Urolithiasis

Summary

Urolithiasis (MONDO:0024647) is a disease with 16 cohort genes (141 GWAS associations across 51 studies) and 402 clinical trials. Top therapeutic interventions include ketorolac, tamsulosin, and potassium citrate anhydrous.

At a glance

• Cohort genes: 16
• GWAS associations: 141
• Clinical trials: 402

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	urolithiasis
Mondo ID	MONDO:0024647
MeSH	D052878
DOID	DOID:0080653
ICD-10-CM	N20-N23, N21
ICD-11	1746821938
NCIT	C114688
SNOMED CT	95566004
UMLS	C0451641
MedGen	141536
Is cancer (heuristic)	no

Also known as: calculus · kidney stone · urinary stones · urolithiasis

Data availability: 141 GWAS associations (51 studies) · 2 cell lines.

Disease family

An umbrella term covering 2 Mondo subtypes.

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

Related subtypes (19): bacteriuria, ureteral disorder, pyuria, urinary tract obstruction, urethral disorder, kidney disorder, urinary bladder disorder, hyperglycinuria, hypercalciuria, absorptive, 2, hypercalciuria, absorptive, 1, megacystis-megaureter syndrome, postorgasmic illness syndrome, congenital urachal anomaly, urinary system neoplasm, urothelial hyperplasia, urinary tract infection, meningitis-retention syndrome, paraneoplastic renal syndrome, idiopathic hypercalciuria

Subtypes (2): lower urinary tract calculus, nephrolithiasis

Genetics & variants

GWAS landscape

141 GWAS associations across 51 studies. Top hits map to 19 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs11748297	2e-31	RGS14 - SLC34A1	A	0.15
chr5:177371039	7e-27		G	0.15
rs9594689	1e-26	DGKH	G	0.12
chr21:36446573	1e-26		G	0.13
chr21:36463203	1e-26		T	0.16
chr16:20381010	2e-22		A	0.16
rs77924615	3e-22	PDILT	A	0.14
rs7328064	4e-22	DGKH	C	1.15
rs1170158	4e-21	DGKH	T	0.14
rs9895661	5e-21	BCAS3, TBX2-AS1	T	0.12
chr20:54118699	8e-21		GT	0.14
rs7277076	1e-20	CLDN14, LNCTSI	C	0.11
rs13353032	6e-20	NBPF3 - ALPL	G	0.12
chr20:54114863	1e-19		T	0.13
rs11746443	2e-19	RGS14	A	1.15
chr1:21561666	2e-19		C	0.12
rs6556314	8e-18	SLC34A1	T	0.13
rs2241358	1e-17	PTGER1 - GIPC1	G	0.11
rs141471965	4e-17	ABCG2	?
rs2079742	6e-17	TBX2-AS1, BCAS3	C	0.13
rs1260326	6e-17	GCKR	C	0.1
rs3798519	1e-15	TFAP2B	C	1.12
rs34422078	1e-15	PKN1	G	0.13
chr13:42100465	2e-15		G	0.13
rs74956940	5e-15	PKN1	G	1.14
chr22:23068739	7e-15		T	0.1
rs838717	8e-15	DGKD	A	0.09
rs2286526	1e-14	TBX2-AS1	T	1.12
rs6975977	1e-14	INMT-MINDY4, MINDY4	A	0.15
rs6123359	2e-14	BCAS1 - CYP24A1	G	0.1

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90474180	UK Biobank Whole-Genome Sequencing Consortium	2025	16,023	442,417	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90667800	UK Biobank Whole-Genome Sequencing Consortium	2025	16,023	442,417	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90474182	UK Biobank Whole-Genome Sequencing Consortium	2025	11,891	446,549	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90667951	UK Biobank Whole-Genome Sequencing Consortium	2025	11,891	446,549	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90681844	Namba S	2026	11,755	155,002	A cross-population compendium of gene-environment interactions.
GCST90681891	Namba S	2026	11,755	155,002	A cross-population compendium of gene-environment interactions.
GCST90018715	Sakaue S	2021	11,699	167,027	A cross-population atlas of genetic associations for 220 human phenotypes.
GCST90681985	Namba S	2026	11,639	152,843	A cross-population compendium of gene-environment interactions.
GCST90681938	Namba S	2026	11,607	152,526	A cross-population compendium of gene-environment interactions.
GCST90682032	Namba S	2026	11,299	149,641	A cross-population compendium of gene-environment interactions.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	2
Tier 2: splice/UTR	0
Tier 3: regulatory	1
Tier 4: intronic/intergenic	47

