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): 1,060 total — 22 pathogenic, 33 likely-pathogenic (top 3% of genes corpus-wide)
• GTEx eGene: eQTL in 16 tissues, sQTL in 1 (q < 0.05)
• Drug target: yes — 5 curated mechanism-of-action drugs; 16 molecules with ChEMBL bioactivity (top 2% of genes corpus-wide)
• Approved drugs (ChEMBL mechanism of action): 3 — Allopurinol, Bendazac, Febuxostat
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.99 (unconstrained)
• MANE Select transcript: NM_000379
• Interaction hub: 1,906 STRING partners (top 8% of genes corpus-wide)

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: 15 — 11 protein_coding, 2 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

MANE Select: ENST00000379416

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 3: 1, TSL 5: 1

ENST00000379416, ENST00000476043, ENST00000491727, ENST00000879520, ENST00000879521, ENST00000879522, ENST00000879523, ENST00000879524, ENST00000879525, ENST00000879526, ENST00000996293, ENST00001108539, ENST00001108540, ENST00001108541, ENST00001138579

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.

Highest expression (Bgee): jejunal mucosa, ileal mucosa, palpebral conjunctiva, colonic mucosa, mucosa of sigmoid colon.

Genetic regulation across tissues (GTEx eQTL / sQTL)

XDH is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 16 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

17 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells Cultured fibroblasts	eqtl	1.8e-26	+1.01	2:31385052:G:A
Esophagus Mucosa	eqtl	6.2e-20	-0.40	2:31429941:A:G
Thyroid	eqtl	8.5e-14	-0.46	2:31495165:A:G
Brain Cerebellum	eqtl	2.4e-06	-0.43	2:31396693:A:G
Pancreas	eqtl	7.2e-05	+1.21	2:31367232:A:G
Skin Not Sun Exposed Suprapubic	eqtl	8.4e-05	-0.27	2:31504863:G:A
Prostate	eqtl	1.5e-04	-0.54	2:31517692:C:T
Muscle Skeletal	eqtl	2.0e-04	+0.68	2:31385052:G:A
Testis	eqtl	2.4e-03	+0.38	2:31360882:T:G
Adipose Visceral Omentum	eqtl	9.1e-03	-0.25	2:31399938:G:A
Vagina	eqtl	1.0e-02	+0.94	2:31339110:C:T
Pituitary	eqtl	1.2e-02	-1.05	2:31203367:A:AGAT
Esophagus Mucosa	sqtl	1.4e-02	-0.33	2:31367919:C:G
Skin Sun Exposed Lower leg	eqtl	1.9e-02	-0.17	2:31396693:A:G
Breast Mammary Tissue	eqtl	2.4e-02	-0.16	2:31433730:A:G
Brain Cerebellar Hemisphere	eqtl	2.5e-02	-0.47	2:32323542:A:G
Minor Salivary Gland	eqtl	4.1e-02	+0.46	2:31378675:TG:T

