XDH

Summary

XDH (xanthine dehydrogenase, HGNC:12805) is a protein-coding gene on chromosome 2p23.1, encoding Xanthine dehydrogenase/oxidase (P47989). Key enzyme in purine degradation.

Xanthine dehydrogenase belongs to the group of molybdenum-containing hydroxylases involved in the oxidative metabolism of purines. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. Xanthine dehydrogenase can be converted to xanthine oxidase by reversible sulfhydryl oxidation or by irreversible proteolytic modification. Defects in xanthine dehydrogenase cause xanthinuria, may contribute to adult respiratory stress syndrome, and may potentiate influenza infection through an oxygen metabolite-dependent mechanism.

Source: NCBI Gene 7498 — RefSeq curated summary.

At a glance

• Gene–disease (curated): xanthinuria type I (Strong, GenCC)
• Clinical variants (ClinVar): 1,049 total — 22 pathogenic, 31 likely-pathogenic
• Druggable target: yes — 16 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000379

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12805
Approved symbol	XDH
Name	xanthine dehydrogenase
Location	2p23.1
Locus type	gene with protein product
Status	Approved
Aliases	XOR, XO, XDH/XO
Ensembl gene	ENSG00000158125
Ensembl biotype	protein_coding
OMIM	607633
Entrez	7498

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 8 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000379416, ENST00000476043, ENST00000491727, ENST00000879520, ENST00000879521, ENST00000879522, ENST00000879523, ENST00000879524, ENST00000879525, ENST00000879526

RefSeq mRNA: 1 — MANE Select: NM_000379 NM_000379

CCDS: CCDS1775

Canonical transcript exons

ENST00000379416 — 36 exons

Exon	Start	End
ENSE00000962553	31398573	31398699
ENSE00000962554	31397668	31397729
ENSE00001037174	31381633	31381726
ENSE00001037176	31347522	31347650
ENSE00001037179	31372228	31372397
ENSE00001037183	31365457	31365544
ENSE00001037184	31342183	31342297
ENSE00001037186	31370355	31370478
ENSE00001037188	31349686	31349831
ENSE00001037191	31367961	31368057
ENSE00001037192	31377053	31377237
ENSE00001037193	31375380	31375554
ENSE00001037194	31344684	31344736
ENSE00001037197	31373873	31373956
ENSE00001037200	31366870	31366994
ENSE00001037202	31337641	31337817
ENSE00001037207	31365976	31366109
ENSE00001037213	31348268	31348363
ENSE00001037216	31379867	31379976
ENSE00001037219	31364158	31364244
ENSE00001037226	31350032	31350223
ENSE00001037230	31368541	31368660
ENSE00001037238	31348899	31348980
ENSE00001037243	31339489	31339677
ENSE00001037245	31346769	31346843
ENSE00001144504	31401220	31401328
ENSE00001190982	31403048	31403144
ENSE00001190986	31414625	31414742
ENSE00001190992	31405907	31405964
ENSE00001480902	31334321	31336008
ENSE00001625471	31341329	31341394
ENSE00003581429	31387811	31387897
ENSE00003598209	31383755	31383847
ENSE00003641759	31386414	31386555
ENSE00003653832	31388227	31388295
ENSE00003687416	31383001	31383152

Expression profiles

Bgee: expression breadth ubiquitous, 169 present calls, max score 98.61.

FANTOM5 (CAGE): breadth broad, TPM avg 1.6216 / max 209.0251, expressed in 189 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
27689	1.3683	131
27685	0.1100	42
27687	0.0852	31
27686	0.0377	10
27690	0.0205	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	98.61	gold quality
ileal mucosa	UBERON:0000331	96.38	gold quality
palpebral conjunctiva	UBERON:0001812	94.21	gold quality
colonic mucosa	UBERON:0000317	93.15	gold quality
mucosa of sigmoid colon	UBERON:0004993	92.90	gold quality
duodenum	UBERON:0002114	92.76	gold quality
liver	UBERON:0002107	90.84	gold quality
right lobe of liver	UBERON:0001114	90.40	gold quality
esophagus squamous epithelium	UBERON:0006920	87.28	gold quality
nasal cavity epithelium	UBERON:0005384	86.43	gold quality
diaphragm	UBERON:0001103	86.18	gold quality
type B pancreatic cell	CL:0000169	85.69	gold quality
olfactory bulb	UBERON:0002264	85.28	gold quality
epithelium of esophagus	UBERON:0001976	84.83	gold quality
cauda epididymis	UBERON:0004360	83.63	gold quality
parotid gland	UBERON:0001831	82.91	gold quality
nasal cavity mucosa	UBERON:0001826	81.58	gold quality
mucosa of transverse colon	UBERON:0004991	81.19	gold quality
squamous epithelium	UBERON:0006914	81.03	gold quality
rectum	UBERON:0001052	80.00	gold quality
jejunum	UBERON:0002115	78.48	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.10	silver quality
small intestine	UBERON:0002108	77.84	gold quality
epithelial cell of pancreas	CL:0000083	76.58	silver quality
esophagus mucosa	UBERON:0002469	76.49	gold quality
gingival epithelium	UBERON:0001949	76.45	gold quality
gingiva	UBERON:0001828	76.18	gold quality
small intestine Peyer’s patch	UBERON:0003454	75.41	gold quality
corpus epididymis	UBERON:0004359	74.76	gold quality
male germ cell	CL:0000015	73.02	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-10855	yes	3848.50
E-MTAB-9841	yes	3353.26
E-ANND-3	yes	6.72

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
BCL2	Repression

Upstream regulators (CollecTRI, top): CEBPA, CEBPB, CEBPG

miRNA regulators (miRDB)

65 targeting XDH, 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-513A-5P	100.00	69.77	2465
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-5696	99.98	72.36	4487
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-4645-3P	99.76	69.33	993
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-1976	99.74	65.48	1127
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-7156-5P	99.64	68.81	1369
HSA-MIR-6126	99.62	68.09	996
HSA-MIR-1290	99.59	69.90	2079

Literature-anchored findings (GeneRIF, showing 40)

