Nephrolithiasis

disease

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Also known as calculus of kidney and ureterCAONkidney stonerenal calculi

Summary

Nephrolithiasis (MONDO:0008171) is a disease with 34 cohort genes (278 GWAS associations across 35 studies) and 448 clinical trials. Top therapeutic interventions include potassium citrate anhydrous, ketorolac, and tamsulosin.

At a glance

Cohort genes: 34
GWAS associations: 278
ClinVar variants: 22
Clinical trials: 448

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	nephrolithiasis
Mondo ID	MONDO:0008171
EFO	EFO:0004253
MeSH	D053040
DOID	DOID:585
NCIT	C114667
SNOMED CT	266556005
UMLS	C0392525
MedGen	98227
Is cancer (heuristic)	no

Also known as: calculus of kidney and ureter · CAON · kidney stone · renal calculi

Data availability: 22 ClinVar variants · 278 GWAS associations (35 studies).

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › urinary system disorder › kidney disorder › nephrolithiasis

Subtypes (3): acute urate nephropathy, nephrolithiasis, X-linked recessive, with renal failure, nephrolithiasis, calcium oxalate

Genetics & variants

GWAS landscape

278 GWAS associations across 35 studies. Top hits map to 27 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs77924615	2e-94	PDILT	G	0.2
rs56235845	8e-73	RGS14	T	0.14
chr21:37832621	2e-61		G	0.15
rs4074995	2e-57	RGS14	G	0.15
rs2231142	5e-51	ABCG2	G	0.18
rs10051765	4e-47	RGS14 - SLC34A1	T	0.88
rs219772	3e-45	CLDN14, LNCTSI	A	0.13
rs2776288	1e-40	LNCTSI	A	1.13
rs6127099	4e-39	BCAS1 - CYP24A1	A	0.12
rs115239632	2e-32	NBPF3 - ALPL	T	1.33
rs1936824	5e-32	NBPF3 - ALPL	A	1.13
chr22:23366323	2e-31		G	0.1
rs670676	2e-31	DGKH	A	1.12
rs2299905	6e-30	AQP1	A	0.09
rs9897621	7e-30	KANSL1	T	0.11
rs9895661	3e-29	BCAS3, TBX2-AS1	C	0.11
rs35194449	3e-29	BCAS1 - CYP24A1	T	0.88
rs1772719	1e-26	ALPL	A	0.1
chr2:234369796	7e-25		G	0.08
rs1037271	1e-24	DGKH	C	1.15
rs9612214	2e-24	ATP5PFP2 - RSPH14	G	0.09
rs838717	6e-23	DGKD	A	0.92
chr16:88516135	2e-21		C	0.07
rs142212375	2e-21	KLK15	C	0.19
chr2:224663808	2e-21		G	0.08
rs12626330	7e-21	CLDN14, LNCTSI	G	1.15
rs2241358	1e-20	PTGER1 - GIPC1	C	0.08
rs13054904	3e-20	RSPH14	A	1.13
rs4142110	3e-20	DGKH	T	0.88
chr4:115593857	7e-20		G	0.09

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90476145	Verma A	2024	33,224	401,930	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90428893	Lovegrove CE	2023	17,101	721,947	Central Adiposity Increases Risk of Kidney Stone Disease via Effects on Serum Calcium Concentrations.
GCST90652506	Cao X	2025	13,746	241,425	Trans-ancestry GWAS identifies 59 loci and improves risk prediction and fine-mapping for kidney stone disease.
GCST90652507	Cao X	2025	13,746	241,425	Trans-ancestry GWAS identifies 59 loci and improves risk prediction and fine-mapping for kidney stone disease.
GCST90428894	Lovegrove CE	2023	8,504	388,819	Central Adiposity Increases Risk of Kidney Stone Disease via Effects on Serum Calcium Concentrations.
GCST009598	Howles SA	2019	6,536	388,508	Genetic variants of calcium and vitamin D metabolism in kidney stone disease.
GCST009599	Howles SA	2019	6,536	388,508	Genetic variants of calcium and vitamin D metabolism in kidney stone disease.
GCST90651223	Liu TY	2025	6,167	217,244	Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.
GCST90428895	Lovegrove CE	2023	5,633	176,738	Central Adiposity Increases Risk of Kidney Stone Disease via Effects on Serum Calcium Concentrations.
GCST90691943	Karczewski KJ	2025	5,530	415,001	Pan-UK Biobank genome-wide association analyses enhance discovery and resolution of ancestry-enriched effects.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	3
Tier 2: splice/UTR	2
Tier 3: regulatory	2
Tier 4: intronic/intergenic	43

MAF distribution

Bucket	Variants
common (>=0.05)	47
low_freq (0.01-0.05)	3
rare (<0.01)	0
unknown	0

Functional consequences

Consequence	Count
intron_variant	30
intergenic_variant	7
unknown	6
regulatory_region_variant	2
missense_variant	2
splice_region_variant	1
stop_gained	1
3_prime_UTR_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs77924615	16	20381010	G>A	0.2	intron_variant	PDILT	2e-94	Tier 4: intronic/intergenic
rs56235845	5	177371039	T>G	0.335	splice_region_variant	RGS14	8e-73	Tier 2: splice/UTR
chr21:37832621				0.25			2e-61	Tier 4: intronic/intergenic
rs4074995	5	177370342	G>A	0.235	intron_variant	RGS14	2e-57	Tier 4: intronic/intergenic
rs2231142	4	88131171	G>A,C,T	0.11	stop_gained	ABCG2	5e-51	Tier 1: coding
rs10051765	5	177372991	T>C	0.357	intergenic_variant	RGS14 - SLC34A1	4e-47	Tier 4: intronic/intergenic
rs219772	21	36463049	A>G,T	0.296	intron_variant	CLDN14, LNCTSI	3e-45	Tier 4: intronic/intergenic
rs2776288	21	36446573	A>G,T	0.357	intron_variant	LNCTSI	1e-40	Tier 4: intronic/intergenic
rs6127099	20	54114863	A>C,T	0.289	intron_variant	BCAS1 - CYP24A1	4e-39	Tier 4: intronic/intergenic
rs115239632	1	21500037	C>T	0.05	intergenic_variant	NBPF3 - ALPL	2e-32	Tier 4: intronic/intergenic
rs1936824	1	21503122	G>A	0.264	intergenic_variant	NBPF3 - ALPL	5e-32	Tier 4: intronic/intergenic
chr22:23366323				0.303			2e-31	Tier 4: intronic/intergenic
rs670676	13	42127603	A>C,G,T	0.352	intron_variant	DGKH	2e-31	Tier 4: intronic/intergenic
rs2299905	7	30918001	A>C,T	0.289	intron_variant	AQP1	6e-30	Tier 4: intronic/intergenic
rs9897621	17	46036026	T>A	0.199	intron_variant	KANSL1	7e-30	Tier 4: intronic/intergenic
rs9895661	17	61379228	C>A,T	0.184	intron_variant	BCAS3, TBX2-AS1	3e-29	Tier 4: intronic/intergenic
rs35194449	20	54125508	C>T	0.185	intron_variant	BCAS1 - CYP24A1	3e-29	Tier 4: intronic/intergenic
rs1772719	1	21577881	A>C	0.198	3_prime_UTR_variant	ALPL	1e-26	Tier 2: splice/UTR
chr2:234369796				0.455			7e-25	Tier 4: intronic/intergenic
rs1037271	13	42205274	T>A,C,G	0.39	intron_variant	DGKH	1e-24	Tier 4: intronic/intergenic
rs9612214	22	23025318	G>C	0.252	intergenic_variant	ATP5PFP2 - RSPH14	2e-24	Tier 4: intronic/intergenic
rs838717	2	233387798	G>A	0.427	intron_variant	DGKD	6e-23	Tier 4: intronic/intergenic
chr16:88516135				0.411			2e-21	Tier 4: intronic/intergenic
rs142212375	19	50833005	C>T	0.038	intron_variant	KLK15	2e-21	Tier 4: intronic/intergenic
chr2:224663808				0.407			2e-21	Tier 4: intronic/intergenic
rs12626330	21	36463684	C>G,T	0.49	intron_variant	CLDN14, LNCTSI	7e-21	Tier 4: intronic/intergenic
rs2241358	19	14477664	C>A,G	0.327	regulatory_region_variant	PTGER1 - GIPC1	1e-20	Tier 3: regulatory
rs13054904	22	23068739	A>G,T	0.23	intron_variant	RSPH14	3e-20	Tier 4: intronic/intergenic
rs4142110	13	42180386	T>A,C	0.464	intron_variant	DGKH	3e-20	Tier 4: intronic/intergenic
chr4:115593857				0.182			7e-20	Tier 4: intronic/intergenic

