Gout

Summary

Gout (MONDO:0005393) is a disease with 75 cohort genes (1,420 GWAS associations across 123 studies) and 285 clinical trials. The dominant Reactome pathway is Neuronal System (10 cohort genes). Top therapeutic interventions include febuxostat, allopurinol, and colchicine.

At a glance

• Cohort genes: 75
• GWAS associations: 1,420
• ClinVar variants: 2
• Clinical trials: 285

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	gout
Mondo ID	MONDO:0005393
EFO	EFO:0004274
MeSH	D006073
DOID	DOID:13189
ICD-10-CM	M10
ICD-11	395622227
NCIT	C34650
SNOMED CT	190828008
UMLS	C0018099
MedGen	42280
Is cancer (heuristic)	no

Also known as: chronic gout · gout · gouty arthropathy · tophaceous disease · tophaceous gout

Data availability: 2 ClinVar variants · 1,420 GWAS associations (123 studies) · 1 cell line.

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › metabolic disease › gout

Related subtypes (36): glutaric aciduria, mineral metabolism disease, xanthinuria, chondrocalcinosis, ochronosis disorder, glucose metabolism disease, diabetic kidney disease, xanthoma, diabetic retinopathy, hypertriglyceridemia, lactic acidosis, acquired metabolic disease, lipodystrophy, developmental anomaly of metabolic origin, dopa-responsive dystonia, hypoalphalipoproteinemia, steroid dehydrogenase deficiency-dental anomalies syndrome, inborn errors of metabolism, vitamin B12 deficiency, proteostasis deficiencies, hyperlipidemia, disorder of GPI anchor biosynthesis, bilirubin metabolism disease, hyperlipoproteinemia, carbohydrate metabolism disease, porphyrin metabolism disease, purine metabolism disease, amino acid metabolism disease, pyrimidine metabolism disease, disorder of acid-base balance, disorder of glutamate decarboxylase, tumor lysis syndrome, collagenous sprue, steroid metabolism disease, disorder of organic acid metabolism, skeletal fluorosis

Genetics & variants

GWAS landscape

1,420 GWAS associations across 123 studies. Top hits map to 20 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs2728099	5e-324	PKD2	C	0.45
rs10805346	1e-323	SLC2A9	T	0.33
chr4:88887327	1e-323		A	0.42
chr4:89025241	1e-323		C	0.49
rs2231142	1e-290	ABCG2	?
chr4:9993558	2e-259		C	0.31
rs1359232	1e-204	SLC17A1	A	0.86
chr4:89054667	4e-179		A	0.65
rs4697701	8e-179	SLC2A9	A	0.71
rs12363578	1e-173	SLC22A12	T	0.86
rs1260326	5e-166	GCKR	T	1.17
rs13129697	4e-157	SLC2A9	G	0.52
rs74904971	3e-119	ABCG2	?	0.71
rs45499402	8e-115	ABCG2	C	1.94
chr11:64364866	4e-107		C	0.16
rs2328895	6e-105	SLC17A1	C	0.15
rs4148155	2e-101	ABCG2	G	2.23
rs3733588	1e-92	SLC2A9	G	0.3
rs1171614	2e-90	SLC16A9	T	0.87
rs9441166	8e-89	PDZK1 - CD160	T	1.13
rs11532071	2e-88	KRT8P26 - AP5B1	A	1.13
rs7964492	2e-88	R3HDM2	A	1.15
rs642803	6e-87	OVOL1	T	0.91
chr4:9926967	2e-81		T	0.38
chr4:89044312	9e-78		A	0.6
rs2581817	2e-76	SFMBT1	C	1.11
rs9847710	3e-76	SFMBT1	T	0.91
chr19:49467772	2e-72		G	2
rs9426886	2e-69	TRIM46	A	1.09
chr6:25798932	2e-69		G	0.15

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90129442	Zorina-Lichtenwalter K	2023	15,069	192,253	Genetic risk shared across 24 chronic pain conditions: identification and characterization with genomic structural equation modeling.
GCST90399700	Zhou W	2022	10,425	338,934	Global Biobank Meta-analysis Initiative: Powering genetic discovery across human disease.
GCST90080396	Backman JD	2021	7,961	375,561	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90084382	Backman JD	2021	7,961	375,561	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90239691	Sumpter NA	2022	7,131	325,239	Association of Gout Polygenic Risk Score with Age at Disease Onset and Tophaceous Disease in European and Polynesian Men with Gout.
GCST012338	Sandoval-Plata G	2021	7,049	64,424	Variants in urate transporters, ADH1B, GCKR and MEPE genes associate with transition from asymptomatic hyperuricaemia to gout: results of the first gout versus asymptomatic hyperuricaemia GWAS in Caucasians using data from the UK Biobank.
GCST90038687	Donertas HM	2021	6,810	477,788	Common genetic associations between age-related diseases.
GCST90077877	Backman JD	2021	6,554	325,200	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90081863	Backman JD	2021	6,554	325,200	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90297584	Auwerx C	2024	6,344	231,839	Rare copy-number variants as modulators of common disease susceptibility.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	4
Tier 2: splice/UTR	2
Tier 3: regulatory	0
Tier 4: intronic/intergenic	44

MAF distribution

Bucket	Variants
common (>=0.05)	47
low_freq (0.01-0.05)	2
rare (<0.01)	1
unknown	0

Functional consequences

Consequence	Count
intron_variant	29
unknown	11
missense_variant	3
intergenic_variant	3
stop_gained	1
5_prime_UTR_variant	1
synonymous_variant	1
3_prime_UTR_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs7675964	4	9939810	C>T	0.28	intron_variant	SLC2A9		Tier 4: intronic/intergenic
rs2231142	4	88131171	G>A,C,T	0.11	stop_gained	ABCG2		Tier 1: coding
rs6449137	4	9930855	A>C,T	0.282	intron_variant	SLC2A9		Tier 4: intronic/intergenic
rs2728099	4	88054586	T>C	0.128	intron_variant	PKD2	5e-324	Tier 4: intronic/intergenic
rs10805346	4	9918723	T>A,C	0.426	intron_variant	SLC2A9	1e-323	Tier 4: intronic/intergenic
chr4:88887327				0.104			1e-323	Tier 4: intronic/intergenic
chr4:89025241				0.095			1e-323	Tier 4: intronic/intergenic
chr4:9993558				0.292			2e-259	Tier 4: intronic/intergenic
rs1359232	6	25809488	C>A,T	0.451	intron_variant	SLC17A1	1e-204	Tier 4: intronic/intergenic
chr4:89054667				0.109			4e-179	Tier 4: intronic/intergenic
rs4697701	4	9944471	G>A	0.274	intron_variant	SLC2A9	8e-179	Tier 4: intronic/intergenic
rs12363578	11	64597394	C>A,G,T	0.416	intron_variant	SLC22A12	1e-173	Tier 4: intronic/intergenic
rs1260326	2	27508073	T>A,C,G	0.419	missense_variant	GCKR	5e-166	Tier 1: coding
rs13129697	4	9925343	T>G	0.27	intron_variant	SLC2A9	4e-157	Tier 4: intronic/intergenic
rs74904971	4	88128874	C>A,G	0.05	intron_variant	ABCG2	3e-119	Tier 4: intronic/intergenic
rs45499402	4	88122482	G>A,C,T	0.134	intron_variant	ABCG2	8e-115	Tier 4: intronic/intergenic
chr11:64364866				0.416			4e-107	Tier 4: intronic/intergenic
rs2328895	6	25801855	C>T	0.454	intron_variant	SLC17A1	6e-105	Tier 4: intronic/intergenic
rs4148155	4	88133515	A>C,G,T	0.277	intron_variant	ABCG2	2e-101	Tier 4: intronic/intergenic
rs3733588	4	9995679	G>A,C,T	0.326	intron_variant	SLC2A9	1e-92	Tier 4: intronic/intergenic
rs1171614	10	59709780	T>A,C,G	0.227	5_prime_UTR_variant	SLC16A9	2e-90	Tier 2: splice/UTR
rs9441166	1	145715457	A>G,T	0.476	intergenic_variant	PDZK1 - CD160	8e-89	Tier 4: intronic/intergenic
rs11532071	11	65732727	C>A	0.355	intron_variant	KRT8P26 - AP5B1	2e-88	Tier 4: intronic/intergenic
rs7964492	12	57429802	A>C,T	0.225	intron_variant	R3HDM2	2e-88	Tier 4: intronic/intergenic
rs642803	11	65793149	C>A,T	0.456	intron_variant	OVOL1	6e-87	Tier 4: intronic/intergenic
chr4:9926967				0.273			2e-81	Tier 4: intronic/intergenic
chr4:89044312				0.148			9e-78	Tier 4: intronic/intergenic
rs2581817	3	53037781	G>C	0.419	intron_variant	SFMBT1	2e-76	Tier 4: intronic/intergenic
rs9847710	3	53028645	T>A,C	0.417	intron_variant	SFMBT1	3e-76	Tier 4: intronic/intergenic
chr19:49467772				0.006			2e-72	Tier 4: intronic/intergenic