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

showing 100 of 273 tissues 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
tibialis anterior	UBERON:0001385	72.98	silver quality
lower esophagus mucosa	UBERON:0035834	72.79	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	72.01	gold quality
oral cavity	UBERON:0000167	71.81	gold quality
sperm	CL:0000019	71.60	gold quality
vermiform appendix	UBERON:0001154	70.94	gold quality
transverse colon	UBERON:0001157	70.80	gold quality
tongue squamous epithelium	UBERON:0006919	70.51	gold quality
tonsil	UBERON:0002372	70.33	gold quality
pancreatic ductal cell	CL:0002079	70.26	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	70.22	gold quality
gall bladder	UBERON:0002110	70.11	gold quality
hair follicle	UBERON:0002073	69.96	gold quality
mucosa of paranasal sinus	UBERON:0005030	69.91	gold quality
epithelium of nasopharynx	UBERON:0001951	69.89	gold quality
islet of Langerhans	UBERON:0000006	68.50	gold quality
intestine	UBERON:0000160	68.05	gold quality
caecum	UBERON:0001153	67.23	gold quality
saliva-secreting gland	UBERON:0001044	66.72	gold quality
decidua	UBERON:0002450	66.47	gold quality
superficial temporal artery	UBERON:0001614	66.22	gold quality
quadriceps femoris	UBERON:0001377	66.15	gold quality
mucosa of urinary bladder	UBERON:0001259	66.05	gold quality
minor salivary gland	UBERON:0001830	65.82	gold quality
epithelium of mammary gland	UBERON:0003244	65.59	gold quality
buccal mucosa cell	CL:0002336	65.58	gold quality
mammary duct	UBERON:0001765	65.49	gold quality
mouth mucosa	UBERON:0003729	65.46	gold quality
vastus lateralis	UBERON:0001379	65.29	gold quality
upper arm skin	UBERON:0004263	64.96	gold quality
mammary gland	UBERON:0001911	64.84	gold quality
amniotic fluid	UBERON:0000173	64.57	gold quality
thoracic mammary gland	UBERON:0005200	64.55	gold quality
large intestine	UBERON:0000059	64.39	gold quality
cervix squamous epithelium	UBERON:0006922	64.13	gold quality
placenta	UBERON:0001987	63.84	gold quality
colon	UBERON:0001155	63.27	gold quality
endometrium	UBERON:0001295	62.82	gold quality
mammalian vulva	UBERON:0000997	62.56	gold quality
upper leg skin	UBERON:0004262	62.45	gold quality
cardiac muscle of right atrium	UBERON:0003379	62.36	gold quality
CA1 field of hippocampus	UBERON:0003881	61.96	gold quality
urinary bladder	UBERON:0001255	61.86	gold quality
left ventricle myocardium	UBERON:0006566	61.58	gold quality
cervix epithelium	UBERON:0004801	61.55	gold quality
triceps brachii	UBERON:0001509	61.34	gold quality
gluteal muscle	UBERON:0002000	61.30	gold quality
thymus	UBERON:0002370	60.88	gold quality
substantia nigra pars reticulata	UBERON:0001966	60.47	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	60.40	gold quality
caput epididymis	UBERON:0004358	60.22	silver quality
skin of leg	UBERON:0001511	59.84	gold quality
nephron tubule	UBERON:0001231	59.58	gold quality
lateral globus pallidus	UBERON:0002476	59.49	gold quality
myocardium	UBERON:0002349	59.43	gold quality
muscle tissue	UBERON:0002385	59.42	gold quality
trachea	UBERON:0003126	59.39	silver quality
adenohypophysis	UBERON:0002196	59.31	gold quality
metanephric glomerulus	UBERON:0004736	58.90	gold quality
zone of skin	UBERON:0000014	58.78	gold quality
kidney epithelium	UBERON:0004819	58.40	gold quality
renal glomerulus	UBERON:0000074	58.18	gold quality
germinal epithelium of ovary	UBERON:0001304	58.12	gold quality
pituitary gland	UBERON:0000007	58.10	gold quality
biceps brachii	UBERON:0001507	57.75	gold quality
secondary oocyte	CL:0000655	57.66	gold quality
visceral pleura	UBERON:0002401	57.66	gold quality
pancreas	UBERON:0001264	57.58	gold quality
vagina	UBERON:0000996	57.40	gold quality
cranial nerve II	UBERON:0000941	57.35	silver 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