ClinVar germline variants

22 retrieved; paginated sample, class counts are floors:

8 pathogenic, 4 pathogenic/likely pathogenic, 4 uncertain significance, 3 conflicting classifications of pathogenicity, 2 likely pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
267830	46;X;t(X;5)(q24;q13)dn		Pathogenic	criteria provided, single submitter
204105	NM_000030.3(AGXT):c.481G>A (p.Gly161Ser)	AGXT	Pathogenic	criteria provided, multiple submitters, no conflicts
5644	NM_000030.3(AGXT):c.121G>A (p.Gly41Arg)	AGXT	Pathogenic	criteria provided, multiple submitters, no conflicts
5646	NM_000030.3(AGXT):c.731T>C (p.Ile244Thr)	AGXT	Pathogenic	criteria provided, multiple submitters, no conflicts
12228	NM_001692.4(ATP6V1B1):c.242T>C (p.Leu81Pro)	ATP6V1B1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
548673	NM_012203.2(GRHPR):c.404+5G>A	GRHPR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
5636	NM_012203.2(GRHPR):c.103del (p.Asp35fs)	GRHPR	Pathogenic	criteria provided, multiple submitters, no conflicts
265999	NM_000338.3(SLC12A1):c.1163del (p.Phe388fs)	SLC12A1	Pathogenic	criteria provided, single submitter
548675	NM_000338.3(SLC12A1):c.769G>A (p.Gly257Ser)	SLC12A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
981158	NM_001330988.2(SLC25A25):c.1083G>C (p.Gln361His)	SLC25A25	Pathogenic	no assertion criteria provided
234926	NM_003052.5(SLC34A1):c.644+1G>A	SLC34A1	Pathogenic	criteria provided, multiple submitters, no conflicts
548674	NM_000341.4(SLC3A1):c.592del (p.Ala198fs)	SLC3A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
548671	NM_000030.3(AGXT):c.1079G>C (p.Arg360Pro)	AGXT	Likely pathogenic	no assertion criteria provided
548676	NM_000338.3(SLC12A1):c.1424G>A (p.Cys475Tyr)	SLC12A1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
548672	NM_148960.3(CLDN19):c.535G>A (p.Gly179Ser)	CLDN19	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1679240	NM_003052.5(SLC34A1):c.937-2A>C	SLC34A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
548679	NM_003052.5(SLC34A1):c.1724C>T (p.Thr575Ile)	SLC34A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
5931	NM_006580.4(CLDN16):c.485T>G (p.Phe162Cys)	CLDN16	Uncertain significance	criteria provided, single submitter
523307	NC_012920.1(MT-CO3):m.9355A>T	MT-CO3	Uncertain significance	criteria provided, single submitter
3592146	NM_003052.5(SLC34A1):c.1325C>T (p.Pro442Leu)	SLC34A1	Uncertain significance	criteria provided, multiple submitters, no conflicts
548678	NM_003052.5(SLC34A1):c.1204G>C (p.Gly402Arg)	SLC34A1	Uncertain significance	criteria provided, multiple submitters, no conflicts
5272	NM_004252.5(NHERF1):c.673G>A (p.Glu225Lys)	NHERF1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 50 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 1

Dual-evidence genes (GWAS + Mendelian — highest-confidence targets)

Gene	HGNC	Evidence routes
SLC34A1	SLC34A1	GWAS, Orphanet

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLC34A1	Orphanet:157215	Hereditary hypophosphatemic rickets with hypercalciuria
SLC34A1	Orphanet:244305	Dominant hypophosphatemia with nephrolithiasis or osteoporosis
SLC34A1	Orphanet:300547	Autosomal recessive infantile hypercalcemia
SLC34A1	Orphanet:3337	Primary Fanconi renotubular syndrome
BCR	Orphanet:261330	Distal 22q11.2 microdeletion syndrome
BCR	Orphanet:521	Chronic myeloid leukemia
BCR	Orphanet:585909	B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2)
BCR	Orphanet:99861	Precursor T-cell acute lymphoblastic leukemia
SCNN1B	Orphanet:171876	Generalized pseudohypoaldosteronism type 1
SCNN1B	Orphanet:526	Liddle syndrome
SCNN1B	Orphanet:60033	Idiopathic bronchiectasis
SLC3A1	Orphanet:163690	Hypotonia-cystinuria syndrome
SLC3A1	Orphanet:163693	2p21 microdeletion syndrome
SLC3A1	Orphanet:238523	Atypical hypotonia-cystinuria syndrome
SLC3A1	Orphanet:93612	Cystinuria type A
NHERF1	Orphanet:244305	Dominant hypophosphatemia with nephrolithiasis or osteoporosis
SOX9	Orphanet:140	Campomelic dysplasia
SOX9	Orphanet:2138	46,XX ovotesticular difference of sex development
SOX9	Orphanet:242	46,XY complete gonadal dysgenesis
SOX9	Orphanet:251510	46,XY partial gonadal dysgenesis
SOX9	Orphanet:393	46,XX testicular difference of sex development
SOX9	Orphanet:718	Isolated Pierre Robin sequence
GIPC1	Orphanet:98897	Oculopharyngodistal myopathy
UMOD	Orphanet:88950	UMOD-related autosomal dominant tubulointerstitial kidney disease
CASR	Orphanet:417	Neonatal severe primary hyperparathyroidism
CASR	Orphanet:428	Autosomal dominant hypocalcemia
CASR	Orphanet:676	Autosomal dominant hereditary chronic pancreatitis
CASR	Orphanet:93372	Familial hypocalciuric hypercalcemia type 1
CLDN14	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB
CLDN16	Orphanet:31043	Primary hypomagnesemia with hypercalciuria and nephrocalcinosis without severe ocular involvement
CLDN19	Orphanet:2196	Primary hypomagnesemia with hypercalciuria and nephrocalcinosis with severe ocular involvement
CYP24A1	Orphanet:300547	Autosomal recessive infantile hypercalcemia
WDR72	Orphanet:100033	Hypomaturation amelogenesis imperfecta
WDR72	Orphanet:402041	Autosomal recessive distal renal tubular acidosis
AGXT	Orphanet:93598	Primary hyperoxaluria type 1
F12	Orphanet:100054	F12-related hereditary angioedema with normal C1Inh
F12	Orphanet:330	Congenital factor XII deficiency
F12	Orphanet:617919	F12-associated cold autoinflammatory syndrome
ALPL	Orphanet:247623	Perinatal lethal hypophosphatasia
ALPL	Orphanet:247638	Prenatal benign hypophosphatasia
ALPL	Orphanet:247651	Infantile hypophosphatasia
ALPL	Orphanet:247667	Childhood-onset hypophosphatasia
ALPL	Orphanet:247676	Adult hypophosphatasia
ALPL	Orphanet:247685	Odontohypophosphatasia
GRHPR	Orphanet:93599	Primary hyperoxaluria type 2
MT-CO3	Orphanet:104	Leber hereditary optic neuropathy
MT-CO3	Orphanet:254905	Isolated cytochrome C oxidase deficiency
MT-CO3	Orphanet:550	MELAS
MT-CO3	Orphanet:99845	Genetic recurrent myoglobinuria
ATP6V1B1	Orphanet:402041	Autosomal recessive distal renal tubular acidosis

