Hydronephrosis

Summary

Hydronephrosis (MONDO:0005510) is a disease with 5 cohort genes (2 GWAS associations across 11 studies) and 38 clinical trials. Top therapeutic interventions include alfuzosin, praziquantel, and tremelimumab.

At a glance

• Cohort genes: 5
• GWAS associations: 2
• ClinVar variants: 6
• Clinical trials: 38

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hydronephrosis
Mondo ID	MONDO:0005510
EFO	EFO:0005562
MeSH	D006869
DOID	DOID:11111
NCIT	C26796
SNOMED CT	43064006
UMLS	C0020295
MedGen	42531
Is cancer (heuristic)	no

Data availability: 6 ClinVar variants · 2 GWAS associations (11 studies).

Disease family

An umbrella term covering 1 Mondo subtype.

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

Related subtypes (1): ureteral obstruction

Subtypes (1): congenital hydronephrosis

Genetics & variants

GWAS landscape

2 GWAS associations across 11 studies. Top hits map to 2 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs79746097	4e-12	PDILT	?
rs28544423	2e-11	UMOD	C	0.13

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90478571	Verma A	2024	7,337	436,719	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90651228	Liu TY	2025	6,589	217,244	Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.
GCST90436442	Zhou W	2018	1,951	401,005	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST90080576	Backman JD	2021	1,654	386,276	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90084562	Backman JD	2021	1,654	386,276	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90478570	Verma A	2024	1,548	118,995	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90480399	Verma A	2024	1,548	118,995	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90044242	Jiang L	2021	1,230	455,118	A generalized linear mixed model association tool for biobank-scale data.
GCST90080575	Backman JD	2021	892	387,038	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90084561	Backman JD	2021	892	387,038	Exome sequencing and analysis of 454,787 UK Biobank participants.

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	0
Tier 4: intronic/intergenic	2

MAF distribution

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

Functional consequences

Consequence	Count
intron_variant	1
synonymous_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs79746097	16	20381488	T>A,C	0.05	intron_variant	PDILT	4e-12	Tier 4: intronic/intergenic
rs28544423	16	20348311	C>A,G,T	0.157	synonymous_variant	UMOD	2e-11	Tier 4: intronic/intergenic

ClinVar germline variants

6 retrieved; paginated sample, class counts are floors:

3 pathogenic, 2 likely pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
267941	46;XY;inv(6)(p22q13)dn		Pathogenic	criteria provided, single submitter
242885	NM_138425.4(C12orf57):c.53-2A>G	C12orf57	Pathogenic	criteria provided, multiple submitters, no conflicts
638159	NM_001321120.2(TBX4):c.402G>A (p.Trp134Ter)	TBX4	Pathogenic	criteria provided, single submitter
997075	GRCh37/hg19 22q11.21(chr22:21075575-21454721)	AIFM3	Likely pathogenic	criteria provided, single submitter
523513	NM_015559.3(SETBP1):c.2614G>A (p.Gly872Arg)	SETBP1	Likely pathogenic	criteria provided, single submitter
617640	NM_001110556.2(FLNA):c.3934C>T (p.Arg1312Cys)	FLNA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 19 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TBX4	Orphanet:1509	Coxopodopatellar syndrome
TBX4	Orphanet:238578	Familial clubfoot due to 17q23.1q23.2 microduplication
TBX4	Orphanet:261279	17q23.1q23.2 microdeletion syndrome
TBX4	Orphanet:275777	Heritable pulmonary arterial hypertension
TBX4	Orphanet:3301	Tetraamelia-multiple malformations syndrome
SETBP1	Orphanet:436151	Intellectual disability-expressive aphasia-facial dysmorphism syndrome
SETBP1	Orphanet:798	Schinzel-Giedion syndrome
C12orf57	Orphanet:1777	Temtamy syndrome
FLNA	Orphanet:1826	Frontometaphyseal dysplasia
FLNA	Orphanet:2301	Congenital short bowel syndrome
FLNA	Orphanet:2484	Melnick-Needles syndrome
FLNA	Orphanet:482606	X-linked keloid scarring-reduced joint mobility-increased optic cup-to-disc ratio syndrome
FLNA	Orphanet:555877	FLNA-related X-linked myxomatous valvular dysplasia
FLNA	Orphanet:75497	X-linked Ehlers-Danlos syndrome
FLNA	Orphanet:88630	Terminal osseous dysplasia-pigmentary defects syndrome
FLNA	Orphanet:90650	Otopalatodigital syndrome type 1
FLNA	Orphanet:90652	Otopalatodigital syndrome type 2
FLNA	Orphanet:98892	Periventricular nodular heterotopia
FLNA	Orphanet:99811	Neuronal intestinal pseudoobstruction

