UGT2B4

Summary

UGT2B4 (UDP glucuronosyltransferase family 2 member B4, HGNC:12553) is a protein-coding gene on chromosome 4q13.3, encoding UDP-glucuronosyltransferase 2B4 (P06133). 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 either the urine or bile.

Enables glucuronosyltransferase activity. Involved in estrogen metabolic process and xenobiotic metabolic process. Predicted to be located in endoplasmic reticulum membrane.

Source: NCBI Gene 7363 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 128 total
• Druggable target: yes
• MANE Select transcript: NM_021139

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12553
Approved symbol	UGT2B4
Name	UDP glucuronosyltransferase family 2 member B4
Location	4q13.3
Locus type	gene with protein product
Status	Approved
Aliases	UGT2B11
Ensembl gene	ENSG00000156096
Ensembl biotype	protein_coding
OMIM	600067
Entrez	7363

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 6 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000305107, ENST00000502655, ENST00000503836, ENST00000506580, ENST00000510114, ENST00000512583, ENST00000876892, ENST00000876893, ENST00000968901

RefSeq mRNA: 3 — MANE Select: NM_021139 NM_001297615, NM_001297616, NM_021139

CCDS: CCDS43234, CCDS75137

Canonical transcript exons

ENST00000305107 — 6 exons

Exon	Start	End
ENSE00003493173	69493693	69493841
ENSE00003525346	69480165	69480910
ENSE00003626115	69486609	69486696
ENSE00003666299	69485208	69485427
ENSE00003682934	69489439	69489570
ENSE00003850649	69495141	69495905

Expression profiles

Bgee: expression breadth broad, 96 present calls, max score 98.77.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.2536 / max 416.0081, expressed in 23 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
52361	1.2201	20
52360	0.0335	9

Top tissues by expression

268 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
liver	UBERON:0002107	98.77	gold quality
right lobe of liver	UBERON:0001114	98.48	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.97	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.55	gold quality
heart left ventricle	UBERON:0002084	75.71	gold quality
cardiac ventricle	UBERON:0002082	75.52	gold quality
right atrium auricular region	UBERON:0006631	73.51	gold quality
heart right ventricle	UBERON:0002080	73.23	gold quality
cardiac atrium	UBERON:0002081	72.19	gold quality
heart	UBERON:0000948	70.58	gold quality
myocardium	UBERON:0002349	68.47	silver quality
islet of Langerhans	UBERON:0000006	61.49	gold quality
left ventricle myocardium	UBERON:0006566	58.97	gold quality
buccal mucosa cell	CL:0002336	57.16	gold quality
upper lobe of left lung	UBERON:0008952	57.16	gold quality
upper lobe of lung	UBERON:0008948	57.08	gold quality
lower lobe of lung	UBERON:0008949	56.13	silver quality
cardiac muscle of right atrium	UBERON:0003379	53.14	silver quality
lung	UBERON:0002048	53.06	gold quality
colonic epithelium	UBERON:0000397	52.57	gold quality
frontal pole	UBERON:0002795	50.41	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality
paraflocculus	UBERON:0005351	50.18	gold quality
Brodmann (1909) area 10	UBERON:0013541	50.18	gold quality
quadriceps femoris	UBERON:0001377	49.78	gold quality
vastus lateralis	UBERON:0001379	49.45	gold quality
thymus	UBERON:0002370	49.35	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
cerebellar vermis	UBERON:0004720	49.25	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.42

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NR1H4

miRNA regulators (miRDB)

29 targeting UGT2B4, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-6512-3P	99.65	66.07	1468
HSA-MIR-6720-5P	99.65	66.22	1459
HSA-MIR-6516-3P	99.65	68.57	1238
HSA-MIR-6083	99.47	68.73	2393
HSA-MIR-4728-3P	99.47	68.94	981
HSA-MIR-513A-3P	99.39	70.63	3620
HSA-MIR-513C-3P	99.39	70.63	3620
HSA-MIR-135B-5P	99.36	71.63	1613
HSA-MIR-135A-5P	99.36	71.85	1601
HSA-MIR-2054	99.20	68.89	1699
HSA-MIR-8077	99.17	66.67	862
HSA-MIR-3606-3P	99.11	69.84	3254
HSA-MIR-670-3P	99.03	68.88	2404
HSA-MIR-4709-5P	98.51	67.25	1335
HSA-MIR-624-3P	98.37	67.06	1067
HSA-MIR-649	97.96	67.21	704
HSA-MIR-10397-5P	97.31	69.06	710