ClinVar germline variants

2 retrieved; paginated sample, class counts are floors:

2 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1057	NM_018122.5(DARS2):c.228-21_228-20delinsC	DARS2	Pathogenic	criteria provided, multiple submitters, no conflicts
1062	NM_018122.5(DARS2):c.492+2T>C	DARS2	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 29 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RREB1	Orphanet:567	22q11.2 deletion syndrome
RUNX2	Orphanet:1452	Cleidocranial dysplasia
RUNX2	Orphanet:2504	Metaphyseal dysplasia-maxillary hypoplasia-brachydacty syndrome
DST	Orphanet:314381	Hereditary sensory and autonomic neuropathy type 6
DST	Orphanet:412181	Epidermolysis bullosa simplex due to BP230 deficiency
BRSK2	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability
TBL2	Orphanet:904	Williams syndrome
VDR	Orphanet:93160	Hypocalcemic vitamin D-resistant rickets
WDR1	Orphanet:652522	Periodic fever-immunodeficiency-thrombocytopenia syndrome
SLC2A9	Orphanet:94088	Hereditary renal hypouricemia
PRDM8	Orphanet:324290	PRDM8-related progressive myoclonus epilepsy
NTNG2	Orphanet:528084	Non-specific syndromic intellectual disability
BCAS3	Orphanet:697067	Global developmental delay-intellectual disability-microcephaly-short stature-brain iron accumulation syndrome
SLC22A12	Orphanet:94088	Hereditary renal hypouricemia
CFTR	Orphanet:399805	Male infertility with azoospermia or oligozoospermia due to single gene mutation
CFTR	Orphanet:48	Congenital bilateral absence of vas deferens
CFTR	Orphanet:498359	Aquagenic palmoplantar keratoderma
CFTR	Orphanet:586	Cystic fibrosis
CFTR	Orphanet:60033	Idiopathic bronchiectasis
CFTR	Orphanet:700124	Autosomal recessive hereditary chronic pancreatitis
CUX2	Orphanet:2382	Lennox-Gastaut syndrome
PIBF1	Orphanet:475	Isolated Joubert syndrome
MED27	Orphanet:528084	Non-specific syndromic intellectual disability
SSUH2	Orphanet:99789	Dentin dysplasia type I
DARS2	Orphanet:137898	Leukoencephalopathy with brain stem and spinal cord involvement-high lactate syndrome
JAZF1	Orphanet:213711	Endometrial stromal sarcoma
JAZF1	Orphanet:536	Systemic lupus erythematosus
ABCA1	Orphanet:31150	Tangier disease
ABCA1	Orphanet:425	Apolipoprotein A-I deficiency