MAF distribution

Bucket	Variants
common (>=0.05)	37
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	13

Functional consequences

Consequence	Count
intron_variant	30
unknown	13
intergenic_variant	4
regulatory_region_variant	1
missense_variant	1
stop_gained	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs11748297	5	177373360	G>A,C,T	0.05	intergenic_variant	RGS14 - SLC34A1	2e-31	Tier 4: intronic/intergenic
chr5:177371039							7e-27	Tier 4: intronic/intergenic
rs9594689	13	42163132	T>A,G	0.05	intron_variant	DGKH	1e-26	Tier 4: intronic/intergenic
chr21:36446573							1e-26	Tier 4: intronic/intergenic
chr21:36463203							1e-26	Tier 4: intronic/intergenic
chr16:20381010							2e-22	Tier 4: intronic/intergenic
rs77924615	16	20381010	G>A	0.05	intron_variant	PDILT	3e-22	Tier 4: intronic/intergenic
rs7328064	13	42171982	A>C,T	0.421	intron_variant	DGKH	4e-22	Tier 4: intronic/intergenic
rs1170158	13	42127805	G>A,C,T	0.494	intron_variant	DGKH	4e-21	Tier 4: intronic/intergenic
rs9895661	17	61379228	C>A,T	0.05	intron_variant	BCAS3, TBX2-AS1	5e-21	Tier 4: intronic/intergenic
chr20:54118699							8e-21	Tier 4: intronic/intergenic
rs7277076	21	36464675	T>A,C	0.05	intron_variant	CLDN14, LNCTSI	1e-20	Tier 4: intronic/intergenic
rs13353032	1	21504166	T>G	0.05	intergenic_variant	NBPF3 - ALPL	6e-20	Tier 4: intronic/intergenic
chr20:54114863							1e-19	Tier 4: intronic/intergenic
rs11746443	5	177371305	G>A,C	0.05	intron_variant	RGS14	2e-19	Tier 4: intronic/intergenic
chr1:21561666							2e-19	Tier 4: intronic/intergenic
rs6556314	5	177392251	C>G,T	0.307	intron_variant	SLC34A1	8e-18	Tier 4: intronic/intergenic
rs2241358	19	14477664	C>A,G	0.05	regulatory_region_variant	PTGER1 - GIPC1	1e-17	Tier 3: regulatory
rs141471965	4	88125050	C>A,T	0.05	intron_variant	ABCG2	4e-17	Tier 4: intronic/intergenic
rs2079742	17	61388336	T>C	0.473	intron_variant	TBX2-AS1, BCAS3	6e-17	Tier 4: intronic/intergenic
rs1260326	2	27508073	T>A,C,G	0.05	missense_variant	GCKR	6e-17	Tier 1: coding
rs3798519	6	50821065	A>C,G	0.283	intron_variant	TFAP2B	1e-15	Tier 4: intronic/intergenic
rs34422078	19	14467542	C>G	0.241	intron_variant	PKN1	1e-15	Tier 4: intronic/intergenic
chr13:42100465							2e-15	Tier 4: intronic/intergenic
rs74956940	19	14461154	C>A,G,T	0.237	intron_variant	PKN1	5e-15	Tier 4: intronic/intergenic
chr22:23068739							7e-15	Tier 4: intronic/intergenic
rs838717	2	233387798	G>A	0.05	intron_variant	DGKD	8e-15	Tier 4: intronic/intergenic
rs2286526	17	61394696	C>G,T	0.325	intron_variant	TBX2-AS1	1e-14	Tier 4: intronic/intergenic
rs6975977	7	30878216	G>A	0.05	intron_variant	INMT-MINDY4, MINDY4	1e-14	Tier 4: intronic/intergenic
rs6123359	20	54098167	A>G	0.05	intron_variant	BCAS1 - CYP24A1	2e-14	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 11 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TFAP2B	Orphanet:46627	Char syndrome
TFAP2B	Orphanet:466729	Familial patent arterial duct
BCAS3	Orphanet:697067	Global developmental delay-intellectual disability-microcephaly-short stature-brain iron accumulation syndrome
CLDN14	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB
FTO	Orphanet:210144	Lethal polymalformative syndrome, Boissel type
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