Cohort genes → proteins

5 cohort genes, 5 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	5

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TBX4	HGNC:11603	ENSG00000121075	P57082	T-box transcription factor TBX4	clinvar
SETBP1	HGNC:15573	ENSG00000152217	Q9Y6X0	SET-binding protein	clinvar
AIFM3	HGNC:26398	ENSG00000183773	Q96NN9	Apoptosis-inducing factor 3	clinvar
C12orf57	HGNC:29521	ENSG00000111678	Q99622	Protein C10	clinvar
FLNA	HGNC:3754	ENSG00000196924	P21333	Filamin-A	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TBX4	T-box transcription factor TBX4	Transcriptional regulator that has an essential role in the organogenesis of lungs, pelvis, and hindlimbs.
AIFM3	Apoptosis-inducing factor 3	Induces apoptosis through a caspase dependent pathway.
C12orf57	Protein C10	In brain, may be required for corpus callosum development.
FLNA	Filamin-A	Promotes orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins.

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 3 · Druggable fraction: 0.2

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
Antibody/Immunoglobulin	1	5.8×	0.480
Transcription factor	1	1.6×	0.608
Other/Unknown	3	1.1×	0.608

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TBX4	Transcription factor	no		TF_T-box, p53-like_TF_DNA-bd_sf, TF_T-box_CS
SETBP1	Other/Unknown	no		AT_hook_DNA-bd_motif
AIFM3	Other/Unknown	no		FAD/NAD-linked_Rdtase_dimer_sf, Rieske_2Fe-2S, FAD/NAD-binding_dom
C12orf57	Other/Unknown	no		Grcc10
FLNA	Antibody/Immunoglobulin	yes		Filamin/ABP280_rpt, Actinin_actin-bd_CS, CH_dom

Expression context

Cohort genes with no expression data: 0.

4 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)	5
unknown	0

Top tissues across cohort

Tissue	Cohort genes
right lung	1
upper lobe of left lung	1
upper lobe of lung	1
buccal mucosa cell	1
caput epididymis	1
ventricular zone	1
mucosa of transverse colon	1
right frontal lobe	1
right hemisphere of cerebellum	1
endocervix	1
left ovary	1
thymus	1
popliteal artery	1
right coronary artery	1
tibial artery	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TBX4	116	tissue_specific	yes	right lung, upper lobe of left lung, upper lobe of lung
SETBP1	280	ubiquitous	marker	ventricular zone, buccal mucosa cell, caput epididymis
AIFM3	180	tissue_specific	marker	mucosa of transverse colon, right frontal lobe, right hemisphere of cerebellum
C12orf57	145	ubiquitous	marker	thymus, left ovary, endocervix
FLNA	285	ubiquitous	marker	right coronary artery, popliteal artery, tibial artery

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FLNA	5,321
SETBP1	2,077
AIFM3	2,051
TBX4	1,054
C12orf57	843

Structural data

PDB: 2 · AlphaFold-only: 3 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FLNA	P21333	26
AIFM3	Q96NN9	7

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
C12orf57	Q99622	81.41
TBX4	P57082	60.96
SETBP1	Q9Y6X0	43.30

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. Enrichment computed across 5 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
OAS antiviral response	1	1268.9×	0.002	FLNA
GP1b-IX-V activation signalling	1	951.7×	0.002	FLNA
Cell-extracellular matrix interactions	1	671.8×	0.002	FLNA
RHO GTPases activate PAKs	1	543.8×	0.002	FLNA
Platelet degranulation	1	87.8×	0.011	FLNA