Cohort genes → proteins

75 cohort genes, 74 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	74
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
BDKRB2	HGNC:1030	ENSG00000168398	P30411	B2 bradykinin receptor	gwas
RREB1	HGNC:10449	ENSG00000124782	Q92766	Ras-responsive element-binding protein 1	gwas
RUNX2	HGNC:10472	ENSG00000124813	Q13950	Runt-related transcription factor 2	gwas
DST	HGNC:1090	ENSG00000151914	Q03001	Dystonin	gwas
SLC17A1	HGNC:10929	ENSG00000124568	Q14916	Sodium-dependent phosphate transport protein 1	gwas
SLC17A4	HGNC:10932	ENSG00000146039	Q9Y2C5	Probable small intestine urate exporter	gwas
SLC22A1	HGNC:10963	ENSG00000175003	O15245	Solute carrier family 22 member 1	gwas
SLC67A1-AS	HGNC:10965	ENSG00000254827	Q8N1D0	Uncharacterized protein SLC67A1-AS	gwas
SMARCC1	HGNC:11104	ENSG00000173473	Q92922	SWI/SNF complex subunit SMARCC1	gwas
BRSK2	HGNC:11405	ENSG00000174672	Q8IWQ3	Serine/threonine-protein kinase BRSK2	gwas
TACR1	HGNC:11526	ENSG00000115353	P25103	Substance-P receptor	gwas
TBL2	HGNC:11586	ENSG00000106638	Q9Y4P3	Transducin beta-like protein 2	gwas
TPST1	HGNC:12020	ENSG00000169902	O60507	Protein-tyrosine sulfotransferase 1	gwas
VDR	HGNC:12679	ENSG00000111424	P11473	Vitamin D3 receptor	gwas
WDR1	HGNC:12754	ENSG00000071127	O75083	WD repeat-containing protein 1	gwas
EIF3IP1	HGNC:13277	ENSG00000237064		eukaryotic translation initiation factor 3 subunit I pseudogene 1	gwas
MEPE	HGNC:13361	ENSG00000152595	Q9NQ76	Matrix extracellular phosphoglycoprotein	gwas
SLC2A9	HGNC:13446	ENSG00000109667	Q9NRM0	Solute carrier family 2, facilitated glucose transporter member 9	gwas
SLC38A1	HGNC:13447	ENSG00000111371	Q9H2H9	Sodium-coupled neutral amino acid symporter 1	gwas
PRDM8	HGNC:13993	ENSG00000152784	Q9NQV8	PR domain zinc finger protein 8	gwas
ATP1A4	HGNC:14073	ENSG00000132681	Q13733	Sodium/potassium-transporting ATPase subunit alpha-4	gwas
NTNG2	HGNC:14288	ENSG00000196358	Q96CW9	Netrin-G2	gwas
BCAS3	HGNC:14347	ENSG00000141376	Q9H6U6	BCAS3 microtubule associated cell migration factor	gwas
SLC13A3	HGNC:14430	ENSG00000158296	Q8WWT9	Na(+)/dicarboxylate cotransporter 3	gwas
CACNA2D3	HGNC:15460	ENSG00000157445	Q8IZS8	Voltage-dependent calcium channel subunit alpha-2/delta-3	gwas
SMYD3	HGNC:15513	ENSG00000185420	Q9H7B4	Histone-lysine N-methyltransferase SMYD3	gwas
WNT5B	HGNC:16265	ENSG00000111186	Q9H1J7	Protein Wnt-5b	gwas
CD2	HGNC:1639	ENSG00000116824	P06729	T-cell surface antigen CD2	gwas
TOLLIP	HGNC:16476	ENSG00000078902	Q9H0E2	Toll-interacting protein	gwas
SLC28A3	HGNC:16484	ENSG00000197506	Q9HAS3	Solute carrier family 28 member 3	gwas
SV2B	HGNC:16874	ENSG00000185518	Q7L1I2	Synaptic vesicle glycoprotein 2B	gwas
MLXIP	HGNC:17055	ENSG00000175727	Q9HAP2	MLX-interacting protein	gwas
ASB10	HGNC:17185	ENSG00000146926	Q8WXI3	Ankyrin repeat and SOCS box protein 10	gwas
ARID5B	HGNC:17362	ENSG00000150347	Q14865	AT-rich interactive domain-containing protein 5B	gwas
CLNK	HGNC:17438	ENSG00000109684	Q7Z7G1	Cytokine-dependent hematopoietic cell linker	gwas
SLC22A12	HGNC:17989	ENSG00000197891	Q96S37	Solute carrier family 22 member 12	gwas
SLC22A11	HGNC:18120	ENSG00000168065	Q9NSA0	Solute carrier family 22 member 11	gwas
RBFOX1	HGNC:18222	ENSG00000078328	Q9NWB1	RNA binding protein fox-1 homolog 1	gwas
MFN1	HGNC:18262	ENSG00000171109	Q8IWA4	Mitofusin-1	gwas
PNPLA3	HGNC:18590	ENSG00000100344	Q9NST1	1-acylglycerol-3-phosphate O-acyltransferase PNPLA3	gwas
CFTR	HGNC:1884	ENSG00000001626	P13569	Cystic fibrosis transmembrane conductance regulator	gwas
UBE2Q2	HGNC:19248	ENSG00000140367	Q8WVN8	Ubiquitin-conjugating enzyme E2 Q2	gwas
CUX2	HGNC:19347	ENSG00000111249	O14529	Homeobox protein cut-like 2	gwas
NAP1L5	HGNC:19968	ENSG00000177432	Q96NT1	Nucleosome assembly protein 1-like 5	gwas
SFMBT1	HGNC:20255	ENSG00000163935	Q9UHJ3	Scm-like with four MBT domains protein 1	gwas
CLIC6	HGNC:2065	ENSG00000159212	Q96NY7	Chloride intracellular channel protein 6	gwas
POLD3	HGNC:20932	ENSG00000077514	Q15054	DNA polymerase delta subunit 3	gwas
FSTL4	HGNC:21389	ENSG00000053108	Q6MZW2	Follistatin-related protein 4	gwas
CARMIL1	HGNC:21581	ENSG00000079691	Q5VZK9	F-actin-uncapping protein LRRC16A	gwas
ACAD10	HGNC:21597	ENSG00000111271	Q6JQN1	Acyl-CoA dehydrogenase family member 10	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BDKRB2	B2 bradykinin receptor	Receptor for bradykinin.
RREB1	Ras-responsive element-binding protein 1	Transcription factor that binds specifically to the RAS-responsive elements (RRE) of gene promoters.
RUNX2	Runt-related transcription factor 2	Transcription factor involved in osteoblastic differentiation and skeletal morphogenesis.
DST	Dystonin	Cytoskeletal linker protein.
SLC17A1	Sodium-dependent phosphate transport protein 1	Important for the resorption of phosphate by the kidney.
SLC17A4	Probable small intestine urate exporter	Acts as a membrane potential-dependent organic anion transporter, the transport requires a low concentration of chloride ions.
SLC22A1	Solute carrier family 22 member 1	Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics.
SMARCC1	SWI/SNF complex subunit SMARCC1	Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).
BRSK2	Serine/threonine-protein kinase BRSK2	Serine/threonine-protein kinase that plays a key role in polarization of neurons and axonogenesis, cell cycle progress and insulin secretion.
TACR1	Substance-P receptor	Receptor for the tachykinin substance P, also able to bind and respond to tachynins neurokinin A/substance K and neurokinin B/neuromedin-K.
TPST1	Protein-tyrosine sulfotransferase 1	Catalyzes the O-sulfation of tyrosine residues within acidic motifs of polypeptides, using 3’-phosphoadenylyl sulfate (PAPS) as cosubstrate.
VDR	Vitamin D3 receptor	Nuclear receptor for calcitriol, the active form of vitamin D3 which mediates the action of this vitamin on cells.
WDR1	WD repeat-containing protein 1	Induces disassembly of actin filaments in conjunction with ADF/cofilin family proteins.
MEPE	Matrix extracellular phosphoglycoprotein	Promotes renal phosphate excretion and inhibits intestinal phosphate absorption.
SLC2A9	Solute carrier family 2, facilitated glucose transporter member 9	High-capacity urate transporter, which may play a role in the urate reabsorption by proximal tubules.
SLC38A1	Sodium-coupled neutral amino acid symporter 1	Symporter that cotransports short-chain neutral amino acids and sodium ions from the extracellular to the intracellular side of the cell membrane.
PRDM8	PR domain zinc finger protein 8	Probable histone methyltransferase, preferentially acting on ‘Lys-9’ of histone H3.
ATP1A4	Sodium/potassium-transporting ATPase subunit alpha-4	This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane.
NTNG2	Netrin-G2	Involved in controlling patterning and neuronal circuit formation at the laminar, cellular, subcellular and synaptic levels.
BCAS3	BCAS3 microtubule associated cell migration factor	Plays a role in angiogenesis.
SLC13A3	Na(+)/dicarboxylate cotransporter 3	High-affinity sodium-dicarboxylate cotransporter that accepts a range of substrates with 4-6 carbon atoms, such as the citric acid cycle intermediates succinate and alpha-ketoglutarate (2-oxoglutarate), as well as other compounds including…
CACNA2D3	Voltage-dependent calcium channel subunit alpha-2/delta-3	The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel.
SMYD3	Histone-lysine N-methyltransferase SMYD3	Histone methyltransferase.
WNT5B	Protein Wnt-5b	Ligand for members of the frizzled family of seven transmembrane receptors.
CD2	T-cell surface antigen CD2	CD2 interacts with lymphocyte function-associated antigen CD58 (LFA-3) and CD48/BCM1 to mediate adhesion between T-cells and other cell types.
TOLLIP	Toll-interacting protein	Component of the signaling pathway of IL-1 and Toll-like receptors.
SLC28A3	Solute carrier family 28 member 3	Sodium-dependent, pyrimidine- and purine-selective.
SV2B	Synaptic vesicle glycoprotein 2B	Probably plays a role in the control of regulated secretion in neural and endocrine cells.
MLXIP	MLX-interacting protein	Binds DNA as a heterodimer with MLX and activates transcription.
ASB10	Ankyrin repeat and SOCS box protein 10	May be a substrate-recognition component of a SCF-like ECS (Elongin-Cullin-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.
ARID5B	AT-rich interactive domain-containing protein 5B	Transcription coactivator that binds to the 5’-AATA[CT]-3’ core sequence and plays a key role in adipogenesis and liver development.
CLNK	Cytokine-dependent hematopoietic cell linker	An adapter protein which plays a role in the regulation of immunoreceptor signaling, including PLC-gamma-mediated B-cell antigen receptor (BCR) signaling and FC-epsilon R1-mediated mast cell degranulation.
SLC22A12	Solute carrier family 22 member 12	Electroneutral antiporter that translocates urate across the apical membrane of proximal tubular cells in exchange for monovalent organic or inorganic anions.
SLC22A11	Solute carrier family 22 member 11	Antiporter that mediates the transport of conjugated steroids and other specific organic anions at the basal membrane of syncytiotrophoblast and at the apical membrane of proximal tubule epithelial cells, in exchange for anionic compounds.
RBFOX1	RNA binding protein fox-1 homolog 1	RNA-binding protein that regulates alternative splicing events by binding to 5’-UGCAUGU-3’ elements.
MFN1	Mitofusin-1	Mitochondrial outer membrane GTPase that mediates mitochondrial clustering and fusion.
PNPLA3	1-acylglycerol-3-phosphate O-acyltransferase PNPLA3	Specifically catalyzes coenzyme A (CoA)-dependent acylation of 1-acyl-sn-glycerol 3-phosphate (2-lysophosphatidic acid/LPA) to generate phosphatidic acid (PA), an important metabolic intermediate and precursor for both triglycerides and gl…
CFTR	Cystic fibrosis transmembrane conductance regulator	Epithelial ion channel that plays an important role in the regulation of epithelial ion and water transport and fluid homeostasis.
UBE2Q2	Ubiquitin-conjugating enzyme E2 Q2	Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins.
CUX2	Homeobox protein cut-like 2	Transcription factor involved in the control of neuronal proliferation and differentiation in the brain.
SFMBT1	Scm-like with four MBT domains protein 1	Histone-binding protein, which is part of various corepressor complexes.
CLIC6	Chloride intracellular channel protein 6	In the soluble state, catalyzes glutaredoxin-like thiol disulfide exchange reactions with reduced glutathione as electron donor.
POLD3	DNA polymerase delta subunit 3	Accessory component of both the DNA polymerase delta complex and the DNA polymerase zeta complex.
CARMIL1	F-actin-uncapping protein LRRC16A	Cell membrane-cytoskeleton-associated protein that plays a role in the regulation of actin polymerization at the barbed end of actin filaments.
ACAD10	Acyl-CoA dehydrogenase family member 10	Acyl-CoA dehydrogenase only active with R- and S-2-methyl-C15-CoA.
GALNTL5	Inactive polypeptide N-acetylgalactosaminyltransferase-like protein 5	Probable inactive glycosyltransferase required during spermatid development.
CNTN5	Contactin-5	Contactins mediate cell surface interactions during nervous system development.
PIBF1	Progesterone-induced-blocking factor 1	Plays a role in ciliogenesis.
SLC16A9	Monocarboxylate transporter 9	Extracellular pH-and Na(+)-sensitive low-affinity creatine transporter.
MED27	Mediator of RNA polymerase II transcription subunit 27	Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes.

