Urinary system disorder

Summary

Urinary system disorder (MONDO:0002118) is a disease (an umbrella term covering 20 Mondo subtypes) with 1 cohort gene (26 GWAS associations across 71 studies) and 153 clinical trials. Top therapeutic interventions include solifenacin, levofloxacin anhydrous, and mirabegron.

At a glance

• Umbrella term: 20 Mondo subtypes
• Cohort genes: 1
• GWAS associations: 26
• Clinical trials: 153

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	urinary system disorder
Mondo ID	MONDO:0002118
EFO	EFO:0009690
MeSH	D014570
DOID	DOID:18
NCIT	C3430
SNOMED CT	128606002
UMLS	C0042075
MedGen	21791
Anatomy (UBERON)	UBERON:0001008
Is cancer (heuristic)	no

Also known as: disease of renal system · disease or disorder of renal system · disease, urinary tract · disease, urologic · disease, urological · diseases, urinary tract · diseases, urologic · diseases, urological · disorder of renal system · disorder of the urinary system · disorder of urinary system · renal system disease · renal system disease or disorder · urinary disease · urinary system disorder · urinary tract disease · urinary tract diseases · urinary tract disorder · urologic disease · urologic disorder (+4 more)

Data availability: 26 GWAS associations (71 studies) · 1 GenCC gene-disease record.

Disease family

An umbrella term covering 20 Mondo subtypes.

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

Related subtypes (18): disorder of orbital region, integumentary system disorder, musculoskeletal system disorder, syndromic disease, auditory system disorder, breast disorder, connective tissue disorder, digestive system disorder, cardiovascular disorder, reproductive system disorder, immune system disorder, nervous system disorder, respiratory system disorder, endocrine system disorder, hematologic disorder, mouth disorder, disorder of visual system, otorhinolaryngologic disease

Subtypes (20): 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, urolithiasis, urinary tract infection, meningitis-retention syndrome, paraneoplastic renal syndrome, idiopathic hypercalciuria

Genetics & variants

GWAS landscape

26 GWAS associations across 71 studies. Top hits map to 15 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs9895661	2e-19	BCAS3, TBX2-AS1	C	0.08
rs846766	2e-16	INVS	G	0.06
rs17191368	1e-13	MACROD2	C	0.05
chr20:14154102	2e-13		C	0.05
rs72725879	3e-13	PCAT1, PRNCR1, CASC19	C	0.05
chr9:103016838	7e-13		C	0.06
chr6:26319360	1e-12		T	0.04
rs78320262	3e-12	VHL	T	0.19
rs6983267	1e-11	PCAT1, CASC8, POU5F1B, CCAT2	G	0.04
rs28703582	2e-11	RNA5SP431 - MAF	G	0.06
chr12:53943743	2e-11		A	0.04
rs377638546	3e-11	ADAM33	?
rs4567978	4e-11	CIMIP6	A	0.06
chr1:218072070	3e-09		G	1.47
chr6:34729158	4e-09		AT	0.05
chr19:22657161	2e-08		G	2.58
chr6:34771213	2e-08		T	0.04
chr4:151873294	3e-08		A	1.19
chr4:1735615	4e-08		A	1.89
chr20:56753765	4e-08		T	0.04
chr2:205248380	5e-08		TTGG	0.09
rs141343296	6e-08	ERC1	?
rs138607504	4e-07	ZEB2P1 - LDB2	?
rs58181275	5e-07	MKLN1	?

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90476149	Verma A	2024	81,875	312,301	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90474197	UK Biobank Whole-Genome Sequencing Consortium	2025	81,555	376,885	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90474210	UK Biobank Whole-Genome Sequencing Consortium	2025	55,333	403,107	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90080616	Backman JD	2021	31,925	337,879	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90084602	Backman JD	2021	31,925	337,879	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90476131	Verma A	2024	29,694	391,141	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90476148	Verma A	2024	25,457	79,118	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90436451	Zhou W	2018	24,031	384,930	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST90038598	Donertas HM	2021	22,855	461,743	Common genetic associations between age-related diseases.
GCST90103424	Fitzgerald T	2022	17,451	153,306	CNest: A novel copy number association discovery method uncovers 862 new associations from 200,629 whole-exome sequence datasets in the UK Biobank.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	0
Tier 3: regulatory	1
Tier 4: intronic/intergenic	23