• XDH may play a role in generating reactive oxygen species in oxidative eye injury (PMID:12168784)
• the molybdenum center of XOR is posttranslationally inactivated by oxygen metabolites in “normal” (21% O2) cell culture atmosphere and this inactivation is reversed in hypoxia and accounts for the apparent induction. (PMID:12637268)
• The activity of XO was determined in lymphocytes, eosinophils and blood serum in patients with bronchial asthma. (PMID:12774669)
• DNA-PK/AREB6-like proteins play a central role in repression of basal hXOR activity (PMID:14761964)
• XOR is expressed primarily in hepatocytes, but is also present in bile duct epithelial cells and is secreted into bile. Its role in bile is unknown but it may be involved in innate immunity of the bowel muscosa. (PMID:15451061)
• The results of this study revealed that, MPO, XO and SOD conditions in gastric mucosa alone were not affected from HP presence. That’s why MPO, XO, and SOD may not have important roles in the pathogenesis of HP related gastric disease in children. (PMID:16758302)
• XOR expression in gastric cancer may be a new marker for a more aggressive gastric cancer biology, similar to that previously reported for breast cancer. (PMID:16935971)
• Xanthine dehydrogenase/oxidase is a moonlighting protein that has two distinct catalytic activities as a dehydrogenase and an oxidase. (PMID:17301077)
• findings show that mutation of two amino acid residues in the active site of XOR for purine substrates results in conversion of the substrate preference to aldehyde oxidase type (PMID:17301077)
• The role of conjunctival epithelial cell XO in oxidative reactions on the ocular surface of dry eye patients with Sjogren’s syndrome was studied. (PMID:17523077)
• These results suggest that polymorphisms -337GA and 565+64CT of XDH gene are related with blood pressure and oxidative stress in hypertension, adding evidence to the role of xanthine oxidoreductase and oxidative stress in blood pressure. (PMID:17622935)
• A role for xanthine oxidase in ageing. (PMID:17906999)
• several single nucleotide polymorphisms in the XO gene are involved in individual variations in XO activity. In addition, such findings will be useful to identify xanthinuria patients. (PMID:18300946)
• Exogenous XO activity is an important contributor to endothelial mechanisms for microvascular rarefaction, by modulation of cell survival signaling pathways; however, endogenous XO is necessary for maintaining endothelial cell survival (PMID:18386220)
• The NAD+ dependent retinol oxidation catalyzed by xanthine dehydrogenase is strictly dependent on cellular retinol binding proteins and is inhibited by oxypurinol (PMID:18569334)
• Report no effect of age and gender on pharmacokinetics, pharmacodynamics, and safety of febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase. (PMID:18635756)
• rhinovirus infection proteolytically activates XO initiating a pro-inflammatory vicious circle driven by virus-induced depletion of intracellular reducing power (PMID:18678861)
• Genetic variations in xanthine dehydrogenase contribute partly to hypertension and its complications, including atherosclerosis and chronic kidney disease. (PMID:18712049)
• XOR derived ROS mediated the migratory effect and also modulated COX-2 and MMP levels and function. (PMID:18767115)
• hXOR is a tumor suppressor-targeted gene and the phosphorylation of SAFB1 is regulated by OSM, which provides a molecular basis for understanding the role of SAFB1-regulated hXOR transcription in cytokine stimulation and tumorigenesis (PMID:18772145)
• XO activity, but not oxidative damage parameters, at the time of sepsis diagnosis was significantly higher in non-survival septic patients. (PMID:18775690)
• Mechanisms underlying erythrocyte and endothelial nitrite reduction to nitric oxide in hypoxia: role for xanthine oxidoreductase and endothelial nitric oxide synthase. (PMID:18818408)
• XO is implicated in the exercise-induced muscle oxidative stress of COPD patients (PMID:18821156)
• this study was to assess the activities of cytochrome P450 (CYP) 1A2, N-acetyltransferase 2, xanthine oxidase, and CYP2D6 in children with isolated idiopathic GH deficiency before and 3 and 6 months after initiation of r-hGH treatment. (PMID:18840375)
• As preeclampsia is characterized by heightened inflammation, oxidative stress, and hyperuricemia, xanthine oxidase may play a pivotal role in preeclampsia, the hypertensive disorder of pregnancy. (PMID:19196876)
• PRY/SPRY/B30.2 domain of butyrophilin 1A1 (BTN1A1) binds to xanthine oxidoreductase (PMID:19531472)
• Exposure of human keratinocytes to ischemia, hyperglycemia and their combination induces oxidative stress via the enzymes inducible nitric oxide synthase and xanthine oxidase. (PMID:19539448)
• xanthine oxidase may have a role in idiopathic pulmonary arterial hypertension (PMID:19567609)
• Decreased paraoxonase activity as well as increased adenosine deaminase and xanthine oxidase activities and nitrite levels indicate that oxidative stress is increased and purine metabolism is altered in pseudoexfoliation syndrome. (PMID:19628957)
• The potential regulatory effect of oestrogen (17beta-estradiol) on one key player in retinoic acid biosynthesis, the xanthine dehydrogenase (XDH), was investigated. (PMID:19693777)
• Non-diabetic, non-smokers, non-hypertensive and untreated patients with familial combined hyperlipidemia present with increased levels of XO and NFKB activity. (PMID:19765958)
• Case Report: hereditary xanthinuria with xanthine dehydrogenase deficiency due to novel sequence variations presenting as rheumatoid arthritis. (PMID:20077140)
• Low XOR expression was associated with shortened survival and also conferred a worse prognosis for patients with non-small cell lung cancer (NSCLC). (PMID:20570389)
• 13 polymorphisms were identified in 196 unrelated Japanese. genetic variation in the promoter region of XO may determine interindividual differences in XO gene expression. (PMID:20930425)
• XOR promotes the inflammatory state of mononuclear phagocytes through effects on chemokine expression, PPARgamma SUMOylation, and HIF-1alpha (PMID:21059659)
• the elevation of serum XOR during the three weeks following LT for the first time, as well as the influence of the graft reperfusion technique on XOR serum levels. (PMID:21382276)
• The results indicated that anti-HXOR antibodies in synovial fluids have a protective role as high concentrations against XOR were detected in inflammatory arthritis. (PMID:21644044)
• These results show that XOR is an important functional component of differentiation whose diminished expression contributes to breast cancer aggressiveness (PMID:21775420)
• Xanthine oxidase plays an important role in the age-related oxidative stress in tissues and immune cells. (PMID:21826556)
• xanthine oxidase activities in patients were 0 and 0.4 pmol/h/mL of plasma. We found three nonsense changes: p.P214QfsX4 and unpublished p.R825X and p.R881X (PMID:21963464)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	xdh	ENSDARG00000055240
mus_musculus	Xdh	ENSMUSG00000024066
rattus_norvegicus	Xdh	ENSRNOG00000007081
drosophila_melanogaster	ry	FBGN0003308
caenorhabditis_elegans		WBGENE00010083

Paralogs (1): AOX1 (ENSG00000138356)

Protein

Protein identifiers

Xanthine dehydrogenase/oxidase — P47989 (reviewed: P47989)

All UniProt accessions (1): P47989

UniProt curated annotations — full annotation on UniProt →

Function. Key enzyme in purine degradation. Catalyzes the oxidation of hypoxanthine to xanthine. Catalyzes the oxidation of xanthine to uric acid. Contributes to the generation of reactive oxygen species. Has also low oxidase activity towards aldehydes (in vitro).

Subunit / interactions. Homodimer. Interacts with BTN1A1.

Subcellular location. Cytoplasm. Peroxisome. Secreted.

Tissue specificity. Detected in milk (at protein level).

Post-translational modifications. Subject to partial proteolysis; this alters the enzyme from the dehydrogenase form (D) to the oxidase form (O). Contains sulfhydryl groups that are easily oxidized (in vitro); this alters the enzyme from the dehydrogenase form (D) to the oxidase form (O).

Disease relevance. Xanthinuria 1 (XAN1) [MIM:278300] A disorder characterized by excretion of very large amounts of xanthine in the urine and a tendency to form xanthine stones. Uric acid is strikingly diminished in serum and urine. XAN1 is due to isolated xanthine dehydrogenase deficiency. Patients can metabolize allopurinol. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Can be converted from the dehydrogenase form (D) to the oxidase form (O) irreversibly by proteolysis or reversibly through the oxidation of sulfhydryl groups.

Cofactor. Binds 2 [2Fe-2S] clusters. Binds 1 Mo-molybdopterin (Mo-MPT) cofactor per subunit.

Similarity. Belongs to the xanthine dehydrogenase family.

RefSeq proteins (1): NP_000370* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000674	Ald_Oxase/Xan_DH_a/b	Domain
IPR001041	2Fe-2S_ferredoxin-type	Domain
IPR002346	Mopterin_DH_FAD-bd	Domain
IPR002888	2Fe-2S-bd	Domain
IPR005107	CO_DH_flav_C	Domain
IPR006058	2Fe2S_fd_BS	Binding_site
IPR008274	AldOxase/xan_DH_MoCoBD1	Domain
IPR012675	Beta-grasp_dom_sf	Homologous_superfamily
IPR014307	Xanthine_DH_ssu	Domain
IPR016166	FAD-bd_PCMH	Domain
IPR016167	FAD-bd_PCMH_sub1	Homologous_superfamily
IPR016169	FAD-bd_PCMH_sub2	Homologous_superfamily
IPR016208	Ald_Oxase/xanthine_DH-like	Family
IPR022407	OxRdtase_Mopterin_BS	Binding_site
IPR036010	2Fe-2S_ferredoxin-like_sf	Homologous_superfamily
IPR036318	FAD-bd_PCMH-like_sf	Homologous_superfamily
IPR036683	CO_DH_flav_C_dom_sf	Homologous_superfamily
IPR036856	Ald_Oxase/Xan_DH_a/b_sf	Homologous_superfamily
IPR036884	2Fe-2S-bd_dom_sf	Homologous_superfamily
IPR037165	AldOxase/xan_DH_Mopterin-bd_sf	Homologous_superfamily
IPR046867	AldOxase/xan_DH_MoCoBD2	Domain