Protein-family classification

Druggable: 25 · Difficult: 16 · Unknown: 34 · Druggable fraction: 0.33

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Transporter	10	10.4×	4e-07
Nuclear receptor	1	5.2×	0.599
Antibody/Immunoglobulin	4	1.6×	0.599
Scaffold/PPI	6	1.4×	0.599
Transcription factor	10	1.1×	0.764
Enzyme (other)	6	1.0×	0.905
Kinase	2	0.7×	0.930
GPCR	2	0.6×	0.930
Other/Unknown	34	0.8×	0.974

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BDKRB2	GPCR	yes		GPCR_Rhodpsn, Brdyknn_rcpt, Brdyknn_2_rcpt
RREB1	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, RREB1
RUNX2	Transcription factor	no		AML1_Runt, p53-like_TF_DNA-bd_sf, p53/RUNT-type_TF_DNA-bd_sf
DST	Scaffold/PPI	no		Plectin_repeat, SH3_domain, Actinin_actin-bd_CS
SLC17A1	Transporter	yes		Pi_cotranspt, MFS, MFS_dom
SLC17A4	Transporter	yes		MFS, MFS_dom, MFS_trans_sf
SLC22A1	Transporter	yes		Orgcat_transp/SVOP, MFS_sugar_transport-like, Sugar_transporter_CS
SLC67A1-AS	Other/Unknown	no
SMARCC1	Transcription factor	no		Chromo/chromo_shadow_dom, SANT/Myb, SWIRM
BRSK2	Kinase	yes		Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
TACR1	GPCR	yes		NK1_rcpt, GPCR_Rhodpsn, Neurokn_rcpt
TBL2	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_PAC1
TPST1	Enzyme (other)	yes	2.8.2.20	TPST-like, P-loop_NTPase
VDR	Nuclear receptor	yes		VitD_rcpt, Nucl_hrmn_rcpt_lig-bd, Znf_hrmn_rcpt
WDR1	Scaffold/PPI	no		WD40_rpt, N2O_reductase_N, WD40/YVTN_repeat-like_dom_sf
EIF3IP1	Other/Unknown	no
MEPE	Other/Unknown	no		MEPE
SLC2A9	Transporter	yes		Sugar/inositol_transpt, MFS_sugar_transport-like, Sugar_transporter_CS
SLC38A1	Other/Unknown	no		AA_transpt_TM
PRDM8	Transcription factor	no		SET_dom, Znf_C2H2_type, Znf_C2H2_sf
ATP1A4	Transcription factor	no		P_typ_ATPase, ATPase_P-typ_cation-transptr_N, P-type_ATPase_IIC
NTNG2	Other/Unknown	no		EGF, LE_dom, Laminin_N
BCAS3	Scaffold/PPI	no		WD40/YVTN_repeat-like_dom_sf, BCAS3_dom, WD40_repeat_dom_sf
SLC13A3	Other/Unknown	no		SLC13A/DASS
CACNA2D3	Other/Unknown	no		VWF_A, VWA_N, VDCC_a2/dsu
SMYD3	Transcription factor	no	2.1.1.354	SET_dom, Znf_MYND, TPR-like_helical_dom_sf
WNT5B	Other/Unknown	no		Wnt, Wnt_CS, Wnt_C
CD2	Antibody/Immunoglobulin	yes		Ig_C2-set, Ig_V-set, Ig-like_fold
TOLLIP	Other/Unknown	no		C2_dom, CUE, UBA-like_sf
SLC28A3	Other/Unknown	no		CNT_N_dom, C_nuclsd_transpt, Gate_dom
SV2B	Transporter	yes		MFS_sugar_transport-like, Sugar_transporter_CS, MFS
MLXIP	Transcription factor	no		bHLH_dom, HLH_DNA-bd_sf, Max-like/E-box_TFs
ASB10	Scaffold/PPI	no		SOCS_box, Ankyrin_rpt, SOCS_box-like_dom_sf
ARID5B	Other/Unknown	no		ARID_dom, ARID5B_ARID/BRIGHT_DNA-bd, ARID_dom_sf
CLNK	Scaffold/PPI	no		SH2, SH2_dom_sf, Immunoreceptor_sig_adapters
SLC22A12	Transporter	yes		MFS, MFS_dom, MFS_trans_sf
SLC22A11	Transporter	yes		MFS_sugar_transport-like, MFS_dom, MFS_trans_sf
RBFOX1	Other/Unknown	no		RRM_dom, Nucleotide-bd_a/b_plait_sf, RBFOX1-3
MFN1	Other/Unknown	no		Fzo/mitofusin_HR2, Mitofusin_fam, P-loop_NTPase
PNPLA3	Other/Unknown	no		PNPLA_dom, Acyl_Trfase/lysoPLipase, PLPL
CFTR	Transporter	yes	2.7.4.3	ABC_transporter-like_ATP-bd, AAA+_ATPase, CFTR/ABCC7
UBE2Q2	Enzyme (other)	yes	2.3.2.23	UBC, RWD_dom, UBQ-conjugating_enzyme/RWD
CUX2	Transcription factor	no		HD, CUT_dom, Homeodomain-like_sf
NAP1L5	Other/Unknown	no		NAP, NAP-like_sf
SFMBT1	Other/Unknown	no		SAM, Mbt, SAM/pointed_sf
CLIC6	Other/Unknown	no		CLIC, Glutathione-S-Trfase_C-like, Thioredoxin-like_sf
POLD3	Other/Unknown	no		POLD3, POLD3_sf
FSTL4	Antibody/Immunoglobulin	yes		EF_hand_dom, Kazal_dom, Ig_sub2
CARMIL1	Other/Unknown	no		Leu-rich_rpt, PH-like_dom_sf, CARMIL_C
ACAD10	Kinase	yes		Aminoglycoside_PTrfase, AcylCoA_DH/ox_M, HAD-SF_hydro_IA

Expression context

Cohort genes with no expression data: 0.