MAF distribution

Bucket	Variants
common (>=0.05)	11
low_freq (0.01-0.05)	1
rare (<0.01)	0
unknown	12

Functional consequences

Consequence	Count
unknown	12
intron_variant	8
non_coding_transcript_exon_variant	2
intergenic_variant	1
regulatory_region_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs9895661	17	61379228	C>A,T	0.267	intron_variant	BCAS3, TBX2-AS1	2e-19	Tier 4: intronic/intergenic
rs846766	9	100150438	G>A,C,T	0.459	intron_variant	INVS	2e-16	Tier 4: intronic/intergenic
rs17191368	20	14134200	C>T	0.2	intron_variant	MACROD2	1e-13	Tier 4: intronic/intergenic
chr20:14154102				0.253			2e-13	Tier 4: intronic/intergenic
rs72725879	8	127091724	C>G,T	0.228	non_coding_transcript_exon_variant	PCAT1, PRNCR1, CASC19	3e-13	Tier 4: intronic/intergenic
chr9:103016838				0.438			7e-13	Tier 4: intronic/intergenic
chr6:26319360							1e-12	Tier 4: intronic/intergenic
rs78320262	3	10147681	T>A	0.018	intron_variant	VHL	3e-12	Tier 4: intronic/intergenic
rs6983267	8	127401060	G>T	0.492	non_coding_transcript_exon_variant	PCAT1, CASC8, POU5F1B, CCAT2	1e-11	Tier 4: intronic/intergenic
rs28703582	16	79434920	G>A,T	0.465	intergenic_variant	RNA5SP431 - MAF	2e-11	Tier 4: intronic/intergenic
chr12:53943743							2e-11	Tier 4: intronic/intergenic
rs377638546	20	3676947	C>G		intron_variant	ADAM33	3e-11	Tier 4: intronic/intergenic
rs4567978	2	54343420	A>G,T	0.222	intron_variant	CIMIP6	4e-11	Tier 4: intronic/intergenic
chr1:218072070							3e-09	Tier 4: intronic/intergenic
chr6:34729158							4e-09	Tier 4: intronic/intergenic
chr19:22657161							2e-08	Tier 4: intronic/intergenic
chr6:34771213							2e-08	Tier 4: intronic/intergenic
chr4:151873294							3e-08	Tier 4: intronic/intergenic
chr4:1735615							4e-08	Tier 4: intronic/intergenic
chr20:56753765							4e-08	Tier 4: intronic/intergenic
chr2:205248380							5e-08	Tier 4: intronic/intergenic
rs141343296	12	1013216	A>G		intron_variant	ERC1	6e-08	Tier 4: intronic/intergenic
rs138607504	4	16390969	T>A,G	0.05	intron_variant	ZEB2P1 - LDB2	4e-07	Tier 4: intronic/intergenic
rs58181275	7	131165049	G>A	0.05	regulatory_region_variant	MKLN1	5e-07	Tier 3: regulatory

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 0 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
TRPV5	Limited	Autosomal recessive	urinary system disorder	2

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TRPV5	HGNC:3145	ENSG00000127412	Q9NQA5	Transient receptor potential cation channel subfamily V member 5	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TRPV5	Transient receptor potential cation channel subfamily V member 5	Constitutively active calcium selective cation channel thought to be involved in Ca(2+) reabsorption in kidney and intestine.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Ion channel	1	111.5×	0.009

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TRPV5	Ion channel	yes		Ankyrin_rpt, Ion_trans_dom, TRPV5/TRPV6

Expression context

Cohort genes with no expression data: 0.

Breadth distribution (Bgee present_calls)

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

Top tissues across cohort

Tissue	Cohort genes
C1 segment of cervical spinal cord	1
adult mammalian kidney	1
kidney	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TRPV5	41	tissue_specific	yes	C1 segment of cervical spinal cord, adult mammalian kidney, kidney

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TRPV5	1,081

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TRPV5	Q9NQA5	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
TRP channels	1	407.9×	0.002	TRPV5

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of urine volume	1	3370.4×	0.002	TRPV5
calcium ion transport into cytosol	1	1203.7×	0.003	TRPV5
calcium ion import across plasma membrane	1	543.6×	0.004	TRPV5
calcium ion homeostasis	1	443.5×	0.004	TRPV5
protein homotetramerization	1	237.3×	0.006	TRPV5
calcium ion transmembrane transport	1	210.7×	0.006	TRPV5
calcium ion transport	1	181.2×	0.006	TRPV5