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 5 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 membrane repolarization during atrial cardiac muscle cell action potential	1	3370.4×	0.008	FLNA
regulation of membrane repolarization during cardiac muscle cell action potential	1	3370.4×	0.008	FLNA
embryonic lung development	1	1685.2×	0.009	TBX4
tubulin deacetylation	1	1123.5×	0.009	FLNA
formation of radial glial scaffolds	1	842.6×	0.009	FLNA
adenylate cyclase-inhibiting dopamine receptor signaling pathway	1	674.1×	0.009	FLNA
third ventricle development	1	674.1×	0.009	C12orf57
psychomotor behavior	1	674.1×	0.009	C12orf57
establishment of Sertoli cell barrier	1	674.1×	0.009	FLNA
regulation of skeletal muscle contraction	1	561.7×	0.009	C12orf57
protein localization to bicellular tight junction	1	561.7×	0.009	FLNA
negative regulation of transcription by RNA polymerase I	1	481.5×	0.009	FLNA
corpus callosum morphogenesis	1	481.5×	0.009	C12orf57
blood coagulation, intrinsic pathway	1	421.3×	0.010	FLNA
positive regulation of platelet activation	1	259.3×	0.013	FLNA
positive regulation of integrin-mediated signaling pathway	1	259.3×	0.013	FLNA
positive regulation of actin filament bundle assembly	1	240.7×	0.013	FLNA
actin crosslink formation	1	240.7×	0.013	FLNA
wound healing, spreading of cells	1	224.7×	0.013	FLNA
limb morphogenesis	1	210.7×	0.013	TBX4
positive regulation of potassium ion transmembrane transport	1	198.3×	0.013	FLNA
positive regulation of neuron migration	1	198.3×	0.013	FLNA
camera-type eye morphogenesis	1	153.2×	0.015	C12orf57
execution phase of apoptosis	1	153.2×	0.015	AIFM3
positive regulation of neural precursor cell proliferation	1	153.2×	0.015	FLNA
obsolete negative regulation of DNA-binding transcription factor activity	1	146.5×	0.015	FLNA
megakaryocyte development	1	140.4×	0.015	FLNA
receptor clustering	1	124.8×	0.016	FLNA
embryonic hindlimb morphogenesis	1	116.2×	0.017	TBX4
cell fate specification	1	105.3×	0.018	TBX4

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 5 evidence-associated genes (20%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FLNA	1	2
TBX4	0	0
SETBP1	0	0
AIFM3	0	0
C12orf57	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	FLNA

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
FLNA	7	Binding:7

Pharmacogenomics

Cohort genes with a PharmGKB record: 5; 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)
MOLIBRESIB	2	FLNA

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	FLNA
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	4	TBX4, SETBP1, AIFM3, C12orf57