Cohort genes → proteins

16 cohort genes, 16 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	16

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TFAP2B	HGNC:11743	ENSG00000008196	Q92481	Transcription factor AP-2-beta	gwas
BCAS3	HGNC:14347	ENSG00000141376	Q9H6U6	BCAS3 microtubule associated cell migration factor	gwas
MRPL33	HGNC:14487	ENSG00000243147	O75394	Large ribosomal subunit protein bL33m	gwas
CLDN14	HGNC:2035	ENSG00000159261	O95500	Claudin-14	gwas
MINDY4	HGNC:21916	ENSG00000106125	Q4G0A6	Probable ubiquitin carboxyl-terminal hydrolase MINDY-4	gwas
FTO	HGNC:24678	ENSG00000140718	Q9C0B1	Alpha-ketoglutarate-dependent dioxygenase FTO	gwas
PDILT	HGNC:27338	ENSG00000169340	Q8N807	Protein disulfide-isomerase-like protein of the testis	gwas
DGKH	HGNC:2854	ENSG00000102780	Q86XP1	Diacylglycerol kinase eta	gwas
EPB41L2	HGNC:3379	ENSG00000079819	O43491	Band 4.1-like protein 2	gwas
ALPL	HGNC:438	ENSG00000162551	P05186	Alkaline phosphatase, tissue-nonspecific isozyme	gwas
INMT	HGNC:6069	ENSG00000241644	O95050	Indolethylamine N-methyltransferase	gwas
KCNK5	HGNC:6280	ENSG00000164626	O95279	Potassium channel subfamily K member 5	gwas
MAP4K5	HGNC:6867	ENSG00000012983	Q9Y4K4	Mitogen-activated protein kinase kinase kinase kinase 5	gwas
PKN1	HGNC:9405	ENSG00000123143	Q16512	Serine/threonine-protein kinase N1	gwas
BCAS1	HGNC:974	ENSG00000064787	O75363	Breast carcinoma-amplified sequence 1	gwas
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)
TFAP2B	Transcription factor AP-2-beta	Sequence-specific DNA-binding protein that interacts with inducible viral and cellular enhancer elements to regulate transcription of selected genes.
BCAS3	BCAS3 microtubule associated cell migration factor	Plays a role in angiogenesis.
CLDN14	Claudin-14	Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity.
MINDY4	Probable ubiquitin carboxyl-terminal hydrolase MINDY-4	Probable hydrolase that can remove ‘Lys-48’-linked conjugated ubiquitin from proteins.
FTO	Alpha-ketoglutarate-dependent dioxygenase FTO	RNA demethylase that mediates oxidative demethylation of different RNA species, such as mRNAs, tRNAs and snRNAs, and acts as a regulator of fat mass, adipogenesis and energy homeostasis.
PDILT	Protein disulfide-isomerase-like protein of the testis	Probable redox-inactive chaperone involved in spermatogenesis.
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.
EPB41L2	Band 4.1-like protein 2	Required for dynein-dynactin complex and NUMA1 recruitment at the mitotic cell cortex during anaphase.
ALPL	Alkaline phosphatase, tissue-nonspecific isozyme	Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis.
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.
MAP4K5	Mitogen-activated protein kinase kinase kinase kinase 5	May play a role in the response to environmental stress.
PKN1	Serine/threonine-protein kinase N1	PKC-related serine/threonine-protein kinase involved in various processes such as regulation of the intermediate filaments of the actin cytoskeleton, cell migration, tumor cell invasion and transcription regulation.
BCAS1	Breast carcinoma-amplified sequence 1	Required for myelination.
RGS14	Regulator of G-protein signaling 14	Regulates G protein-coupled receptor signaling cascades.

