Posterior urethral valve

Summary

Posterior urethral valve (MONDO:0019640) is a disease with 1 cohort gene (20 GWAS associations across 3 studies) and 8 clinical trials. Top therapeutic interventions include oxybutynin, tamsulosin, and trimethoprim.

At a glance

• Prevalence: 1-9 / 100 000 (Europe) [Orphanet-validated]
• Cohort genes: 1
• GWAS associations: 20
• Phenotypes (HPO): 27
• Clinical trials: 8

Clinical features

Epidemiology

Prevalence records

3 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 100 000	2	Europe	Validated
Prevalence at birth	1-9 / 100 000	4.125	Europe	Validated
Prevalence at birth	1-9 / 100 000	6.4	Australia	Validated

Signs & symptoms

Clinical features (HPO)

27 HPO clinical features (Orphanet curated; top 27 by frequency):

HPO ID	Term	Frequency
HP:0000010	Recurrent urinary tract infections	Very frequent (80-99%)
HP:0010957	Congenital posterior urethral valve	Very frequent (80-99%)
HP:0012622	Chronic kidney disease	Very frequent (80-99%)
HP:0000076	Vesicoureteral reflux	Frequent (30-79%)
HP:0000126	Hydronephrosis	Frequent (30-79%)
HP:0041047	Bladder outlet obstruction	Frequent (30-79%)
HP:0006703	Aplasia/Hypoplasia of the lungs	Occasional (5-29%)
HP:0010945	Fetal pyelectasis	Occasional (5-29%)
HP:0010955	Dilatation of the bladder	Occasional (5-29%)
HP:0010956	Fetal megacystis	Occasional (5-29%)
HP:0012330	Pyelonephritis	Occasional (5-29%)
HP:0000015	Bladder diverticulum	Occasional (5-29%)
HP:0000020	Urinary incontinence	Occasional (5-29%)
HP:0000083	Renal insufficiency	Occasional (5-29%)
HP:0000093	Proteinuria	Occasional (5-29%)
HP:0000110	Renal dysplasia	Occasional (5-29%)
HP:0000790	Hematuria	Occasional (5-29%)
HP:0000822	Hypertension	Occasional (5-29%)
HP:0002009	Potter facies	Occasional (5-29%)
HP:0002027	Abdominal pain	Occasional (5-29%)
HP:0003419	Low back pain	Occasional (5-29%)
HP:0003774	Stage 5 chronic kidney disease	Occasional (5-29%)
HP:0000016	Urinary retention	Very rare (<1-4%)
HP:0001254	Lethargy	Very rare (<1-4%)
HP:0001562	Oligohydramnios	Very rare (<1-4%)
HP:0008661	Urethral stenosis	Very rare (<1-4%)
HP:0100518	Dysuria	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	posterior urethral valve
Mondo ID	MONDO:0019640
Orphanet	93110
ICD-10-CM	Q64.2
NCIT	C99021
SNOMED CT	253900005
UMLS	C0238506
MedGen	451008
GARD	0007439
MedDRA	10036369
NORD	242851
Is cancer (heuristic)	no

Also known as: congenital posterior urethral valves · Posterior Urethral Valves · Posterior urethral valves · PUV

Data availability: 20 GWAS associations (3 studies) · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › urinary system disorder › kidney disorder › fetal lower urinary tract obstruction › posterior urethral valve

Related subtypes (4): prune belly syndrome, atresia of urethra, urethral obstruction sequence, anterior urethral valve

Genetics & variants

GWAS landscape

20 GWAS associations across 3 studies. Top hits map to 10 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs10774740	8e-12	GLULP5 - LINC02459	T	0.4
rs144171242	2e-08	PTK7	G	7.2
rs1471950716	1e-07	CHEK2P5 - KSR1P1	A	3.88
rs199975325	3e-07	LINC02303 - LINC00871	G	5.68
rs867542	6e-07	ARK2N - ARK2C	T	1.41
rs60387547	1e-06	NBPF13P	C	1.49
rs7407659	2e-06	ALPK2	G	0.72
rs55712520	2e-06	SIX3 - KRTCAP2P1	G	1.83
rs370998275	2e-06	UBR2	C	1.42
rs4570185	4e-06	RN7SKP159 - MCPH1-DT	C	1.41
rs10521237	5e-06	UNGP1 - HNRNPA1L3	G	1.51
rs737092	5e-06	RBM38 - HMGB1P1	C	1.34
rs7526657	5e-06	FMO5	A	1.47
rs7718640	6e-06	MEGF10 - HNRNPKP1	T	1.45
rs13283755	6e-06	HSPA8P17 - SLC25A6P2	C	1.38
rs9571693	6e-06	PCDH9, PCDH9-AS2	G	1.42
rs36119603	7e-06	RIN3	T	1.41
rs4888913	1e-05	WWOX	C	0.74
rs375313970	1e-05	SMG6	C	0.75

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90134327	van der Zanden LFM	2022	756	4,823	Genome-wide association study in patients with posterior urethral valves.
GCST90134254	Chan MMY	2022	89	19,418	Diverse ancestry whole-genome sequencing association study identifies TBX5 and PTK7 as susceptibility genes for posterior urethral valves.
GCST90165183	Chan MMY	2022	89	19,418	Diverse ancestry whole-genome sequencing association study identifies TBX5 and PTK7 as susceptibility genes for posterior urethral valves.