Therapeutics

Drugs indicated for this disease

1 approved. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Ethacrynic Acid	Approved (phase 4)

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 1 · Undrugged: 0

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TRPV5	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
TETRAHYDROCANNABIVARIN	2	TRPV5

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
TRPV5	3	Binding:2, ADMET:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

1 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)
TETRAHYDROCANNABIVARIN	2	TRPV5

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	1	TRPV5
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 153.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	109
PHASE3	13
PHASE1	10
PHASE2	8
PHASE1/PHASE2	6
PHASE4	4
PHASE2/PHASE3	2
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02444013	PHASE4	UNKNOWN	Folic Acid for Prevention of Contrast Induced Nephropathy
NCT02805504	PHASE4	COMPLETED	Liposomal Bupivacaine for Postoperative Pain Control in Urologic Procedures
NCT03591289	PHASE4	WITHDRAWN	Does Depth of Neuromuscular Blockade (NMB) Affect Surgical Conditions in Obese Patients Undergoing Robotic Surgery
NCT05082142	PHASE4	COMPLETED	Tranexamic Acid to Improve Same-day Discharge Rates After Holmium Laser Enucleation of the Prostate (HoLEP)
NCT04042402	PHASE3	ACTIVE_NOT_RECRUITING	Long Term Extension Study in Patients With Primary Hyperoxaluria
NCT05878951	PHASE2/PHASE3	RECRUITING	Examining the Effects of Intra-detrusor Botox at Time of HoLEP in Men With Overactive Bladder Symptoms
NCT06858319	PHASE3	RECRUITING	Open-label Extension Study of Zigakibart in Adults With IgA Nephropathy.
NCT00239265	PHASE3	COMPLETED	Tamsulosin Phase III Clinical Trial -Double-Blind, Placebo Controlled Study in Female Patients With Lower Urinary Tract Syndrome
NCT00239317	PHASE3	COMPLETED	Tamsulosin Phase III Clinical Trial -Double-Blind, Placebo Controlled Study in Male Patients With Lower Urinary Tract Syndrome
NCT00258089	PHASE3	COMPLETED	A Study of the Safety and Effectiveness of Oral Levofloxacin Compared With Oral Ciprofloxacin in the Treatment of Complicated Urinary Tract Infections
NCT00258102	PHASE3	COMPLETED	A Study of the Safety and Effectiveness of Levofloxacin Compared With Lomefloxacin in the Treatment of Complicated Urinary Tract Infections
NCT00384891	PHASE3	TERMINATED	Hyperthermia Treatment in Conjunction With Mitomycin C Versus Bacillus Calmette-Guérin Immunotherapy (BCG) for Superficial Bladder Cancer
NCT01530620	PHASE3	COMPLETED	Efficacy and Tolerability of Propiverine Hydrochloride in Patients With Neurogenic Detrusor Overactivity
NCT01638000	PHASE3	COMPLETED	A Study to Evaluate the Efficacy and Safety of Mirabegron Compared to Solifenacin in Patients With Overactive Bladder Who Were Previously Treated With Another Medicine But Were Not Satisfied With That Treatment.
NCT01908829	PHASE3	COMPLETED	A Trial Comparing Combination Treatment (Solifenacin Plus Mirabegron) With One Treatment Alone (Solifenacin)
NCT02254915	PHASE3	WITHDRAWN	SHTC - EUROPE-1 Synergo Hyperthermia-Chemotherapy by European Urologists’ Research Operation Preserving Evolution Study I
NCT03927781	PHASE3	COMPLETED	Perioperative Pregabalin in Ureteroscopy: a Pilot
NCT04826484	PHASE3	TERMINATED	Opioid Reduction Initiative During Outpatient Pediatric Urologic Procedures Using Exparel
NCT04972890	PHASE2/PHASE3	UNKNOWN	The Outcomes of Intracavernosal Umbilical Cord Mesenchymal Stem Cells Implantation in Patients With Diabetic Erectile Dysfunction