Cohort genes → proteins

34 cohort genes, 34 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	23
gwas_and_clinvar	1
multi_evidence	10

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SLC34A1	HGNC:11019	ENSG00000131183	Q06495	Sodium-dependent phosphate transport protein 2A	gwas,clinvar
BCR	HGNC:1014	ENSG00000186716	P11274	Breakpoint cluster region protein	gwas
SCNN1B	HGNC:10600	ENSG00000168447	P51168	Epithelial sodium channel subunit beta	gwas
SLC12A1	HGNC:10910	ENSG00000074803	Q13621	Solute carrier family 12 member 1	clinvar
SLC22A2	HGNC:10966	ENSG00000112499	O15244	Solute carrier family 22 member 2	gwas
SLC3A1	HGNC:11025	ENSG00000138079	Q07837	Amino acid transporter heavy chain SLC3A1	clinvar
NHERF1	HGNC:11075	ENSG00000109062	O14745	Na(+)/H(+) exchange regulatory cofactor NHE-RF1	clinvar
SOX9	HGNC:11204	ENSG00000125398	P48436	Transcription factor SOX-9	gwas
GIPC1	HGNC:1226	ENSG00000123159	O14908	PDZ domain-containing protein GIPC1	gwas
UMOD	HGNC:12559	ENSG00000169344	P07911	Uromodulin	gwas
CASR	HGNC:1514	ENSG00000036828	P41180	Extracellular calcium-sensing receptor	gwas
PFN3	HGNC:18627	ENSG00000196570	P60673	Profilin-3	gwas
CLDN14	HGNC:2035	ENSG00000159261	O95500	Claudin-14	gwas
CLDN16	HGNC:2037	ENSG00000113946	Q9Y5I7	Claudin-16	clinvar
CLDN19	HGNC:2040	ENSG00000164007	Q8N6F1	Claudin-19	clinvar
SLC25A25	HGNC:20663	ENSG00000148339	Q6KCM7	Mitochondrial adenyl nucleotide antiporter SLC25A25	clinvar
MINDY4	HGNC:21916	ENSG00000106125	Q4G0A6	Probable ubiquitin carboxyl-terminal hydrolase MINDY-4	gwas
CYP24A1	HGNC:2602	ENSG00000019186	Q07973	1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial	gwas
WDR72	HGNC:26790	ENSG00000166415	Q3MJ13	WD repeat-containing protein 72	gwas
DGKD	HGNC:2851	ENSG00000077044	Q16760	Diacylglycerol kinase delta	gwas
DGKH	HGNC:2854	ENSG00000102780	Q86XP1	Diacylglycerol kinase eta	gwas
AGXT	HGNC:341	ENSG00000172482	P21549	Alanine–glyoxylate aminotransferase	clinvar
F12	HGNC:3530	ENSG00000131187	P00748	Coagulation factor XII	gwas
ALPL	HGNC:438	ENSG00000162551	P05186	Alkaline phosphatase, tissue-nonspecific isozyme	gwas
GRHPR	HGNC:4570	ENSG00000137106	Q9UBQ7	Glyoxylate reductase/hydroxypyruvate reductase	clinvar
HIBADH	HGNC:4907	ENSG00000106049	P31937	3-hydroxyisobutyrate dehydrogenase, mitochondrial	gwas
INMT	HGNC:6069	ENSG00000241644	O95050	Indolethylamine N-methyltransferase	gwas
KCNK5	HGNC:6280	ENSG00000164626	O95279	Potassium channel subfamily K member 5	gwas
AQP1	HGNC:633	ENSG00000240583	P29972	Aquaporin-1	gwas
MAP4K5	HGNC:6867	ENSG00000012983	Q9Y4K4	Mitogen-activated protein kinase kinase kinase kinase 5	gwas
ABCG2	HGNC:74	ENSG00000118777	Q9UNQ0	Broad substrate specificity ATP-binding cassette transporter ABCG2	gwas
MT-CO3	HGNC:7422	ENSG00000198938	P00414	Cytochrome c oxidase subunit 3	clinvar
ATP6V1B1	HGNC:853	ENSG00000116039	P15313	V-type proton ATPase subunit B, kidney isoform	clinvar
RGS14	HGNC:9996	ENSG00000169220	O43566	Regulator of G-protein signaling 14	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC34A1	Sodium-dependent phosphate transport protein 2A	Involved in actively transporting phosphate into cells via Na(+) cotransport in the renal brush border membrane.
BCR	Breakpoint cluster region protein	Protein with a unique structure having two opposing regulatory activities toward small GTP-binding proteins.
SCNN1B	Epithelial sodium channel subunit beta	This is one of the three pore-forming subunits of the heterotrimeric epithelial sodium channel (ENaC), a critical regulator of sodium balance and fluid homeostasis.
SLC12A1	Solute carrier family 12 member 1	Renal sodium, potassium and chloride non-electrogenic ion symporter that mediates the transepithelial NaCl reabsorption in the thick ascending limb and plays an essential role in the urinary concentration and volume regulation.
SLC22A2	Solute carrier family 22 member 2	Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics.
SLC3A1	Amino acid transporter heavy chain SLC3A1	Acts as a chaperone that facilitates biogenesis and trafficking of functional transporter heteromers to the plasma membrane.
NHERF1	Na(+)/H(+) exchange regulatory cofactor NHE-RF1	Scaffold protein that connects plasma membrane proteins with members of the ezrin/moesin/radixin family and thereby helps to link them to the actin cytoskeleton and to regulate their surface expression.
SOX9	Transcription factor SOX-9	Transcription factor that plays a key role in chondrocytes differentiation and skeletal development.
GIPC1	PDZ domain-containing protein GIPC1	May be involved in G protein-linked signaling.
UMOD	Uromodulin	Functions in biogenesis and organization of the apical membrane of epithelial cells of the thick ascending limb of Henle’s loop (TALH), where it promotes formation of complex filamentous gel-like structure that may play a role in the water…
CASR	Extracellular calcium-sensing receptor	G-protein-coupled receptor that senses changes in the extracellular concentration of calcium ions and plays a key role in maintaining calcium homeostasis.
PFN3	Profilin-3	Binds to actin and affects the structure of the cytoskeleton.
CLDN14	Claudin-14	Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity.
CLDN16	Claudin-16	Forms paracellular channels: coassembles with CLDN19 into tight junction strands with cation-selective channels through the strands, conveying epithelial permeability in a process known as paracellular tight junction permeability.
CLDN19	Claudin-19	Forms paracellular channels: coassembles with CLDN16 into tight junction strands with cation-selective channels through the strands, conveying epithelial permeability in a process known as paracellular tight junction permeability.
SLC25A25	Mitochondrial adenyl nucleotide antiporter SLC25A25	Electroneutral antiporter that most probably mediates the transport of adenyl nucleotides through the inner mitochondrial membrane.
MINDY4	Probable ubiquitin carboxyl-terminal hydrolase MINDY-4	Probable hydrolase that can remove ‘Lys-48’-linked conjugated ubiquitin from proteins.
CYP24A1	1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial	A cytochrome P450 monooxygenase with a key role in vitamin D catabolism and calcium homeostasis.
WDR72	WD repeat-containing protein 72	Plays a major role in formation of tooth enamel.
DGKD	Diacylglycerol kinase delta	Diacylglycerol kinase that converts diacylglycerol/DAG into phosphatidic acid/phosphatidate/PA and regulates the respective levels of these two bioactive lipids.
DGKH	Diacylglycerol kinase eta	Diacylglycerol kinase that converts diacylglycerol/DAG into phosphatidic acid/phosphatidate/PA and regulates the respective levels of these two bioactive lipids.
AGXT	Alanine–glyoxylate aminotransferase	Peroxisomal aminotransferase that catalyzes the transamination of glyoxylate to glycine and contributes to the glyoxylate detoxification.
F12	Coagulation factor XII	Factor XII is a serum glycoprotein that participates in the initiation of blood coagulation, fibrinolysis, and the generation of bradykinin and angiotensin.
ALPL	Alkaline phosphatase, tissue-nonspecific isozyme	Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis.
GRHPR	Glyoxylate reductase/hydroxypyruvate reductase	Enzyme with hydroxy-pyruvate reductase, glyoxylate reductase and D-glycerate dehydrogenase enzymatic activities.
INMT	Indolethylamine N-methyltransferase	Functions as a thioether S-methyltransferase and is active with a variety of thioethers and the corresponding selenium and tellurium compounds, including 3-methylthiopropionaldehyde, dimethyl selenide, dimethyl telluride, 2-methylthioethyl…
KCNK5	Potassium channel subfamily K member 5	K(+) channel that conducts voltage-dependent outward rectifying currents upon membrane depolarization.
AQP1	Aquaporin-1	Forms a water channel that facilitates the transport of water across cell membranes, playing a crucial role in water homeostasis in various tissues.
MAP4K5	Mitogen-activated protein kinase kinase kinase kinase 5	May play a role in the response to environmental stress.
ABCG2	Broad substrate specificity ATP-binding cassette transporter ABCG2	Broad substrate specificity ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes a wide variety of physiological compounds, dietary toxins and xenobiotics from cells.
MT-CO3	Cytochrome c oxidase subunit 3	Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation.
ATP6V1B1	V-type proton ATPase subunit B, kidney isoform	Non-catalytic subunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons.
RGS14	Regulator of G-protein signaling 14	Regulates G protein-coupled receptor signaling cascades.

