Crigler-Najjar syndrome type 1

Summary

Crigler-Najjar syndrome type 1 (MONDO:0021020) is a disease caused by UGT1A1 (GenCC Definitive), with 10 cohort genes. The dominant Reactome pathway is Glucuronidation (9 cohort genes).

At a glance

• Prevalence: Unknown (Worldwide)
• Causal gene: UGT1A1 (GenCC Definitive)
• Cohort genes: 10
• ClinVar variants: 67
• Phenotypes (HPO): 14

Clinical features

Signs & symptoms

Clinical features (HPO)

14 HPO clinical features (Orphanet curated; top 14 by frequency):

HPO ID	Term	Frequency
HP:0001080	Biliary tract abnormality	Very frequent (80-99%)
HP:0001343	Kernicterus	Very frequent (80-99%)
HP:0001392	Abnormality of the liver	Very frequent (80-99%)
HP:0003265	Neonatal hyperbilirubinemia	Very frequent (80-99%)
HP:0006579	Prolonged neonatal jaundice	Very frequent (80-99%)
HP:0008282	Unconjugated hyperbilirubinemia	Very frequent (80-99%)
HP:0008947	Floppy infant	Very frequent (80-99%)
HP:0000365	Hearing impairment	Occasional (5-29%)
HP:0000750	Delayed speech and language development	Occasional (5-29%)
HP:0001249	Intellectual disability	Occasional (5-29%)
HP:0001250	Seizure	Occasional (5-29%)
HP:0001337	Tremor	Occasional (5-29%)
HP:0002354	Memory impairment	Occasional (5-29%)
HP:0012246	Oculomotor nerve palsy	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Crigler-Najjar syndrome type 1
Mondo ID	MONDO:0021020
OMIM	218800
Orphanet	79234
ICD-11	1098453659
SNOMED CT	8933000
UMLS	C0010324
MedGen	41346
GARD	0000047
MedDRA	10057034
Is cancer (heuristic)	no

Also known as: bilirubin uridinediphosphate glucuronosyltransferase deficiency type 1 · bilirubin-UGT deficiency type 1 · Crigler Najjar syndrome, type 1 · Crigler-Najjar syndrome, type 1 · Crigler-Najjar syndrome, type I · hereditary unconjugated hyperbilirubinemia type 1 · hyperbilirubinemia, Crigler-Najjar type 1 · UGT deficiency type 1

Data availability: 67 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Crigler-Najjar syndrome › Crigler-Najjar syndrome type 1

Related subtypes (1): Crigler-Najjar syndrome type 2

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

67 retrieved; paginated sample, class counts are floors:

16 uncertain significance, 15 pathogenic, 12 pathogenic/likely pathogenic, 11 likely pathogenic, 6 conflicting classifications of pathogenicity, 4 conflicting classifications of pathogenicity; other, 1 conflicting classifications of pathogenicity; drug response; other, 1 conflicting classifications of pathogenicity; drug response, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
12273	NM_000463.3(UGT1A1):c.840C>A (p.Cys280Ter)	UGT1A	Pathogenic	no assertion criteria provided
437211	NM_000463.3(UGT1A1):c.625C>T (p.Arg209Trp)	UGT1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1686290	NM_000463.3(UGT1A1):c.1304+1G>T	UGT1A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1694445	NM_000463.3(UGT1A1):c.725del (p.Val242fs)	UGT1A1	Pathogenic	criteria provided, single submitter
3586191	NM_000463.3(UGT1A1):c.1305-1G>A	UGT1A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1195873	NM_000463.3(UGT1A1):c.931del (p.Val311fs)	UGT1A10	Pathogenic	no assertion criteria provided
1206193	NM_000463.3(UGT1A1):c.1220del (p.Lys407fs)	UGT1A10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
12281	NM_000463.3(UGT1A1):c.1456T>G (p.Tyr486Asp)	UGT1A10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
266037	NM_000463.3(UGT1A1):c.353dup (p.Asp119fs)	UGT1A10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1164006	NM_000463.3(UGT1A1):c.380_381insGG (p.Cys127fs)	UGT1A3	Pathogenic	no assertion criteria provided
12277	NM_000463.3(UGT1A1):c.864+1G>C	UGT1A3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
12279	NM_000463.3(UGT1A1):c.1085-2A>G	UGT1A3	Pathogenic	no assertion criteria provided
12267	NM_000463.3(UGT1A1):c.1124C>T (p.Ser375Phe)	UGT1A4	Pathogenic	criteria provided, multiple submitters, no conflicts
3066040	NM_000463.3(UGT1A1):c.1216_1225del (p.Thr406fs)	UGT1A4	Pathogenic	no assertion criteria provided
3242206	NM_000463.3(UGT1A1):c.247T>C (p.Phe83Leu)	UGT1A4	Pathogenic/Likely pathogenic	criteria provided, single submitter
12266	NM_000463.3(UGT1A1):c.877_890delinsA (p.Tyr293fs)	UGT1A5	Pathogenic	criteria provided, multiple submitters, no conflicts
12272	NM_000463.3(UGT1A1):c.923G>A (p.Gly308Glu)	UGT1A5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3892814	NM_000463.3(UGT1A1):c.877_883del (p.Tyr293fs)	UGT1A5	Pathogenic	criteria provided, single submitter
12269	NM_000463.3(UGT1A1):c.1021C>T (p.Arg341Ter)	UGT1A6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
212545	NM_000463.3(UGT1A1):c.722_723del (p.Glu241fs)	UGT1A6	Pathogenic	criteria provided, multiple submitters, no conflicts
2417123	NM_000463.3(UGT1A1):c.1382G>A (p.Trp461Ter)	UGT1A6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
12268	NM_000463.3(UGT1A1):c.991C>T (p.Gln331Ter)	UGT1A7	Pathogenic	no assertion criteria provided
12271	NM_000463.3(UGT1A1):c.510CTT[1] (p.Phe171del)	UGT1A7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4747148	NM_000463.3(UGT1A1):c.1007G>A (p.Arg336Gln)	UGT1A7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3586187	NM_000463.3(UGT1A1):c.847C>T (p.Gln283Ter)	UGT1A8	Pathogenic	criteria provided, single submitter
1185041	NM_000463.3(UGT1A1):c.389dup (p.Leu130fs)	UGT1A9	Pathogenic	no assertion criteria provided
12276	NM_000463.3(UGT1A1):c.474_475insT (p.Ile159fs)	UGT1A9	Pathogenic	no assertion criteria provided
597250	NM_000463.3(UGT1A1):c.1160_1161delinsGT (p.Pro387Arg)	UGT1A1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
12287	NM_000463.3(UGT1A1):c.44T>G (p.Leu15Arg)	UGT1A10	Likely pathogenic	criteria provided, single submitter
12283	NM_000463.3(UGT1A1):c.1070A>G (p.Gln357Arg)	UGT1A3	Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
UGT1A1	Definitive	Autosomal recessive	Crigler-Najjar syndrome type 1	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
UGT1A1	Orphanet:2312	Transient familial neonatal hyperbilirubinemia
UGT1A1	Orphanet:79234	Crigler-Najjar syndrome type 1
UGT1A1	Orphanet:79235	Crigler-Najjar syndrome type 2

Cohort genes → proteins

10 cohort genes, 9 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	10

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
UGT1A1	HGNC:12530	ENSG00000241635	P22309	UDP-glucuronosyltransferase 1A1	gencc,clinvar
UGT1A	HGNC:12529			UDP glucuronosyltransferase family 1 member A complex locus	clinvar
UGT1A10	HGNC:12531	ENSG00000242515	Q9HAW8	UDP-glucuronosyltransferase 1A10	clinvar
UGT1A3	HGNC:12535	ENSG00000288702	P35503	UDP-glucuronosyltransferase 1A3	clinvar
UGT1A4	HGNC:12536	ENSG00000244474	P22310	UDP-glucuronosyltransferase 1A4	clinvar
UGT1A5	HGNC:12537	ENSG00000288705	P35504	UDP-glucuronosyltransferase 1A5	clinvar
UGT1A6	HGNC:12538	ENSG00000167165	P19224	UDP-glucuronosyltransferase 1A6	clinvar
UGT1A7	HGNC:12539	ENSG00000244122	Q9HAW7	UDP-glucuronosyltransferase 1A7	clinvar
UGT1A8	HGNC:12540	ENSG00000242366	Q9HAW9	UDP-glucuronosyltransferase 1A8	clinvar
UGT1A9	HGNC:12541	ENSG00000241119	O60656	UDP-glucuronosyltransferase 1A9	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
UGT1A1	UDP-glucuronosyltransferase 1A1	UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite’s water solubility, thereby facilitating excretion into eit…
UGT1A10	UDP-glucuronosyltransferase 1A10	UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite’s water solubility, thereby facilitating excretion into eit…
UGT1A3	UDP-glucuronosyltransferase 1A3	UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite’s water solubility, thereby facilitating excretion into eit…
UGT1A4	UDP-glucuronosyltransferase 1A4	UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite’s water solubility, thereby facilitating excretion into eit…
UGT1A5	UDP-glucuronosyltransferase 1A5	UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite’s water solubility, thereby facilitating excretion into eit…
UGT1A6	UDP-glucuronosyltransferase 1A6	UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to facilitate their inactivation and excretion from the body.
UGT1A7	UDP-glucuronosyltransferase 1A7	UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite’s water solubility, thereby facilitating excretion into eit…
UGT1A8	UDP-glucuronosyltransferase 1A8	UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite’s water solubility, thereby facilitating excretion into eit…
UGT1A9	UDP-glucuronosyltransferase 1A9	UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite’s water solubility, thereby facilitating excretion into eit…

