UGT2B28

Summary

UGT2B28 (UDP glucuronosyltransferase family 2 member B28, HGNC:13479) is a protein-coding gene on chromosome 4q13.2, encoding UDP-glucuronosyltransferase 2B28 (Q9BY64). 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 member of the uridine diphosphoglucuronosyltransferase protein family. The encoded enzyme catalyzes the transfer of glucuronic acid from uridine diphosphoglucuronic acid to a diverse array of substrates including steroid hormones and lipid-soluble drugs. This process, known as glucuronidation, is an intermediate step in the metabolism of steroids. Two transcript variants encoding different isoforms have been found for this gene. While both isoforms are targeted to the endoplasmic reticulum, only the longer isoform appears to be active.

Source: NCBI Gene 54490 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 115 total
• Druggable target: yes
• MANE Select transcript: NM_053039

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13479
Approved symbol	UGT2B28
Name	UDP glucuronosyltransferase family 2 member B28
Location	4q13.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000135226
Ensembl biotype	protein_coding
OMIM	606497
Entrez	54490

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000335568, ENST00000511240

RefSeq mRNA: 2 — MANE Select: NM_053039 NM_001207004, NM_053039

CCDS: CCDS3528, CCDS56330

Canonical transcript exons

ENST00000335568 — 6 exons

Exon	Start	End
ENSE00002445426	69282514	69282662
ENSE00002513746	69290592	69290811
ENSE00002515116	69286752	69286883
ENSE00002526568	69289665	69289752
ENSE00003572632	69294530	69295050
ENSE00003894123	69280475	69281221

Expression profiles

Bgee: expression breadth broad, 27 present calls, max score 78.38.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0195 / max 19.9388, expressed in 6 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
203191	0.0195	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gall bladder	UBERON:0002110	78.38	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	77.55	silver quality
tonsil	UBERON:0002372	54.20	gold quality
urinary bladder	UBERON:0001255	44.29	gold quality
monocyte	CL:0000576	44.25	gold quality
leukocyte	CL:0000738	43.98	gold quality
liver	UBERON:0002107	43.98	gold quality
bone marrow cell	CL:0002092	40.96	gold quality
granulocyte	CL:0000094	38.56	gold quality
hindlimb stylopod muscle	UBERON:0004252	37.68	silver quality
colonic epithelium	UBERON:0000397	37.20	gold quality
islet of Langerhans	UBERON:0000006	36.58	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
bone marrow	UBERON:0002371	35.38	gold quality
kidney	UBERON:0002113	35.29	gold quality
saliva-secreting gland	UBERON:0001044	34.98	gold quality
duodenum	UBERON:0002114	34.08	gold quality
thoracic mammary gland	UBERON:0005200	33.47	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
blood	UBERON:0000178	33.08	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	32.50	silver quality
vermiform appendix	UBERON:0001154	32.47	gold quality
minor salivary gland	UBERON:0001830	32.26	gold quality
cortex of kidney	UBERON:0001225	31.62	gold quality
lymph node	UBERON:0000029	31.31	gold quality
muscle tissue	UBERON:0002385	31.06	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
placenta	UBERON:0001987	29.88	silver quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.99

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

12 targeting UGT2B28, 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-3064-3P	100.00	70.09	1254
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-12122	99.56	69.33	1672
HSA-MIR-146A-3P	99.13	68.99	1881
HSA-MIR-7851-3P	98.72	64.88	980
HSA-MIR-4317	98.49	67.09	987
HSA-MIR-624-3P	98.37	67.06	1067
HSA-MIR-4483	98.09	64.12	1642
HSA-MIR-1293	96.16	64.69	916

Literature-anchored findings (GeneRIF, showing 10)