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 146 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Liver	tissue	253.4	high
Cervix	tissue	161.0	high
Thyroid gland	tissue	99.8	high
Prostate	tissue	85.0	high
Liver	tissue	64.0	not detected
Kidney	tissue	56.3	medium
Breast	tissue	53.1	low
Small intestine	tissue	46.6	low
Duodenum	tissue	42.3	low
Breast	tissue	39.2	not detected
Seminal vesicle	tissue	29.1	high
Caudate putamen	tissue	18.4
Frontal cortex	tissue	18.0
Corpus callosum	tissue	16.8
Skin 1	tissue	16.7	not detected
Postcentral gyrus	tissue	16.5
Hippocampus	tissue	13.4	not detected
Nucleus accumbens	tissue	12.5
Locus coeruleus	tissue	12.5
Adrenal gland	tissue	11.8	low
Urinary bladder	tissue	11.0	medium
Spinal cord	tissue	10.8
Choroid plexus	tissue	10.6
Colon	tissue	10.4	not detected
Testis	tissue	9.7	low
Medulla oblongata	tissue	9.3
Midbrain	tissue	8.9
Rectum	tissue	8.9	not detected
Gallbladder	tissue	8.8	medium
Substantia nigra	tissue	8.4
Rectum	tissue	8.0
Small intestine	tissue	8.0	medium
Duodenum	tissue	7.9	low
Fallopian tube	tissue	7.7	high
Hippocampal formation	tissue	7.6
Superior colliculi	tissue	7.5
Stomach 1	tissue	7.3	medium
Thalamus	tissue	7.3
Epididymis	tissue	6.8	not detected
Esophagus	tissue	6.5	not detected
Pons	tissue	6.4
Putamen	tissue	6.1
Colon	tissue	5.7	low
Ventral forebrain	tissue	5.5
Periaqueductal gray	tissue	5.5
Pancreas	tissue	5.4	low
Heart muscle	tissue	5.3	not detected
Hypothalamus	tissue	5.0
Septum	tissue	5.0
Cerebral cortex	tissue	4.7	not detected
Somatosensory cortex	tissue	4.7
Appendix	tissue	4.5	not detected
Retina	tissue	4.4
Salivary gland	tissue	4.4	low
Retrosplenial cortex	tissue	4.2
Occipital cortex	tissue	4.2
Gallbladder	tissue	4.2	not detected
Vagina	tissue	4.1	not detected
Parathyroid gland	tissue	4.1	not detected
Motor cortex	tissue	4.0

Brain sub-regions (HPA Brain Atlas): detected in 379; highest nTPM — Vermis (20.8), Flocculonodular lobe (19.9), Cerebellar cortex (17.9), Somatomor cortex, precentral gyrus (white matter) (17.6), Dorsal funiculus (white matter) (17.3).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting XDH by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 65 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 5.93e-40, LOEUF 0.99, missense Z -0.795 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000379416 — one region, missense o/e 1.10.

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:98973) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 48 distinct phenotype terms.

Mouse phenotype (MP)	Records
premature death	3
dilated renal tubule	3
decreased body size	2
abnormal kidney morphology	2
abnormal renal tubule morphology	2
small kidney	2
renal interstitial fibrosis	2
oxidative stress	2
pale kidney	2
increased blood urea nitrogen level	2
slow postnatal weight gain	2
decreased blood uric acid level	2
abnormal renal tubule epithelium morphology	2
increased circulating calcium level	1
abnormal kidney cortex morphology	1
abnormal kidney development	1
abnormal skeletal muscle morphology	1
abnormal lung morphology	1
decreased body weight	1
persistence of hyaloid vascular system	1
cataract	1
abnormal lactation	1
male infertility	1
abnormal skin morphology	1
abnormal lipid homeostasis	1