Protein-family classification

Druggable: 6 · Difficult: 2 · Unknown: 8 · Druggable fraction: 0.38

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
Kinase	3	5.2×	0.129
Ion channel	1	7.0×	0.408
Phosphatase	1	5.2×	0.408
Scaffold/PPI	1	1.1×	0.873
Other/Unknown	8	0.9×	0.873
Enzyme (other)	1	0.8×	0.873
Transcription factor	1	0.5×	0.873

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TFAP2B	Transcription factor	no		TF_AP2, TF_AP2_beta, TF_AP2_C
BCAS3	Scaffold/PPI	no		WD40/YVTN_repeat-like_dom_sf, BCAS3_dom, WD40_repeat_dom_sf
MRPL33	Other/Unknown	no		Ribosomal_bL33, Ribosomal_zn-bd, Ribosomal_bL33_sf
CLDN14	Other/Unknown	no		PMP22/EMP/MP20/Claudin, Claudin, Claudin_CS
MINDY4	Other/Unknown	no		MINDY-3/4_CD, MINY3/4, MINDY4_N
FTO	Enzyme (other)	yes	1.14.11.53	FTO_C, FTO_cat_dom, FTO
PDILT	Other/Unknown	no		Thioredoxin_domain, Thioredoxin-like_sf
DGKH	Kinase	yes	2.7.1.107	Diacylglycerol_kin_accessory, Diacylglycerol_kinase_cat_dom, SAM
EPB41L2	Other/Unknown	no		FERM_domain, Ez/rad/moesin-like, SAB_dom
ALPL	Phosphatase	yes	3.1.3.1	Alkaline_phosphatase, Alkaline_phosphatase_core_sf, Alkaline_phosphatase_AS
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
MAP4K5	Kinase	yes		Prot_kinase_dom, CNH_dom, Kinase-like_dom_sf
PKN1	Kinase	yes	2.7.11.13	C2_dom, Prot_kinase_dom, AGC-kinase_C
BCAS1	Other/Unknown	no		NABC1
RGS14	Other/Unknown	no		GoLoco_motif, RBD_dom, RGS

Expression context

Cohort genes with no expression data: 0.

16 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)	16
unknown	0

Top tissues across cohort

Tissue	Cohort genes
sural nerve	3
colonic epithelium	2
right uterine tube	2
left adrenal gland cortex	2
right adrenal gland	2
right adrenal gland cortex	2
male germ line stem cell (sensu Vertebrata) in testis	2
calcaneal tendon	2
granulocyte	2
cauda epididymis	1
corpus epididymis	1
oocyte	1
liver	1
right lobe of liver	1
right coronary artery	1
Brodmann (1909) area 10	1
bronchial epithelial cell	1
cortical plate	1
body of stomach	1
left testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TFAP2B	128	broad	marker	corpus epididymis, cauda epididymis, oocyte
BCAS3	214	ubiquitous	marker	colonic epithelium, sural nerve, right uterine tube
MRPL33	295	ubiquitous	marker	right adrenal gland cortex, right adrenal gland, left adrenal gland cortex
CLDN14	84	tissue_specific	marker	right lobe of liver, liver, male germ line stem cell (sensu Vertebrata) in testis
MINDY4	133	ubiquitous	marker	right uterine tube, male germ line stem cell (sensu Vertebrata) in testis, right coronary artery
FTO	294	ubiquitous	marker	cortical plate, bronchial epithelial cell, Brodmann (1909) area 10
PDILT	39	tissue_specific	marker	left testis, right testis, body of stomach
DGKH	237	ubiquitous	marker	endothelial cell, dorsal root ganglion, epithelial cell of pancreas
EPB41L2	292	ubiquitous	marker	calcaneal tendon, colonic epithelium, sural nerve
ALPL	200	broad	marker	right adrenal gland, right adrenal gland cortex, left adrenal gland cortex
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
MAP4K5	296	ubiquitous	marker	corpus callosum, sural nerve, calcaneal tendon
PKN1	228	ubiquitous	marker	apex of heart, granulocyte, ventricular zone
BCAS1	243	broad	marker	C1 segment of cervical spinal cord, spinal cord, inferior vagus X ganglion
RGS14	236	ubiquitous	marker	granulocyte, caudate nucleus, putamen

Protein interactions among cohort

Intra-cohort edges: 3.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MRPL33	2,743
FTO	2,496
PKN1	2,324
ALPL	2,146
EPB41L2	1,484
TFAP2B	1,380
BCAS1	1,327
BCAS3	1,299
RGS14	1,271
DGKH	1,137