Pfam: PF00111, PF00941, PF01315, PF01799, PF02738, PF03450, PF20256

Enzyme classification (BRENDA):

• EC 1.17.1.4 — xanthine dehydrogenase (BRENDA: 71 organisms, 363 substrates, 163 inhibitors, 164 Km, 55 kcat entries)
• EC 1.17.3.2 — xanthine oxidase (BRENDA: 38 organisms, 227 substrates, 585 inhibitors, 133 Km, 23 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
XANTHINE	0.0003–80.09	59
NAD+	0.0022–0.171	39
XANTHINE	0.0015–6.8	35
HYPOXANTHINE	0.0041–0.5	14
BENZALDEHYDE	0.06–1.517	12
HYPOXANTHINE	0.0017–0.133	8
O2	0.026–0.129	8
2-AMINO-4-HYDROXYPTERIN	0.001–0.011	7
NADH	0.0057–6	6
NITRITE	0.04–1.2	4
4-HYDROXYPYRAZOLO(3,4-D)PYRIMIDINE	0.0258–1	3
PTERIN	0.0015–0.036	3
DCPIP	0.0809–0.0823	2
2,3-DIHYDROXYBENZALDEHYDE	0.0253–0.035	2
2-AMINO-4-HYDROXYPTERIDINE	0.0014–0.0067	2

Catalyzed reactions (Rhea), 3 shown:

• xanthine + NAD(+) + H2O = urate + NADH + H(+) (RHEA:16669)
• xanthine + O2 + H2O = urate + H2O2 (RHEA:21132)
• hypoxanthine + NAD(+) + H2O = xanthine + NADH + H(+) (RHEA:24670)

UniProt features (168 total): helix 53, strand 46, sequence variant 24, binding site 22, turn 11, sequence conflict 4, domain 2, disulfide bond 2, mutagenesis site 2, chain 1, active site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2E1Q	X-RAY DIFFRACTION	2.6
2CKJ	X-RAY DIFFRACTION	3.59

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P47989-F1	96.17	0.94

Functional residue map

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

Catalytic / active sites (1): 1262 (proton acceptor)

Ligand- & substrate-binding residues (22): 148; 150; 257–264; 337; 347–351; 360; 404; 422; 768; 799; 803; 881 …

Disulfide bonds (2): 509–1318, 536–993

Mutagenesis-validated functional residues (2):

Position	Phenotype
803	strongly decreased activity towards xanthine and hypoxanthine. increased affinity and activity towards aromatic aldehyde
881	abolishes xanthine oxidase activity.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-74259	Purine catabolism
R-HSA-8851680	Butyrophilin (BTN) family interactions
R-HSA-9748787	Azathioprine ADME

MSigDB gene sets: 328 (showing top): GSE45365_NK_CELL_VS_BCELL_DN, MODULE_93, GOBP_EPITHELIUM_DEVELOPMENT, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, YAO_HOXA10_TARGETS_VIA_PROGESTERONE_UP, MODULE_45, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, DARWICHE_PAPILLOMA_PROGRESSION_RISK, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_REGULATION_OF_EPITHELIAL_CELL_DIFFERENTIATION, MARTINEZ_RB1_TARGETS_UP

GO Biological Process (18): allantoin metabolic process (GO:0000255), guanine catabolic process (GO:0006147), inosine catabolic process (GO:0006148), deoxyinosine catabolic process (GO:0006149), adenosine catabolic process (GO:0006154), deoxyadenosine catabolic process (GO:0006157), deoxyguanosine catabolic process (GO:0006161), AMP catabolic process (GO:0006196), IMP catabolic process (GO:0006204), lactation (GO:0007595), hypoxanthine catabolic process (GO:0009114), xanthine catabolic process (GO:0009115), iron-sulfur cluster assembly (GO:0016226), regulation of epithelial cell differentiation (GO:0030856), obsolete amide catabolic process (GO:0043605), GMP catabolic process (GO:0046038), dGMP catabolic process (GO:0046055), dAMP catabolic process (GO:0046059)

GO Molecular Function (15): xanthine dehydrogenase activity (GO:0004854), xanthine oxidase activity (GO:0004855), iron ion binding (GO:0005506), protein homodimerization activity (GO:0042803), molybdopterin cofactor binding (GO:0043546), flavin adenine dinucleotide binding (GO:0050660), 2 iron, 2 sulfur cluster binding (GO:0051537), hypoxanthine dehydrogenase activity (GO:0070674), hypoxanthine oxidase activity (GO:0070675), FAD binding (GO:0071949), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), molybdenum ion binding (GO:0030151), metal ion binding (GO:0046872), iron-sulfur cluster binding (GO:0051536)

GO Cellular Component (6): obsolete extracellular space (GO:0005615), peroxisome (GO:0005777), cytosol (GO:0005829), sarcoplasmic reticulum (GO:0016529), extracellular region (GO:0005576), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Nucleotide catabolism	1
Adaptive Immune System	1
Drug ADME	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
purine nucleobase catabolic process	3
2’-deoxyribonucleoside catabolic process	3
purine deoxyribonucleoside catabolic process	3
purine ribonucleotide catabolic process	3
purine ribonucleoside monophosphate catabolic process	3
cellular anatomical structure	3
purine ribonucleoside catabolic process	2
purine deoxyribonucleotide catabolic process	2
purine deoxyribonucleoside monophosphate catabolic process	2
oxidoreductase activity, acting on CH or CH2 groups, NAD or NADP as acceptor	2
oxidoreductase activity, acting on CH or CH2 groups, oxygen as acceptor	2
transition metal ion binding	2
binding	2
metabolic process	1
guanine metabolic process	1
inosine metabolic process	1
deoxyinosine metabolic process	1
adenosine metabolic process	1
deoxyadenosine metabolic process	1
AMP metabolic process	1
IMP metabolic process	1
body fluid secretion	1
mammary gland development	1
milk ejection reflex	1
hypoxanthine metabolic process	1
xanthine metabolic process	1
metallo-sulfur cluster assembly	1
epithelial cell differentiation	1
regulation of cell differentiation	1
regulation of multicellular organismal development	1
GMP metabolic process	1
dGMP metabolic process	1
dAMP metabolic process	1
identical protein binding	1
protein dimerization activity	1
nucleotide binding	1
anion binding	1
iron-sulfur cluster binding	1
flavin adenine dinucleotide binding	1
catalytic activity	1

Protein interactions and networks

STRING

2106 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
XDH	BTN2A1	P78408	988
XDH	BTNL9	Q6UXG8	988
XDH	BTN2A2	Q8WVV5	988
XDH	BTN1A1	Q13410	987
XDH	BTNL3	Q6UXE8	969
XDH	BTNL8	Q6UX41	969
XDH	ERMAP	Q96PL5	969
XDH	BTN3A3	O00478	968
XDH	BTN3A2	P78410	968
XDH	BTN3A1	O00481	966
XDH	PNP	P00491	931
XDH	NOS1	P29475	924
XDH	PLIN2	Q99541	904
XDH	GPX6	P59796	884
XDH	GPX7	Q96SL4	884
XDH	GPX5	O75715	884

IntAct

13 interactions, top by confidence:

A	B	Type	Score
COPS6	RHOBTB1	psi-mi:“MI:0914”(association)	0.730
XDH	GRIP1	psi-mi:“MI:0915”(physical association)	0.560
PLXNA4	CRYZL1	psi-mi:“MI:0914”(association)	0.560
CCDC110	XDH	psi-mi:“MI:0915”(physical association)	0.400
Xpo1	XPO1	psi-mi:“MI:0915”(physical association)	0.400
MYC	PDZD2	psi-mi:“MI:0914”(association)	0.350
GOT1	A2ML1	psi-mi:“MI:0914”(association)	0.350
MTRFR	LPL	psi-mi:“MI:0914”(association)	0.350
RARS2	C3	psi-mi:“MI:0914”(association)	0.350
RPP25L	GTPBP1	psi-mi:“MI:0914”(association)	0.350
XDH	GRIP1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (22): XDH (Affinity Capture-MS), XDH (Two-hybrid), USP15 (Affinity Capture-MS), USP15 (Affinity Capture-Western), XDH (Affinity Capture-Western), XDH (Affinity Capture-MS), XDH (Affinity Capture-MS), XDH (Affinity Capture-MS), XDH (Affinity Capture-MS), XDH (Affinity Capture-MS), XDH (Co-fractionation), XDH (Positive Genetic), XDH (Cross-Linking-MS (XL-MS)), NIPBL (Cross-Linking-MS (XL-MS)), PGD (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A1U8QNG8, B9FK36, C4NYZ3, F4JLI5, G3X982, H9TB17, H9TB18, H9TB19, O23887, O23888, O54754, P08793, P10351, P14882, P22811, P22985, P47989, P47990, P48034, P80456, P80457, P91711, Q00519, Q06278, Q12553, Q38970, Q3TYQ9, Q54FB7, Q5FB27, Q5I0C3, Q5QE78, Q5QE79, Q5QE80, Q5SGK3, Q69R21, Q6AUV1, Q6Z351, Q7G191, Q7G192, Q7G193

Diamond homologs: A0A1U8QNG8, C4NYZ3, D7REY5, F4JLI5, G3X982, H9TB17, H9TB18, H9TB19, O32143, O33818, O54754, O87682, P08793, P10351, P19915, P19921, P22811, P22985, P47989, P47990, P48034, P77165, P80456, P80457, P91711, Q00519, Q06278, Q0QLF1, Q0QLF3, Q12553, Q3TYQ9, Q46801, Q4J6M5, Q51697, Q54FB7, Q59128, Q5FB27, Q5QE78, Q5QE79, Q5QE80

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CDK5	“up-regulates activity”	XDH	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

1049 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	22
Likely pathogenic	31
Uncertain significance	531
Likely benign	254
Benign	112

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1027672	NM_000379.4(XDH):c.2751del (p.Gln919fs)	Pathogenic
1075330	NM_000379.4(XDH):c.1343_1350del (p.Glu448fs)	Pathogenic
1369362	NM_000379.4(XDH):c.2164A>T (p.Lys722Ter)	Pathogenic
1451493	NM_000379.4(XDH):c.598G>T (p.Glu200Ter)	Pathogenic
1457782	NM_000379.4(XDH):c.641del (p.Pro214fs)	Pathogenic
2015541	NM_000379.4(XDH):c.3711del (p.Ile1238fs)	Pathogenic
2073968	NM_000379.4(XDH):c.1664dup (p.Ala556fs)	Pathogenic
2422980	NC_000002.11:g.(?31558824)(31637532_?)del	Pathogenic
2422981	NC_000002.11:g.(?31588418)(31589011_?)del	Pathogenic
2731116	NM_000379.4(XDH):c.2473C>T (p.Arg825Ter)	Pathogenic
2743120	NM_000379.4(XDH):c.134del (p.Glu45fs)	Pathogenic
2744635	NM_000379.4(XDH):c.575C>A (p.Ser192Ter)	Pathogenic
2868102	NM_000379.4(XDH):c.547C>T (p.Gln183Ter)	Pathogenic
2918237	NM_000379.4(XDH):c.2751dup (p.Pro918fs)	Pathogenic
2955	NM_000379.4(XDH):c.2567del (p.Thr856fs)	Pathogenic
3247316	NC_000002.11:g.(?31621419)(31624214_?)del	Pathogenic
335758	NM_000379.4(XDH):c.3847C>T (p.Arg1283Ter)	Pathogenic
4728699	NM_000379.4(XDH):c.1418_1424dup (p.Lys476fs)	Pathogenic
570826	NM_000379.4(XDH):c.3507del (p.Gly1170fs)	Pathogenic
579351	NM_000379.4(XDH):c.2274del (p.Glu760fs)	Pathogenic
635517	NM_000379.4(XDH):c.3520-1G>C	Pathogenic
641114	NM_000379.4(XDH):c.140dup (p.Cys48fs)	Pathogenic
1179049	NM_000379.4(XDH):c.2198-2A>C	Likely pathogenic
1466652	NM_000379.4(XDH):c.3052-2A>G	Likely pathogenic
1511440	NM_000379.4(XDH):c.651+1G>A	Likely pathogenic
1511643	NM_000379.4(XDH):c.887-1G>A	Likely pathogenic
2140318	NM_000379.4(XDH):c.2457-2A>G	Likely pathogenic
2145159	NM_000379.4(XDH):c.565-1G>A	Likely pathogenic
2585395	NM_000379.4(XDH):c.3352-2A>G	Likely pathogenic
2956	NM_000379.4(XDH):c.445C>T (p.Arg149Cys)	Likely pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

8762 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:31366035:A:C	F799L	1.000
2:31366035:A:T	F799L	1.000
2:31366037:A:G	F799L	1.000
2:31341350:G:C	N1188K	0.999
2:31341350:G:T	N1188K	0.999
2:31398661:G:C	F115L	0.999
2:31398661:G:T	F115L	0.999
2:31398663:A:G	F115L	0.999
2:31398665:C:T	G114E	0.999
2:31398668:C:G	C113S	0.999
2:31398669:A:G	C113R	0.999
2:31398669:A:T	C113S	0.999
2:31339656:C:G	G1203R	0.998
2:31350108:C:T	G916E	0.998
2:31350110:A:C	F915L	0.998
2:31350110:A:T	F915L	0.998
2:31350112:A:G	F915L	0.998
2:31365481:T:A	R840S	0.998
2:31365481:T:G	R840S	0.998
2:31365482:C:G	R840T	0.998
2:31366033:C:T	G800E	0.998
2:31366037:A:T	F799I	0.998
2:31397713:G:C	C150W	0.998
2:31397714:C:G	C150S	0.998
2:31397715:A:G	C150R	0.998
2:31397715:A:T	C150S	0.998
2:31398658:G:C	C116W	0.998
2:31398659:C:T	C116Y	0.998
2:31398660:A:G	C116R	0.998
2:31398666:C:A	G114W	0.998

dbSNP variants (sampled 300 via entrez): RS1000009924 (2:31373095 C>T), RS1000010175 (2:31389136 G>A), RS1000010614 (2:31410825 A>G), RS1000076658 (2:31371832 C>A,G), RS1000143827 (2:31415818 A>G), RS1000164267 (2:31367894 A>C,G,T), RS1000319290 (2:31399395 T>A), RS1000340058 (2:31394726 T>C), RS1000453102 (2:31350661 C>T), RS1000530237 (2:31404348 G>A,C), RS1000580824 (2:31392654 A>C), RS1000596850 (2:31405571 A>C), RS1000623113 (2:31358631 T>C), RS1000651632 (2:31368920 T>C), RS1000688622 (2:31404675 C>T)

Disease associations

OMIM: gene MIM:607633 | disease phenotypes: MIM:603592, MIM:278300

GenCC curated gene-disease

Disease	Classification	Inheritance
xanthinuria type I	Strong	Autosomal recessive

Mondo (2): xanthinuria type II (MONDO:0011346), xanthinuria type I (MONDO:0010209)

Orphanet (3): Hereditary xanthinuria (Orphanet:3467), Xanthinuria type II (Orphanet:93602), Xanthinuria type I (Orphanet:93601)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C562584	Xanthinuria, Type I (supp.)
C566358	Xanthinuria, Type II (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1929 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

16 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,349,113 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1164729	FEBUXOSTAT	4	3,499
CHEMBL1467	ALLOPURINOL	4	85,212
CHEMBL6	INDOMETHACIN	4	156,366
CHEMBL727	THIOGUANINE	4	294,612
CHEMBL226335	RUTIN	3	57,988
CHEMBL226345	ADENINE	3	541,090
CHEMBL50	QUERCETIN	3	74,559
CHEMBL1078685	TOPIROXOSTAT	2	556
CHEMBL151	LUTEOLIN	2	23,523
CHEMBL250450	ISOQUERCETIN	2	1,626
CHEMBL31574	FISETIN	2	7,745
CHEMBL37387	BROPIRIMINE	2	14,150
CHEMBL44	GENISTEIN	2	44,212
CHEMBL8260	BAICALEIN	2	8,592
CHEMBL859	OXYPURINOL	2	9,443
CHEMBL150	KAEMPFEROL	1	25,940