Protein-family classification

Druggable: 12 · Difficult: 5 · Unknown: 17 · Druggable fraction: 0.35

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	2	4.6×	0.437
Kinase	3	2.5×	0.437
Scaffold/PPI	4	2.0×	0.437
Ion channel	1	3.3×	0.660
Phosphatase	1	2.5×	0.670
Protease	1	1.1×	0.872
Enzyme (other)	3	1.1×	0.872
Other/Unknown	17	0.9×	0.894
GPCR	1	0.7×	0.894
Transcription factor	1	0.2×	0.988

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLC34A1	Other/Unknown	no		Na/Pi_transpt
BCR	Scaffold/PPI	no		C2_dom, RhoGAP_dom, DH_dom
SCNN1B	Other/Unknown	no		ENaC, ENaC_chordates, ENaC_CS
SLC12A1	Other/Unknown	no		SLC12A1/SLC12A2, Slc12a1, AA-permease/SLC12A_dom
SLC22A2	Transporter	yes		Orgcat_transp/SVOP, MFS_sugar_transport-like, Sugar_transporter_CS
SLC3A1	Other/Unknown	no		GH13_cat_dom, Glyco_hydro_b, GH_hydrolase_sf
NHERF1	Scaffold/PPI	no		PDZ, EBP50_C, NHERF-1/NHERF-2
SOX9	Transcription factor	no		HMG_box_dom, Sox_N, HMG_box_dom_sf
GIPC1	Scaffold/PPI	no		PDZ, GIPC1/2/3, PDZ_sf
UMOD	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, ZP_dom
CASR	GPCR	yes		GPCR_3_Ca_sens_rcpt-rel, GPCR_3, ANF_lig-bd_rcpt
PFN3	Other/Unknown	no		Profilin1/2/3_vertebrate, PFN_euk, PFN_sf
CLDN14	Other/Unknown	no		PMP22/EMP/MP20/Claudin, Claudin, Claudin_CS
CLDN16	Other/Unknown	no		Claudin16, PMP22/EMP/MP20/Claudin, Claudin
CLDN19	Other/Unknown	no		PMP22/EMP/MP20/Claudin, Claudin, Claudin_CS
SLC25A25	Other/Unknown	no		EF_hand_dom, MCP, GDC-like
MINDY4	Other/Unknown	no		MINDY-3/4_CD, MINY3/4, MINDY4_N
CYP24A1	Enzyme (other)	yes	1.14.14.24	Cyt_P450, Cyt_P450_E_grp-I, Cyt_P450_CS
WDR72	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_CS
DGKD	Kinase	yes	2.7.1.107	Diacylglycerol_kin_accessory, Diacylglycerol_kinase_cat_dom, SAM
DGKH	Kinase	yes	2.7.1.107	Diacylglycerol_kin_accessory, Diacylglycerol_kinase_cat_dom, SAM
AGXT	Enzyme (other)	yes	2.6.1.44	Aminotrans_V_dom, PyrdxlP-dep_Trfase_major, PyrdxlP-dep_Trfase_small
F12	Protease	yes	3.4.21.38	Kringle, Fibronectin_type1, FN_type2_dom
ALPL	Phosphatase	yes	3.1.3.1	Alkaline_phosphatase, Alkaline_phosphatase_core_sf, Alkaline_phosphatase_AS
GRHPR	Enzyme (other)	yes	1.1.1.26	D-isomer_2_OHA_DH_cat_dom, D-isomer_DH_NAD-bd, D-isomer_DH_CS
HIBADH	Other/Unknown	no		3-OH-isobutyrate_DH-rel_CS, 6PGDH_NADP-bd, 6-PGluconate_DH-like_C_sf
INMT	Other/Unknown	no		NNMT_TEMT_trans, NNMT/PNMT/TEMT_CS, SAM-dependent_MTases_sf
KCNK5	Ion channel	yes		2pore_dom_K_chnl_TASK, 2pore_dom_K_chnl, K_chnl_dom
AQP1	Other/Unknown	no		MIP, MIP_CS, Aquaporin-like
MAP4K5	Kinase	yes		Prot_kinase_dom, CNH_dom, Kinase-like_dom_sf
ABCG2	Transporter	yes	7.6.2.2	ABC_transporter-like_ATP-bd, AAA+_ATPase, ABC2_TM
MT-CO3	Other/Unknown	no		Cyt_c_oxidase-like_su3, Cyt_c_oxidase_su3_a-hlx, Cyt_c/ubiquinol_Oxase_su3
ATP6V1B1	Other/Unknown	no		ATPase_F1/V1/A1_a/bsu_nucl-bd, ATPase_F1/V1/A1_a/bsu_N, ATPase_V1-cplx_bsu
RGS14	Other/Unknown	no		GoLoco_motif, RBD_dom, RGS

Expression context

Cohort genes with no expression data: 0.