70 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	1
moderate (6-20)	0
broad (>20)	74
unknown	0

Top tissues across cohort

Tissue	Cohort genes
right lobe of liver	8
secondary oocyte	7
buccal mucosa cell	6
calcaneal tendon	6
adult mammalian kidney	5
Brodmann (1909) area 23	5
middle temporal gyrus	5
oocyte	5
sperm	5
stromal cell of endometrium	4
tibia	4
jejunal mucosa	4
liver	4
cortical plate	4
endothelial cell	4
primordial germ cell in gonad	4
adrenal tissue	4
trabecular bone tissue	3
mucosa of transverse colon	3
rectum	3

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BDKRB2	215	broad	marker	stromal cell of endometrium, mucosa of urinary bladder, pancreatic ductal cell
RREB1	278	ubiquitous	marker	buccal mucosa cell, epithelium of nasopharynx, oral cavity
RUNX2	241	ubiquitous	marker	tibia, mucosa of paranasal sinus, trabecular bone tissue
DST	305	ubiquitous	marker	corpus callosum, calcaneal tendon, medial globus pallidus
SLC17A1	58	tissue_specific	marker	adult mammalian kidney, right lobe of liver, kidney
SLC17A4	60	tissue_specific	marker	mucosa of transverse colon, jejunal mucosa, rectum
SLC22A1	163	tissue_specific	marker	right lobe of liver, liver, cartilage tissue
SLC67A1-AS	124	broad	marker	mucosa of transverse colon, duodenum, transverse colon
SMARCC1	290	ubiquitous	marker	ventricular zone, embryo, ganglionic eminence
BRSK2	176	broad	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
TACR1	183	broad	marker	male germ line stem cell (sensu Vertebrata) in testis, endocervix, subcutaneous adipose tissue
TBL2	292	ubiquitous	marker	adult organism, left testis, right testis
TPST1	254	ubiquitous	marker	stromal cell of endometrium, gall bladder, endocervix
VDR	224	ubiquitous	marker	tibia, hair follicle, jejunal mucosa
WDR1	295	ubiquitous	marker	popliteal artery, tibial artery, aorta
EIF3IP1	1		yes	male germ line stem cell (sensu Vertebrata) in testis, granulocyte, colonic epithelium
MEPE	52	tissue_specific	marker	tibia, periodontal ligament, trabecular bone tissue
SLC2A9	182	broad	marker	buccal mucosa cell, monocyte, mononuclear cell
SLC38A1	282	ubiquitous	marker	lateral nuclear group of thalamus, seminal vesicle, superficial temporal artery
PRDM8	159	ubiquitous	marker	cortical plate, ganglionic eminence, mucosa of stomach
ATP1A4	140	tissue_specific	marker	left testis, right testis, testis
NTNG2	173	broad	marker	pancreatic ductal cell, monocyte, leukocyte
BCAS3	214	ubiquitous	marker	colonic epithelium, sural nerve, right uterine tube
SLC13A3	223	ubiquitous	marker	nephron tubule, adult mammalian kidney, kidney epithelium
CACNA2D3	205	broad	marker	middle temporal gyrus, Brodmann (1909) area 23, endothelial cell
SMYD3	252	ubiquitous	marker	corpus epididymis, primordial germ cell in gonad, olfactory segment of nasal mucosa
WNT5B	192	ubiquitous	yes	stromal cell of endometrium, lower esophagus muscularis layer, lower esophagus
CD2	206	broad	marker	granulocyte, thymus, lymph node
TOLLIP	263	ubiquitous	marker	right frontal lobe, anterior cingulate cortex, cingulate cortex
SLC28A3	174	broad	marker	cartilage tissue, secondary oocyte, germinal epithelium of ovary

Protein interactions among cohort

Intra-cohort edges: 41.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PXDNL	9,051
CFTR	7,664
RUNX2	4,101
SMARCC1	3,999
ABCA1	3,551
ALDH16A1	3,339
DARS2	3,288
MFN1	3,256
RBFOX1	2,990
CD2	2,965

Intra-cohort edges

A	B	Sources
ACAD10	CUX2	string_interaction
ACAD10	NAA25	string_interaction
ADH1B	CYP2E1	string_interaction
ALDH16A1	SLC17A4	string_interaction
ALDH16A1	SLC2A9	string_interaction
BCAS3	SLC2A9	string_interaction
CARMIL1	SLC16A9	string_interaction
CARMIL1	SLC17A1	string_interaction
CARMIL1	SLC17A4	string_interaction
CARMIL1	SLC22A11	string_interaction
CARMIL1	SLC22A12	string_interaction
CARMIL1	SLC2A9	string_interaction
CFTR	CLIC6	string_interaction
CFTR	DARS2	intact
CFTR	DST	intact
CFTR	SLC38A1	intact
CFTR	SMYD3	intact
CFTR	TBL2	intact
CFTR	WDR1	intact
CLNK	SFMBT1	biogrid_interaction, intact
CUX2	NAA25	string_interaction
MEPE	RUNX2	string_interaction
NIPAL1	SHLD2	string_interaction
RBFOX1	TOLLIP	biogrid_interaction
RREB1	SFMBT1	biogrid_interaction, intact
SFMBT1	UBE2Q2	string_interaction
SLC13A3	SLC17A1	string_interaction
SLC13A3	SLC22A11	string_interaction
SLC16A9	SLC17A1	string_interaction
SLC16A9	SLC17A4	string_interaction
SLC16A9	SLC22A11	string_interaction
SLC16A9	SLC22A12	string_interaction
SLC16A9	SLC2A9	string_interaction
SLC17A1	SLC22A11	string_interaction
SLC17A1	SLC22A12	string_interaction
SLC17A1	SLC2A9	string_interaction
SLC17A4	SLC22A11	string_interaction
SLC17A4	SLC22A12	string_interaction
SLC17A4	SLC2A9	string_interaction
SLC22A11	SLC2A9	string_interaction
SLC22A12	SLC2A9	string_interaction

Structural data

PDB: 40 · AlphaFold-only: 34 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CFTR	P13569	58
VDR	P11473	52
SMYD3	Q9H7B4	34
SLC22A12	Q96S37	28
SLC22A1	O15245	16
TACR1	P25103	15
MED27	Q6P2C8	11
MFN1	Q8IWA4	9
POLD3	Q15054	9
ADH1B	P00325	9
SLC2A9	Q9NRM0	7
CD2	P06729	7
CNIH2	Q6PI25	7
ABCA1	O95477	7
BDKRB2	P30411	6
SLC13A3	Q8WWT9	6
SV2B	Q7L1I2	6
CXXC1	Q9P0U4	6
CYP2E1	P05181	6
SMARCC1	Q92922	5
CYP2C8	P10632	5
RUNX2	Q13950	4
RBFOX1	Q9NWB1	4
TPST1	O60507	3
NTNG2	Q96CW9	3
SLC22A11	Q9NSA0	3
CUX2	O14529	3
CARMIL1	Q5VZK9	3
NAA25	Q14CX7	3
SHLD2	Q86V20	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ALDH16A1	Q8IZ83	91.58
WNT5B	Q9H1J7	89.83
TBL2	Q9Y4P3	87.11
ACAD10	Q6JQN1	86.83
SLC17A1	Q14916	86.54
GALNTL5	Q7Z4T8	85.63
SLC17A4	Q9Y2C5	83.87
CACNA2D3	Q8IZS8	83.30
PXDNL	A1KZ92	81.78
FSTL4	Q6MZW2	81.18
NIPAL1	Q6NVV3	80.98
SSUH2	Q9Y2M2	80.93
CNPY4	Q8N129	79.97
SLC38A1	Q9H2H9	79.81
ASB10	Q8WXI3	78.98
PIBF1	Q8WXW3	77.70
SLC16A9	Q7RTY1	76.70
SFMBT1	Q9UHJ3	74.62
MALRD1	Q5VYJ5	71.95
PNPLA3	Q9NST1	71.70
JAZF1	Q86VZ6	70.25
BRSK2	Q8IWQ3	68.46
NAP1L5	Q96NT1	66.85
BCAS3	Q9H6U6	65.25
EVA1A	Q9H8M9	64.06
FRMD4B	Q9Y2L6	62.91
CLIC6	Q96NY7	60.24
CLNK	Q7Z7G1	56.93
PRDM8	Q9NQV8	55.64
MLXIP	Q9HAP2	54.60