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

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1429376	Toxicity	3	didanosine	HIV infectious disease
rs1594160	Toxicity	3	didanosine	HIV infectious disease

PharmGKB variants

13 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs494852	XDH		0.00	0
rs1429376	XDH	3	1.75	1	didanosine
rs1594160	XDH	3	1.75	1	didanosine
rs2236168	XDH		0.00	0
rs4407290	XDH		0.00	0
rs1884725	XDH		0.00	0
rs45442092	XDH		0.00	0
rs2295474	XDH		0.00	0
rs2295475	XDH		0.00	0
rs2281547	XDH		0.00	0
rs755854585	XDH		0.00	0
rs139515054	XDH		0.00	0
rs6710015	XDH		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — 1.-.-.- Oxidoreductases

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
WN1703	Inhibition	8.24	pIC50
febuxostat	Inhibition	7.52	pIC50
allopurinol	Inhibition	5.15	pKi

Binding affinities (BindingDB)

107 measured of 126 human assays (127 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
6-(N-benzoylamino)purine, 2	KI	0.0475 nM
2-(3-cyano-4-propan-2-ylsulfanylphenyl)-4-methyl-1,3-selenazole-5-carboxylic acid	IC50	1.32 nM	US-9802907: 2-aryl selenazole compound and pharmaceutical composition thereof
2-[3-cyano-4-(2-methoxyphenyl)phenyl]-4-methyl-1,3-selenazole-5-carboxylic acid	IC50	1.67 nM	US-9802907: 2-aryl selenazole compound and pharmaceutical composition thereof
2-(3-cyano-4-phenylphenyl)-4-methyl-1,3-selenazole-5-carboxylic acid	IC50	1.7 nM	US-9802907: 2-aryl selenazole compound and pharmaceutical composition thereof
2-[3-cyano-4-(2-methylpropoxy)phenyl]-4-methyl-1,3-selenazole-5-carboxylic acid	IC50	2.05 nM	US-9802907: 2-aryl selenazole compound and pharmaceutical composition thereof
2-(4-tert-butylsulfanyl-3-cyanophenyl)-4-methyl-1,3-selenazole-5-carboxylic acid	IC50	2.29 nM	US-9802907: 2-aryl selenazole compound and pharmaceutical composition thereof
2-(3-cyano-4-ethoxyphenyl)-4-methyl-1,3-selenazole-5-carboxylic acid	IC50	2.29 nM	US-9802907: 2-aryl selenazole compound and pharmaceutical composition thereof
2-(3-cyano-4-morpholin-4-ylphenyl)-4-methyl-1,3-selenazole-5-carboxylic acid	IC50	2.3 nM	US-9802907: 2-aryl selenazole compound and pharmaceutical composition thereof
2-(3-cyano-4-propan-2-yloxyphenyl)-4-methyl-1,3-selenazole-5-carboxylic acid	IC50	2.4 nM	US-9802907: 2-aryl selenazole compound and pharmaceutical composition thereof
2-(3-cyano-4-cyclohexylsulfanylphenyl)-4-methyl-1,3-selenazole-5-carboxylic acid	IC50	2.43 nM	US-9802907: 2-aryl selenazole compound and pharmaceutical composition thereof
2-[3-cyano-4-(dimethylamino)phenyl]-4-methyl-1,3-selenazole-5-carboxylic acid	IC50	2.52 nM	US-9802907: 2-aryl selenazole compound and pharmaceutical composition thereof
2-(3-cyano-4-pyridin-4-ylphenyl)-4-methyl-1,3-selenazole-5-carboxylic acid	IC50	2.53 nM	US-9802907: 2-aryl selenazole compound and pharmaceutical composition thereof
2-[3-cyano-4-(2-methylpropylsulfanyl)phenyl]-4-methyl-1,3-selenazole-5-carboxylic acid	IC50	2.56 nM	US-9802907: 2-aryl selenazole compound and pharmaceutical composition thereof
2-[4-(4-chlorophenyl)-3-cyanophenyl]-4-methyl-1,3-selenazole-5-carboxylic acid	IC50	2.61 nM	US-9802907: 2-aryl selenazole compound and pharmaceutical composition thereof
2-(3-cyano-4-pyridin-3-ylphenyl)-4-methyl-1,3-selenazole-5-carboxylic acid	IC50	2.67 nM	US-9802907: 2-aryl selenazole compound and pharmaceutical composition thereof
2-[3-cyano-4-(4-methoxyphenyl)phenyl]-4-methyl-1,3-selenazole-5-carboxylic acid	IC50	2.7 nM	US-9802907: 2-aryl selenazole compound and pharmaceutical composition thereof
2-(3-cyano-4-naphthalen-1-ylphenyl)-4-methyl-1,3-selenazole-5-carboxylic acid	IC50	2.78 nM	US-9802907: 2-aryl selenazole compound and pharmaceutical composition thereof
2-(3-cyano-4-propan-2-yloxyphenyl)-4-methyl-1,3-thiazole-5-carboxylic acid	IC50	2.78 nM	US-9802907: 2-aryl selenazole compound and pharmaceutical composition thereof
2-[3-cyano-4-[4-(trifluoromethyl)phenyl]phenyl]-4-methyl-1,3-selenazole-5-carboxylic acid	IC50	2.84 nM	US-9802907: 2-aryl selenazole compound and pharmaceutical composition thereof
2-(3-cyano-4-phenylmethoxyphenyl)-4-methyl-1,3-selenazole-5-carboxylic acid	IC50	2.85 nM	US-9802907: 2-aryl selenazole compound and pharmaceutical composition thereof
2-[3-cyano-4-(cyclopropylmethoxy)phenyl]-4-methyl-1,3-selenazole-5-carboxylic acid	IC50	2.97 nM	US-9802907: 2-aryl selenazole compound and pharmaceutical composition thereof
2-[3-cyano-4-(3-fluoro-4-methoxyphenyl)phenyl]-4-methyl-1,3-selenazole-5-carboxylic acid	IC50	2.99 nM	US-9802907: 2-aryl selenazole compound and pharmaceutical composition thereof
4-methyl-2-[4-(2-methylpropoxy)-3-(trifluoromethyl)phenyl]-1,3-selenazole-5-carboxylic acid	IC50	3.06 nM	US-9802907: 2-aryl selenazole compound and pharmaceutical composition thereof
2-(4-benzylsulfanyl-3-cyanophenyl)-4-methyl-1,3-selenazole-5-carboxylic acid	IC50	3.07 nM	US-9802907: 2-aryl selenazole compound and pharmaceutical composition thereof
2-[3-cyano-4-(3,4-difluorophenyl)phenyl]-4-methyl-1,3-selenazole-5-carboxylic acid	IC50	3.24 nM	US-9802907: 2-aryl selenazole compound and pharmaceutical composition thereof
2-[3-cyano-4-(3,4-dimethoxyphenyl)phenyl]-4-methyl-1,3-selenazole-5-carboxylic acid	IC50	3.25 nM	US-9802907: 2-aryl selenazole compound and pharmaceutical composition thereof
2-[3-cyano-4-(3-methylbutoxy)phenyl]-4-methyl-1,3-selenazole-5-carboxylic acid	IC50	3.28 nM	US-9802907: 2-aryl selenazole compound and pharmaceutical composition thereof
2-[3-cyano-4-(2,4-dimethoxyphenyl)phenyl]-4-methyl-1,3-selenazole-5-carboxylic acid	IC50	3.47 nM	US-9802907: 2-aryl selenazole compound and pharmaceutical composition thereof
2-[4-(4-chlorophenyl)sulfanyl-3-cyanophenyl]-4-methyl-1,3-selenazole-5-carboxylic acid	IC50	3.58 nM	US-9802907: 2-aryl selenazole compound and pharmaceutical composition thereof
2-[3-cyano-4-(3,4,5-trimethoxyphenyl)phenyl]-4-methyl-1,3-selenazole-5-carboxylic acid	IC50	3.79 nM	US-9802907: 2-aryl selenazole compound and pharmaceutical composition thereof
2-[3-cyano-4-[3-(trifluoromethoxy)phenyl]phenyl]-4-methyl-1,3-selenazole-5-carboxylic acid	IC50	3.92 nM	US-9802907: 2-aryl selenazole compound and pharmaceutical composition thereof
2-[3-cyano-4-(4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)phenyl]-4-methyl-1,3-selenazole-5-carboxylic acid	IC50	4.11 nM	US-9802907: 2-aryl selenazole compound and pharmaceutical composition thereof
2-[3-cyano-4-(3-methoxyphenyl)phenyl]-4-methyl-1,3-selenazole-5-carboxylic acid	IC50	4.61 nM	US-9802907: 2-aryl selenazole compound and pharmaceutical composition thereof
2-[3-cyano-4-(4-ethylphenyl)phenyl]-4-methyl-1,3-selenazole-5-carboxylic acid	IC50	4.84 nM	US-9802907: 2-aryl selenazole compound and pharmaceutical composition thereof
2-(3-cyano-4-pyridin-2-ylsulfanylphenyl)-4-methyl-1,3-selenazole-5-carboxylic acid	IC50	5.19 nM	US-9802907: 2-aryl selenazole compound and pharmaceutical composition thereof
2-[3-cyano-4-(propan-2-ylsulfanylmethyl)phenyl]-4-methyl-1,3-selenazole-5-carboxylic acid	IC50	8.56 nM	US-9802907: 2-aryl selenazole compound and pharmaceutical composition thereof
2-[3-cyano-4-(4-methylpiperazin-1-yl)phenyl]-4-methyl-1,3-selenazole-5-carboxylic acid	IC50	9.13 nM	US-9802907: 2-aryl selenazole compound and pharmaceutical composition thereof
2-[3-cyano-4-(2-methylpropoxy)phenyl]-4-(hydroxymethyl)-1,3-selenazole-5-carboxylic acid	IC50	10.1 nM	US-9802907: 2-aryl selenazole compound and pharmaceutical composition thereof
2-[3-chloro-4-(2-methylpropoxy)phenyl]-4-methyl-1,3-selenazole-5-carboxylic acid	IC50	10.2 nM	US-9802907: 2-aryl selenazole compound and pharmaceutical composition thereof
2-[3-cyano-4-[3-(trifluoromethyl)phenyl]sulfanylphenyl]-4-methyl-1,3-selenazole-5-carboxylic acid	IC50	12.1 nM	US-9802907: 2-aryl selenazole compound and pharmaceutical composition thereof
2-[3-cyano-4-(cyclohexylmethoxy)phenyl]-4-methyl-1,3-selenazole-5-carboxylic acid	IC50	12.4 nM	US-9802907: 2-aryl selenazole compound and pharmaceutical composition thereof
2-(3-cyano-4-propan-2-ylsulfonylphenyl)-4-methyl-1,3-selenazole-5-carboxylic acid	IC50	13.9 nM	US-9802907: 2-aryl selenazole compound and pharmaceutical composition thereof
4-(2-chloro-6-cyano-1-benzofuran-4-yl)-2-hydroxybenzoic acid	IC50	14 nM	US-10266496: Carboxy substituted (hetero) aromatic ring derivatives and preparation method and uses thereof
4-(6-cyano-2-fluoro-1-benzothiophen-4-yl)-2-hydroxybenzoic acid	IC50	15 nM	US-10266496: Carboxy substituted (hetero) aromatic ring derivatives and preparation method and uses thereof
4-(3-cyanonaphthalen-1-yl)-2-hydroxybenzoic acid	IC50	19 nM	US-10266496: Carboxy substituted (hetero) aromatic ring derivatives and preparation method and uses thereof
4-methyl-2-[3-(trifluoromethyl)phenyl]-1,3-selenazole-5-carboxylic acid	IC50	25.4 nM	US-9802907: 2-aryl selenazole compound and pharmaceutical composition thereof
4-(2-chloro-5-cyano-1-benzofuran-7-yl)-2-hydroxybenzoic acid	IC50	30 nM	US-10266496: Carboxy substituted (hetero) aromatic ring derivatives and preparation method and uses thereof
2-[3-cyano-4-[3-(trifluoromethyl)phenyl]phenyl]-4-methyl-1,3-selenazole-5-carboxylic acid	IC50	31.1 nM	US-9802907: 2-aryl selenazole compound and pharmaceutical composition thereof
4-(6-cyano-2-fluoro-1-benzofuran-4-yl)-2-hydroxybenzoic acid	IC50	34 nM	US-10266496: Carboxy substituted (hetero) aromatic ring derivatives and preparation method and uses thereof
4-(5-cyano-2-fluoro-1-benzofuran-7-yl)-2-hydroxybenzoic acid	IC50	38 nM	US-10266496: Carboxy substituted (hetero) aromatic ring derivatives and preparation method and uses thereof