Literature-anchored findings (GeneRIF, showing 13)

• Farnesoid X receptor (FXR) induces the UGT2B4 enzyme in hepatocytes; this study identifies UGT2B4 as a novel FXR target gene. (PMID:12806625)
• UGT2B4 expression is regulated by PPARalpha (PMID:12810707)
• P.1053: “…UGT2B4…is…fairly common in Caucasians…and Africans…“but…still rare in …Japanese…” P.1054: “…genotyping UGT2B4…in Japanese…would be useful for studies on… association between haplotypes and pharmacokinetic…parameters.” (PMID:15319348)
• Results strongly indicated that the presence of an aromatic residue at position 33 is important for the activity and specificity of UGTB4. (PMID:17263731)
• Extensive splicing of transcripts of the bile acid-conjugating enzyme UGT2B4 modulates glucuronidation. (PMID:20139797)
• The variation pattern upstream UGT2B4 is highly unusual and may be the result of balancing selection. (PMID:21660508)
• Methadone inhibits CYP2D6 and UGT2B7/2B4 in vivo (PMID:22092298)
• The UGT1A8 and UGT2B4 genotypes associated with decreased predicted enzyme activities, were significantly associated with an increased risk of esophageal squamous cell carcinoma. (PMID:22367021)
• These data indicate that knocking down PAPSS increases UGT2B4 transcription and mRNA stability as a compensatory response to the loss of SULT2A1 activity (PMID:25948711)
• UGT2B4 previously implicated in the risk of breast cancer is associated with menarche timing in Ukrainian females. (PMID:27282283)
• Clopidogrel carboxylic acid is metabolized mainly by UGT2B7 and UGT2B4 in the liver and by UGT2B17 in the small intestinal wall. (PMID:29138287)
• Absence of significant association between UGT2B4 genetic variants and the susceptibility to anti-tuberculosis drug-induced liver injury in a Western Chinese population. (PMID:32170986)
• Distilling functional variations for human UGT2B4 upstream region based on selection signals and implications for phenotypes of Neanderthal and Denisovan. (PMID:36823244)

