UGT2B15

Summary

UGT2B15 (UDP glucuronosyltransferase family 2 member B15, HGNC:12546) is a protein-coding gene on chromosome 4q13.2, encoding UDP-glucuronosyltransferase 2B15 (P54855). 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.

This gene encodes a glycosyltransferase that is invovled in the metabolism and elimination of toxic compounts, both endogenous and of xenobiotic origin. This gene plays a role in the regulation of estrogens and androgens. This locus is present in a cluster of similar genes and pseudogenes on chromosome 4.

Source: NCBI Gene 7366 — RefSeq curated summary.

At a glance

• GWAS associations: 12
• Clinical variants (ClinVar): 104 total
• Druggable target: yes
• MANE Select transcript: NM_001076

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12546
Approved symbol	UGT2B15
Name	UDP glucuronosyltransferase family 2 member B15
Location	4q13.2
Locus type	gene with protein product
Status	Approved
Aliases	UGT2B8
Ensembl gene	ENSG00000196620
Ensembl biotype	protein_coding
OMIM	600069
Entrez	7366

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000338206, ENST00000871508, ENST00000962480

RefSeq mRNA: 1 — MANE Select: NM_001076 NM_001076

CCDS: CCDS3524

Canonical transcript exons

ENST00000338206 — 6 exons

Exon	Start	End
ENSE00001434112	68646597	68647383
ENSE00001603552	68668040	68668188
ENSE00001623789	68663008	68663139
ENSE00001691487	68655095	68655182
ENSE00001728589	68669895	68670652
ENSE00001790311	68654037	68654256

Expression profiles

Bgee: expression breadth broad, 60 present calls, max score 98.67.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.5455 / max 166.6044, expressed in 67 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
52340	0.4968	46
52339	0.0487	29

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gall bladder	UBERON:0002110	98.67	gold quality
liver	UBERON:0002107	96.43	gold quality
right lobe of liver	UBERON:0001114	95.42	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	94.85	gold quality
islet of Langerhans	UBERON:0000006	91.95	gold quality
duodenum	UBERON:0002114	90.41	gold quality
mucosa of transverse colon	UBERON:0004991	87.80	gold quality
pancreas	UBERON:0001264	84.61	gold quality
body of pancreas	UBERON:0001150	82.32	gold quality
transverse colon	UBERON:0001157	74.53	gold quality
small intestine	UBERON:0002108	73.31	gold quality
small intestine Peyer’s patch	UBERON:0003454	72.82	gold quality
body of stomach	UBERON:0001161	72.68	gold quality
rectum	UBERON:0001052	72.57	gold quality
stomach	UBERON:0000945	72.42	gold quality
fundus of stomach	UBERON:0001160	68.18	gold quality
vermiform appendix	UBERON:0001154	67.04	gold quality
intestine	UBERON:0000160	62.88	gold quality
colonic epithelium	UBERON:0000397	61.52	gold quality
colon	UBERON:0001155	58.60	gold quality
right uterine tube	UBERON:0001302	47.68	gold quality
urinary bladder	UBERON:0001255	47.26	gold quality
bone marrow cell	CL:0002092	45.06	gold quality
fallopian tube	UBERON:0003889	43.41	gold quality
lymph node	UBERON:0000029	40.22	gold quality
smooth muscle tissue	UBERON:0001135	37.96	gold quality
muscle tissue	UBERON:0002385	37.73	gold quality
kidney	UBERON:0002113	37.09	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.54
E-GEOD-99795	no	2183.77

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, AR, CDX2, ESR1, FOSL2, FOXA1, HNF1A, JUN, SP1

miRNA regulators (miRDB)