Intra-cohort edges

A	B	Sources
DGKH	MINDY4	string_interaction
INMT	MINDY4	string_interaction
MINDY4	RGS14	string_interaction

Structural data

PDB: 8 · AlphaFold-only: 8 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MRPL33	O75394	86
FTO	Q9C0B1	28
PKN1	Q16512	9
ALPL	P05186	5
RGS14	O43566	5
PDILT	Q8N807	2
TFAP2B	Q92481	1
INMT	O95050	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CLDN14	O95500	80.00
MAP4K5	Q9Y4K4	74.15
DGKH	Q86XP1	71.33
KCNK5	O95279	69.94
MINDY4	Q4G0A6	68.40
BCAS3	Q9H6U6	65.25
EPB41L2	O43491	60.14
BCAS1	O75363	51.00

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 40. Enrichment computed across 16 evidence-associated genes (11 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 11 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Methylation of MeSeH for excretion	1	1038.2×	0.039	INMT
Reversal of alkylation damage by DNA dioxygenases	1	148.3×	0.085	FTO
Negative regulation of activity of TFAP2 (AP-2) family transcription factors	1	103.8×	0.085	TFAP2B
Activation of the TFAP2 (AP-2) family of transcription factors	1	86.5×	0.085	TFAP2B
TFAP2 (AP-2) family regulates transcription of growth factors and their receptors	1	69.2×	0.085	TFAP2B
Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors	1	57.7×	0.085	TFAP2B
Specification of the neural plate border	1	57.7×	0.085	TFAP2B
Phase 4 - resting membrane potential	1	54.6×	0.085	KCNK5
SUMOylation of transcription factors	1	51.9×	0.085	TFAP2B
Effects of PIP2 hydrolysis	1	41.5×	0.095	DGKH
Tight junction interactions	1	33.5×	0.107	CLDN14
RHO GTPases activate PKNs	1	28.8×	0.114	PKN1
Gastrulation	1	23.6×	0.128	TFAP2B
Selenoamino acid metabolism	1	17.9×	0.138	INMT
Neurexins and neuroligins	1	17.9×	0.138	EPB41L2
SUMO E3 ligases SUMOylate target proteins	1	16.2×	0.138	TFAP2B
Post-translational modification: synthesis of GPI-anchored proteins	1	15.3×	0.138	ALPL
Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3	1	15.3×	0.138	PKN1
SUMOylation	1	14.8×	0.138	TFAP2B
RHOB GTPase cycle	1	14.0×	0.138	PKN1
RHOC GTPase cycle	1	13.3×	0.138	PKN1
Mitochondrial translation	1	12.5×	0.138	MRPL33
Mitochondrial translation initiation	1	11.5×	0.138	MRPL33
Mitochondrial translation elongation	1	11.5×	0.138	MRPL33
Mitochondrial ribosome-associated quality control	1	11.2×	0.138	MRPL33
Mitochondrial translation termination	1	10.0×	0.143	MRPL33
Cardiac conduction	1	9.9×	0.143	KCNK5
Muscle contraction	1	7.0×	0.190	KCNK5
RHOA GTPase cycle	1	6.8×	0.190	PKN1
Metabolism of amino acids and derivatives	1	6.1×	0.202	INMT