NCT04684602	PHASE1/PHASE2	RECRUITING	Mesenchymal Stem Cells for the Treatment of Various Chronic and Acute Conditions
NCT01060254	PHASE2	TERMINATED	A Study to Evaluate the Pain Relieving Effects, Safety, and Tolerability of JNJ-42160443 for the Relief of Bladder Pain
NCT01340027	PHASE2	COMPLETED	A Study to Evaluate the Efficacy, Safety and Tolerability of Mirabegron and Solifenacin Succinate Alone and in Combination for the Treatment of Overactive Bladder
NCT01613586	PHASE2	COMPLETED	A Randomized Study Comparing Placebo and ASP3652 in the Treatment of Women With Bladder Pain Syndrome / Interstitial Cystitis (BPS/IC)
NCT02291432	PHASE1/PHASE2	COMPLETED	Autologous Cell Therapy for Stress Urinary Incontinence in Males Following Prostate Surgery
NCT02307487	PHASE2	COMPLETED	Safety of Pre-TURBT Intravesical Instillation of Escalating Doses of TC-3 Gel and MMC in NMIBC Patients
NCT02401542	PHASE1/PHASE2	TERMINATED	Dose Escalation, Expansion Study of Vofatamab (B-701) in Treatment of Locally Advanced or Metastatic Urothelial Cell Carcinoma
NCT03081858	PHASE1/PHASE2	COMPLETED	Proliposomal Intravesical Paclitaxel for Treatment of Low-Grade, Stage Ta, Non Muscle Invasive Bladder Cancer
NCT03123055	PHASE1/PHASE2	TERMINATED	A Study of B-701 in Combination With Pembrolizumab in Treatment of Locally Advanced or Metastatic Urothelial Cell Carcinoma
NCT03847909	PHASE2	COMPLETED	A Study to Evaluate DCR-PHXC in Children and Adults With Primary Hyperoxaluria Type 1 and Primary Hyperoxaluria Type 2
NCT04387448	PHASE2	TERMINATED	A Study of TRPC5 Channel Inhibitor in Patients With Diabetic Nephropathy, Focal Segmental Glomerulosclerosis, and Treatment-Resistant Minimal Change Disease
NCT04555343	PHASE1/PHASE2	COMPLETED	Intravesical Antifibrinolytic for Patients With Hematuria and Clot Retention
NCT05935748	PHASE2	TERMINATED	Ph2 Study NKT2152 With Palbociclib & Sasanlimab in Subjects With Advanced Clear Cell Renal Cell Carcinoma (ccRcc)
NCT06164600	PHASE2	COMPLETED	Bovine Colostrum for Prophylaxis Against Recurrent Urinary Tract Infection in Children
NCT03258658	PHASE1	RECRUITING	Safety and Feasibility Study of Autologous Engineered Urethral Constructs for the Treatment of Strictures
NCT03463239	PHASE1	NOT_YET_RECRUITING	Bioengineered Penile Tissue Constructs for Irreversibly Damaged Penile Corpora
NCT03899298	PHASE1	NOT_YET_RECRUITING	Safety and Clinical Outcomes With Amniotic and Umbilical Cord Tissue Therapy for Numerous Medical Conditions
NCT04731376	PHASE1	ACTIVE_NOT_RECRUITING	Perioperative Testosterone Replacement Therapy for the Improvement of Post-Operative Outcomes in Patients With Low Testosterone
NCT01231997	PHASE1	COMPLETED	Clinical Study to Investigate the Safety and Pharmacokinetics of Udenafil Tablet in Renal Impaired Male Patients
NCT01232010	PHASE1	COMPLETED	Clinical Study to Investigate the Safety and Pharmacokinetics of SK3530 Tablet in Renal Impaired Male Patients
NCT02052713	PHASE1	COMPLETED	Bioequivalence Study of the Second Generation Dutasteride and Tamsulosin Hydrochloride (HCL) Combination Capsule in Fasted State

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
SOLIFENACIN	4	9
LEVOFLOXACIN ANHYDROUS	4	4
MIRABEGRON	4	3
BUPIVACAINE	4	2
MITOMYCIN	4	2
NEDOSIRAN SODIUM	4	2
OFLOXACIN	4	2
DESFLURANE	4	1
DROPERIDOL	4	1
FINASTERIDE	4	1
FOLIC ACID	4	1
FOSFOMYCIN	4	1
IOHEXOL	4	1
IOPAMIDOL	4	1
ONABOTULINUMTOXINA	4	1
PROPIVERINE	4	1
TESTOSTERONE CYPIONATE	4	1
FULRANUMAB	3	1
SASANLIMAB	3	1
UDENAFIL	3	1
ZIGAKIBART	3	1
VOFATAMAB	2	2
MIRODENAFIL	2	1
CHEMBL1335195	0	1
CHEMBL4777013	0	1
CHEMBL3220716	0	1