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 509. Enrichment computed across 134 evidence-associated genes (85 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 85 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Neuronal System	10	5.2×	0.010	SLC22A1, SLC38A1, CACNA2D3, ALDH2, ABCC8, ABCC9, KCNJ2, KCNQ1 (+2 more)
Regulation of MITF-M dependent genes involved in metabolism	2	89.6×	0.017	MITF, PPARGC1A
R-HSA-549132	3	26.9×	0.017	SLC22A1, SLC22A12, SLC22A11
Transmission across Chemical Synapses	7	6.3×	0.017	SLC22A1, SLC38A1, CACNA2D3, ALDH2, KCNJ2, PRKAG2, PRKCA
Transport of small molecules	12	3.5×	0.017	SLC22A1, SLC38A1, ATP1A4, SLC13A3, SLC28A3, SLC22A12, SLC22A11, ABCA1 (+4 more)
Inwardly rectifying K+ channels	3	25.2×	0.018	ABCC8, ABCC9, KCNJ2
ATP sensitive Potassium channels	2	67.2×	0.024	ABCC8, ABCC9
Abacavir transmembrane transport	2	53.7×	0.025	SLC22A1, ABCG2
Organic anion transport by SLC22 transporters	2	53.7×	0.025	SLC22A12, SLC22A11
Ciprofloxacin ADME	2	53.7×	0.025	SLC22A1, ABCG2
Drug ADME	4	10.8×	0.025	SLC22A1, SLC28A3, ACSM2B, ABCG2
Biosynthesis of maresin-like SPMs	2	44.8×	0.029	CYP2C8, CYP2E1
Transcriptional activation of mitochondrial biogenesis	4	9.6×	0.029	GABPA, GLUD1, IDH2, PPARGC1A
Muscle contraction	6	5.5×	0.029	ATP1A4, ALDH2, ABCC9, KCNJ2, KCNQ1, MYL2
ABC transporter disorders	3	15.5×	0.031	ABCA1, ABCC8, ABCC9
R-HSA-425366	4	8.5×	0.039	SLC22A1, SLC13A3, SLC22A12, SLC22A11
Abacavir ADME	2	33.6×	0.045	SLC22A1, ABCG2
Neurotransmitter clearance	2	29.9×	0.054	SLC22A1, ALDH2
Activation of PPARGC1A (PGC-1alpha) by phosphorylation	2	26.9×	0.061	PPARGC1A, PRKAG2
Aspirin ADME	3	11.2×	0.061	CYP2C8, CYP2E1, ACSM2B
CYP2E1 reactions	2	22.4×	0.073	CYP2C8, CYP2E1
Ethanol oxidation	2	22.4×	0.073	ADH1B, ALDH2
Disorders of transmembrane transporters	4	6.5×	0.073	SLC22A12, ABCA1, ABCC8, ABCC9
SLC-mediated transmembrane transport	6	4.2×	0.073	SLC22A1, SLC38A1, SLC13A3, SLC28A3, SLC22A12, SLC22A11
Potassium Channels	4	6.3×	0.075	ABCC8, ABCC9, KCNJ2, KCNQ1
Vitamin D (calciferol) metabolism	2	20.7×	0.079	VDR, LRP2
Carnitine shuttle	2	17.9×	0.102	PPARD, PRKAG2
Plasma lipoprotein assembly, remodeling, and clearance	3	8.1×	0.110	ABCA1, LIPC, ABCG1
Defective SLC2A9 causes hypouricemia renal 2 (RHUC2)	1	134.3×	0.126	SLC2A9
Defective SLC22A12 causes renal hypouricemia 1 (RHUC1)	1	134.3×	0.126	SLC22A12

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 121 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
urate metabolic process	7	88.6×	3e-10	SLC17A1, SLC2A9, SLC22A12, SLC22A11, CARMIL1, SLC16A9, ABCG2
transport across blood-brain barrier	7	10.4×	0.003	SLC22A1, SLC38A1, ATP1A4, SLC13A3, ABCC9, LRP2, ABCG2
urate transport	3	59.7×	0.004	SLC17A1, SLC2A9, SLC22A12
potassium ion import across plasma membrane	5	15.1×	0.005	ATP1A4, ABCC8, ABCC9, KCNJ2, KCNQ1
negative regulation of cholesterol storage	3	38.0×	0.012	ABCA1, ABCG1, PPARD
renal urate salt excretion	2	92.8×	0.027	SLC22A12, ABCG2
endocrine pancreas development	3	23.2×	0.029	FOXA2, IL6, RFX3
reverse cholesterol transport	3	23.2×	0.029	ABCA1, LIPC, ABCG1
obsolete inorganic cation transmembrane transport	3	23.2×	0.029	ABCC8, ABCC9, PKD2
potassium ion transmembrane transport	6	6.7×	0.029	ATP1A4, ABCC8, ABCC9, KCNJ2, KCNQ1, PKD2
obsolete organic anion transport	3	19.9×	0.040	SLC22A12, SLC22A11, ABCG2
positive regulation of transcription by RNA polymerase II	19	2.3×	0.040	RREB1, RUNX2, SMARCC1, VDR, BCAS3, SMYD3, MLXIP, ZNF639 (+11 more)
carnitine transmembrane transport	2	46.4×	0.055	SLC16A9, PDZK1
xenobiotic transport across blood-brain barrier	2	46.4×	0.055	SLC22A1, ABCG2
transmembrane transport	5	7.0×	0.055	CFTR, ABCC8, ABCC9, ABCG1, ABCG2
lipid hydroxylation	2	39.8×	0.064	CYP2C8, CYP2E1
positive regulation of fatty acid oxidation	2	39.8×	0.064	PPARD, PPARGC1A
monoatomic ion transport	5	6.5×	0.064	SLC17A1, ATP1A4, SLC22A12, SLC22A11, TRPA1
negative regulation of natural killer cell activation	2	34.8×	0.074	CLNK, PIBF1
xenobiotic metabolic process	5	6.2×	0.074	SLC22A1, SLC28A3, CYP2C8, CYP2E1, ACSM2B
positive regulation of synapse assembly	4	8.1×	0.078	CUX2, NTRK2, PRKCA, PTPRD
gastrin-induced gastric acid secretion	1	139.3×	0.079	KCNQ1
regulation of skeletal muscle contraction via regulation of action potential	1	139.3×	0.079	KCNJ2
pyrimidine nucleoside transport	1	139.3×	0.079	SLC28A3
carbon tetrachloride metabolic process	1	139.3×	0.079	CYP2E1
benzene metabolic process	1	139.3×	0.079	CYP2E1
nitroglycerin metabolic process	1	139.3×	0.079	ALDH2
4-nitrophenol metabolic process	1	139.3×	0.079	CYP2E1
negative regulation of brain-derived neurotrophic factor receptor signaling pathway	1	139.3×	0.079	FSTL4
diol metabolic process	1	139.3×	0.079	LRP2

Therapeutics

Drugs indicated for this disease

19 approved, 9 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Allopurinol	Approved (phase 4)
Benzbromarone	Approved (phase 4)
Canakinumab	Approved (phase 4)
Cinchophen	Approved (phase 4)
Colchicine	Approved (phase 4)
Cortisone Acetate	Approved (phase 4)
Dexamethasone	Approved (phase 4)
Febuxostat	Approved (phase 4)
Indomethacin	Approved (phase 4)
Lesinurad	Approved (phase 4)
Naproxen	Approved (phase 4)
Pegloticase	Approved (phase 4)
Prednisolone	Approved (phase 4)
Prednisone	Approved (phase 4)
Probenecid	Approved (phase 4)
Rasburicase	Approved (phase 4)
Sulfinpyrazone	Approved (phase 4)
Tisopurine	Approved (phase 4)
Triamcinolone Acetonide	Approved (phase 4)
Betamethasone	Phase 3 (in late-stage trials)
Betamethasone Dipropionate	Phase 3 (in late-stage trials)
Celecoxib	Phase 3 (in late-stage trials)
Dotinurad	Phase 3 (in late-stage trials)
Lansoprazole	Phase 3 (in late-stage trials)
Pegadricase	Phase 3 (in late-stage trials)
Rilonacept	Phase 3 (in late-stage trials)
SHR-4640	Phase 3 (in late-stage trials)
Sodium Chloride	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Anakinra, Apremilast, Azathioprine, Bucillamine, Denosumab, Diacerein, Methylprednisolone Acetate, Mycophenolate Mofetil.