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 16 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
zygote asymmetric cell division	1	1053.2×	0.035	RGS14
pyridoxal 5’-phosphate metabolic process	1	1053.2×	0.035	ALPL
regulation of white fat cell proliferation	1	1053.2×	0.035	FTO
response to vitamin B6	1	526.6×	0.035	ALPL
metanephric nephron development	1	526.6×	0.035	TFAP2B
futile creatine cycle	1	526.6×	0.035	ALPL
RNA repair	1	351.1×	0.035	FTO
regulation of respiratory system process	1	351.1×	0.035	FTO
distal tubule development	1	351.1×	0.035	TFAP2B
response to macrophage colony-stimulating factor	1	263.3×	0.035	ALPL
collecting duct development	1	263.3×	0.035	TFAP2B
regulation of brown fat cell differentiation	1	263.3×	0.035	FTO
inhibition of non-skeletal tissue mineralization	1	263.3×	0.035	ALPL
developmental process involved in reproduction	1	210.7×	0.035	ALPL
negative regulation of synaptic plasticity	1	210.7×	0.035	RGS14
ductus arteriosus closure	1	210.7×	0.035	TFAP2B
positive regulation of protein localization to cell cortex	1	210.7×	0.035	EPB41L2
regulation of germinal center formation	1	175.5×	0.035	PKN1
hindlimb morphogenesis	1	175.5×	0.035	TFAP2B
phosphatidic acid metabolic process	1	175.5×	0.035	DGKH
phospholipase C/protein kinase C signal transduction	1	175.5×	0.035	DGKH
regulation of immunoglobulin production	1	150.5×	0.035	PKN1
amine metabolic process	1	150.5×	0.035	INMT
regulation of lipid storage	1	150.5×	0.035	FTO
positive regulation of catalytic activity	1	150.5×	0.035	BCAS3
cementum mineralization	1	150.5×	0.035	ALPL
forelimb morphogenesis	1	131.7×	0.038	TFAP2B
intracellular signal transduction	3	7.2×	0.038	DGKH, MAP4K5, PKN1
primordial germ cell migration	1	117.0×	0.040	PDILT
hyperosmotic response	1	105.3×	0.040	PKN1

Therapeutics

Drugs indicated for this disease

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

Drug	Development status
Ciprofloxacin	Phase 3 (in late-stage trials)
Silodosin	Phase 3 (in late-stage trials)
Tamsulosin	Phase 3 (in late-stage trials)

Drug target analysis

Approved (phase 4): 4 · Phase ≥3: 4 · Phased (≥1): 5 · Undrugged: 11

Druggability breadth: 8 of 16 evidence-associated genes (50%) 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
FTO	FLUORESCEIN
ALPL	SULCONAZOLE NITRATE
MAP4K5	VEMURAFENIB
PKN1	FEDRATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MAP4K5	67	4
PKN1	46	4
FTO	18	4
ALPL	7	4
INMT	1	2
TFAP2B	0	0
BCAS3	0	0
MRPL33	0	0
CLDN14	0	0
MINDY4	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
FLUORESCEIN	4	FTO
DEMECLOCYCLINE	4	FTO
ROXADUSTAT	4	FTO
MECLOFENAMIC ACID	4	FTO
AMILORIDE	4	FTO
TACRINE	4	FTO
ENTACAPONE	4	FTO
SULCONAZOLE NITRATE	4	ALPL
THEOPHYLLINE	4	ALPL
LEVAMISOLE	4	ALPL
MICONAZOLE NITRATE	4	ALPL
LEVAMISOLE HYDROCHLORIDE	4	ALPL
VEMURAFENIB	4	MAP4K5
LENVATINIB	4	MAP4K5
AXITINIB	4	MAP4K5
SORAFENIB	4	MAP4K5
NERATINIB	4	MAP4K5
PALBOCICLIB	4	MAP4K5
ENTRECTINIB	4	MAP4K5
VANDETANIB	4	MAP4K5
BOSUTINIB	4	MAP4K5, PKN1
GILTERITINIB	4	MAP4K5
PAZOPANIB	4	MAP4K5
NINTEDANIB	4	MAP4K5, PKN1
SUNITINIB	4	MAP4K5, PKN1
DASATINIB	4	MAP4K5, PKN1
QUIZARTINIB	4	MAP4K5
CRIZOTINIB	4	MAP4K5
MIDOSTAURIN	4	MAP4K5, PKN1
GEFITINIB	4	MAP4K5

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 4.

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

Symbol	Assays	Type breakdown
PKN1	268	Binding:268
MAP4K5	262	Binding:261, Functional:1
FTO	153	Binding:153
ALPL	58	Binding:50, Functional:4, ADMET:3, Toxicity:1
INMT	41	Binding:38, ADMET:3
DGKH	10	Binding:10
KCNK5	4	Binding:4
EPB41L2	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
FTO	1.14.11.53	mRNA N6-methyladenine demethylase
DGKH	2.7.1.107	diacylglycerol kinase (ATP)
ALPL	3.1.3.1	alkaline phosphatase
PKN1	2.7.11.13	protein kinase C

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
FTO	153
MAP4K5	262
PKN1	268

Pharmacogenomics

Cohort genes with a PharmGKB record: 16; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