37 targeting UGT2B15, 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-656-3P	100.00	72.15	2788
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-221-3P	99.86	71.56	1329
HSA-MIR-222-3P	99.86	71.35	1337
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-548AV-5P	99.60	70.84	2107
HSA-MIR-548K	99.60	70.84	2107
HSA-MIR-12122	99.56	69.33	1672
HSA-MIR-8054	99.48	70.81	2084
HSA-MIR-135A-5P	99.36	71.85	1601
HSA-MIR-135B-5P	99.36	71.63	1613
HSA-MIR-329-5P	99.27	68.11	1597
HSA-MIR-4292	99.16	65.57	1767
HSA-MIR-6791-5P	99.16	65.92	1844
HSA-MIR-323B-3P	99.14	68.89	725
HSA-MIR-5100	99.11	67.52	1098
HSA-MIR-4716-5P	98.82	68.57	1168
HSA-MIR-605-5P	98.79	68.24	1161
HSA-MIR-3611	98.76	68.76	1290
HSA-MIR-624-3P	98.37	67.06	1067
HSA-MIR-376C-3P	97.63	68.88	1263

Literature-anchored findings (GeneRIF, showing 40)

• UGT2B15 polymorphism cannot be considered as a susceptibility marker for prostate cancer, but it involoved in glucuronidation of numerous phytochemicals. This polymorphism could contribute to interindividual variability in chemopreventive effects. (PMID:12010866)
• Single-nucleotide polymorphisms (SNPs) were found in UGT2B15 gene (PMID:12376738)
• S-oxazepam is stereoselectively glucuronidated by UGT2B15, whereas R-oxazepam is glucuronidated by multiple UGT isoforms. Allelic variation associated with the UGT2B15 gene may explain polymorphic S-oxazepam glucuronidation in humans. (PMID:12386133)
• The alteration of UGT2B15 expression in LNCaP-SF cells is proposed as a biological characteristic involved in the growth of hormone-refractory prostate cancer. (PMID:12646996)
• Although D85 and Y85 appear to be common variants, we cannot exclude the possibility that the UGT2B15 gene represents a minor modifying locus. (PMID:12880121)
• Gender and UGT2B15 D85Y genotype are identified as major determinants of S-oxazepam glucuronidation by human liver and may explain in part polymorphic oxazepam glucuronidation by human subjects. (PMID:15044558)
• In human prostate, UGT2B15 and UGT2B17 genes have complementary roles and are expressed in cells where their specific substrates are synthesized. (PMID:15666817)
• Tamoxifen-treated patients with UGT2B15 high activity genotypes had increased risk of recurrence (PMID:15952058)
• estrogen-induced up-regulation of UGT2B15 might have a significant moderating effect on estrogen and androgen concentrations, thereby reducing their signaling in breast cancer cells (PMID:16690804)
• 5-(4’-Hydroxyphenyl)-5-phenylhydantoin O-glucuronide formation in human liver microsomes is catalyzed by UGT1A1, UGT1A9, and UGT2B15 in a stereoselective manner (PMID:17576806)
• UGT2B15 and -B17 are critical enzymes for the local inactivation of androgens and that glucuronidation is a major determinant of androgen action in prostate cells (PMID:17848572)
• Androsterone reduces the glucuronidation of androgens catalysed by UGT2B15 and UGT2B17 in a prostate tumor cell line. (PMID:17988216)
• Vitamin D receptor activator calcitriol as a negative regulator of the UGT2B15- and UGT2B17-dependent inactivation of androgens in prostate cancer LNCaP cells. (PMID:18281521)
• UGT2B15 ia a primary androgen-regulated genes and androgen receptor is required for basal expression and androgen-regulated expression. (PMID:18302198)
• Estrogen receptor alpha, fos-related antigen-2, and c-jun coordinately regulate human UGT2B15 expression in response to 17beta-estradiol in MCF-7 cells. (PMID:19487245)
• UGT2B15 functional polymorphism along with Copy-number variations (PMID:19572376)
• SNPs in strong linkage disequilibrium with G253T regulate UGT2B15 expression in liver. (PMID:19847790)
• regulation of the UGT2B15 and UGT2B17 genes by FOXA1 may have an important role in the maintenance of androgen homeostasis within prostate cancer cells. (PMID:20736324)