Protein-family classification

Druggable: 9 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.9

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Enzyme (other)	9	10.8×	4e-09
Other/Unknown	1	0.2×	1.000

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
UGT1A1	Enzyme (other)	yes	2.4.1.17	UDP_glucos_trans, UDP_glycos_trans_CS, UDP-glycosyltransferase
UGT1A	Other/Unknown	no
UGT1A10	Enzyme (other)	yes	2.4.1.17	UDP_glucos_trans, UDP_glycos_trans_CS, UDP-glycosyltransferase
UGT1A3	Enzyme (other)	yes	2.4.1.17	UDP_glucos_trans, UDP_glycos_trans_CS, UDP-glycosyltransferase
UGT1A4	Enzyme (other)	yes	2.4.1.17	UDP_glucos_trans, UDP_glycos_trans_CS, UDP-glycosyltransferase
UGT1A5	Enzyme (other)	yes	2.4.1.17	UDP_glucos_trans, UDP_glycos_trans_CS, UDP-glycosyltransferase
UGT1A6	Enzyme (other)	yes	2.4.1.17	UDP_glucos_trans, UDP_glycos_trans_CS, UDP-glycosyltransferase
UGT1A7	Enzyme (other)	yes	2.4.1.17	UDP_glucos_trans, UDP_glycos_trans_CS, UDP-glycosyltransferase
UGT1A8	Enzyme (other)	yes	2.4.1.17	UDP_glucos_trans, UDP_glycos_trans_CS, UDP-glycosyltransferase
UGT1A9	Enzyme (other)	yes	2.4.1.17	UDP_glucos_trans, UDP_glycos_trans_CS, UDP-glycosyltransferase

Expression context

Cohort genes with no expression data: 2.

6 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	7
unknown	3

Top tissues across cohort

Tissue	Cohort genes
liver	4
right lobe of liver	4
duodenum	3
mucosa of transverse colon	2
rectum	2
adult mammalian kidney	2
esophagus mucosa	1
lower esophagus mucosa	1
male germ line stem cell (sensu Vertebrata) in testis	1
gall bladder	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
UGT1A1	79	tissue_specific	marker	duodenum, right lobe of liver, liver
UGT1A
UGT1A10	60	tissue_specific	marker	mucosa of transverse colon, duodenum, rectum
UGT1A3
UGT1A4	50	tissue_specific	yes	right lobe of liver, liver, duodenum
UGT1A5		tissue_specific
UGT1A6	88	broad	marker	liver, right lobe of liver, adult mammalian kidney
UGT1A7	68	tissue_specific	marker	lower esophagus mucosa, esophagus mucosa, male germ line stem cell (sensu Vertebrata) in testis
UGT1A8	44	tissue_specific	marker	mucosa of transverse colon, rectum, gall bladder
UGT1A9	45	tissue_specific	marker	adult mammalian kidney, right lobe of liver, liver

Protein interactions among cohort

Intra-cohort edges: 12.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
UGT1A1	1,446
UGT1A6	1,415
UGT1A10	1,373
UGT1A7	1,312
UGT1A4	1,292
UGT1A8	1,277
UGT1A3	855
UGT1A5	829
UGT1A9	26
UGT1A	0

Intra-cohort edges

A	B	Sources
UGT1A1	UGT1A10	intact
UGT1A1	UGT1A3	intact
UGT1A1	UGT1A4	intact
UGT1A1	UGT1A6	intact
UGT1A1	UGT1A7	intact
UGT1A1	UGT1A8	intact
UGT1A1	UGT1A9	intact
UGT1A10	UGT1A7	biogrid_interaction, intact
UGT1A10	UGT1A9	biogrid_interaction, intact
UGT1A3	UGT1A5	biogrid_interaction, intact
UGT1A7	UGT1A8	biogrid_interaction, intact
UGT1A7	UGT1A9	biogrid_interaction, intact