Cross-species orthologs

107 orthologs

Organism	Symbol	Gene ID
danio_rerio	ugt5d1	ENSDARG00000002394
danio_rerio	ugt5c2	ENSDARG00000006372
danio_rerio	ugt5a1	ENSDARG00000016479
danio_rerio	ugt5g1	ENSDARG00000032862
danio_rerio	ugt5g2	ENSDARG00000043901
danio_rerio	ugt5f1	ENSDARG00000054835
danio_rerio	ugt5e1	ENSDARG00000058048
danio_rerio	ugt5c3	ENSDARG00000061439
danio_rerio	ugt5c1	ENSDARG00000061444
danio_rerio	si:ch73-334d15.1	ENSDARG00000061672
danio_rerio	ugt2a7	ENSDARG00000091624
danio_rerio	ugt5b4	ENSDARG00000091916
danio_rerio	ugt2b1	ENSDARG00000093043
danio_rerio	ugt5a2	ENSDARG00000093640
danio_rerio	ugt5b3	ENSDARG00000099276
danio_rerio	ugt5b2	ENSDARG00000101495
danio_rerio	ugt5b5	ENSDARG00000104203
danio_rerio	ugt5b1	ENSDARG00000104995
danio_rerio	ugt2b3	ENSDARG00000109611
danio_rerio		ENSDARG00000110614
danio_rerio		ENSDARG00000113218
danio_rerio	ugt2b5	ENSDARG00000116986
drosophila_melanogaster	Ugt36A1	FBGN0015663
drosophila_melanogaster	Ugt35B1	FBGN0026314
drosophila_melanogaster	Ugt35A1	FBGN0026315
drosophila_melanogaster	Ugt37C1	FBGN0026754
drosophila_melanogaster	Ugt37B1	FBGN0026755
drosophila_melanogaster	Ugt37A1	FBGN0026756
drosophila_melanogaster	Ugt36E1	FBGN0027070
drosophila_melanogaster	Ugt49B1	FBGN0027073
drosophila_melanogaster	Ugt36F1	FBGN0027074
drosophila_melanogaster	Ugt307A1	FBGN0031887
drosophila_melanogaster	Ugt36D1	FBGN0032713
drosophila_melanogaster	Ugt49C1	FBGN0034605
drosophila_melanogaster	Ugt316A1	FBGN0036842
drosophila_melanogaster	Ugt37A2	FBGN0038082
drosophila_melanogaster	Ugt37A3	FBGN0038083
drosophila_melanogaster	Ugt49B2	FBGN0038886
drosophila_melanogaster	Ugt303B3	FBGN0039085
drosophila_melanogaster	Ugt303B1	FBGN0039086
drosophila_melanogaster	Ugt303B2	FBGN0039087
drosophila_melanogaster	Ugt304A1	FBGN0040250
drosophila_melanogaster	Ugt302K1	FBGN0040251
drosophila_melanogaster	Ugt303A1	FBGN0040252
drosophila_melanogaster	Ugt35E1	FBGN0040253
drosophila_melanogaster	Ugt35E2	FBGN0040255
drosophila_melanogaster	Ugt302E1	FBGN0040257
drosophila_melanogaster	Ugt302C1	FBGN0040259
drosophila_melanogaster	Ugt37D1	FBGN0040260
drosophila_melanogaster	Ugt37E1	FBGN0040261
drosophila_melanogaster	Ugt37C2	FBGN0040262
drosophila_melanogaster	Ugt305A1	FBGN0042179
drosophila_melanogaster	Ugt35D1	FBGN0051002
caenorhabditis_elegans		WBGENE00007072
caenorhabditis_elegans		WBGENE00007073
caenorhabditis_elegans		WBGENE00007402
caenorhabditis_elegans		WBGENE00007422
caenorhabditis_elegans		WBGENE00007455
caenorhabditis_elegans		WBGENE00007885
caenorhabditis_elegans		WBGENE00007946
caenorhabditis_elegans		WBGENE00008097
caenorhabditis_elegans		WBGENE00008486
caenorhabditis_elegans		WBGENE00009255
caenorhabditis_elegans		WBGENE00010904
caenorhabditis_elegans		WBGENE00011006
caenorhabditis_elegans		WBGENE00011340
caenorhabditis_elegans		WBGENE00011452
caenorhabditis_elegans		WBGENE00011453
caenorhabditis_elegans		WBGENE00012788
caenorhabditis_elegans		WBGENE00013900
caenorhabditis_elegans		WBGENE00013905
caenorhabditis_elegans		WBGENE00013906
caenorhabditis_elegans		WBGENE00015141
caenorhabditis_elegans		WBGENE00015369
caenorhabditis_elegans		WBGENE00015371
caenorhabditis_elegans		WBGENE00015449
caenorhabditis_elegans		WBGENE00015577
caenorhabditis_elegans	ugt-28	WBGENE00015693
caenorhabditis_elegans	ugt-27	WBGENE00015694
caenorhabditis_elegans	ugt-26	WBGENE00015695
caenorhabditis_elegans		WBGENE00015739
caenorhabditis_elegans		WBGENE00015965
caenorhabditis_elegans		WBGENE00016013
caenorhabditis_elegans		WBGENE00017315
caenorhabditis_elegans		WBGENE00017329
caenorhabditis_elegans		WBGENE00017331
caenorhabditis_elegans		WBGENE00017332
caenorhabditis_elegans		WBGENE00017333
caenorhabditis_elegans		WBGENE00017334
caenorhabditis_elegans		WBGENE00017336
caenorhabditis_elegans		WBGENE00017959
caenorhabditis_elegans		WBGENE00018206
caenorhabditis_elegans		WBGENE00018543
caenorhabditis_elegans		WBGENE00018931
caenorhabditis_elegans		WBGENE00019232
caenorhabditis_elegans		WBGENE00019233
caenorhabditis_elegans		WBGENE00019234
caenorhabditis_elegans		WBGENE00019235
caenorhabditis_elegans		WBGENE00019515
caenorhabditis_elegans		WBGENE00019516
caenorhabditis_elegans		WBGENE00020587
caenorhabditis_elegans		WBGENE00020592
caenorhabditis_elegans		WBGENE00020593
caenorhabditis_elegans		WBGENE00020594
caenorhabditis_elegans		WBGENE00021709
caenorhabditis_elegans		WBGENE00044282
caenorhabditis_elegans		WBGENE00044286