+23 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Escherichia coli K-12	Q46801	99.4%	Diamond
Escherichia coli O157:H7	Q8X6C4	99.4%	Diamond
Macaca fascicularis	Q5FB27	95.6%	Diamond
Oryza sativa Japonica Group	Q852M1	95.3%	Diamond
Drosophila pseudoobscura pseudoobscura	P22811	94.7%	Diamond
Drosophila subobscura	P91711	94.7%	Diamond
Arabidopsis thaliana	F4JLI5	93.2%	Diamond
Felis catus	Q9MYW6	90.5%	Diamond
Bos taurus	P80457	89.6%	Diamond
Oryctolagus cuniculus	P80456	84.0%	Diamond
Zea mays	O23888	83.9%	Diamond
Cavia porcellus	H9TB17	77.7%	Diamond
Calliphora vicina	P08793	76.4%	Diamond
Gallus gallus	P47990	71.8%	Diamond
Hydrogenophaga pseudoflava	P19915	68.6%	Diamond
Afipia carboxidovorans OM5	P19921	68.6%	Diamond
Sulfolobus acidocaldarius DSM 639	Q4J6M5	58.3%	Diamond
Paenarthrobacter nicotinovorans	Q59128	54.5%	Diamond
Brevundimonas diminuta	Q51697	54.4%	Diamond
Pseudomonas putida KT2440	Q88FX9	54.4%	Diamond
Pseudomonas sp. CBB1	D7REY5	54.3%	Diamond
Aspergillus nidulans FGSC A4	Q12553	53.5%	Diamond
Blastobotrys adeninivorans	R4ZGN4	53.4%	Diamond
Thauera aromatica	O33818	50.4%	Diamond
Eubacterium barkeri	Q0QLF3	48.6%	Diamond
Bacillus subtilis subsp. subtilis str. 168	O32143	48.2%	Diamond
Dictyostelium discoideum	Q54FB7	47.6%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
LINC01946	ncRNA	105374449
SRD5A2	protein-coding	6716
EHD3	protein-coding	30845
CAPN14	protein-coding	440854

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)

• 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 (176 total): helix 61, 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 by resolution:

PDB	Title	Method	Resolution (Å)
2E1Q	Crystal Structure of Human Xanthine Oxidoreductase mutant, Glu803Val	X-RAY DIFFRACTION	2.6
2CKJ	Human milk xanthine oxidoreductase	X-RAY DIFFRACTION	3.59

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Oxidoreductases, Metabolic proteins, Predicted intracellular proteins, Plasma proteins, Disease related genes, Potential drug targets, Human disease related genes, Congenital disorders of metabolism, Congenital disorders of carbohydrate metabolism

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol; acrosome; equatorial segment

Antibody reliability (HPA): IH enhanced · IF approved

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)

Position	Role
1262	proton acceptor

Ligand- & substrate-binding residues (22)

Position	Role
148	[2Fe-2S] cluster
150	[2Fe-2S] cluster
257–264	FAD
337	FAD
347–351	FAD
360	FAD
404	FAD
422	FAD
768	Mo-molybdopterin
799	Mo-molybdopterin
803	substrate
881	substrate
913	Mo-molybdopterin
915	substrate
1011	substrate
1080	Mo-molybdopterin
43	[2Fe-2S] cluster
48	[2Fe-2S] cluster
51	[2Fe-2S] cluster
73	[2Fe-2S] cluster
113	[2Fe-2S] cluster
116	[2Fe-2S] cluster

Disulfide bonds (2)

Type	Positions
In oxidase form	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 aldehydes.
881	abolishes xanthine oxidase activity.

Function

Pathways and Gene Ontology

Reactome pathways

3 curated (TAS) of 9; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

9 pathways:

ID	Pathway	Evidence
R-HSA-9748787	Azathioprine ADME	curated
R-HSA-8851680	Butyrophilin (BTN) family interactions	curated
R-HSA-74259	Purine catabolism	curated
R-HSA-1280218	Adaptive Immune System	—
R-HSA-9748784	Drug ADME	—
R-HSA-168256	Immune System	—
R-HSA-1430728	Metabolism	—
R-HSA-15869	Metabolism of nucleotides	—
R-HSA-8956319	Nucleotide catabolism	—

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 (14): 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), hypoxanthine catabolic process (GO:0009114), xanthine catabolic process (GO:0009115), 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 (5): peroxisome (GO:0005777), cytosol (GO:0005829), sarcoplasmic reticulum (GO:0016529), extracellular region (GO:0005576), cytoplasm (GO:0005737)