Drug target analysis

Approved (phase 4): 14 · Phase ≥3: 15 · Phased (≥1): 16 · Undrugged: 59

Druggability breadth: 62 of 134 evidence-associated genes (46%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
BDKRB2	PYRVINIUM
SLC22A1	PROGESTERONE
BRSK2	BRIGATINIB
TACR1	CLOTRIMAZOLE
VDR	CHOLECALCIFEROL
ATP1A4	OMEPRAZOLE
CACNA2D3	NIMODIPINE
SLC28A3	ADENOSINE
SLC22A12	BENZARONE
SLC22A11	CEFAMANDOLE
CFTR	IVACAFTOR
ACAD10	GEFITINIB
CYP2C8	CLOTRIMAZOLE
CYP2E1	PAZOPANIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SLC22A1	86	4
CYP2C8	62	4
TACR1	42	4
BDKRB2	18	4
CFTR	14	4
SLC22A12	13	4
SLC22A11	11	4
BRSK2	10	4
VDR	10	4
ACAD10	7	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PYRVINIUM	4	BDKRB2
INDOCYANINE GREEN ACID FORM	4	BDKRB2
NITAZOXANIDE	4	BDKRB2
RIFAXIMIN	4	BDKRB2
ICATIBANT	4	BDKRB2
RIFAMPIN	4	BDKRB2
AMSACRINE	4	BDKRB2, SLC22A1
SUNITINIB	4	BDKRB2, BRSK2, SLC22A1
NIMESULIDE	4	BDKRB2
AMIODARONE	4	BDKRB2, CYP2C8
TAMOXIFEN	4	BDKRB2, CYP2C8, TACR1
PROGESTERONE	4	SLC22A1
CLOTRIMAZOLE	4	CYP2C8, SLC22A1, TACR1
IMIPRAMINE	4	SLC22A1
TAPENTADOL	4	SLC22A1
ETHOPROPAZINE	4	SLC22A1
TRAMADOL	4	SLC22A1
REPAGLINIDE	4	SLC22A1
QUINIDINE	4	SLC22A1
CLONIDINE	4	SLC22A1
ESTRADIOL	4	SLC22A1
KETOCONAZOLE	4	CYP2C8, SLC22A1
CLEMASTINE	4	SLC22A1
DOXEPIN	4	SLC22A1
RITONAVIR	4	SLC22A1, TACR1
QUININE	4	SLC22A1
PHENFORMIN	4	SLC22A1
MEPENZOLATE BROMIDE	4	SLC22A1
RANITIDINE	4	SLC22A1
PRAZOSIN	4	SLC22A1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 9.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
CYP2C8	1,025	ADMET:1005, Binding:19, Toxicity:1
TACR1	620	Binding:506, Functional:111, ADMET:3
VDR	561	Binding:459, Functional:99, ADMET:3
CFTR	520	Binding:497, Functional:17, ADMET:5, Toxicity:1
CYP2E1	393	ADMET:388, Binding:5
BRSK2	230	Binding:230
BDKRB2	225	Binding:186, Functional:38, ADMET:1
SMYD3	129	Binding:127, Functional:2
SLC22A12	108	Binding:108
SLC22A1	97	Functional:41, Binding:35, ADMET:21
SLC22A11	63	Functional:53, Binding:6, ADMET:3, Toxicity:1
ATP1A4	45	Binding:45
SLC2A9	13	Binding:11, Functional:2
CACNA2D3	13	Binding:13
ADH1B	13	Binding:13
SMARCC1	8	Binding:8
SFMBT1	6	Binding:6
CD2	5	Binding:5
SLC13A3	4	Binding:3, Functional:1
SLC28A3	3	ADMET:2, Binding:1
ACAD10	3	Binding:3
ALDH16A1	3	Binding:3
SLC38A1	2	Binding:2
ABCA1	2	Binding:2
SLC17A1	1	Binding:1
TBL2	1	Binding:1
WDR1	1	Binding:1
PRDM8	1	Binding:1
POLD3	1	Binding:1
CXXC1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
TPST1	2.8.2.20	protein-tyrosine sulfotransferase
SMYD3	2.1.1.354	[histone H3]-lysine4 N-trimethyltransferase
CFTR	2.7.4.3, 5.6.1.6	adenylate kinase, channel-conductance-controlling ATPase
UBE2Q2	2.3.2.23, 2.3.2.24	E2 ubiquitin-conjugating enzyme, (E3-independent) E2 ubiquitin-conjugating enzyme
GALNTL5	2.4.1.41	polypeptide N-acetylgalactosaminyltransferase
DARS2	6.1.1.12	aspartate-tRNA ligase
NAA25	2.3.1.254	N-terminal methionine Nalpha-acetyltransferase NatB
CYP2C8	1.14.14.1	unspecific monooxygenase
PXDNL	1.11.1.7	peroxidase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
BDKRB2	225
BRSK2	230
TACR1	620
VDR	561
SMYD3	129
SLC22A12	108
CFTR	520
CYP2C8	1,025
CYP2E1	393

Pharmacogenomics

Cohort genes with a PharmGKB record: 74; with CPIC/DPWG dosing guidelines: 2.

Cohort genes with a CPIC/DPWG dosing guideline

Symbol	CPIC guidelines
CFTR	1
CYP2C8	1

Chemical tractability of cohort targets

30 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
PYRVINIUM	4	BDKRB2
INDOCYANINE GREEN ACID FORM	4	BDKRB2
NITAZOXANIDE	4	BDKRB2
RIFAXIMIN	4	BDKRB2
ICATIBANT	4	BDKRB2
RIFAMPIN	4	BDKRB2
AMSACRINE	4	BDKRB2, SLC22A1
SUNITINIB	4	BDKRB2, BRSK2, SLC22A1
NIMESULIDE	4	BDKRB2
AMIODARONE	4	BDKRB2, CYP2C8
TAMOXIFEN	4	BDKRB2, CYP2C8, TACR1
PROGESTERONE	4	SLC22A1
CLOTRIMAZOLE	4	CYP2C8, SLC22A1, TACR1
IMIPRAMINE	4	SLC22A1
TAPENTADOL	4	SLC22A1
ETHOPROPAZINE	4	SLC22A1
TRAMADOL	4	SLC22A1
REPAGLINIDE	4	SLC22A1
QUINIDINE	4	SLC22A1
CLONIDINE	4	SLC22A1
ESTRADIOL	4	SLC22A1
KETOCONAZOLE	4	CYP2C8, SLC22A1
CLEMASTINE	4	SLC22A1
DOXEPIN	4	SLC22A1
RITONAVIR	4	SLC22A1, TACR1
QUININE	4	SLC22A1
PHENFORMIN	4	SLC22A1
MEPENZOLATE BROMIDE	4	SLC22A1
RANITIDINE	4	SLC22A1
PRAZOSIN	4	SLC22A1

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	14	BDKRB2, SLC22A1, BRSK2, TACR1, VDR, ATP1A4, CACNA2D3, SLC28A3, SLC22A12, SLC22A11 (+4 more)
B	Phased (≥1) drug, not yet approved	2	SMARCC1, SLC2A9
C	Druggable family + PDB, no drug	8	TPST1, CD2, SV2B, UBE2Q2, CNTN5, DARS2, NAA25, ABCA1
D	Druggable family + AlphaFold only, no drug	6	SLC17A1, SLC17A4, FSTL4, GALNTL5, SLC16A9, PXDNL
E	Difficult family or no structure, no drug	45	RREB1, RUNX2, DST, SLC67A1-AS, TBL2, WDR1, EIF3IP1, MEPE, SLC38A1, PRDM8 (+35 more)