Paralogs (21): UGT2B10 (ENSG00000109181), UGT2A3 (ENSG00000135220), UGT2B28 (ENSG00000135226), UGT3A1 (ENSG00000145626), UGT1A6 (ENSG00000167165), UGT3A2 (ENSG00000168671), UGT2B7 (ENSG00000171234), UGT2A1 (ENSG00000173610), UGT8 (ENSG00000174607), UGT2B15 (ENSG00000196620), UGT2B17 (ENSG00000197888), UGT2B11 (ENSG00000213759), UGT1A9 (ENSG00000241119), UGT1A1 (ENSG00000241635), UGT1A8 (ENSG00000242366), UGT1A10 (ENSG00000242515), UGT1A7 (ENSG00000244122), UGT1A4 (ENSG00000244474), UGT2A2 (ENSG00000271271), UGT1A3 (ENSG00000288702), UGT1A5 (ENSG00000288705)

Protein

Protein identifiers

UDP-glucuronosyltransferase 2B4 — P06133 (reviewed: P06133)

Alternative names: HLUG25, Hyodeoxycholic acid-specific UDPGT, UDPGTh-1

All UniProt accessions (2): P06133, D6RGY0

UniProt curated annotations — full annotation on UniProt →

Function. 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 either the urine or bile. Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds. Catalyzes the glucuronidation of the endogenous estrogen hormones such as estradiol and estriol.

Subcellular location. Endoplasmic reticulum membrane.

Similarity. Belongs to the UDP-glycosyltransferase family.

Isoforms (3)

UniProt ID	Names	Canonical?
P06133-1	1	yes
P06133-2	2
P06133-3	3

RefSeq proteins (3): NP_001284544, NP_001284545, NP_066962* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002213	UDP_glucos_trans	Family
IPR035595	UDP_glycos_trans_CS	Conserved_site
IPR050271	UDP-glycosyltransferase	Family

Pfam: PF00201

Enzyme classification (BRENDA):

• EC 2.4.1.17 — glucuronosyltransferase (BRENDA: 32 organisms, 1285 substrates, 660 inhibitors, 855 Km, 6 kcat entries)

Substrate kinetics (BRENDA)

189 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
4-METHYLUMBELLIFERONE	0.0001–4.204	44
MORPHINE	0.0355–37.4	31
4-NITROPHENOL	0.0102–2	24
PROPOFOL	0.0072–0.9	19
ZIDOVUDINE	0.508–1.54	19
1-NAPHTHOL	0.0025–27	18
IMIPRAMINE	0.0072–1.442	13
TRANS-4-HYDROXYTAMOXIFEN	0.0037–0.319	13
SCOPOLETIN	0.061–7.64	11
SEROTONIN	3.7–55.9	11
2-HYDROXYESTRONE	0.0102–6	10
CIS-4-HYDROXYTAMOXIFEN	0.0074–0.193	10
DOPAMINE	1.89–3.11	10
1-HYDROXYBENZO(A)PYRENE	0.0113–2.869	9
1-HYDROXYPYRENE	0.0032–2.326	9

Catalyzed reactions (Rhea), 3 shown:

• glucuronate acceptor + UDP-alpha-D-glucuronate = acceptor beta-D-glucuronoside + UDP + H(+) (RHEA:21032)
• 17alpha-estradiol + UDP-alpha-D-glucuronate = 17alpha-estradiol 17-O-(beta-D-glucuronate) + UDP + H(+) (RHEA:52872)
• 16alpha,17alpha-estriol + UDP-alpha-D-glucuronate = 16alpha,17alpha-estriol 17-O-(beta-D-glucuronate) + UDP + H(+) (RHEA:52916)

UniProt features (21 total): sequence variant 8, sequence conflict 5, splice variant 4, signal peptide 1, chain 1, transmembrane region 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P06133-F1	94.03	0.88

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Glycosylation sites (1): 315

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-156588	Glucuronidation
R-HSA-9749641	Aspirin ADME

MSigDB gene sets: 141 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, REACTOME_BIOLOGICAL_OXIDATIONS, GOBP_REGULATION_OF_HORMONE_LEVELS, chr4q13, CAIRO_HEPATOBLASTOMA_CLASSES_DN, MORF_ZNF10, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM4, HSIAO_LIVER_SPECIFIC_GENES, GOBP_LIPID_METABOLIC_PROCESS, MORF_EPHA7, KEGG_STARCH_AND_SUCROSE_METABOLISM, MORF_RAB3A, MORF_BMPR2, KEGG_STEROID_HORMONE_BIOSYNTHESIS, VECCHI_GASTRIC_CANCER_EARLY_DN

GO Biological Process (3): xenobiotic metabolic process (GO:0006805), estrogen metabolic process (GO:0008210), lipid metabolic process (GO:0006629)

GO Molecular Function (4): glucuronosyltransferase activity (GO:0015020), UDP-glycosyltransferase activity (GO:0008194), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757)

GO Cellular Component (3): endoplasmic reticulum membrane (GO:0005789), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Phase II - Conjugation of compounds	1
Drug ADME	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
metabolic process	1
cellular response to xenobiotic stimulus	1
steroid metabolic process	1
hormone metabolic process	1
primary metabolic process	1
UDP-glycosyltransferase activity	1
hexosyltransferase activity	1
glycosyltransferase activity	1
catalytic activity	1
transferase activity	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

938 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
UGT2B4	SLC35A2	P78381	972
UGT2B4	CYP2C9	P11712	783
UGT2B4	CYP1A2	P05177	775
UGT2B4	CYP3A4	P05184	768
UGT2B4	PPIG	Q13427	763
UGT2B4	SLCO1B1	Q9Y6L6	735
UGT2B4	SULT2A1	Q06520	734
UGT2B4	B3GAT2	Q9NPZ5	664
UGT2B4	CYP2C19	P33259	629
UGT2B4	SULT1B1	O43704	620
UGT2B4	SULT1C3	Q6IMI6	619
UGT2B4	CYP2D6	P10635	618
UGT2B4	SULT1C4	O75897	615
UGT2B4	CYP2B6	P20813	606
UGT2B4	CYP2C8	P10632	593

IntAct

3 interactions, top by confidence:

A	B	Type	Score
UGT2B4	STAT5A	psi-mi:“MI:0915”(physical association)	0.370
M		psi-mi:“MI:0914”(association)	0.350

BioGRID (1): UGT2B4 (Two-hybrid)

ESM2 similar proteins: A0A291PQF1, A0A291PQG3, A0A291PQH4, A8WLF6, O02663, O19103, O75310, O97951, P06133, P08541, P08542, P09875, P16662, P17717, P18569, P19488, P34317, P36511, P36513, P36514, P36537, Q09426, Q10941, Q16880, Q18081, Q1LZI1, Q20086, Q21706, Q22295, Q3SY77, Q3UP75, Q5RFJ3, Q62789, Q63ZR6, Q64676, Q6K1J1, Q6NUS8, Q6PDD0, Q6UWM9, Q83140