Reactome top-level categories

6 top-level categories:

Category	Pathways
Nucleotide catabolism	1
Adaptive Immune System	1
Drug ADME	1
Immune System	1
Metabolism	1
Metabolism of nucleotides	1

GO top-level categories

40 GO namespaces:

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
hypoxanthine metabolic process	1
xanthine metabolic process	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
cation binding	1
metal cluster binding	1
microbody	1
cytoplasm	1
endoplasmic reticulum	1
sarcoplasm	1
intracellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 15 of 35 annotations. The rest are phylogenetic / computational / electronic (IEA).

15 experimentally-supported GO terms:

GO term	NS	Evidence
AMP catabolic process	BP	direct assay
IMP catabolic process	BP	direct assay
allantoin metabolic process	BP	direct assay
deoxyinosine catabolic process	BP	direct assay
hypoxanthine catabolic process	BP	direct assay
inosine catabolic process	BP	direct assay
xanthine catabolic process	BP	direct assay
cytosol	CC	direct assay
2 iron, 2 sulfur cluster binding	MF	direct assay
flavin adenine dinucleotide binding	MF	direct assay
hypoxanthine dehydrogenase activity	MF	direct assay
molybdopterin cofactor binding	MF	direct assay
protein homodimerization activity	MF	physical interaction
xanthine dehydrogenase activity	MF	direct assay
xanthine oxidase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,906 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
XDH	F5H3C5	F5H3C5	856
XDH	BTN2A2	Q8WVV5	826
XDH	NOS3	P29474	821
XDH	BTNL9	Q6UXG8	820
XDH	BTN1A1	Q13410	817
XDH	BTN2A1	P78408	817
XDH	NOS1	P29475	809
XDH	GPX6	P59796	780
XDH	GPX7	Q96SL4	780
XDH	GPX5	O75715	780
XDH	GPX8	Q8TED1	780
XDH	GPX2	P18283	778
XDH	GPX3	P22352	778
XDH	SLC22A12	Q96S37	741
XDH	CYBB	P04839	738

IntAct

Human interaction partners of XDH in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

2 partners by confidence:

Partner	Interaction type	MIscore	Records
GRIP1	physical association	0.560	3
CCDC110	physical association	0.400	1

BioGRID (23 interactions; top human partners by supporting records): USP15 (Affinity Capture-MS; 3 records), PGD (Cross-Linking-MS (XL-MS); 2 records), AMBRA1 (Affinity Capture-MS), C12orf65 (Affinity Capture-MS), CBR1 (Co-fractionation), CCDC110 (Affinity Capture-MS), CPVL (Affinity Capture-MS), GOT1 (Affinity Capture-MS), GRIP1 (Two-hybrid), KIF14 (Affinity Capture-MS), KIF23 (Affinity Capture-MS), MYC (Affinity Capture-MS), NIPBL (Cross-Linking-MS (XL-MS)), PARP1 (Proximity Label-MS), SPPL3 (Positive Genetic)

SIGNOR signaling

1 signaling interactions:

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

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
★ Xanthine oxidase	1	XDH

Disease & clinical

Genetic variants

Variant evidence for XDH: 1,060 ClinVar records (55 pathogenic / likely pathogenic). Per-variant detail is on Sugi Variant.