• Data show that steroidogenic enzymes (AKR1C3, HSD17B2, UGT2B15 and UGT2B17) and stem/progenitor cell markers CK5 and ABCG2 were upregulated in castration resistant prostate cancer. (PMID:21365123)
• The D85Y substitution in UGT2B15 decreases enzymatic function, and the polymorphic alleles of UGT2B15 are closely associated with variations in the metabolism and toxicity of bisphenol A. (PMID:21404072)
• For UGT2B15, the percentage of APAPG decreased (P < 0.0001) and that of APAP sulfate increased (P = 0.002) in an allelic dose-dependent manner across genotypes from *1/*1 to *2/*2. (PMID:21666065)
• The study revealed that UGT2B15 and UGT2B17 are differentially regulated during prostate cancer progression. (PMID:22170718)
• Data indicates that 2B15 requires regulated phosphorylation by both PKCalpha and Src, which is consistent with the complexity of synthesis and metabolism of its major substrate, DHT. (PMID:22532564)
• Sipoglitazar clearance is substantially modified by UGT2B15 enzyme variants, with higher exposure observed in the UGT2B15*2/*2 genotype group. (PMID:22960998)
• Report UGT2B15 expression in fetal/adult tissues. (PMID:23223495)
• Report the influence of functionally relevant polymorphic UGT2B15, the enzyme mediating bisphenol A metabolism using kinetic based modelling. (PMID:23404680)
• In the tamoxifen-treated subgroup poor prognosis was related to the combined presence of ESR1 PvuII wt/wt and UGT2B15 wt/wt or wt/*2 genotype. (PMID:23951298)
• UGT2B15 is a possible target for androgen deprivation therapy of prostate cancer. (PMID:24121496)
• UGT2B15 genotype is a major determinant for differences in fasting plasma glucose and HbA1c response to sipoglitazar treatment between Type 2 Diabetes mellitus patients, due to related differences in drug exposure. (PMID:24214217)
• Novel associations between UGT2B15 and UGT2B17 single nucleotide polymorphism variants and prostate cancer risk. (PMID:24267955)
• A haplotype in UGT2B15 containing a functional variant (rs4148269, K523T) and an intronic SNP (rs6837575) was found to affect rectal cancer risk overall (OR = 2.57, 95% CI = 1.21-5.04) and in females (OR = 3.08, 95% CI = 1.08-8.74). (PMID:24822274)
• Hepatic UGT2B15 protein onset begins in late gestation; however, the greatest rate of change occurs during the first few weeks after birth. (PMID:24980262)
• Data suggest that both 17beta-estradiol and the antiestrogen 4-OHTAM (4-hydroxytamoxifen, a metabolite of tamoxifen and substrate of UGT2B15) up-regulate UGT2B15 in breast cancer cells via the same estrogen receptor alpha- (ERa-)signaling pathway. (PMID:25795461)
• Expression of UGT2B15 and UGT2B17 is negatively regulated by the binding of miR-376c. (PMID:26163549)
• This descriptive study examines correlations between concentrations of tamoxifen’s glucuronide metabolites and genotypes UGT1A4, UGT2B7, UGT2B15 and UGT2B17 in 132 patients with estrogen receptor-positive breast cancer under treatment with tamoxifen (PMID:26176234)
• CYP3A4, CYP3A7, UGT2B11 and UGT2B15 genes are significantly downregulated in melanosis coli. (PMID:26238215)
• miR-376c is inversely linked to UGT2B15 and UGT2B17 expression in high-grade prostate cancer and metastasis.UGT2B15 and UGT2B17 genes are direct targets of miR-376c and thus may influence steroid metabolism during prostate cancer progression. (PMID:26385605)
• Our findings highlight the influence of UGTT1A4 haplotypes on tamoxifen disposition in Asian breast cancer patients, while genetic variants in UGT2B7 and UGT2B15 appear to be of minor importance. (PMID:27098059)
• Report frequency of UGT2B15 genetic polymorphisms in Pakistani population and genotype/phenotype correlation for glucuronidation of paracetamol. (PMID:27383482)
• the UGT2B15 and UGT2B17 enzymes are transcriptionally regulated by sex hormone signaling in ERalpha+ breast cancer cells and are highly expressed in a subset of primary breast cancers. (PMID:27496708)