• Copy-number variations (CNVs) of the human sex steroid metabolizing genes UGT2B28 (PMID:19572376)
• UGT2B28 was clearly detected in breast and adipose tissue; GT2B28 expression in the breast was comparatively low, about 1.6% of GAPDH mRNA levels, and was less than 5% of normalized (against GAPDH) UGT2B7 and 2B10 mRNA expression levels in the liver (PMID:21679149)
• The androgen-inactivating UGT2B28 enzyme influences hormone levels, clinical and pathologic factors, and the risk of prostate cancer progression. (PMID:26215610)
• Findings suggest that the D85Y polymorphism of UGT2B15 and CNVs in UGT2B28 and UGT2B17 genes is not associated with prostate cancer risk in Iranian patients. (PMID:28882566)
• Our effort identified 2 novel functional regulatory SNPs for UGT2B28, which might contribute to metabolism variation of related steroid hormones in breast. (PMID:29357108)
• further analysis revealed 2 hemizygous deletions in the grandmother that segregate in several of her affected offspring. The first deletion was found in the UGT2B28 locus, spanning 7 informative sequence variants across at least 14 kb. The second deletion, located in USP17L2, spans 3 informative variants across at least 2 kb. On the whole, the findings of the presents study implicate 2 additional genes in the pathogenesis (PMID:30628680)
• Patients with UGT2B28-rs2132039 - TT variant type had an earlier presentation of hepatocellular carcinoma (HCC), earlier post-surgery recurrence, metastasis and HCC-related death. (PMID:31805979)
• Uridine Diphosphate Glucuronosyl Transferase 2B28 (UGT2B28) Promotes Tumor Progression and Is Elevated in African American Prostate Cancer Patients. (PMID:35954173)
• UGT2B28 accelerates prostate cancer progression through stabilization of the endocytic adaptor protein HIP1 regulating AR and EGFR pathways. (PMID:36343786)
• Extensive metabolic consequences of human glycosyltransferase gene knockouts in prostate cancer. (PMID:36347965)

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), UGT3A1 (ENSG00000145626), UGT2B4 (ENSG00000156096), 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 2B28 — Q9BY64 (reviewed: Q9BY64)

All UniProt accessions (1): Q9BY64

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 (androsterone, 3alpha-androstanediol) and estrogens (estradiol, estrone). Catalyzes the glucuronidation of bile acid substrates, which are natural detergents for dietary lipids absorption. Displays glucuronidation activity toward the phenolic compounds eugenol. Lack UDP-glucuronosyltransferase (UGT) activity.

Subcellular location. Endoplasmic reticulum membrane. Cytoplasm. Perinuclear region.

Tissue specificity. Expressed in the liver, breast and kidney.

Similarity. Belongs to the UDP-glycosyltransferase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9BY64-1	1, I	yes
Q9BY64-2	2, II

RefSeq proteins (2): NP_001193933, NP_444267* (*=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), 1 shown:

• glucuronate acceptor + UDP-alpha-D-glucuronate = acceptor beta-D-glucuronoside + UDP + H(+) (RHEA:21032)

UniProt features (11 total): sequence variant 3, splice variant 2, signal peptide 1, chain 1, sequence conflict 1, transmembrane region 1, modified residue 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BY64-F1	92.59	0.83

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): 135

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: 62 (showing top): REACTOME_BIOLOGICAL_OXIDATIONS, GNF2_HPN, GOBP_REGULATION_OF_HORMONE_LEVELS, chr4q13, GOBP_LIPID_METABOLIC_PROCESS, KEGG_STARCH_AND_SUCROSE_METABOLISM, KEGG_STEROID_HORMONE_BIOSYNTHESIS, GOBP_ESTROGEN_METABOLIC_PROCESS, GOBP_STEROID_METABOLIC_PROCESS, KEGG_METABOLISM_OF_XENOBIOTICS_BY_CYTOCHROME_P450, GOCC_NUCLEAR_ENVELOPE, GOCC_NUCLEAR_OUTER_MEMBRANE, GOCC_NUCLEAR_OUTER_MEMBRANE_ENDOPLASMIC_RETICULUM_MEMBRANE_NETWORK, GOCC_NUCLEAR_MEMBRANE, KEGG_DRUG_METABOLISM_OTHER_ENZYMES

GO Biological Process (2): steroid metabolic process (GO:0008202), estrogen metabolic process (GO:0008210)