ClinVar

1,060 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	22
Likely pathogenic	33
Uncertain significance	535
Likely benign	256
Benign	109

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 55 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
641114	NM_000379.4(XDH):c.140dup (p.Cys48fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	9
1457782	NM_000379.4(XDH):c.641del (p.Pro214fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
1369362	NM_000379.4(XDH):c.2164A>T (p.Lys722Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
335758	NM_000379.4(XDH):c.3847C>T (p.Arg1283Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
579351	NM_000379.4(XDH):c.2274del (p.Glu760fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
566280	NM_000379.4(XDH):c.1602+1G>A	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
2145159	NM_000379.4(XDH):c.565-1G>A	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
3586548	NM_000379.4(XDH):c.442_443del (p.Cys148fs)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
3586556	NM_000379.4(XDH):c.169A>T (p.Lys57Ter)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
570826	NM_000379.4(XDH):c.3507del (p.Gly1170fs)	Pathogenic	criteria provided, single submitter	1
1027672	NM_000379.4(XDH):c.2751del (p.Gln919fs)	Pathogenic	criteria provided, single submitter	1
1075330	NM_000379.4(XDH):c.1343_1350del (p.Glu448fs)	Pathogenic	criteria provided, single submitter	1
1451493	NM_000379.4(XDH):c.598G>T (p.Glu200Ter)	Pathogenic	criteria provided, single submitter	1
2015541	NM_000379.4(XDH):c.3711del (p.Ile1238fs)	Pathogenic	criteria provided, single submitter	1
2073968	NM_000379.4(XDH):c.1664dup (p.Ala556fs)	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore XDH’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

AlphaMissense

3,156 missense substitutions predicted likely pathogenic (of 8,762 scored), across 845 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M122	9	0.877	0.989
M1039	9	0.845	0.993
D1192	8	0.988	0.996
D596	8	0.982	0.995
D833	8	0.978	0.996
D1182	8	0.973	0.992
D360	8	0.972	0.986
F799	8	0.969	1.000
D1085	8	0.967	0.991
D873	8	0.956	0.989
F915	8	0.947	0.998
H841	8	0.925	0.991
F212	8	0.919	0.989
D1312	8	0.918	0.975
F912	8	0.917	0.984
H580	8	0.899	0.990
N351	8	0.896	0.996
H1034	8	0.893	0.983
N146	8	0.888	0.995
F337	8	0.886	0.986

HPA cancer prognostics

RNA cancer specificity: Group enriched (Liver Hepatocellular Carcinoma, Prostate Adenocarcinoma, Thyroid Carcinoma)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Lung Squamous Cell Carcinoma (TCGA)	favorable	4.76e-05
Liver Hepatocellular Carcinoma (validation)	favorable	0.000804

Disease associations

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

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
xanthinuria type I	Strong	Autosomal recessive	4

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (8 panels, 8 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

8 panels:

Panel	Rating
Hypotonic infant	green
Leukodystrophy, childhood onset	green
Likely inborn error of metabolism	green
Nephrocalcinosis or nephrolithiasis	green
Paediatric disorders	green
Undiagnosed metabolic disorders	green
Unexplained death in infancy and sudden unexplained death in childhood	green
Unexplained young onset end-stage renal disease	green

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

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

MeSH disease descriptors

2 disease descriptors:

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)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the XDH protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

5 curated-mechanism drugs:

Drug	Modality	Max phase
ALLOPURINOL	Small molecule	4
BENDAZAC	Small molecule	4
FEBUXOSTAT	Small molecule	4
OXYPURINOL	Small molecule	2
TOPIROXOSTAT	Small molecule	2

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,363,714 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

16 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL1467	ALLOPURINOL	4	85,872
CHEMBL1164729	FEBUXOSTAT	4	3,580
CHEMBL6	INDOMETHACIN	4	157,305
CHEMBL727	THIOGUANINE	4	297,677
CHEMBL226345	ADENINE	3	547,828
CHEMBL50	QUERCETIN	3	75,572
CHEMBL226335	RUTIN	3	58,533
CHEMBL859	OXYPURINOL	2	9,542
CHEMBL1078685	TOPIROXOSTAT	2	568
CHEMBL8260	BAICALEIN	2	8,718
CHEMBL37387	BROPIRIMINE	2	14,289
CHEMBL31574	FISETIN	2	7,874
CHEMBL44	GENISTEIN	2	44,589
CHEMBL250450	ISOQUERCETIN	2	1,676
CHEMBL151	LUTEOLIN	2	23,845
CHEMBL150	KAEMPFEROL	1	26,246