ChEMBL bioactivities

664 potent at pChembl≥5 of 851 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.82	IC50	0.015	nM	CHEMBL5911881
10.70	IC50	0.02	nM	CHEMBL5395750
10.54	IC50	0.029	nM	CHEMBL5893388
10.40	IC50	0.04	nM	CHEMBL5753958
10.40	IC50	0.04	nM	CHEMBL5765459
10.22	IC50	0.06	nM	CHEMBL5886087
10.22	IC50	0.06	nM	CHEMBL5919922
10.22	IC50	0.06	nM	CHEMBL5765233
10.19	IC50	0.064	nM	CHEMBL5947643
10.15	IC50	0.07	nM	CHEMBL5803335
10.14	Ki	0.073	nM	CHEMBL6163117
10.00	Ki	0.1	nM	FEBUXOSTAT
10.00	IC50	0.1	nM	CHEMBL5968055
9.99	IC50	0.103	nM	CHEMBL6059324
9.93	Ki	0.118	nM	CHEMBL6168594
9.92	IC50	0.12	nM	CHEMBL5904234
9.74	IC50	0.18	nM	CHEMBL5795784
9.72	IC50	0.19	nM	CHEMBL6028932
9.70	IC50	0.2	nM	CHEMBL5806577
9.69	IC50	0.206	nM	CHEMBL5973769
9.68	IC50	0.21	nM	CHEMBL5819142
9.66	IC50	0.22	nM	CHEMBL5815550
9.56	Ki	0.275	nM	CHEMBL6163835
9.55	IC50	0.28	nM	CHEMBL6057356
9.50	IC50	0.315	nM	CHEMBL5781892
9.48	IC50	0.33	nM	CHEMBL5939746
9.42	IC50	0.38	nM	CHEMBL5417928
9.42	IC50	0.377	nM	CHEMBL5970628
9.40	Ki	0.401	nM	CHEMBL6163117
9.30	IC50	0.5012	nM	CHEMBL3127130
9.29	IC50	0.519	nM	CHEMBL6040108
9.28	IC50	0.53	nM	CHEMBL5991322
9.28	IC50	0.52	nM	CHEMBL6012949
9.22	Ki	0.6	nM	FEBUXOSTAT
9.20	IC50	0.631	nM	CHEMBL3127135
9.18	IC50	0.66	nM	CHEMBL5814665
9.18	Ki	0.663	nM	CHEMBL6163835
9.12	Ki	0.759	nM	CHEMBL6168594
9.00	IC50	1	nM	CHEMBL3127117
9.00	IC50	1	nM	CHEMBL5436777
8.99	IC50	1.02	nM	CHEMBL6038530
8.96	IC50	1.1	nM	CHEMBL5410457
8.94	IC50	1.14	nM	CHEMBL6032122
8.90	IC50	1.259	nM	CHEMBL3127137
8.90	IC50	1.259	nM	CHEMBL3127134
8.90	IC50	1.259	nM	FEBUXOSTAT
8.88	IC50	1.32	nM	CHEMBL5408075
8.82	Ki	1.5	nM	CHEMBL5400293
8.80	IC50	1.585	nM	CHEMBL3127114
8.80	IC50	1.585	nM	CHEMBL3127131