Diamond homologs: A0A0A1H7N4, A0A0A1HA03, A0A0C1EH92, A0A0D5ZDC8, A0A0G2EAR7, A0A193AU77, A0A193AUF6, A0A1L7U2E9, A0A224AKZ9, A0A224AM54, A0A291PQF1, A0A2Z5CV93, A0A364KRL8, A0A478EC03, B3VI56, F8WKW0, G2WW48, K4GHR9, K4GHS2, K4GKX2, K7NBW3, O02663, O23401, O60656, O75310, O81498, O97951, P06133, P08430, P08542, P09875, P0DTE4, P0DTE5, P17717, P19224, P20720, P22309, P36510, P36513, P36537

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

128 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	108
Likely benign	10
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

618 predictions. Top by Δscore:

Variant	Effect	Δscore
4:69486602:GACTT:G	donor_loss	1.0000
4:69486603:ACTT:A	donor_loss	1.0000
4:69486604:CTT:C	donor_loss	1.0000
4:69486605:TTA:T	donor_loss	1.0000
4:69486606:T:TG	donor_loss	1.0000
4:69486607:A:AC	donor_gain	1.0000
4:69486608:C:CC	donor_gain	1.0000
4:69486693:GAACC:G	acceptor_loss	1.0000
4:69486696:CC:C	acceptor_loss	1.0000
4:69486697:C:A	acceptor_loss	1.0000
4:69486698:T:A	acceptor_loss	1.0000
4:69489435:TTA:T	donor_loss	1.0000
4:69489436:TA:T	donor_loss	1.0000
4:69489437:A:AC	donor_gain	1.0000
4:69489438:C:CC	donor_gain	1.0000
4:69489438:C:CG	donor_loss	1.0000
4:69489438:CCTT:C	donor_gain	1.0000
4:69489567:TTTC:T	acceptor_gain	1.0000
4:69489568:TTC:T	acceptor_gain	1.0000
4:69489569:TC:T	acceptor_gain	1.0000
4:69489570:CC:C	acceptor_gain	1.0000
4:69489571:C:CC	acceptor_gain	1.0000
4:69489571:CTGTG:C	acceptor_loss	1.0000
4:69489572:T:A	acceptor_loss	1.0000
4:69493687:GTTTA:G	donor_loss	1.0000
4:69493688:TTTAC:T	donor_loss	1.0000
4:69493689:TTAC:T	donor_loss	1.0000
4:69493690:TA:T	donor_loss	1.0000
4:69493692:CCT:C	donor_loss	1.0000
4:69493838:CTTC:C	acceptor_gain	1.0000

AlphaMissense

3499 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:69486690:A:G	W337R	0.992
4:69486690:A:T	W337R	0.992
4:69485371:C:G	A383P	0.989
4:69486614:A:G	L362P	0.986
4:69489527:A:T	V305E	0.984
4:69486622:C:A	Q359H	0.983
4:69486622:C:G	Q359H	0.983
4:69495349:G:C	S171R	0.983
4:69495349:G:T	S171R	0.983
4:69495351:T:G	S171R	0.983
4:69480823:A:C	F466L	0.982
4:69480823:A:T	F466L	0.982
4:69480825:A:G	F466L	0.982
4:69485284:C:G	A412P	0.982
4:69485403:A:T	I372K	0.982
4:69485232:A:G	L429P	0.981
4:69486695:A:T	V335D	0.981
4:69486631:C:A	W356C	0.980
4:69486631:C:G	W356C	0.980
4:69495232:C:A	R210S	0.980
4:69495232:C:G	R210S	0.980
4:69485406:A:G	F371S	0.979
4:69485409:G:T	A370D	0.978
4:69489468:C:G	A325P	0.978
4:69495725:A:G	L46P	0.978
4:69489512:C:T	G310E	0.977
4:69485394:C:T	G375D	0.976
4:69486633:A:G	W356R	0.976
4:69486633:A:T	W356R	0.976
4:69485373:T:A	E382V	0.975

dbSNP variants (sampled 300 via entrez): RS1000049786 (4:69513347 T>C), RS1000141981 (4:69510655 T>C), RS1000185556 (4:69501964 C>G), RS1000187125 (4:69513669 T>A,C), RS1000348008 (4:69518726 C>G), RS1000384422 (4:69502402 G>A), RS1000426049 (4:69502258 C>T), RS1000463035 (4:69485868 TCTC>T), RS1000518469 (4:69527959 T>A,G), RS1000521069 (4:69501118 G>A), RS1000690286 (4:69507886 C>A,T), RS1000718651 (4:69501307 G>C), RS1000744567 (4:69503621 A>C), RS1000796763 (4:69503312 T>C), RS1000866539 (4:69480071 C>T)