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Nucleoside synthesis and metabolism

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)

667 measured of 825 human assays (900 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
2-[2-(dimethylamino)ethylsulfanyl]-4,6-dioxo-N-[4-(2H-triazol-4-yl)phenyl]-1H-pyrimidine-5-carboxamide	IC50	0.015 nM	US-11020397: Compounds and their use for reducing uric acid levels
N-[2-chloro-4-(2H-triazol-4-yl)phenyl]-2-methylsulfanyl-4,6-dioxo-1H-pyrimidine-5-carboxamide	IC50	0.029 nM	US-11020397: Compounds and their use for reducing uric acid levels
2-methylsulfanyl-4,6-dioxo-N-[4-(2H-triazol-4-yl)-2-(trifluoromethyl)phenyl]-1H-pyrimidine-5-carboxamide	IC50	0.064 nM	US-11020397: Compounds and their use for reducing uric acid levels
CHEMBL5403463	IC50	0.07 nM
CHEMBL5421553	IC50	0.09 nM
2-methylsulfanyl-4,6-dioxo-N-[2-(2H-triazol-4-yl)-5-(trifluoromethyl)quinolin-6-yl]-1H-pyrimidine-5-carboxamide	IC50	0.22 nM	US-11020397: Compounds and their use for reducing uric acid levels
2-methylsulfanyl-4,6-dioxo-N-[6-(2H-triazol-4-yl)pyridazin-3-yl]-1H-pyrimidine-5-carboxamide	IC50	0.315 nM	US-11020397: Compounds and their use for reducing uric acid levels
N-[2,6-dichloro-4-(2H-triazol-4-yl)phenyl]-2-methylsulfanyl-4,6-dioxo-1H-pyrimidine-5-carboxamide	IC50	0.33 nM	US-11020397: Compounds and their use for reducing uric acid levels
CHEMBL3127130	IC50	0.501 nM
N-[2,5-difluoro-4-(2H-triazol-4-yl)phenyl]-2-methylsulfanyl-4,6-dioxo-1H-pyrimidine-5-carboxamide	IC50	0.519 nM	US-11020397: Compounds and their use for reducing uric acid levels
N-[3-fluoro-5-(2H-triazol-4-yl)-2-pyridinyl]-2-methylsulfanyl-4,6-dioxo-1H-pyrimidine-5-carboxamide	IC50	0.52 nM	US-11020397: Compounds and their use for reducing uric acid levels
N-[3-chloro-4-(2H-triazol-4-yl)phenyl]-2-methylsulfanyl-4,6-dioxo-1H-pyrimidine-5-carboxamide	IC50	0.53 nM	US-11020397: Compounds and their use for reducing uric acid levels
CHEMBL3127135	IC50	0.631 nM
CHEMBL3127117	IC50	1 nM
CHEMBL5436777	IC50	1 nM
2-ethylimino-4,6-dioxo-N-[4-(2H-triazol-4-yl)phenyl]-1,3-diazinane-5-carboxamide	IC50	1.02 nM	US-11020397: Compounds and their use for reducing uric acid levels
CHEMBL5410457	IC50	1.1 nM
2-(cyclopropylmethylsulfanyl)-4,6-dioxo-N-[4-(2H-triazol-4-yl)phenyl]-1H-pyrimidine-5-carboxamide	IC50	1.14 nM	US-11020397: Compounds and their use for reducing uric acid levels
CHEMBL3127137	IC50	1.3 nM
CHEMBL3127134	IC50	1.3 nM
CHEMBL5400293	KI	1.5 nM
CHEMBL3127114	IC50	1.6 nM
CHEMBL3127131	IC50	1.6 nM
CHEMBL5433965	KI	1.7 nM
2-methoxy-N-[4-(5-methyl-2H-triazol-4-yl)phenyl]-4,6-dioxo-1H-pyrimidine-5-carboxamide	IC50	1.73 nM	US-11020397: Compounds and their use for reducing uric acid levels
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-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-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-[ethyl(methyl)amino]-4,6-dioxo-N-[4-(2H-triazol-4-yl)phenyl]-1H-pyrimidine-5-carboxamide	IC50	2.86 nM	US-11020397: Compounds and their use for reducing uric acid levels
2-(3-CYANO-4-ISOBUTOXY-PHENYL)-4-METHYL-5-THIAZOLE-CARBOXYLIC ACID	IC50	2.9 nM
2-methylsulfanyl-N-[4-(5-methyl-2H-triazol-4-yl)phenyl]-4,6-dioxo-1H-pyrimidine-5-carboxamide	IC50	2.92 nM	US-11020397: Compounds and their use for reducing uric acid levels
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
CHEMBL3402699	IC50	3 nM
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
CHEMBL5406281	IC50	3.1 nM
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-(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
CHEMBL5437185	IC50	3.5 nM
4-hydroxy-6-oxo-2-propan-2-ylsulfanyl-N-[4-(1H-1,2,4-triazol-5-yl)phenyl]-1,3-diazinane-5-carboxamide	IC50	3.57 nM	US-11020397: Compounds and their use for reducing uric acid levels