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

GO Cellular Component (6): nuclear outer membrane (GO:0005640), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), perinuclear region of cytoplasm (GO:0048471), cytoplasm (GO:0005737), 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
cellular anatomical structure	3
nuclear outer membrane-endoplasmic reticulum membrane network	2
cytoplasm	2
lipid metabolic process	1
steroid metabolic process	1
hormone metabolic process	1
UDP-glycosyltransferase activity	1
hexosyltransferase activity	1
glycosyltransferase activity	1
catalytic activity	1
transferase activity	1
nuclear membrane	1
organelle outer membrane	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
endoplasmic reticulum subcompartment	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

766 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
UGT2B28	SLC35A2	P78381	925
UGT2B28	B3GAT2	Q9NPZ5	815
UGT2B28	PPIG	Q13427	761
UGT2B28	CYP3A4	P05184	726
UGT2B28	SULT1B1	O43704	631
UGT2B28	SULT1C3	Q6IMI6	631
UGT2B28	CYP2C9	P11712	629
UGT2B28	CYP1A2	P05177	628
UGT2B28	SULT1C4	O75897	620
UGT2B28	CYP2C19	P33259	617
UGT2B28	CYP2D6	P10635	591
UGT2B28	CYP2B6	P20813	590
UGT2B28	SLCO1B1	Q9Y6L6	571
UGT2B28	CYP2C8	P10632	538
UGT2B28	ABCC2	Q92887	510

IntAct

2 interactions, top by confidence:

A	B	Type	Score
UGT2B28	POTEF	psi-mi:“MI:0914”(association)	0.350

BioGRID (5): UGT2B28 (Affinity Capture-MS), UGT2B10 (Affinity Capture-MS), UGT2B11 (Affinity Capture-MS), POTEF (Affinity Capture-MS), HSPA5 (Affinity Capture-MS)

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: A0A0C1EH92, A0A0G2EAR7, A0A0M4KE44, A0A193AUF6, A0A1L7U2E9, A0A291PQF1, A0A291PQG3, A0A2R6Q8R5, A0A2R6QXF8, A0A2Z5CV93, A0A364KRL8, A0A478EC03, A0AAW1M2U7, A6XNC6, D3UAG0, F8WKW8, G2WW48, O02663, O23382, O31853, O60656, O75310, O81498, P08430, P0DO67, P0DO71, P0DO73, P0DTE4, P0DTE5, P14726, P16165, P16166, P16167, P16662, P20720, P22309, P22310, P35503, P35504, P36537

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	87
Likely benign	18
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

970 predictions. Top by Δscore:

Variant	Effect	Δscore
4:69286882:AGGT:A	donor_loss	1.0000
4:69286884:G:A	donor_loss	1.0000
4:69286885:T:G	donor_loss	1.0000
4:69280650:TCATG:T	donor_gain	0.9900
4:69281741:GG:G	donor_gain	0.9900
4:69281742:GG:G	donor_gain	0.9900
4:69282503:A:AG	acceptor_gain	0.9800
4:69282508:T:A	acceptor_gain	0.9800
4:69286746:TCACA:T	acceptor_loss	0.9800
4:69286747:CACA:C	acceptor_loss	0.9800
4:69286748:ACAGG:A	acceptor_loss	0.9800
4:69286749:CAGGA:C	acceptor_loss	0.9800
4:69286750:A:T	acceptor_loss	0.9800
4:69286751:G:GC	acceptor_loss	0.9800
4:69286751:GGAA:G	acceptor_gain	0.9800
4:69291985:A:G	donor_gain	0.9800
4:69282513:GGAA:G	acceptor_gain	0.9700
4:69286750:A:AG	acceptor_gain	0.9700
4:69286751:G:GG	acceptor_gain	0.9700
4:69291985:A:AG	donor_gain	0.9700
4:69286750:AG:A	acceptor_gain	0.9600
4:69286751:GG:G	acceptor_gain	0.9600
4:69286751:GGA:G	acceptor_gain	0.9600
4:69290818:AGAAC:A	donor_gain	0.9600
4:69280723:G:GT	donor_gain	0.9500
4:69282504:T:G	acceptor_gain	0.9500
4:69282512:A:AG	acceptor_gain	0.9500
4:69282513:G:GG	acceptor_gain	0.9500
4:69286748:A:AG	acceptor_gain	0.9500
4:69286748:ACAG:A	acceptor_gain	0.9500