Structural data

PDB: 0 · AlphaFold-only: 9 · No structure: 1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
UGT1A9	O60656	92.26
UGT1A10	Q9HAW8	92.11
UGT1A7	Q9HAW7	91.76
UGT1A3	P35503	91.59
UGT1A8	Q9HAW9	91.56
UGT1A5	P35504	91.53
UGT1A6	P19224	91.50
UGT1A1	P22309	91.19
UGT1A4	P22310	90.87

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 10. Enrichment computed across 10 evidence-associated genes (9 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 9 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Glucuronidation	9	761.3×	5e-27	UGT1A1, UGT1A10, UGT1A3, UGT1A4, UGT1A5, UGT1A6, UGT1A7, UGT1A8 (+1 more)
Aspirin ADME	8	282.0×	2e-19	UGT1A1, UGT1A3, UGT1A4, UGT1A5, UGT1A6, UGT1A7, UGT1A8, UGT1A9
Paracetamol ADME	4	188.0×	9e-09	UGT1A1, UGT1A10, UGT1A6, UGT1A9
Heme degradation	2	181.3×	1e-04	UGT1A1, UGT1A4
Defective UGT1A1 causes hyperbilirubinemia	1	1268.9×	0.001	UGT1A1
NR1H2 & NR1H3 regulate gene expression to control bile acid homeostasis	1	158.6×	0.008	UGT1A3
Atorvastatin ADME	1	158.6×	0.008	UGT1A3
Prednisone ADME	1	141.0×	0.008	UGT1A3
PPARA activates gene expression	1	10.5×	0.091	UGT1A9
Defective UGT1A4 causes hyperbilirubinemia	1	—	—	UGT1A4

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 9 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
flavone metabolic process	5	9362.2×	0e+00	UGT1A1, UGT1A10, UGT1A7, UGT1A8, UGT1A9
negative regulation of fatty acid metabolic process	8	3744.9×	0e+00	UGT1A1, UGT1A10, UGT1A3, UGT1A4, UGT1A6, UGT1A7, UGT1A8, UGT1A9
glucuronate metabolic process	4	3744.9×	0e+00	UGT1A1, UGT1A10, UGT1A4, UGT1A6
bilirubin conjugation	2	3744.9×	0e+00	UGT1A1, UGT1A4
toxin catabolic process	2	3744.9×	0e+00	UGT1A10, UGT1A7
flavonoid metabolic process	5	1170.3×	3e-15	UGT1A1, UGT1A3, UGT1A7, UGT1A8, UGT1A9
xenobiotic metabolic process	7	116.0×	8e-14	UGT1A1, UGT1A10, UGT1A3, UGT1A6, UGT1A7, UGT1A8, UGT1A9
retinoic acid metabolic process	5	445.8×	9e-13	UGT1A1, UGT1A3, UGT1A7, UGT1A8, UGT1A9
liver development	5	123.2×	7e-10	UGT1A1, UGT1A10, UGT1A7, UGT1A8, UGT1A9
negative regulation of steroid metabolic process	2	1872.4×	7e-07	UGT1A1, UGT1A8
vitamin D3 metabolic process	2	1872.4×	7e-07	UGT1A3, UGT1A4
estrogen metabolic process	3	208.1×	8e-07	UGT1A1, UGT1A3, UGT1A7
steroid metabolic process	3	112.3×	5e-06	UGT1A1, UGT1A5, UGT1A8
coumarin metabolic process	2	624.1×	8e-06	UGT1A7, UGT1A8
heme catabolic process	2	340.4×	3e-05	UGT1A1, UGT1A4
xenobiotic catabolic process	2	124.8×	2e-04	UGT1A10, UGT1A7
fatty acid metabolic process	2	43.0×	0.002	UGT1A7, UGT1A8
pigment accumulation	1	936.2×	0.002	UGT1A1
hepatic stellate cell activation	1	624.1×	0.003	UGT1A1
bile acid secretion	1	374.5×	0.004	UGT1A3
connective tissue replacement	1	267.5×	0.006	UGT1A1
response to arsenic-containing substance	1	133.8×	0.011	UGT1A1
protein heterooligomerization	1	117.0×	0.011	UGT1A1
digestive tract development	1	58.5×	0.022	UGT1A1
canonical NF-kappaB signal transduction	1	40.7×	0.030	UGT1A1
response to toxic substance	1	23.4×	0.050	UGT1A1
protein homooligomerization	1	13.6×	0.082	UGT1A1
lipid metabolic process	1	10.2×	0.104	UGT1A10
gene expression	1	8.9×	0.115	UGT1A1
DNA damage response	1	5.9×	0.161	UGT1A1