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), UGT2B4 (ENSG00000156096), UGT1A6 (ENSG00000167165), UGT3A2 (ENSG00000168671), UGT2B7 (ENSG00000171234), UGT2A1 (ENSG00000173610), UGT8 (ENSG00000174607), 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 2B15 — P54855 (reviewed: P54855)

Alternative names: HLUG4, UDP-glucuronosyltransferase 2B8, UDPGTh-3

All UniProt accessions (1): P54855

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 endogenous steroid hormones such as androgens (testosterone, androsterone) and estrogens (estradiol, epiestradiol, estriol, catechol estrogens). Displays glucuronidation activity toward several classes of xenobiotic substrates, including phenolic compounds (eugenol, 4-nitrophenol, 4-hydroxybiphenyl) and phenylpropanoids (naringenin, coumarins). Catalyzes the glucuronidation of monoterpenoid alcohols such as borneol, menthol and isomenthol, a class of natural compounds used in essential oils.

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. Expressed in many tissues. Present in liver, prostate and testis.

Similarity. Belongs to the UDP-glycosyltransferase family.

RefSeq proteins (1): NP_001067* (*=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), 4 shown:

• glucuronate acceptor + UDP-alpha-D-glucuronate = acceptor beta-D-glucuronoside + UDP + H(+) (RHEA:21032)
• 17alpha-estradiol + UDP-alpha-D-glucuronate = 17alpha-estradiol 3-O-(beta-D-glucuronate) + UDP + H(+) (RHEA:52868)
• 16alpha,17alpha-estriol + UDP-alpha-D-glucuronate = 16alpha,17alpha-estriol 3-O-(beta-D-glucuronate) + UDP + H(+) (RHEA:52924)
• 17beta-hydroxy-5alpha-androstan-3-one + UDP-alpha-D-glucuronate = 5alpha-dihydrotestosterone 17-O-(beta-D-glucuronate) + UDP + H(+) (RHEA:53000)

UniProt features (37 total): sequence conflict 12, helix 9, strand 6, glycosylation site 3, sequence variant 2, signal peptide 1, chain 1, transmembrane region 1, modified residue 1, turn 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
6IPB	X-RAY DIFFRACTION	1.78
7CJX	X-RAY DIFFRACTION	1.99

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P54855-F1	93.40	0.84

Functional residue map

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

Post-translational modifications (1): 136

Glycosylation sites (3): 65, 316, 483

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-156588	Glucuronidation
R-HSA-9749641	Aspirin ADME
R-HSA-9753281	Paracetamol ADME

MSigDB gene sets: 123 (showing top): MORF_RAGE, MULLIGHAN_NPM1_SIGNATURE_3_UP, REACTOME_BIOLOGICAL_OXIDATIONS, GRUETZMANN_PANCREATIC_CANCER_DN, BECKER_TAMOXIFEN_RESISTANCE_UP, MODULE_45, GOBP_REGULATION_OF_HORMONE_LEVELS, MODULE_16, chr4q13, CCTGTGA_MIR513, HSIAO_LIVER_SPECIFIC_GENES, GOBP_LIPID_METABOLIC_PROCESS, KEGG_STARCH_AND_SUCROSE_METABOLISM, MODULE_88, FLECHNER_BIOPSY_KIDNEY_TRANSPLANT_REJECTED_VS_OK_DN

GO Biological Process (4): xenobiotic metabolic process (GO:0006805), steroid metabolic process (GO:0008202), 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
Drug ADME	2
Phase II - Conjugation of compounds	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
metabolic process	1
cellular response to xenobiotic stimulus	1
lipid metabolic process	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