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

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	34
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	6
right lobe of liver	5
adult mammalian kidney	4
kidney epithelium	4
renal medulla	4
liver	4
nephron tubule	3
esophagus mucosa	3
lower esophagus mucosa	3
metanephros cortex	3
caudate nucleus	2
putamen	2
rectum	2
granulocyte	2
hair follicle	2
mucosa of transverse colon	2
olfactory segment of nasal mucosa	2
dorsal root ganglion	2
right uterine tube	2
pancreatic ductal cell	2

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC34A1	52	tissue_specific	marker	nephron tubule, adult mammalian kidney, kidney epithelium
BCR	275	ubiquitous	marker	nucleus accumbens, caudate nucleus, putamen
SCNN1B	188	broad	marker	lower esophagus mucosa, esophagus mucosa, rectum
SLC12A1	185	tissue_specific	marker	renal medulla, nephron tubule, metanephros cortex
SLC22A2	108	tissue_specific	marker	adult mammalian kidney, nephron tubule, renal medulla
SLC3A1	163	tissue_specific	marker	body of pancreas, gall bladder, metanephros cortex
NHERF1	284	ubiquitous	marker	granulocyte, lower esophagus mucosa, esophagus mucosa
SOX9	274	ubiquitous	marker	ventricular zone, cranial nerve II, hair follicle
GIPC1	292	ubiquitous	marker	lower esophagus mucosa, mucosa of transverse colon, esophagus mucosa
UMOD	104	tissue_specific	marker	renal medulla, adult organism, adult mammalian kidney
CASR	63	tissue_specific	marker	islet of Langerhans, diaphragm, hair follicle
PFN3	24	tissue_specific	yes	male germ line stem cell (sensu Vertebrata) in testis, right testis, left testis
CLDN14	84	tissue_specific	marker	right lobe of liver, liver, male germ line stem cell (sensu Vertebrata) in testis
CLDN16	127	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, olfactory segment of nasal mucosa, adult mammalian kidney
CLDN19	143	broad	marker	trigeminal ganglion, dorsal root ganglion, pigmented layer of retina
SLC25A25	248	ubiquitous	marker	mucosa of stomach, kidney epithelium, right lobe of liver
MINDY4	133	ubiquitous	marker	right uterine tube, male germ line stem cell (sensu Vertebrata) in testis, right coronary artery
CYP24A1	163	broad	marker	olfactory segment of nasal mucosa, secondary oocyte, male germ line stem cell (sensu Vertebrata) in testis
WDR72	139	tissue_specific	marker	kidney epithelium, pancreatic ductal cell, renal medulla
DGKD	141	ubiquitous	marker	body of stomach, cerebellar hemisphere, cerebellum
DGKH	237	ubiquitous	marker	endothelial cell, dorsal root ganglion, epithelial cell of pancreas
AGXT	125	tissue_specific	marker	right lobe of liver, liver, endometrium epithelium
F12	191	broad	marker	right lobe of liver, liver, gingival epithelium
ALPL	200	broad	marker	right adrenal gland, right adrenal gland cortex, left adrenal gland cortex
GRHPR	292	ubiquitous	marker	right lobe of liver, liver, right adrenal gland
HIBADH	260	ubiquitous	marker	kidney epithelium, left ventricle myocardium, cardiac muscle of right atrium
INMT	188	broad	marker	right lung, upper lobe of left lung, upper lobe of lung
KCNK5	213	broad	marker	pancreatic ductal cell, mucosa of transverse colon, ileal mucosa
AQP1	283	broad	marker	descending thoracic aorta, ascending aorta, thoracic aorta
MAP4K5	296	ubiquitous	marker	corpus callosum, sural nerve, calcaneal tendon

Protein interactions among cohort

Intra-cohort edges: 18.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SOX9	4,935
AQP1	4,259
F12	3,850
ABCG2	3,743
SLC34A1	3,362
GRHPR	2,785
CASR	2,692
AGXT	2,648
NHERF1	2,599
HIBADH	2,364

Intra-cohort edges

A	B	Sources
ABCG2	SLC22A2	string_interaction
AGXT	GRHPR	string_interaction
AQP1	KCNK5	biogrid_interaction, intact
AQP1	SLC12A1	string_interaction
CASR	CLDN14	string_interaction
CASR	CLDN16	string_interaction
CASR	CLDN19	string_interaction
CASR	SLC12A1	string_interaction
CLDN16	CLDN19	intact, string_interaction
CLDN19	SLC12A1	string_interaction
DGKD	DGKH	biogrid_interaction
DGKH	MINDY4	string_interaction
GRHPR	SLC3A1	string_interaction
INMT	MINDY4	string_interaction
MINDY4	RGS14	string_interaction
NHERF1	SLC34A1	string_interaction
SCNN1B	SLC12A1	string_interaction
SLC12A1	UMOD	string_interaction

Structural data

PDB: 19 · AlphaFold-only: 15 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CASR	P41180	31
ABCG2	Q9UNQ0	29
NHERF1	O14745	22
AGXT	P21549	17
F12	P00748	17
UMOD	P07911	10
AQP1	P29972	10
BCR	P11274	5
SCNN1B	P51168	5
SLC3A1	Q07837	5
ALPL	P05186	5
RGS14	O43566	5
GRHPR	Q9UBQ7	4
MT-CO3	P00414	3
DGKD	Q16760	2
HIBADH	P31937	2
SLC22A2	O15244	1
SOX9	P48436	1
INMT	O95050	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PFN3	P60673	94.41
CYP24A1	Q07973	89.03
ATP6V1B1	P15313	87.21
GIPC1	O14908	81.92
CLDN19	Q8N6F1	81.08
CLDN14	O95500	80.00
SLC12A1	Q13621	78.39
CLDN16	Q9Y5I7	76.74
MAP4K5	Q9Y4K4	74.15
SLC25A25	Q6KCM7	73.65
SLC34A1	Q06495	72.24
DGKH	Q86XP1	71.33
KCNK5	O95279	69.94
MINDY4	Q4G0A6	68.40
WDR72	Q3MJ13	67.22