Disease associations

OMIM: gene MIM:600067 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST003650_5	Bacteremia	7.000000e-07
GCST007684_1	Plasma clozapine-norclozapine ratio in treatment-resistant schizophrenia	9.000000e-66
GCST007684_3	Plasma clozapine-norclozapine ratio in treatment-resistant schizophrenia	4.000000e-13
GCST009144_26	Disease progression in age-related macular degeneration (adjusted for baseline)	3.000000e-06
GCST009391_2123	Metabolite levels	5.000000e-06
GCST009391_410	Metabolite levels	4.000000e-06
GCST009391_799	Metabolite levels	9.000000e-07

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0600040	plasma clozapine-to-N-desmethylclozapine ratio measurement
EFO:0008336	disease progression measurement
EFO:0010382	phosphatidylcholine 36:4 measurement
EFO:0010387	phosphatidylcholine 38:5 measurement
EFO:0010396	sphingomyelin 22:1 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4523985 (PROTEIN FAMILY), CHEMBL6196 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs4557343	UGT2B4		0.00	0

CTD chemical–gene interactions

72 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	affects expression, affects cotreatment, decreases expression, increases expression	6
Chenodeoxycholic Acid	affects cotreatment, decreases expression, increases expression	5
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation	4
Acetaminophen	affects cotreatment, decreases expression	3
Deoxycholic Acid	affects cotreatment, decreases expression	3
Glycochenodeoxycholic Acid	affects cotreatment, decreases expression	3
Glycocholic Acid	affects cotreatment, decreases expression	3
Glycodeoxycholic Acid	decreases expression, affects cotreatment	3
Hymecromone	decreases reaction, increases glucuronidation, increases chemical synthesis, increases activity, increases metabolic processing	3
Aflatoxin B1	affects expression, decreases methylation	3
4-methylumbelliferyl glucuronide	increases glucuronidation, increases metabolic processing, decreases reaction, increases chemical synthesis	2
perfluorooctane sulfonic acid	decreases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
7-hydroxy-4-(trifluoromethyl)coumarin	increases glucuronidation	1
mivebresib	decreases expression	1
dicrotophos	decreases expression	1
muricholic acid	increases glucuronidation	1
lasiocarpine	decreases expression	1
bisphenol A	increases glucuronidation	1
chlortoluron	decreases expression	1
deoxynivalenol	increases glucuronidation	1
gingerol	increases glucuronidation	1
hyodeoxycholic acid	increases glucuronidation	1
amentoflavone	decreases activity	1
hydroxyhydroquinone	increases expression	1
tris(2-butoxyethyl) phosphate	decreases expression	1
mono-(2-ethylhexyl)phthalate	increases glucuronidation	1
sodium arsenite	decreases expression	1
perfluorooctanoic acid	decreases expression	1
aflatoxin B2	decreases methylation	1

ChEMBL screening assays

58 unique, capped per target: 57 admet, 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4339708	ADMET	Drug metabolism in human hepatocytes assessed as UGT-mediated glucuronidation by measuring O-glucuronide formation at 10 uM measured after 4 hrs by LC-MS analysis	Discovery of Imidazo[1,2-a]pyrazines and Pyrazolo[1,5-c]pyrimidines as TARP γ-8 Selective AMPAR Negative Modulators. — ACS Med Chem Lett
CHEMBL904749	Binding	Inhibition of human recombinant UGT2B4 at 25 uM by fluorescence spectroscopy	Isoform-selective inhibition of the human UDP-glucuronosyltransferase 2B7 by isolongifolol derivatives. — J Med Chem

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.