0 interactions, top by confidence (×1000):

IntAct

5 interactions, top by confidence:

A	B	Type	Score
UGT2A3	UGT2A2	psi-mi:“MI:0914”(association)	0.530
UGT2A1	UGT2B15	psi-mi:“MI:0915”(physical association)	0.400
UGT2B7	ACTN4	psi-mi:“MI:0914”(association)	0.350

BioGRID (6): UGT2B15 (Affinity Capture-MS), UGT2B15 (Affinity Capture-MS), UGT2B15 (Affinity Capture-MS), UGT2B15 (Affinity Capture-MS), UGT2B15 (Affinity Capture-MS), UGT2B15 (Affinity Capture-MS)

ESM2 similar proteins: A0A291PQH4, O02663, O19103, O75310, O75795, O77649, O97951, P06133, P08430, P08541, P08542, P09875, P0DTE4, P0DTE5, P16662, P17717, P19488, P36510, P36511, P36512, P36513, P36514, P36537, P54855, P70691, Q09426, Q16880, Q18081, Q1LZI1, Q28611, Q3SY77, Q3UP75, Q5RFJ3, Q62789, Q63ZR6, Q64435, Q64676, Q6K1J1, Q6NUS8, Q6PDD0

Diamond homologs: A0A096SRM5, A0A0B6VIJ5, A0A0D1CFF0, A0A0M4KE44, A0A193AU77, A0A1L7U2E9, A0A224AKZ9, A0A224AM54, A0A291PQF1, A0A291PQG3, A0A291PQH4, A0A2Z5CV93, A5U6W6, B4G072, C3W7B0, G2WW48, K7NBW3, O02663, O19103, O23401, O31853, O60656, O75310, O75795, O77649, O82385, O97951, P06133, P08430, P08541, P08542, P09875, P0DTE4, P0DTE5, P16662, P17717, P19224, P19488, P20720, P22309

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	85
Likely benign	6
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

464 predictions. Top by Δscore:

Variant	Effect	Δscore
4:68647180:A:AC	donor_gain	1.0000
4:68654035:A:AC	donor_gain	1.0000
4:68654036:C:CC	donor_gain	1.0000
4:68654036:CA:C	donor_gain	1.0000
4:68654036:CACA:C	donor_gain	1.0000
4:68654036:CACAG:C	donor_gain	1.0000
4:68654084:TG:T	donor_gain	1.0000
4:68668035:TTTA:T	donor_loss	1.0000
4:68668036:TTAC:T	donor_loss	1.0000
4:68668037:TACCT:T	donor_loss	1.0000
4:68668038:ACC:A	donor_loss	1.0000
4:68668039:CCTTA:C	donor_loss	1.0000
4:68668185:CTTC:C	acceptor_gain	1.0000
4:68668189:C:CC	acceptor_gain	1.0000
4:68668192:A:AC	acceptor_gain	1.0000
4:68668192:A:C	acceptor_gain	1.0000
4:68647379:TATAG:T	acceptor_gain	0.9900
4:68647381:TAG:T	acceptor_gain	0.9900
4:68647384:C:CC	acceptor_gain	0.9900
4:68654055:G:T	donor_gain	0.9900
4:68654056:A:AC	donor_gain	0.9900
4:68654057:C:CC	donor_gain	0.9900
4:68654058:T:C	donor_gain	0.9900
4:68663136:TTTC:T	acceptor_gain	0.9900
4:68668038:A:AC	donor_gain	0.9900
4:68668039:C:CC	donor_gain	0.9900
4:68668186:TTC:T	acceptor_gain	0.9900
4:68668187:TC:T	acceptor_gain	0.9900
4:68668188:CCTGA:C	acceptor_gain	0.9900
4:68668189:C:CG	acceptor_loss	0.9900

