about *28, not a reading of it. rs4148323 (*6) is sometimes genotyped. Consumer data is genuinely informative for Gilbert syndrome, but it is supporting context, not a diagnosis, and for irinotecan or other chemotherapy the dosing decision belongs to the oncology team using a clinical-grade test.","drugs":[{"drug":"irinotecan","guideline":"DPWG; FDA label","level":"CPIC A (provisional)","summary":"Active metabolite SN-38 is cleared by UGT1A1. The FDA label notes a higher risk of severe neutropenia with *28/*28, *6/*6 or *6/*28 and advises considering a starting dose reduced by at least one level. DPWG recommends 70% of the standard starting dose for poor metabolizers (two decreased-function alleles such as *6, *28 or *37), to lower the risk of severe neutropenia or diarrhea, and no reduction for intermediate metabolizers."},{"drug":"atazanavir","guideline":"CPIC","level":"CPIC A","summary":"CPIC (Gammal et al. 2016): poor metabolizers (two decreased-function alleles, e.g. *28/*28) have a high likelihood of jaundice leading to atazanavir discontinuation (at least 20%, up to 60%); CPIC suggests considering an alternative where jaundice would be a concern. For normal and intermediate metabolizers, CPIC finds no need to avoid atazanavir (less than about a 1 in 20 chance of stopping it because of jaundice)."}],"sources":[{"label":"CPIC — UGT1A1 gene page","url":"https://cpicpgx.org/gene/ugt1a1/"},{"label":"PharmGKB UGT1A1 (PA420)","url":"https://www.pharmgkb.org/gene/PA420"},{"label":"MedlinePlus — UGT1A1","url":"https://medlineplus.gov/genetics/gene/ugt1a1/"},{"label":"NCBI Gene 54658","url":"https://www.ncbi.nlm.nih.gov/gene/54658"},{"label":"Gammal et al., Clin Pharmacol Ther 2016 (CPIC UGT1A1–atazanavir guideline)","url":"https://pubmed.ncbi.nlm.nih.gov/26417955/"},{"label":"Hulshof et al., Eur J Hum Genet 2023 (DPWG UGT1A1–irinotecan guideline; correction PMID 36797469)","url":"https://pubmed.ncbi.nlm.nih.gov/36443464/"},{"label":"Camptosar (irinotecan) prescribing information, FDA/DailyMed (sections 2.3 and 5.3, reduced UGT1A1 activity)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e518dfc6-7e93-4fee-a66c-51e1ab71c056"}],"related_blog":"/blog/pharmacogenomics-europe-guide/","disclaimer":"Educational information only, not medical advice or diagnosis. Consult a clinician before acting on genetic information."},"meta":{"disclaimer":"Educational information only, not medical advice or diagnosis. Consult a clinician before acting on genetic information.","api_version":"2026-09-20","docs":"https://deepdna.ai/docs/","status":"live","data_as_of":"2026-10-25T21:32:19.251Z","freshness":"https://deepdna.ai/api/v1/freshness"}}