Undrugged target profiles

59 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
SLC17A1	1	SLC22A12, SLC22A11, SLC2A9
SLC17A4	0	SLC2A9, SLC22A11
SLC16A9	0	SLC22A11, SLC2A9, SLC22A12
ADH1B	13	CYP2E1
ALDH16A1	3	SLC2A9
SMYD3	129	—
RREB1	0	—
RUNX2	0	—
DST	0	—
SLC67A1-AS	0	—
TBL2	1	—
TPST1	0	—
WDR1	1	—
EIF3IP1	0	—
MEPE	0	—
SLC38A1	2	—
PRDM8	1	—
NTNG2	0	—
BCAS3	0	—
SLC13A3	4	—
WNT5B	0	—
CD2	5	—
TOLLIP	0	—
SV2B	0	—
MLXIP	0	—
ASB10	0	—
ARID5B	0	—
CLNK	0	—
RBFOX1	0	—
MFN1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 285.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	100
PHASE2	56
PHASE1	46
PHASE3	39
PHASE4	29
PHASE1/PHASE2	6
PHASE2/PHASE3	5
EARLY_PHASE1	4

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04875702	PHASE4	RECRUITING	Treat-to-Target Serum Urate Versus Treat-to-Avoid Symptoms in Gout
NCT06622603	PHASE4	RECRUITING	the Effects of Febuxostat Dose Tapering in Gout Patients Optimally Controlled for 5 Years or More
NCT06834230	PHASE4	RECRUITING	Effect of Dotinurad in Hyperuricemia With Hypertension
NCT06966635	PHASE4	RECRUITING	Exploratory Study on the Treatment of Gout With Potassium Citrate Sustained-release Tablets
NCT07346079	PHASE4	RECRUITING	Purified Cortrophin® Gel Efficacy and Safety Study of 2 Dose Levels in Patients With Acute Gout Flares
NCT00142558	PHASE4	COMPLETED	A Study Evaluating the Effect of Etoricoxib and Indomethacin in the Treatment of Acute Gout (0663-081)(COMPLETED)
NCT01112982	PHASE4	COMPLETED	An Assessment of Chronic Synovial-Based Inflammation and Its Role With Serum Urate Levels.
NCT01310673	PHASE4	COMPLETED	Initiation of Allopurinol at First Medical Contact for Acute Attacks of Gout
NCT01391325	PHASE4	COMPLETED	Allopurinol Outcome Study
NCT01472692	PHASE4	COMPLETED	Study of Febuxostat Effect on Blood Pressure in Patients With High Normal Blood Pressure
NCT01529099	PHASE4	COMPLETED	Postmarketing Study to Determine Performance of the SIGMA HP® PARTIAL KNEE SYSTEM
NCT01654276	PHASE4	COMPLETED	Effects of Hyperuricemia Reversal on Features of the Metabolic Syndrome
NCT01988402	PHASE4	COMPLETED	Does Allopurinol Prolong a Treated, Acute Gout Flare?
NCT01994226	PHASE4	COMPLETED	Colchicine Or Naproxen Treatment for ACute gouT
NCT02060552	PHASE4	COMPLETED	Immune Molecular and Inflammatory Cytokines Dysfunction Analysis in Gout Patients With Different Urate Levels
NCT02462421	PHASE4	TERMINATED	Pharmacogenetics of SGLT2 Inhibitors
NCT02477488	PHASE4	COMPLETED	Optimal Administration of Allopurinol in Dialysis Patients
NCT02500641	PHASE4	COMPLETED	Intensive Urate Lowering Therapy of Febuxostat Compared to Allopurinol on Cardiovascular Risk in Patients With Gout
NCT02579096	PHASE4	COMPLETED	CSP594 Comparative Effectiveness in Gout: Allopurinol vs. Febuxostat
NCT02956278	PHASE4	COMPLETED	The Effects of BCRP Q141K on Allopurinol Pharmacokinetics and Dynamics
NCT03226899	PHASE4	TERMINATED	A Phase 4 Safety and Efficacy Study to Evaluate Lesinurad 200 mg in Participants With Gout and Renal Impairment
NCT03336203	PHASE4	UNKNOWN	The Impact of Urate-lowering Therapy on Kidney Function (IMPULsKF)
NCT03635957	PHASE4	COMPLETED	Study of Pegloticase (KRYSTEXXA®) Plus Methotrexate in Patients With Uncontrolled Gout
NCT03994731	PHASE4	COMPLETED	Study of KRYSTEXXA® (Pegloticase) Plus Methotrexate in Participants With Uncontrolled Gout
NCT04511702	PHASE4	COMPLETED	Infusion Duration Study To Assess Tolerability of Pegloticase Administered With a Shorter Infusion Duration in Subjects With Uncontrolled Gout Receiving Methotrexate
NCT04762498	PHASE4	COMPLETED	A Phase 4, Open-label Study of KRYSTEXXA® (Pegloticase) Co-administered With Methotrexate (MTX) in Patients With Uncontrolled Gout (FORWARD OL)
NCT05312268	PHASE4	UNKNOWN	Rasburicase Treatment in Chronic Gouty Arthritis
NCT05698680	PHASE4	TERMINATED	Prednisolone Versus Colchicine for Acute Gout in Primary Care
NCT06229145	PHASE4	COMPLETED	A Trial to Investigate the Non-inferiority of Pegloticase Administered Every 4 Weeks (Q4W) With MTX Compared With Every 2 Weeks (Q2W) With MTX in Participants With Uncontrolled Refractory Gout
NCT05109936	PHASE3	RECRUITING	Immediate Prescription of a Hypouricemic Treatment, Febuxostat, Compared to Its Delayed Administration
NCT05658575	PHASE2/PHASE3	RECRUITING	Study of Dapansutrile Tablets in Subjects With an Acute Gout Flare
NCT06603142	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Phase II/III Study of AR882 Capsules Compared to Febuxostat Tablets in Patients with Primary Gout and Hyperuricemia
NCT06846515	PHASE3	ACTIVE_NOT_RECRUITING	Phase 3 Evaluation of Efficacy and Safety of AR882 in Gout Patients (AR882-301)
NCT07089875	PHASE3	RECRUITING	A Study of Dotinurad Versus Allopurinol in Participants With Gout
NCT07089888	PHASE3	RECRUITING	A Study of Dotinurad Versus Allopurinol in Tophaceous Gout
NCT07414394	PHASE3	RECRUITING	Tigulixostat (IBI128) vs Febuxostat in Gout
NCT00102440	PHASE3	COMPLETED	Febuxostat Versus Allopurinol Control Trial in Subjects With Gout
NCT00174915	PHASE3	COMPLETED	Phase 3, Febuxostat, Allopurinol and Placebo-Controlled Study in Gout Subjects.
NCT00175019	PHASE3	COMPLETED	Allopurinol Versus Febuxostat in Subjects Completing the Phase 3 Trials C02-009 or C02-010
NCT00325195	PHASE3	COMPLETED	Safety and Efficacy Study of PEG-uricase in the Treatment of Hyperuricemic Patients With Symptomatic Gout

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
FEBUXOSTAT	4	35
ALLOPURINOL	4	28
COLCHICINE	4	22
LESINURAD	4	12
PEGLOTICASE	4	11
CANAKINUMAB	4	4
NAPROXEN	4	4
RILONACEPT	4	4
CANAGLIFLOZIN ANHYDROUS	4	3
FEXOFENADINE	4	3
SUMATRIPTAN	4	3
THEOPHYLLINE ANHYDROUS	4	3
FOLIC ACID	4	2
METFORMIN	4	2
POTASSIUM CITRATE ANHYDROUS	4	2
TIZANIDINE	4	2
TRIAMCINOLONE ACETONIDE	4	2
APREMILAST	4	1
AZATHIOPRINE	4	1
BACLOFEN	4	1
CORTICOTROPIN	4	1
CYCLOBENZAPRINE	4	1
ESFLURBIPROFEN	4	1
ESOMEPRAZOLE	4	1
ETORICOXIB	4	1
FLURBIPROFEN	4	1
INDOMETHACIN	4	1
LANSOPRAZOLE	4	1
MELOXICAM	4	1
MENTHOL	4	1