AlphaMissense

3512 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:68655176:A:G	W338R	0.995
4:68655176:A:T	W338R	0.995
4:68654200:C:G	A384P	0.993
4:68668144:A:G	W257R	0.993
4:68668144:A:T	W257R	0.993
4:68670103:A:C	S172R	0.992
4:68670103:A:T	S172R	0.992
4:68670105:T:G	S172R	0.992
4:68655100:A:G	L363P	0.989
4:68670482:A:G	L46P	0.989
4:68647288:C:G	R470P	0.988
4:68647296:A:C	F467L	0.988
4:68647296:A:T	F467L	0.988
4:68647298:A:G	F467L	0.988
4:68654141:G:C	N403K	0.988
4:68654141:G:T	N403K	0.988
4:68670181:A:C	F146L	0.988
4:68670181:A:T	F146L	0.988
4:68670183:A:G	F146L	0.988
4:68647267:A:G	L477P	0.987
4:68654232:A:T	I373K	0.987
4:68655108:C:A	Q360H	0.987
4:68655108:C:G	Q360H	0.987
4:68670534:A:G	W29R	0.986
4:68670534:A:T	W29R	0.986
4:68654202:T:A	E383V	0.985
4:68647316:C:G	A461P	0.984
4:68655181:A:T	V336D	0.984
4:68670517:G:C	S34R	0.984
4:68670517:G:T	S34R	0.984

dbSNP variants (sampled 300 via entrez): RS1000116040 (4:68648679 A>G), RS1000216121 (4:68646306 A>C), RS1000421166 (4:68650909 G>A), RS1000763226 (4:68655421 A>G), RS1000774377 (4:68651207 G>A,C), RS1000828723 (4:68655244 A>T), RS1001138323 (4:68666983 G>A), RS1001229556 (4:68647343 C>A,G,T), RS1001369230 (4:68652464 CT>C,CTT), RS1001424532 (4:68652279 C>T), RS1001438766 (4:68661069 G>A), RS1001480499 (4:68658220 TAC>T), RS1001588597 (4:68663957 C>T), RS1001641179 (4:68663760 C>A,T), RS1001871336 (4:68656499 T>C)

Disease associations

OMIM: gene MIM:600069 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): primary ovarian failure (MONDO:0005387)

Orphanet (1): NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619)

HPO phenotypes

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

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST001612_11	Sex hormone-binding globulin levels	3.000000e-08
GCST001612_17	Sex hormone-binding globulin levels	6.000000e-06
GCST006667_4	Lipid traits (pleiotropy) (HIPO component 2)	8.000000e-09
GCST007684_1	Plasma clozapine-norclozapine ratio in treatment-resistant schizophrenia	9.000000e-66
GCST009733_232	Urinary metabolite levels in chronic kidney disease	1.000000e-13
GCST010204_105	Low density lipoprotein cholesterol levels	4.000000e-27
GCST010241_143	Apolipoprotein A1 levels	2.000000e-21
GCST010242_204	HDL cholesterol levels	6.000000e-09
GCST012020_285	Serum metabolite levels	7.000000e-25
GCST90002390_211	Mean corpuscular hemoglobin	2.000000e-10
GCST90002392_657	Mean corpuscular volume	3.000000e-10
GCST90013407_188	Liver enzyme levels (gamma-glutamyl transferase)	1.000000e-41

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0004696	sex hormone-binding globulin measurement
EFO:0004530	triglyceride measurement
EFO:0004574	total cholesterol measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0600040	plasma clozapine-to-N-desmethylclozapine ratio measurement
EFO:0005116	urinary metabolite measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004527	mean corpuscular hemoglobin
EFO:0004532	serum gamma-glutamyl transferase measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4523985 (PROTEIN FAMILY), CHEMBL6161 (SINGLE PROTEIN)

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

PharmGKB clinical annotations

4 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1902023	Efficacy	3	acetaminophen	Pain
rs1902023	Metabolism/PK	3	oxazepam
rs1902023	Metabolism/PK	3	lorazepam
UGT2B151, UGT2B152	Efficacy	3	sipoglitazar