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)
FLUORESCEIN	4	FTO
DEMECLOCYCLINE	4	FTO
ROXADUSTAT	4	FTO
MECLOFENAMIC ACID	4	FTO
AMILORIDE	4	FTO
TACRINE	4	FTO
ENTACAPONE	4	FTO
SULCONAZOLE NITRATE	4	ALPL
THEOPHYLLINE	4	ALPL
LEVAMISOLE	4	ALPL
MICONAZOLE NITRATE	4	ALPL
LEVAMISOLE HYDROCHLORIDE	4	ALPL
VEMURAFENIB	4	MAP4K5
LENVATINIB	4	MAP4K5
AXITINIB	4	MAP4K5
SORAFENIB	4	MAP4K5
NERATINIB	4	MAP4K5
PALBOCICLIB	4	MAP4K5
ENTRECTINIB	4	MAP4K5
VANDETANIB	4	MAP4K5
BOSUTINIB	4	MAP4K5, PKN1
GILTERITINIB	4	MAP4K5
PAZOPANIB	4	MAP4K5
NINTEDANIB	4	MAP4K5, PKN1
SUNITINIB	4	MAP4K5, PKN1
DASATINIB	4	MAP4K5, PKN1
QUIZARTINIB	4	MAP4K5
CRIZOTINIB	4	MAP4K5
MIDOSTAURIN	4	MAP4K5, PKN1
GEFITINIB	4	MAP4K5

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	4	FTO, ALPL, MAP4K5, PKN1
B	Phased (≥1) drug, not yet approved	1	INMT
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	2	DGKH, KCNK5
E	Difficult family or no structure, no drug	9	TFAP2B, BCAS3, MRPL33, CLDN14, MINDY4, PDILT, EPB41L2, BCAS1, RGS14