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 127. Enrichment computed across 34 evidence-associated genes (28 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 28 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Abacavir transmembrane transport	2	163.1×	0.004	SLC22A2, ABCG2
Tight junction interactions	3	39.5×	0.004	CLDN14, CLDN16, CLDN19
Abacavir ADME	2	102.0×	0.007	SLC22A2, ABCG2
Glyoxylate metabolism and glycine degradation	2	54.4×	0.017	AGXT, GRHPR
Transport of small molecules	6	5.4×	0.017	SCNN1B, SLC12A1, SLC22A2, SLC3A1, AQP1, ABCG2
Methylation of MeSeH for excretion	1	407.9×	0.035	INMT
Defective CYP24A1 causes HCAI	1	407.9×	0.035	CYP24A1
Defective SLC12A1 causes Bartter syndrome 1 (BS1)	1	407.9×	0.035	SLC12A1
Effects of PIP2 hydrolysis	2	32.6×	0.035	DGKD, DGKH
Defective SLC34A1 causes hypophosphatemic nephrolithiasis/osteoporosis 1 (NPHLOP1)	1	203.9×	0.048	SLC34A1
Defective SLC3A1 causes cystinuria (CSNU)	1	203.9×	0.048	SLC3A1
Defective amino acid transport by SLC7A9 causes cystinuria (CSNU)	1	203.9×	0.048	SLC3A1
Aggregated β-amyloid induces FXII autocatalysis	1	203.9×	0.048	F12
Drug ADME	2	16.3×	0.054	SLC22A2, ABCG2
Developmental Lineage of Pancreatic Ductal Cells	2	16.3×	0.054	SOX9, AQP1
Developmental Cell Lineages	2	16.0×	0.054	SOX9, ABCG2
TGFBR3 regulates FGF2 signaling	1	135.9×	0.055	GIPC1
SLC transporter disorders	2	14.6×	0.055	SLC12A1, SLC3A1
Metabolism of amino acids and derivatives	3	7.2×	0.055	AGXT, HIBADH, INMT
Type II Na+/Pi cotransporters	1	102.0×	0.056	SLC34A1
Defective factor XII causes hereditary angioedema	1	102.0×	0.056	F12
Defective SERPING1 causes hereditary angioedema	1	102.0×	0.056	F12
SLC-mediated transmembrane transport	3	6.3×	0.063	SLC12A1, SLC22A2, SLC3A1
Ciprofloxacin ADME	1	81.6×	0.065	ABCG2
Vitamins	1	68.0×	0.071	CYP24A1
Sensory perception of salty taste	1	68.0×	0.071	SCNN1B
Cation-coupled Chloride cotransporters	1	58.3×	0.077	SLC12A1
Metabolism of porphyrins	1	51.0×	0.077	ABCG2
NFE2L2 regulating MDR associated enzymes	1	51.0×	0.077	ABCG2
TGFBR3 regulates TGF-beta signaling	1	51.0×	0.077	GIPC1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 34 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
potassium ion homeostasis	4	90.1×	5e-05	SCNN1B, SLC12A1, UMOD, ATP6V1B1
renal absorption	3	148.7×	2e-04	NHERF1, CLDN16, CLDN19
intracellular phosphate ion homeostasis	3	135.2×	2e-04	SLC34A1, NHERF1, UMOD
renal urate salt excretion	2	330.4×	0.001	UMOD, ABCG2
calcium-independent cell-cell adhesion	3	70.8×	0.001	CLDN14, CLDN16, CLDN19
renal sodium ion transport	2	247.8×	0.002	NHERF1, ATP6V1B1
bile acid secretion	2	198.3×	0.003	NHERF1, CASR
renal water homeostasis	3	45.1×	0.003	UMOD, AQP1, ATP6V1B1
glyoxylate metabolic process	2	165.2×	0.003	AGXT, GRHPR
xenobiotic transport across blood-brain barrier	2	165.2×	0.003	SLC22A2, ABCG2
paracellular transport	2	141.6×	0.004	CLDN16, CLDN19
lipid phosphorylation	2	99.1×	0.006	DGKD, DGKH
multicellular organismal-level water homeostasis	2	99.1×	0.006	SCNN1B, AQP1
export across plasma membrane	2	99.1×	0.006	SLC22A2, ABCG2
bicellular tight junction assembly	3	29.2×	0.006	CLDN14, CLDN16, CLDN19
chloride ion homeostasis	2	90.1×	0.007	SLC12A1, ATP6V1B1
diacylglycerol metabolic process	2	70.8×	0.011	DGKD, DGKH
renal system process	2	66.1×	0.012	BCR, SCNN1B
cellular detoxification	2	66.1×	0.012	SLC22A2, ABCG2
ossification	3	20.1×	0.012	SLC34A1, CASR, ATP6V1B1
phosphate ion homeostasis	2	62.0×	0.012	SLC34A1, ALPL
glomerular filtration	2	55.1×	0.014	UMOD, AQP1
sodium ion homeostasis	2	55.1×	0.014	SCNN1B, SLC12A1
fibroblast migration	2	49.6×	0.017	NHERF1, AQP1
cellular homeostasis	2	47.2×	0.017	ALPL, AQP1
response to vitamin D	2	47.2×	0.017	CYP24A1, ALPL
intracellular sodium ion homeostasis	2	45.1×	0.017	SCNN1B, UMOD
transport across blood-brain barrier	3	15.8×	0.017	SLC22A2, NHERF1, ABCG2
actin cytoskeleton organization	4	9.3×	0.017	BCR, NHERF1, PFN3, CLDN19
sodium ion import across plasma membrane	2	36.7×	0.024	SLC34A1, SCNN1B

Therapeutics

Drugs indicated for this disease

0 approved, 17 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Acetaminophen	Phase 3 (in late-stage trials)
Alfuzosin	Phase 3 (in late-stage trials)
Ampicillin	Phase 3 (in late-stage trials)
Ciprofloxacin	Phase 3 (in late-stage trials)
Clindamycin	Phase 3 (in late-stage trials)
Doxazosin	Phase 3 (in late-stage trials)
Furosemide	Phase 3 (in late-stage trials)
Gentamicin	Phase 3 (in late-stage trials)
Hydrochlorothiazide	Phase 3 (in late-stage trials)
Ketorolac	Phase 3 (in late-stage trials)
Mirabegron	Phase 3 (in late-stage trials)
Morphine	Phase 3 (in late-stage trials)
Nifedipine	Phase 3 (in late-stage trials)
Oxycodone	Phase 3 (in late-stage trials)
Prazosin	Phase 3 (in late-stage trials)
Silodosin	Phase 3 (in late-stage trials)
Tamsulosin	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Allopurinol, Chlorthalidone, Citric Acid, Empagliflozin, Febuxostat, Isoproterenol, Lumasiran, Tolterodine.

Drug target analysis

Approved (phase 4): 8 · Phase ≥3: 9 · Phased (≥1): 10 · Undrugged: 24

Druggability breadth: 23 of 34 evidence-associated genes (68%) 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
SLC34A1	SODIUM PHOSPHATE, DIBASIC, ANHYDROUS
BCR	PONATINIB
SLC22A2	PROGESTERONE
CASR	CINACALCET HYDROCHLORIDE
CYP24A1	KETOCONAZOLE
ALPL	SULCONAZOLE NITRATE
MAP4K5	VEMURAFENIB
ABCG2	CANDESARTAN CILEXETIL