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1902023	UGT2B15	3	2.50	4	oxazepam;acetaminophen;lorazepam
rs4148269	UGT2B15		0.00	0
rs3100	UGT2B15		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects activity, affects metabolic processing, increases glucuronidation, increases expression, increases methylation	7
Hymecromone	increases chemical synthesis, increases activity, increases metabolic processing, decreases reaction, increases glucuronidation	5
Acetaminophen	affects cotreatment, decreases expression	4
Estradiol	increases expression, decreases reaction, affects cotreatment, decreases expression, increases glucuronidation (+2 more)	4
Phenobarbital	affects expression, decreases expression, increases expression	4
4-phenylphenol	increases glucuronidation, increases metabolic processing	3
Androstane-3,17-diol	increases glucuronidation, increases metabolic processing	3
Genistein	increases expression	3
naringenin	increases metabolic processing	2
androstane-3,17-diol glucuronide	increases abundance	2
4-methylumbelliferyl glucuronide	decreases reaction, increases chemical synthesis, increases glucuronidation, increases metabolic processing	2
galangin	decreases activity, increases metabolic processing	2
Chenodeoxycholic Acid	affects cotreatment, decreases expression	2
Deoxycholic Acid	affects cotreatment, decreases expression	2
Diclofenac	decreases activity, increases glucuronidation	2
Estriol	increases glucuronidation, increases metabolic processing	2
Eugenol	increases metabolic processing	2
Glycochenodeoxycholic Acid	affects cotreatment, decreases expression	2
Glycocholic Acid	affects cotreatment, decreases expression	2
Glycodeoxycholic Acid	affects cotreatment, decreases expression	2
Quercetin	affects cotreatment, decreases expression, increases metabolic processing	2
Dihydrotestosterone	increases expression, increases glucuronidation, increases reaction, decreases reaction	2
Testosterone	decreases expression, increases metabolic processing, affects cotreatment	2
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression, increases expression	2
Valproic Acid	decreases expression, decreases methylation	2
Cyclosporine	decreases expression, affects cotreatment	2
Aflatoxin B1	decreases methylation, increases expression	2
Phenolphthalein	increases glucuronidation, increases metabolic processing	2
osimertinib	decreases activity	1
7-hydroxy-4-(trifluoromethyl)coumarin	increases glucuronidation	1

ChEMBL screening assays

74 unique, capped per target: 71 admet, 3 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
CHEMBL1908121	Binding	Drug glucuronidation reaction catalyzed by human recombinant UGT2B15	UDP-glucuronosyltransferases and clinical drug-drug interactions. — Pharmacol Ther