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
MINDY4	0	INMT
TFAP2B	0	—
BCAS3	0	—
MRPL33	0	—
CLDN14	0	—
PDILT	0	—
DGKH	10	—
EPB41L2	1	—
KCNK5	4	—
BCAS1	0	—
RGS14	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 402.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	334
PHASE4	24
PHASE2	17
PHASE3	15
EARLY_PHASE1	4
PHASE2/PHASE3	3
PHASE1	3
PHASE1/PHASE2	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06350045	PHASE4	ACTIVE_NOT_RECRUITING	High Supracostal Versus Subcostal Puncture in Adult PCNL
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
NCT01318187	PHASE4	COMPLETED	Intravenous Paracetamol or Morphine for the Treatment of Acute Flank Pain
NCT01451931	PHASE4	COMPLETED	Study of Tomography of Nephrolithiasis Evaluation
NCT01736358	PHASE4	TERMINATED	The Use of Intranasal Ketoralac for Pain Management (Sprix)
NCT02373384	PHASE4	COMPLETED	The Predictors of Successful Oral Dissolution Therapy in Radiolucent Renal Stones; A Prospective Evaluation
NCT02375295	PHASE4	UNKNOWN	Struvite Stones Antibiotic Study
NCT02430168	PHASE4	UNKNOWN	Comparison of RIRS Versus PCNL Methods, According to Postoperative Pain and Analgesic Demand in 2 to 4 cm Renal Stones
NCT02519153	PHASE4	UNKNOWN	Phosphodiesterase 5 Inhibitors (PDE5i) (Sildenafil) as Medical Expulsive Therapy in Distal Ureteral Stones
NCT02818140	PHASE4	COMPLETED	Ultrasound-guided Transmuscular Quadratus Lumborum Block for Percutaneous Nephrolithotomy
NCT03007160	PHASE4	UNKNOWN	A Study on the Effection of Potassium Citrate Extended-release Tablets on Urolithiasis Formation or Recurrence
NCT03032458	PHASE4	COMPLETED	Efficacy of Pethidine, Ketorolac And Xylocaine Gel As Analgesics For Pain Control In Shockwave Lithotripsy
NCT03614052	PHASE4	TERMINATED	Tamsulosin as Adjuvant Treatment Prior to Endoscopic Ureterolithotomy
NCT03872843	PHASE4	COMPLETED	Opioid Free Management After Ureteroscopy
NCT04095975	PHASE4	COMPLETED	Effectiveness of Urinary Alkalinizing Agents on Kidney Stone Risk
NCT04398251	PHASE4	UNKNOWN	A Randomized Clinical Trail of The Effect of Postoperative Uric Acid Control on Stone Recurrence and Renal Function in Patients With Hyperuricemia of Urolithiasis.
NCT04663269	PHASE4	TERMINATED	Regional Erector Spinae Analgesic Block vs Standard of Care Undergoing Percutaneous Nephrolithotomy
NCT05365477	PHASE4	COMPLETED	Empiric Versus Selective Prevention Strategies for Kidney Stone Disease
NCT05443932	PHASE4	UNKNOWN	Dapagliflozin and Hydrochlorothiazide in Recurring Kidney Stone Patients
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
NCT06653738	PHASE3	NOT_YET_RECRUITING	Trial to Assess the Efficacy of EMPAgliflozin and Personalized Dietary Counseling for Kidney STONE Prevention
NCT06819553	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	A Randomized Clinical Trial to Evaluate the Effectiveness of Oral Potassium Citrate in Preventing Ureteral Stent Encrustation in Patients Undergoing Ureteroscopy for Uric Acid Kidney Stones
NCT00428428	PHASE2/PHASE3	COMPLETED	Pharmacological Modulation of the Intrarenal Pressure During Endourological Procedures in the Upper Urinary Tract
NCT00713739	PHASE3	UNKNOWN	Alfuzosin for Medical Expulsion Therapy of Ureteral Stones
NCT00784472	PHASE3	COMPLETED	Visceral Pain From the Upper Urinary Tract - a Trial on the Effect of Morphine and Oxycodone in Patients Undergoing PCNL
NCT00959153	PHASE3	UNKNOWN	Extracorporeal Shock Wave Lithotriptor Indicated for Fragmenting Urinary Stones in the Kidney
NCT01560091	PHASE3	WITHDRAWN	Differential Effect of Silodosin Versus Tamsulosin on Stone Clearance After Extra-corporeal Shock Wave Lithotripsy
NCT01873690	PHASE3	TERMINATED	Efficacy of Antimicrobial Prophylaxis for Shock Wave Lithotripsy (SWL) on Reducing Urinary Tract Infection (UTI)
NCT02090439	PHASE3	TERMINATED	Effectiveness of Silodosin in Medical Expulsive Therapy for Ureteral Pelvic Stone From 4 to 10 mm.
NCT02579161	PHASE3	COMPLETED	Trial of Randomized Antibiotic Administration in Percutaneous Nephrolithotomy
NCT03927781	PHASE3	COMPLETED	Perioperative Pregabalin in Ureteroscopy: a Pilot
NCT04021381	PHASE3	UNKNOWN	Citrate Salts for Stone-free Result After Flexible Ureterorenoscopy for Inferior Calyx Calculi
NCT04122196	PHASE2/PHASE3	COMPLETED	Perioperative Pregabalin in Ureteroscopy
NCT04559321	PHASE3	UNKNOWN	Holmium Vs Trilogy Kidney Stones GUY’s 1-2
NCT05197088	PHASE3	UNKNOWN	Tamsulosin Assisted Ureteral Access Sheath Insertion

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
KETOROLAC	4	10
TAMSULOSIN	4	9
POTASSIUM CITRATE ANHYDROUS	4	8
ALFUZOSIN	4	6
SILODOSIN	4	4
CHLORTHALIDONE	4	3
CLINDAMYCIN	4	3
DOXAZOSIN	4	3
FUROSEMIDE	4	3
PRAZOSIN	4	3
SILDENAFIL	4	3
CIPROFLOXACIN	4	2
ISOPROTERENOL	4	2
SODIUM BICARBONATE	4	2
ACETAMINOPHEN	4	1
ACETIC ACID	4	1
ALLOPURINOL	4	1
AMPICILLIN	4	1
DAPAGLIFLOZIN	4	1
ERGOCALCIFEROL	4	1
FEBUXOSTAT	4	1
GENTAMICIN	4	1
HYDROCHLOROTHIAZIDE	4	1
INDAPAMIDE	4	1
MAGNESIUM CITRATE	4	1
MEPERIDINE	4	1
METHOCARBAMOL	4	1
METHYLTESTOSTERONE	4	1
MIRABEGRON	4	1
MORPHINE	4	1