PubChem BioAssay actives

468 with measured affinity, of 1199 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N-(7H-purin-6-yl)benzamide	1799677: Xanthine Oxidase Inhibition Assay from Article 10.1080/14756360500112326: “6-(N-benzoylamino)purine as a novel and potent inhibitor of xanthine oxidase: inhibition mechanism and molecular modeling studies.”	ki	<0.0001	uM
Febuxostat	1485265: Non-competitive inhibition of human xanthine oxidase	ki	0.0001	uM
2-[4-[(4-chlorophenyl)carbamoyl]phenyl]-4-methyl-1,3-thiazole-5-carboxylic acid	2004164: Inhibition of XO (unknown origin)	ic50	0.0004	uM
2-amino-4-[3-cyano-4-(2-methylpropoxy)phenyl]-6-oxo-1H-pyrimidine-5-carbonitrile	1075890: Competitive reversible inhibition of C-terminally FLAG-tagged human xanthine oxidase (amino acid 1 to 1333) expressed in baculovirus system after 15 mins by spectrophotometry	ic50	0.0005	uM
2-amino-6-oxo-4-[4-(oxolan-3-ylmethoxy)-3-(trifluoromethoxy)phenyl]-1H-pyrimidine-5-carbonitrile	1075890: Competitive reversible inhibition of C-terminally FLAG-tagged human xanthine oxidase (amino acid 1 to 1333) expressed in baculovirus system after 15 mins by spectrophotometry	ic50	0.0006	uM
2-amino-5-chloro-4-[4-(oxolan-3-ylmethoxy)-3-(trifluoromethoxy)phenyl]-1H-pyrimidin-6-one	1075893: Inhibition of C-terminally FLAG-tagged human xanthine oxidase (amino acid 1 to 1333) expressed in baculovirus system after 15 mins by spectrophotometry	ic50	0.0010	uM
4-methyl-2-[4-(2-methylpropoxy)-3-(tetrazol-1-yl)phenyl]-1,3-thiazole-5-carboxylic acid	2004164: Inhibition of XO (unknown origin)	ic50	0.0010	uM
2-[3-cyano-4-(heptylamino)phenyl]pyridine-4-carboxylic acid	2004164: Inhibition of XO (unknown origin)	ic50	0.0011	uM
2-amino-4-[4-(2-methylpropoxy)-3-(trifluoromethyl)phenyl]-6-oxo-1H-pyrimidine-5-carbonitrile	1075893: Inhibition of C-terminally FLAG-tagged human xanthine oxidase (amino acid 1 to 1333) expressed in baculovirus system after 15 mins by spectrophotometry	ic50	0.0013	uM
2-amino-4-[3-cyano-4-(cyclopropylmethoxy)phenyl]-6-oxo-1H-pyrimidine-5-carbonitrile	1075893: Inhibition of C-terminally FLAG-tagged human xanthine oxidase (amino acid 1 to 1333) expressed in baculovirus system after 15 mins by spectrophotometry	ic50	0.0013	uM
methyl 5-phenoxy-1H-indole-2-carboxylate	2004187: Binding affinity to XO (unknown origin) assessed as inhibition constant	ki	0.0015	uM
5-(2-amino-5-chloro-6-oxo-1H-pyrimidin-4-yl)-2-(2-methylpropoxy)benzonitrile	1075893: Inhibition of C-terminally FLAG-tagged human xanthine oxidase (amino acid 1 to 1333) expressed in baculovirus system after 15 mins by spectrophotometry	ic50	0.0016	uM
5-(2-amino-5-chloro-6-oxo-1H-pyrimidin-4-yl)-2-(oxolan-3-ylmethoxy)benzonitrile	1075890: Competitive reversible inhibition of C-terminally FLAG-tagged human xanthine oxidase (amino acid 1 to 1333) expressed in baculovirus system after 15 mins by spectrophotometry	ic50	0.0016	uM
methyl 5-(2-methylpropoxy)-1H-indole-2-carboxylate	2004187: Binding affinity to XO (unknown origin) assessed as inhibition constant	ki	0.0017	uM
2-[3-cyano-1-(1-hydroxypropan-2-yl)indol-5-yl]-4-methyl-1,3-thiazole-5-carboxylic acid	2004164: Inhibition of XO (unknown origin)	ic50	0.0030	uM
2-(7-cyano-2-phenyl-1H-indol-5-yl)-4-methyl-1,3-thiazole-5-carboxylic acid	2004164: Inhibition of XO (unknown origin)	ic50	0.0031	uM
2-[3-cyano-1-[2-(2-methoxyethoxy)ethyl]indol-5-yl]-4-methyl-1,3-thiazole-5-carboxylic acid	2004164: Inhibition of XO (unknown origin)	ic50	0.0035	uM
Allopurinol	1330574: Inhibition of xanthine oxidase (unknown origin) assessed as reduction in uric acid formation preincubated for 5 mins followed by addition of xanthine substrate measured every minute up to 8 mins	ic50	0.0036	uM
5-(3-oxo-1,2-dihydropyrazolo[3,4-d]pyrimidin-6-yl)-2-propan-2-yloxybenzonitrile	1900626: Mixed-type inhibition of xanthine oxidase (unknown origin) assessed as inhibitory constant of enzyme-substrate complex using xanthine as substrate at varying concentrations preincubated for 15 mins followed by substrate addition by UV spectrophotometric analysis	ki	0.0037	uM
5-(2-amino-5-chloro-6-oxo-1H-pyrimidin-4-yl)-2-(4-hydroxybutoxy)benzonitrile	1075893: Inhibition of C-terminally FLAG-tagged human xanthine oxidase (amino acid 1 to 1333) expressed in baculovirus system after 15 mins by spectrophotometry	ic50	0.0040	uM
2-hydroxy-4-[5-(4-methylanilino)-3-pyridinyl]benzoic acid	2076338: Inhibition of XOR (unknown origin) using xanthine as substrate measured for 10 mins by spectrophotometry	ic50	0.0040	uM
4-amino-2-[3-cyano-4-(3-methylbutoxy)phenyl]pyrimidine-5-carboxylic acid	1900626: Mixed-type inhibition of xanthine oxidase (unknown origin) assessed as inhibitory constant of enzyme-substrate complex using xanthine as substrate at varying concentrations preincubated for 15 mins followed by substrate addition by UV spectrophotometric analysis	ki	0.0042	uM
2-amino-3-iodo-5-nitrobenzonitrile	2004187: Binding affinity to XO (unknown origin) assessed as inhibition constant	ki	0.0042	uM
2-(7-cyano-3-methyl-1-propylindol-5-yl)-4-methyl-1,3-thiazole-5-carboxylic acid	2004164: Inhibition of XO (unknown origin)	ic50	0.0050	uM
2-(7-cyano-1-ethyl-3-methylindol-5-yl)-4-methyl-1,3-thiazole-5-carboxylic acid	2004164: Inhibition of XO (unknown origin)	ic50	0.0050	uM
2-(7-cyano-1-methylindol-5-yl)-4-methyl-1,3-thiazole-5-carboxylic acid	2004164: Inhibition of XO (unknown origin)	ic50	0.0050	uM
4-(5-pyridin-4-yl-1H-1,2,4-triazol-3-yl)pyridine-2-carbonitrile	1649918: Inhibition of xanthine oxidase (unknown origin)	ki	0.0057	uM
(2E,6E)-2-[(4-bromophenyl)methylidene]-6-[(3,5-dimethoxyphenyl)methylidene]cyclohexan-1-one	1330574: Inhibition of xanthine oxidase (unknown origin) assessed as reduction in uric acid formation preincubated for 5 mins followed by addition of xanthine substrate measured every minute up to 8 mins	ic50	0.0057	uM
1-[3-cyano-4-(2,2-dimethylpropoxy)phenyl]pyrazole-4-carboxylic acid	1536863: Inhibition of xanthine oxidase (unknown origin)	ic50	0.0058	uM
4-[5-(3-chloroanilino)-3-pyridinyl]-2-hydroxybenzoic acid	2076338: Inhibition of XOR (unknown origin) using xanthine as substrate measured for 10 mins by spectrophotometry	ic50	0.0060	uM
methyl 2-(7-cyano-5-nitro-1H-indol-2-yl)-4-methyl-1,3-thiazole-5-carboxylate	2004187: Binding affinity to XO (unknown origin) assessed as inhibition constant	ki	0.0062	uM
5-(2-amino-5-chloro-6-oxo-1H-pyrimidin-4-yl)-3-methyl-2-(oxolan-3-ylmethoxy)benzonitrile	1075893: Inhibition of C-terminally FLAG-tagged human xanthine oxidase (amino acid 1 to 1333) expressed in baculovirus system after 15 mins by spectrophotometry	ic50	0.0063	uM