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00417066	PHASE4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	PHASE4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	PHASE4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	PHASE4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	PHASE4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	PHASE4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
NCT00140998	PHASE3	COMPLETED	Estrogen Treatment (Oral vs. Patches) in Turner Syndrome
NCT00001951	PHASE2	COMPLETED	Hormone Replacement in Young Women With Premature Ovarian Failure
NCT00370019	PHASE2	WITHDRAWN	Effects of an Estrogen Replacement Therapy Skin Patch on Ovulation in Women With Premature Ovarian Failure
NCT00429494	PHASE2	COMPLETED	GnRH Analogue for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients
NCT03816852	PHASE2	SUSPENDED	The Safety and Efficiency Study of Mesenchymal Stem Cell (19#iSCLife®-POI) in Premature Ovarian Insufficiency
NCT04536467	PHASE2	UNKNOWN	Prevention of Chemotherapy-Induced Ovarian Failure With Goserelin in Premenopausal Lymphoma Patients
NCT06117982	PHASE2	COMPLETED	The Impact of Granulocyte Colony Stimulating Factor on Premature Ovarian Insufficiency
NCT02912104	PHASE1	COMPLETED	A Therapeutic Trial of Human Amniotic Epithelial Cells Transplantation for Primary Ovarian Failure
NCT03178695	PHASE1	COMPLETED	Inovium Ovarian Rejuvenation Trials
NCT04815213	PHASE1	ACTIVE_NOT_RECRUITING	The Use of Expandeded Mesenchymal Stromal Cells (MSC) in Premature Ovarian Failure (POF) in Adult Humans
NCT05138367	PHASE1	COMPLETED	Effects of UCA-PSCs in Women With POF
NCT06132542	PHASE1	UNKNOWN	Autologous ADMSC Transplantation in Patients With POI
NCT00948857	PHASE2/PHASE3	TERMINATED	Dehydroepiandrosterone (DHEA) Treatment and Premature Ovarian Failure (POF)
NCT04031456	PHASE2/PHASE3	RECRUITING	Autologous PRP Infusion May Restore Ovarian Function and May Promote Folliculogenesis in POI Patients
NCT02043743	PHASE1/PHASE2	UNKNOWN	Autologous Stem Cells Transplantation in Patients With Idiopathic and Drug Induced Premature Ovarian Failure
NCT02062931	PHASE1/PHASE2	UNKNOWN	Autologous Mesenchymal Stem Cells Transplantation In Women With Premature Ovarian Failure
NCT02151890	PHASE1/PHASE2	COMPLETED	Pregnancy After Stem Cell Transplantation in Premature Ovarian Failure
NCT02372474	PHASE1/PHASE2	COMPLETED	It is a Real The First Baby Of Autologous Stem Cell Therapy in Premature Ovarian Failure
NCT02603744	PHASE1/PHASE2	UNKNOWN	Autologous Adipose Derived Mesenchymal Stromal Cells Transplantation in Women With Premature Ovarian Failure (POF)
NCT02644447	PHASE1/PHASE2	COMPLETED	Transplantation of HUC-MSCs With Injectable Collagen Scaffold for POF
NCT03069209	PHASE1/PHASE2	UNKNOWN	Autologous Bone Marrow-Derived Stem Cell Transplantation in Patients With Premature Ovarian Failure (POF)
NCT03985462	PHASE1/PHASE2	WITHDRAWN	Very Small Embryonic-like Stem Cells for Ovary
NCT04009473	PHASE1/PHASE2	UNKNOWN	Stem Cell Therapy and Growth Factor Ovarian in Vitro Activation
NCT04071574	PHASE1/PHASE2	COMPLETED	Comparative Study on the Efficacy of Ovarian Stimulation Protocols on the Success Rate of ICSI in Female Infertility
NCT04922398	PHASE1/PHASE2	UNKNOWN	Ovarian Injection of PRP (Platelet -Rich Plasma) Vs Normal Saline in Premature Ovarian Insufficiency
NCT05462379	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Autologous Heterotopic Fresh Ovarian Graft in Woman With LACC Eligible for Pelvic Radiotherapy Treatment.
NCT06202547	PHASE1/PHASE2	UNKNOWN	Intra-ovarian Injection of MSC-EVs in Idiopathic Premature Ovarian Failure
NCT01129947	EARLY_PHASE1	WITHDRAWN	The Use of DHEA in Women With Premature Ovarian Failure
NCT05522634	EARLY_PHASE1	UNKNOWN	A Clinical Study of Chinese Herbal Compound TJAOA101 in the Treatment of Premature Ovarian Insufficiency
NCT07308327	EARLY_PHASE1	ACTIVE_NOT_RECRUITING	The Influence of Gut Microbiota on Ovarian Function: A Single-center, Randomized,Double Blind, Parallel-controlled, Exploratory Clinical Trial
NCT00001275	Not specified	COMPLETED	Ovarian Follicle Function in Patients With Primary Ovarian Failure
NCT00001306	Not specified	COMPLETED	Steroid Therapy in Autoimmune Premature Ovarian Failure
NCT00006156	Not specified	COMPLETED	Feasibility Study for Development of an Early Test for Ovarian Failure
NCT00119925	Not specified	UNKNOWN	‘SPRING’-Study: Subfertility Guidelines: Patient Related Implementation in the Netherlands Among Gynaecologists