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ABCG2	92	4
MAP4K5	67	4
BCR	64	4
SLC22A2	47	4
CASR	10	4
ALPL	7	4
CYP24A1	4	4
F12	3	3
SLC34A1	2	4
INMT	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
SODIUM PHOSPHATE, DIBASIC, ANHYDROUS	4	SLC34A1
POTASSIUM PHOSPHATE, MONOBASIC	4	SLC34A1
PONATINIB	4	ABCG2, BCR
DASATINIB ANHYDROUS	4	BCR
IMATINIB MESYLATE	4	BCR
INFIGRATINIB	4	BCR
NILOTINIB	4	ABCG2, BCR
BOSUTINIB	4	ABCG2, BCR, MAP4K5
ASCIMINIB	4	BCR
DASATINIB	4	ABCG2, BCR, MAP4K5
TIRBANIBULIN	4	BCR
IMATINIB	4	ABCG2, BCR, SLC22A2
FEDRATINIB	4	BCR
TIVOZANIB	4	ABCG2, BCR
LENVATINIB	4	BCR, MAP4K5
AXITINIB	4	BCR, MAP4K5
IBRUTINIB	4	BCR
REGORAFENIB	4	ABCG2, BCR
CABOZANTINIB	4	BCR
VANDETANIB	4	ABCG2, BCR, MAP4K5
TOVORAFENIB	4	BCR
NINTEDANIB	4	BCR, MAP4K5
ERLOTINIB	4	ABCG2, BCR
CRIZOTINIB	4	BCR, MAP4K5
PROGESTERONE	4	SLC22A2
IMIPRAMINE	4	SLC22A2
EPINASTINE	4	SLC22A2
VECURONIUM BROMIDE	4	SLC22A2
DOLUTEGRAVIR	4	ABCG2, SLC22A2
PIMOZIDE	4	SLC22A2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 8.

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

Symbol	Assays	Type breakdown
ABCG2	878	Binding:651, ADMET:115, Functional:111, Toxicity:1
BCR	486	Binding:478, Functional:6, Toxicity:2
MAP4K5	262	Binding:261, Functional:1
F12	128	Binding:123, Functional:3, ADMET:2
SLC22A2	101	Functional:62, ADMET:21, Binding:18
ALPL	58	Binding:50, Functional:4, ADMET:3, Toxicity:1
CASR	45	Functional:32, Binding:13
INMT	41	Binding:38, ADMET:3
CYP24A1	35	Binding:28, ADMET:7
DGKH	10	Binding:10
SLC34A1	8	Binding:7, Functional:1
AGXT	8	Binding:8
AQP1	8	Binding:8
SCNN1B	5	Binding:3, ADMET:1, Functional:1
NHERF1	5	Binding:5
KCNK5	4	Binding:4
SOX9	3	Binding:3
DGKD	2	Binding:2
GRHPR	2	Binding:2
HIBADH	2	Binding:2
MT-CO3	1	Binding:1
ATP6V1B1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CYP24A1	1.14.14.24, 1.14.15.16	vitamin D 25-hydroxylase, vitamin D3 24-hydroxylase
DGKD	2.7.1.107	diacylglycerol kinase (ATP)
DGKH	2.7.1.107	diacylglycerol kinase (ATP)
AGXT	2.6.1.44, 2.6.1.51	alanine-glyoxylate transaminase, serine-pyruvate transaminase
F12	3.4.21.38	coagulation factor XIIa
ALPL	3.1.3.1	alkaline phosphatase
GRHPR	1.1.1.26, 1.1.1.79, 1.1.1.81	glyoxylate reductase, glyoxylate reductase (NADP+), hydroxypyruvate reductase
ABCG2	7.6.2.2, 7.6.2.3	ABC-type xenobiotic transporter, ABC-type glutathione-S-conjugate transporter

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
BCR	486
SLC22A2	101
F12	128
MAP4K5	262
ABCG2	878

Pharmacogenomics

Cohort genes with a PharmGKB record: 34; with CPIC/DPWG dosing guidelines: 1.