AlphaMissense

3528 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:69289671:T:A	W337R	0.966
4:69289671:T:C	W337R	0.966
4:69286764:T:C	F295L	0.947
4:69286766:T:A	F295L	0.947
4:69286766:T:G	F295L	0.947
4:69290612:T:C	F371L	0.946
4:69290614:T:A	F371L	0.946
4:69290614:T:G	F371L	0.946
4:69280933:T:C	F145L	0.945
4:69280935:T:A	F145L	0.945
4:69280935:T:G	F145L	0.945
4:69281130:G:C	R210S	0.941
4:69281130:G:T	R210S	0.941
4:69290775:T:C	L425P	0.940
4:69294615:T:C	F466L	0.934
4:69294617:T:A	F466L	0.934
4:69294617:T:G	F466L	0.934
4:69286854:G:C	A325P	0.933
4:69281139:C:A	N213K	0.928
4:69281139:C:G	N213K	0.928
4:69289677:T:C	F339L	0.922
4:69289679:T:A	F339L	0.922
4:69289679:T:G	F339L	0.922
4:69290616:T:A	I372K	0.919
4:69286800:T:C	F307L	0.918
4:69286802:T:A	F307L	0.918
4:69286802:T:G	F307L	0.918
4:69290648:G:C	A383P	0.917
4:69289673:G:C	W337C	0.914
4:69289673:G:T	W337C	0.914

dbSNP variants (sampled 300 via entrez): RS10000077 (4:69291017 G>A), RS1000114389 (4:69284310 G>A,C), RS10002503 (4:69291286 G>A,T), RS1000335510 (4:69290283 A>G), RS1000436254 (4:69291119 A>C), RS10008843 (4:69293214 G>T), RS10011666 (4:69291513 C>A,T), RS10013145 (4:69290674 A>G), RS1001895219 (4:69279793 T>C,G), RS10023367 (4:69278712 G>A,C), RS1004175516 (4:69288871 C>T), RS1005341312 (4:69278945 C>T), RS1005591963 (4:69292428 A>G), RS1006397685 (4:69279574 A>C), RS1006680837 (4:69280982 C>A)

Disease associations

OMIM: gene MIM:606497 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
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
GCST008153_8	Lean body mass	3.000000e-06
GCST009391_2124	Metabolite levels	6.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0600040	plasma clozapine-to-N-desmethylclozapine ratio measurement
EFO:0004995	lean body mass
EFO:0010382	phosphatidylcholine 36:4 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4523985 (PROTEIN FAMILY), CHEMBL6189 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases expression, decreases methylation	4
Vorinostat	increases expression, affects cotreatment	2
Aflatoxin B1	increases expression, decreases methylation	2
methylmercuric chloride	decreases expression	1
trichostatin A	increases expression	1
alpha-terpineol	decreases reaction, increases expression	1
linalool	increases expression, decreases reaction	1
terpinenol-4	decreases reaction, increases expression	1
lavender oil	decreases reaction, increases expression	1
linalyl acetate	increases expression, decreases reaction	1
CGP 52608	increases reaction, affects binding	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Panobinostat	affects cotreatment, increases expression	1
Biological Factors	decreases expression	1
Carbamazepine	increases expression	1
Flutamide	decreases reaction, increases expression	1
Phenobarbital	decreases expression	1
Testosterone	decreases reaction, increases expression	1
Urethane	decreases expression	1
Isotretinoin	decreases expression	1
Tea Tree Oil	increases expression, decreases reaction	1

ChEMBL screening assays

39 unique, capped per target: 37 admet, 2 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
CHEMBL1908122	Binding	Drug glucuronidation reaction catalyzed by human recombinant UGT2B28	UDP-glucuronosyltransferases and clinical drug-drug interactions. — Pharmacol Ther

Clinical trials (associated diseases)

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