2-amino-5-chloro-4-[4-(oxolan-3-ylmethoxy)-3-(trifluoromethyl)phenyl]-1H-pyrimidin-6-one	1075890: Competitive reversible inhibition of C-terminally FLAG-tagged human xanthine oxidase (amino acid 1 to 1333) expressed in baculovirus system after 15 mins by spectrophotometry	ic50	0.0063	uM
methyl 7-bromo-5-methyl-1H-indole-2-carboxylate	2004187: Binding affinity to XO (unknown origin) assessed as inhibition constant	ki	0.0076	uM
4-[5-cyano-3-(trifluoromethyl)-1-benzofuran-7-yl]-2-hydroxybenzoic acid	2121182: Inhibition of xanthine oxidase (unknown origin) by absorbance based assay	ic50	0.0080	uM
methyl 5-(methanesulfonamidomethyl)-7-nitro-1H-indole-2-carboxylate	2004187: Binding affinity to XO (unknown origin) assessed as inhibition constant	ki	0.0080	uM
methyl 7-nitro-5-phenoxy-1H-indole-2-carboxylate	2004187: Binding affinity to XO (unknown origin) assessed as inhibition constant	ki	0.0080	uM
2-hexylsulfanyl-1,7-dihydropurin-6-one	219741: Inhibitory activity against Xanthine Oxidase	ki	0.0098	uM
(2E,6E)-2-[(3,5-dimethoxyphenyl)methylidene]-6-[(4-methylsulfonylphenyl)methylidene]cyclohexan-1-one	1330574: Inhibition of xanthine oxidase (unknown origin) assessed as reduction in uric acid formation preincubated for 5 mins followed by addition of xanthine substrate measured every minute up to 8 mins	ic50	0.0108	uM
4-(5-cyano-1H-indol-7-yl)-2-hydroxybenzoic acid	2121182: Inhibition of xanthine oxidase (unknown origin) by absorbance based assay	ic50	0.0110	uM
4-[5-(4-chloroanilino)-3-pyridinyl]-2-hydroxybenzoic acid	2076338: Inhibition of XOR (unknown origin) using xanthine as substrate measured for 10 mins by spectrophotometry	ic50	0.0130	uM
4-[5-(4-fluoroanilino)-3-pyridinyl]-2-hydroxybenzoic acid	2076338: Inhibition of XOR (unknown origin) using xanthine as substrate measured for 10 mins by spectrophotometry	ic50	0.0150	uM
2-hydroxy-4-[5-(4-methoxyanilino)-3-pyridinyl]benzoic acid	2076338: Inhibition of XOR (unknown origin) using xanthine as substrate measured for 10 mins by spectrophotometry	ic50	0.0160	uM
4-[5-(3-chloro-4-fluoroanilino)-3-pyridinyl]-2-hydroxybenzoic acid	2076338: Inhibition of XOR (unknown origin) using xanthine as substrate measured for 10 mins by spectrophotometry	ic50	0.0160	uM
(2E,5E)-2-[(3,5-dimethoxyphenyl)methylidene]-5-[(4-methylsulfonylphenyl)methylidene]cyclopentan-1-one	1330574: Inhibition of xanthine oxidase (unknown origin) assessed as reduction in uric acid formation preincubated for 5 mins followed by addition of xanthine substrate measured every minute up to 8 mins	ic50	0.0177	uM
N-(3-cyano-1-propylindol-5-yl)-1H-imidazole-5-carboxamide	2037816: Inhibition of XO (unknown origin)	ic50	0.0180	uM
4-[3-cyano-4-(2-methylpropoxy)phenyl]-2-hydroxybenzoic acid	2121182: Inhibition of xanthine oxidase (unknown origin) by absorbance based assay	ic50	0.0180	uM
(2E,6E)-2-[(3-bromophenyl)methylidene]-6-[(3,5-dimethoxyphenyl)methylidene]cyclohexan-1-one	1330574: Inhibition of xanthine oxidase (unknown origin) assessed as reduction in uric acid formation preincubated for 5 mins followed by addition of xanthine substrate measured every minute up to 8 mins	ic50	0.0189	uM
4-[5-(3,4-dichloroanilino)-3-pyridinyl]-2-hydroxybenzoic acid	2076338: Inhibition of XOR (unknown origin) using xanthine as substrate measured for 10 mins by spectrophotometry	ic50	0.0190	uM
2-amino-4-[4-(2,2-dimethylpropoxy)-3-(trifluoromethoxy)phenyl]-6-oxo-1H-pyrimidine-5-carbonitrile	1075893: Inhibition of C-terminally FLAG-tagged human xanthine oxidase (amino acid 1 to 1333) expressed in baculovirus system after 15 mins by spectrophotometry	ic50	0.0199	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Caffeine	affects metabolic processing	5
Tobacco Smoke Pollution	affects expression, decreases expression, increases expression	5
sodium arsenite	decreases expression, decreases methylation, increases expression	3
Benzo(a)pyrene	affects methylation, decreases expression	3
Xanthine	increases activity, affects cotreatment, decreases reaction, increases abundance, increases secretion (+1 more)	3
ochratoxin A	decreases expression, increases expression	2
(+)-JQ1 compound	decreases expression, increases expression	2
Acetaldehyde	increases expression, affects binding, affects cotreatment, affects metabolic processing, increases reaction	2
Acetaminophen	decreases expression	2
Arsenic	affects methylation, increases abundance, increases expression	2
Estradiol	increases expression, affects cotreatment	2
Nickel	increases expression	2
Oxygen	affects cotreatment, decreases activity, affects metabolic processing, affects reaction, increases activity (+3 more)	2
Superoxides	affects cotreatment, decreases reaction, increases abundance, increases secretion, increases chemical synthesis	2
Tetrachlorodibenzodioxin	increases expression, affects activity, affects cotreatment, decreases activity, increases activity	2
Cyclosporine	affects expression, increases expression	2
Aflatoxin B1	affects expression, decreases expression, decreases methylation	2
Cadmium Chloride	decreases expression, increases expression	2
Hypoxanthine	affects abundance, affects metabolic processing, affects reaction, increases abundance, affects cotreatment (+1 more)	2
aristolochic acid I	increases expression	1
taxifolin	decreases reaction, increases chemical synthesis	1
methyleugenol	decreases expression	1
2-nitroanisole	increases reduction	1
propionaldehyde	increases expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
senkirkine	decreases expression	1
sodium arsenate	increases abundance, increases expression	1
palytoxin	increases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
trichostatin A	decreases expression	1

ChEMBL screening assays

184 unique, capped per target: 184 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1006074	Binding	Inhibition of xanthine oxidase	Structural revision of aspernigrin A, reisolated from Cladosporium herbarum IFB-E002. — J Nat Prod

Cellosaurus cell lines

7 cell lines: 4 cancer cell line, 3 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A7Y1	SEES3-1V human XDH, clone1	Embryonic stem cell	Male
CVCL_A7Y2	SEES3-1V human XDH, clone2	Embryonic stem cell	Male
CVCL_A7Y3	SEES3-1V human XDH, clone3	Embryonic stem cell	Male
CVCL_D1ZM	Abcam A-549 XDH KO	Cancer cell line	Male
CVCL_D2DN	Abcam HCT 116 XDH KO	Cancer cell line	Male
CVCL_D2PG	Abcam THP-1 XDH KO	Cancer cell line	Male
CVCL_E0T5	Ubigene HeLa XDH KO	Cancer cell line	Female

Clinical trials (associated diseases)

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