Cohort genes with a CPIC/DPWG dosing guideline

Symbol	CPIC guidelines
ABCG2	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)
SODIUM PHOSPHATE, DIBASIC, ANHYDROUS	4	SLC34A1
POTASSIUM PHOSPHATE, MONOBASIC	4	SLC34A1
PONATINIB	4	ABCG2, BCR
DASATINIB ANHYDROUS	4	BCR
IMATINIB MESYLATE	4	BCR
INFIGRATINIB	4	BCR
NILOTINIB	4	ABCG2, BCR
BOSUTINIB	4	ABCG2, BCR, MAP4K5
ASCIMINIB	4	BCR
DASATINIB	4	ABCG2, BCR, MAP4K5
TIRBANIBULIN	4	BCR
IMATINIB	4	ABCG2, BCR, SLC22A2
FEDRATINIB	4	BCR
TIVOZANIB	4	ABCG2, BCR
LENVATINIB	4	BCR, MAP4K5
AXITINIB	4	BCR, MAP4K5
IBRUTINIB	4	BCR
REGORAFENIB	4	ABCG2, BCR
CABOZANTINIB	4	BCR
VANDETANIB	4	ABCG2, BCR, MAP4K5
TOVORAFENIB	4	BCR
NINTEDANIB	4	BCR, MAP4K5
ERLOTINIB	4	ABCG2, BCR
CRIZOTINIB	4	BCR, MAP4K5
PROGESTERONE	4	SLC22A2
IMIPRAMINE	4	SLC22A2
EPINASTINE	4	SLC22A2
VECURONIUM BROMIDE	4	SLC22A2
DOLUTEGRAVIR	4	ABCG2, SLC22A2
PIMOZIDE	4	SLC22A2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	8	SLC34A1, BCR, SLC22A2, CASR, CYP24A1, ALPL, MAP4K5, ABCG2
B	Phased (≥1) drug, not yet approved	2	F12, INMT
C	Druggable family + PDB, no drug	3	DGKD, AGXT, GRHPR
D	Druggable family + AlphaFold only, no drug	2	DGKH, KCNK5
E	Difficult family or no structure, no drug	19	SCNN1B, SLC12A1, SLC3A1, NHERF1, SOX9, GIPC1, UMOD, PFN3, CLDN14, CLDN16 (+9 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CLDN14	0	CASR
MINDY4	0	INMT
SCNN1B	5	—
SLC12A1	0	—
SLC3A1	0	—
NHERF1	5	—
SOX9	3	—
GIPC1	0	—
UMOD	0	—
PFN3	0	—
CLDN16	0	—
CLDN19	0	—
SLC25A25	0	—
WDR72	0	—
DGKD	2	—
DGKH	10	—
AGXT	8	—
GRHPR	2	—
HIBADH	2	—
KCNK5	4	—
AQP1	8	—
MT-CO3	1	—
ATP6V1B1	1	—
RGS14	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 448.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	351
PHASE4	35
PHASE2	25
PHASE3	20
EARLY_PHASE1	6
PHASE2/PHASE3	4
PHASE1/PHASE2	4
PHASE1	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06966635	PHASE4	RECRUITING	Exploratory Study on the Treatment of Gout With Potassium Citrate Sustained-release Tablets
NCT07124299	PHASE4	RECRUITING	Alpha-Blockers Prior to Ureteral Access Sheath Placement in Flexible Ureteroscopy: A Randomized Prospective Study
NCT07225764	PHASE4	RECRUITING	CaOx Stone Prevention
NCT07512297	PHASE4	NOT_YET_RECRUITING	Pain Control During ESWL Using Non-Opioid Analgesics
NCT00765128	PHASE4	COMPLETED	Intravenous Ketorolac for Postoperative Pain in Percutaneous Nephrolithotomy
NCT01295879	PHASE4	COMPLETED	Vitamin D Repletion in Stone Formers With Hypercalciuria
NCT01329042	PHASE4	COMPLETED	Efficacy of Potassium Sodium Hydrogen Citrate Therapy on Renal Stone Recurrence and/or Residual Fragments After Shockwave Lithotripsy and Percutaneous Nephrolithotomy in Calcium Oxalate Urolithiasis
NCT01452880	PHASE4	COMPLETED	Remifentanil in Extracorporeal Shock Wave Lithotripsy
NCT01675362	PHASE4	COMPLETED	Are There Protective Effects of Antioxidants, Calcium Channel Blocker and Angiotensin Receptor Blocker Against Extracorporeal Shockwaves Lithotripsy Induced Renal Injury?
NCT02011737	PHASE4	UNKNOWN	Naftopidil 75mg for Improving Clearance of Urinary Stones
NCT02095665	PHASE4	COMPLETED	Ureteral Stent-related Pain and Mirabegron (SPAM) Trial
NCT02375295	PHASE4	UNKNOWN	Struvite Stones Antibiotic Study
NCT02384200	PHASE4	COMPLETED	A Randomized Trial of Preoperative Prophylactic Antibiotics Prior to Kidney Stone Surgery (Percutaneous Nephrolithotomy [PCNL])
NCT02430168	PHASE4	UNKNOWN	Comparison of RIRS Versus PCNL Methods, According to Postoperative Pain and Analgesic Demand in 2 to 4 cm Renal Stones
NCT02430883	PHASE4	UNKNOWN	Is There Any Relation Between Pain and Stone Location in Retrograde Intrarenal Surgery?
NCT02443909	PHASE4	UNKNOWN	Comparison of Safety and Efficiency of 20w and 30w Holmium Laser Device in Management of 2-3 cm Diameter Kidney Stones With Retrograde Intrarenal Surgery
NCT02451319	PHASE4	UNKNOWN	Comparison of Safety and Efficiency of 20w 30w Holmium Laser Device in Treatment of 1-2 cm Diameter Kidney Stones With RIRS
NCT02489656	PHASE4	UNKNOWN	Quality of Life in Patients With Double Loop Ureteral Stent (JJ Silicone Hydrogel Study)
NCT02818140	PHASE4	COMPLETED	Ultrasound-guided Transmuscular Quadratus Lumborum Block for Percutaneous Nephrolithotomy
NCT02966236	PHASE4	UNKNOWN	Impact of Tranexamic Acid Use in Percutaneous Nephrolithotomy
NCT03035812	PHASE4	COMPLETED	Alkalinization by Urologists & Nephrologists
NCT03229889	PHASE4	COMPLETED	Trial of Tadalafil, Tamsulosin and Combination for Access Sheath Deployment
NCT03332056	PHASE4	COMPLETED	The Use of Belladonna and Opium Suppository in the Treatment of Postoperative Stent Pain
NCT03549611	PHASE4	WITHDRAWN	Pre-induction Analgesia: Multimodel Regimen vs Aceteminophen for Post Ureteroscopy Pain
NCT03692715	PHASE4	COMPLETED	Antibiotic Prophylaxis Before Shock Wave Lithotripsy
NCT03872843	PHASE4	COMPLETED	Opioid Free Management After Ureteroscopy
NCT03888144	PHASE4	COMPLETED	Study of Ketorolac Versus Opioid for Pain After Endoscopy
NCT04095975	PHASE4	COMPLETED	Effectiveness of Urinary Alkalinizing Agents on Kidney Stone Risk
NCT04663269	PHASE4	TERMINATED	Regional Erector Spinae Analgesic Block vs Standard of Care Undergoing Percutaneous Nephrolithotomy
NCT05082142	PHASE4	COMPLETED	Tranexamic Acid to Improve Same-day Discharge Rates After Holmium Laser Enucleation of the Prostate (HoLEP)
NCT05365477	PHASE4	COMPLETED	Empiric Versus Selective Prevention Strategies for Kidney Stone Disease
NCT05414669	PHASE4	COMPLETED	Allopurinol Effect on MDA,NO,KIM-1 Urine Levels, RI and Renal Elastography in Kidney Stone Patients Post ESWL
NCT05924165	PHASE4	COMPLETED	Narcotic-Free Percutaneous Nephrolithotomy
NCT06124066	PHASE4	COMPLETED	THE EFFECTS OF MIRABEGRON AND TAMSULOSIN FOR PATIENTS WITH URETERAL STENTS
NCT07582341	PHASE4	COMPLETED	Combined Intravenous and Irrigation Tranexamic Acid During Percutaneous Nephrolithotomy
NCT05916963	PHASE3	RECRUITING	Impact of Forced Diuresis on the Residual Fragment Rate After Flexible Ureteroscopy for Destruction of Kidney Stones With Laser
NCT06349668	PHASE3	RECRUITING	Spinal Morphine or Intravenous Lidocaine in Robot-assisted Upper Urologic Surgery
NCT06653738	PHASE3	NOT_YET_RECRUITING	Trial to Assess the Efficacy of EMPAgliflozin and Personalized Dietary Counseling for Kidney STONE Prevention
NCT00004284	PHASE3	COMPLETED	Phase III Randomized, Double-Blind Study of Potassium Phosphate Vs Potassium Citrate for Absorptive Hypercalciuria
NCT00177086	PHASE3	COMPLETED	Alfuzosin Hydrochloride to Promote Passage of Distal Ureteral Calculi

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
POTASSIUM CITRATE ANHYDROUS	4	14
KETOROLAC	4	12
TAMSULOSIN	4	10
ALFUZOSIN	4	7
AMPICILLIN	4	3
CHLORTHALIDONE	4	3
CLINDAMYCIN	4	3
DOXAZOSIN	4	3
GENTAMICIN	4	3
MIRABEGRON	4	3
PRAZOSIN	4	3
SILODOSIN	4	3
SODIUM BICARBONATE	4	3
CIPROFLOXACIN	4	2
FUROSEMIDE	4	2
ISOPROTERENOL	4	2
MORPHINE	4	2
NITROFURANTOIN	4	2
OXYCODONE	4	2
ACETIC ACID	4	1
ALFENTANIL	4	1
ALLOPURINOL	4	1
CALCIUM CARBONATE	4	1
CEFTRIAXONE	4	1
CITRIC ACID	4	1
ERGOCALCIFEROL	4	1
FEBUXOSTAT	4	1
FLUCONAZOLE	4	1
INDAPAMIDE	4	1
LANTHANUM CARBONATE	4	1

Cohort genes: SLC34A1, BCR, SCNN1B, SLC12A1, SLC22A2, SLC3A1, NHERF1, SOX9, GIPC1, UMOD, CASR, PFN3, CLDN14, CLDN16, CLDN19, SLC25A25, MINDY4, CYP24A1, WDR72, DGKD, DGKH, AGXT, F12, ALPL, GRHPR, HIBADH, INMT, KCNK5, AQP1, MAP4K5, ABCG2, MT-CO3, ATP6V1B1, RGS14
Drugs: Potassium, Ketorolac, Tamsulosin, Alfuzosin, Ampicillin, Chlorthalidone, Clindamycin, Doxazosin, Gentamicin, Mirabegron, Prazosin, Silodosin, Sodium Bicarbonate, Ciprofloxacin, Furosemide, Isoproterenol, Morphine, Nitrofurantoin, Oxycodone, Acetic Acid, Alfentanil, Allopurinol, Calcium Carbonate, Ceftriaxone, Citric Acid, Ergocalciferol, Febuxostat, Fluconazole, Indapamide, Lanthanum Carbonate