Therapeutics

Drug target analysis

Approved (phase 4): 6 · Phase ≥3: 6 · Phased (≥1): 6 · Undrugged: 4

Druggability breadth: 9 of 10 evidence-associated genes (90%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
UGT1A1	ATAZANAVIR
UGT1A10	DICLOFENAC
UGT1A4	ANASTROZOLE
UGT1A6	DICLOFENAC
UGT1A7	DICLOFENAC
UGT1A9	DICLOFENAC

Top cohort targets by molecule count

Symbol	Molecules	Max phase
UGT1A1	12	4
UGT1A10	2	4
UGT1A6	2	4
UGT1A7	2	4
UGT1A4	1	4
UGT1A9	1	4
UGT1A	0	0
UGT1A3	0	0
UGT1A5	0	0
UGT1A8	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
ATAZANAVIR	4	UGT1A1
DICLOFENAC	4	UGT1A1, UGT1A10, UGT1A6, UGT1A7, UGT1A9
KETOCONAZOLE	4	UGT1A1
LEVOTHYROXINE	4	UGT1A1
RITONAVIR	4	UGT1A1
ETHINYL ESTRADIOL	4	UGT1A1
CARVEDILOL	4	UGT1A1
ANASTROZOLE	4	UGT1A4
TROGLITAZONE	4	UGT1A6
PROBENECID	4	UGT1A7
HYMECROMONE	2	UGT1A1
FIPRAVIRIMAT	2	UGT1A1
NIFLUMIC ACID	2	UGT1A1
DAIDZEIN	2	UGT1A1
BAICALEIN	2	UGT1A1
EPIESTRIOL	2	UGT1A10

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 9.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
UGT1A1	174	ADMET:159, Binding:15
UGT1A9	153	ADMET:149, Binding:4
UGT1A3	131	ADMET:129, Binding:2
UGT1A10	101	ADMET:99, Binding:2
UGT1A4	99	ADMET:96, Binding:3
UGT1A8	87	ADMET:86, Binding:1
UGT1A6	76	ADMET:71, Binding:5
UGT1A7	76	ADMET:74, Binding:2
UGT1A5	35	ADMET:35

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
UGT1A1	2.4.1.17	glucuronosyltransferase
UGT1A10	2.4.1.17	glucuronosyltransferase
UGT1A3	2.4.1.17	glucuronosyltransferase
UGT1A4	2.4.1.17	glucuronosyltransferase
UGT1A5	2.4.1.17	glucuronosyltransferase
UGT1A6	2.4.1.17	glucuronosyltransferase
UGT1A7	2.4.1.17	glucuronosyltransferase
UGT1A8	2.4.1.17	glucuronosyltransferase
UGT1A9	2.4.1.17	glucuronosyltransferase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
UGT1A1	174
UGT1A10	101
UGT1A3	131
UGT1A9	153

Pharmacogenomics

Cohort genes with a PharmGKB record: 10; with CPIC/DPWG dosing guidelines: 1.

Cohort genes with a CPIC/DPWG dosing guideline

Symbol	CPIC guidelines
UGT1A1	1

Chemical tractability of cohort targets

16 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
ATAZANAVIR	4	UGT1A1
DICLOFENAC	4	UGT1A1, UGT1A10, UGT1A6, UGT1A7, UGT1A9
KETOCONAZOLE	4	UGT1A1
LEVOTHYROXINE	4	UGT1A1
RITONAVIR	4	UGT1A1
ETHINYL ESTRADIOL	4	UGT1A1
CARVEDILOL	4	UGT1A1
ANASTROZOLE	4	UGT1A4
TROGLITAZONE	4	UGT1A6
PROBENECID	4	UGT1A7
HYMECROMONE	2	UGT1A1
FIPRAVIRIMAT	2	UGT1A1
NIFLUMIC ACID	2	UGT1A1
DAIDZEIN	2	UGT1A1
BAICALEIN	2	UGT1A1
EPIESTRIOL	2	UGT1A10

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	6	UGT1A1, UGT1A10, UGT1A4, UGT1A6, UGT1A7, UGT1A9
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	3	UGT1A3, UGT1A5, UGT1A8
E	Difficult family or no structure, no drug	1	UGT1A

Undrugged target profiles

4 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
UGT1A3	131	—
UGT1A	0	—
UGT1A5	35	—
UGT1A8	87	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.