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
TBX4	0	—
SETBP1	0	—
AIFM3	0	—
C12orf57	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 38.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	36
PHASE3	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00576823	PHASE3	COMPLETED	Alfuzosin Treatment in Children and Adolescents With Hydronephrosis of Neuropathic Etiology
NCT02812420	EARLY_PHASE1	ACTIVE_NOT_RECRUITING	Durvalumab and Tremelimumab in Treating Patients With Muscle-Invasive, High-Risk Urothelial Cancer That Cannot Be Treated With Cisplatin-Based Therapy Before Surgery
NCT05455307	Not specified	RECRUITING	Efficacy and Safety of Allium Ureteral Stent for Treating Refractory Ureteral Stricture
NCT06896149	Not specified	NOT_YET_RECRUITING	Mild Fetal Hydronephrosis, Gestational Diabetes and Spontaneous Resolution vs Moderate-severe Fetal Hydronephrosis, Obstructive Causes and Worse Postnatal Outcome
NCT06983067	Not specified	RECRUITING	Application of the Sentire C1000 for Ureteral Stricture Repair
NCT07126847	Not specified	ACTIVE_NOT_RECRUITING	Use of POCUS and STONE Criteria Together in the Diagnosis of Nephrolithiasis
NCT07547891	Not specified	RECRUITING	Shear Wave Elastography for Evaluation of Hydronephrosis in Pregnancy
NCT07581223	Not specified	NOT_YET_RECRUITING	Integrating an AI-Driven Hydronephrosis Decision-Making Tool
NCT00231322	Not specified	COMPLETED	Influence of Transmission Season on Outcome of Treatment of Schistosoma Haematobium Infection in Mozambique
NCT00555308	Not specified	COMPLETED	Emergency Department Targeted Ultrasound for the Detection of Hydronephrosis
NCT00585767	Not specified	WITHDRAWN	Functional, Dynamic, and Anatomic MR Urography
NCT00591968	Not specified	COMPLETED	Telesonography Adaptation and Use to Improve the Standard of Patient Care Within a Dominican Community
NCT00764543	Not specified	NO_LONGER_AVAILABLE	Ambulatory Blood Pressure Measurement in Children With Congenital Urine Flow Obstruction
NCT00786708	Not specified	COMPLETED	Sensitivity and Specificity of NGAL in an Emergency Room Population
NCT00882544	Not specified	COMPLETED	Prospective Pediatric Pyeloplasty Robotic Surgical Database
NCT01140516	Not specified	UNKNOWN	Effectiveness of Antibiotics Versus Placebo to Treat Antenatal Hydronephrosis
NCT01323842	Not specified	COMPLETED	Emergency Department Ultrasound in Renal Colic
NCT01349244	Not specified	COMPLETED	Hydronephrosis on Ultrasound With CT Finding in Patients With Renal Colic
NCT01542593	Not specified	COMPLETED	Evaluating Ureteral Length Using Computed Tomography (CT)
NCT01588340	Not specified	WITHDRAWN	MRI Hydronephrosis Study
NCT01739738	Not specified	WITHDRAWN	The Impact of Ureteral Stents on Peristalsis
NCT01781845	Not specified	COMPLETED	Hydronephrosis ARFI Study
NCT01839006	Not specified	COMPLETED	Clinical Significance of Supranormal Differential Renal Function in the Recovery of Hydronephrosis
NCT02007980	Not specified	UNKNOWN	Indwelling Stent Discoloration Project
NCT02929160	Not specified	WITHDRAWN	Percutaneous Nephrostomy Versus Stent In Sepsis Trial
NCT02976870	Not specified	COMPLETED	Hydronephrosis After Anterior Lumbar Interbody Fusion (ALIF)
NCT03296280	Not specified	COMPLETED	Evaluation of Implementation of a National Point-of-Care Ultrasound Training Program
NCT03327688	Not specified	COMPLETED	Point-of-care Ultrasound in Finland
NCT03695991	Not specified	UNKNOWN	Effect of Per-cutaneous Nephrosotomy Drainage on Radioisotope Imaging of Hydronephrotic Kidneys
NCT03774719	Not specified	TERMINATED	Hand-carried Ultrasound to Assess Hydronephrosis
NCT03794102	Not specified	COMPLETED	Water Versus Saline as Irrigation Fluid for Ureteroscopy
NCT03873701	Not specified	COMPLETED	Bedside Ultrasonography in Acute Patients With Suspected Kidney Involvement
NCT04090255	Not specified	UNKNOWN	Us vs Fluoroscopic Guided Renal Access
NCT04250090	Not specified	UNKNOWN	Post-Marketing Follow-Up of Long-term Type Ureteral Stent Set
NCT04441320	Not specified	UNKNOWN	Coated Metal Ureteral Stent in the Treatment of Radiation Induced Ureteral Stricture
NCT04594161	Not specified	COMPLETED	Effectiveness of Drainage by PCN vs. JJ in Patients With Symptoms of Obstructive Kidney Disease Caused by Urolithiasis
NCT04869462	Not specified	COMPLETED	DS Titanium Ligation Clip in Urology (Prostatectomy and Nephrectomy)
NCT05280145	Not specified	COMPLETED	Efficacy of the echOpen Device to Detect Pyelocaliceal Dilation and Hepatic Steatosis

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ALFUZOSIN	4	3
PRAZIQUANTEL	4	1
TREMELIMUMAB	4	1
TRIMETHOPRIM	4	1
SYRUP	3	1
CHEMBL3264245	0	1