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

491 with measured affinity, of 1229 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
4-hydroxy-3-[(E)-3-[4-(methylamino)phenyl]-3-oxoprop-1-enyl]benzoic acid	2255697: Competitive inhibition of xanthine oxidase (unknown origin) assessed as inhibition constant using xanthine as substrate by Lineweaver-Burk plot analysis	ki	0.0001	uM
3-[(E)-3-(2,3-dihydro-1H-indol-5-yl)-3-oxoprop-1-enyl]-4-hydroxybenzoic acid	2255697: Competitive inhibition of xanthine oxidase (unknown origin) assessed as inhibition constant using xanthine as substrate by Lineweaver-Burk plot analysis	ki	0.0001	uM
3-[(E)-3-(4-ethylphenyl)-3-oxoprop-1-enyl]-4-hydroxybenzoic acid	2255697: Competitive inhibition of xanthine oxidase (unknown origin) assessed as inhibition constant using xanthine as substrate by Lineweaver-Burk plot analysis	ki	0.0003	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-(3-ethyl-2-oxo-1,3-benzothiazol-6-yl)-2-hydroxybenzoic acid	2231219: Inhibition of Xanthine oxidase (unknown origin)	ic50	0.0120	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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Caffeine	affects metabolic processing	5
Tobacco Smoke Pollution	increases expression, affects expression, decreases expression	5
sodium arsenite	decreases expression, decreases methylation, increases expression	3
Benzo(a)pyrene	affects methylation, decreases expression	3
Xanthine	increases secretion, decreases activity, increases activity, affects cotreatment, decreases reaction (+1 more)	3
ochratoxin A	decreases expression, increases expression	2
(+)-JQ1 compound	decreases expression, increases expression	2
Acetaldehyde	affects metabolic processing, increases reaction, increases expression, affects binding, affects cotreatment	2
Acetaminophen	decreases expression	2
Arsenic	affects methylation, increases abundance, increases expression	2
Estradiol	affects cotreatment, increases expression	2
Nickel	increases expression	2
Oxygen	affects cotreatment, decreases activity, affects metabolic processing, affects reaction, increases abundance (+3 more)	2
Superoxides	affects cotreatment, decreases reaction, increases abundance, increases secretion, increases chemical synthesis	2
Tetrachlorodibenzodioxin	affects cotreatment, decreases activity, increases activity, increases expression, affects 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 metabolic processing, affects reaction, increases abundance, affects cotreatment, increases secretion (+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)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for XDH across ~30M SureChEMBL compounds — explore on Sugi Predict.