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	19

MAF distribution

Bucket	Variants
common (>=0.05)	15
low_freq (0.01-0.05)	1
rare (<0.01)	0
unknown	3

Functional consequences

Consequence	Count
intron_variant	9
intergenic_variant	8
non_coding_transcript_exon_variant	2

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs10774740	12	114228397	G>A,C,T	0.37	intergenic_variant	GLULP5 - LINC02459	8e-12	Tier 4: intronic/intergenic
rs144171242	6	43120356	A>G	0.01	intron_variant	PTK7	2e-08	Tier 4: intronic/intergenic
rs1471950716	10	41863786	G>A,C,T		intergenic_variant	CHEK2P5 - KSR1P1	1e-07	Tier 4: intronic/intergenic
rs199975325	14	45784776	A>G		intergenic_variant	LINC02303 - LINC00871	3e-07	Tier 4: intronic/intergenic
rs867542	18	46313600	G>T	0.05	intergenic_variant	ARK2N - ARK2C	6e-07	Tier 4: intronic/intergenic
rs60387547	1	147114957	T>A,C,G	0.05	intron_variant	NBPF13P	1e-06	Tier 4: intronic/intergenic
rs7407659	18	58551518	T>G	0.05	intron_variant	ALPK2	2e-06	Tier 4: intronic/intergenic
rs55712520	2	44968650	T>G	0.05	non_coding_transcript_exon_variant	SIX3 - KRTCAP2P1	2e-06	Tier 4: intronic/intergenic
rs370998275	6	42601689	CAAAAA>C,CA,CAA,CAAA,CAAAA,CAAAAAA,CAAAAAAA,CAAAAAAAA,CAAAAAAAAA,CAAAAAAAAAAAAAA	0.05	intron_variant	UBR2	2e-06	Tier 4: intronic/intergenic
rs4570185	8	6263429	T>C	0.05	intergenic_variant	RN7SKP159 - MCPH1-DT	4e-06	Tier 4: intronic/intergenic
rs10521237	16	51533320	T>G	0.05	intergenic_variant	UNGP1 - HNRNPA1L3	5e-06	Tier 4: intronic/intergenic
rs737092	20	57415349	T>A,C,G	0.05	non_coding_transcript_exon_variant	RBM38 - HMGB1P1	5e-06	Tier 4: intronic/intergenic
rs7526657	1	147232733	G>A,C,T	0.05	intron_variant	FMO5	5e-06	Tier 4: intronic/intergenic
rs7718640	5	127486350	C>A,T	0.05	intergenic_variant	MEGF10 - HNRNPKP1	6e-06	Tier 4: intronic/intergenic
rs13283755	9	31244219	A>C,G,T	0.05	intergenic_variant	HSPA8P17 - SLC25A6P2	6e-06	Tier 4: intronic/intergenic
rs9571693	13	66928471	A>C,G,T	0.05	intron_variant	PCDH9, PCDH9-AS2	6e-06	Tier 4: intronic/intergenic
rs36119603	14	92549015	TC>T	0.05	intron_variant	RIN3	7e-06	Tier 4: intronic/intergenic
rs4888913	16	78998088	G>A,C,T	0.05	intron_variant	WWOX	1e-05	Tier 4: intronic/intergenic
rs375313970	17	2118898			intron_variant	SMG6	1e-05	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · 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
BNC2	Supportive	Autosomal recessive	posterior urethral valve	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BNC2	Orphanet:93110	Posterior urethral valve

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
BNC2	HGNC:30988	ENSG00000173068	Q6ZN30	Zinc finger protein basonuclin-2	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BNC2	Zinc finger protein basonuclin-2	Probable transcription factor specific for skin keratinocytes.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.0

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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BNC2	Transcription factor	no		Znf_C2H2_type, Disconnected-like

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
germinal epithelium of ovary	1
parietal pleura	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BNC2	229	ubiquitous	marker	germinal epithelium of ovary, sural nerve, parietal pleura

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BNC2	1,104

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
BNC2	Q6ZN30	54.10

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
mesenchyme development	1	2407.4×	1e-03	BNC2
tongue development	1	2106.5×	1e-03	BNC2
endochondral bone growth	1	1685.2×	1e-03	BNC2
roof of mouth development	1	247.8×	0.005	BNC2
regulation of DNA-templated transcription	1	31.6×	0.032	BNC2

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
BNC2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

0 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.

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	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	BNC2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
BNC2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 8.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	5
PHASE3	1
PHASE2	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06737016	PHASE3	RECRUITING	Efficacy and Safety of Tamsulosin for Children with Posterior Urethral Valve.
NCT07527442	PHASE2	NOT_YET_RECRUITING	Efficacy and Safety of Circumcision Alone on Risk of Febrile Urinary Tract Infections in Boys With Posterior Urethral Valves: a Prospective Randomized Open-label Multicentric Trial Enriched With Historic Controls.
NCT04626167	EARLY_PHASE1	RECRUITING	Concomitant Renal and Urinary Bladder Allograft Transplantation
NCT06439862	Not specified	RECRUITING	Study of the Quality of Life in School Aged-children With Posterior Urethral Valves
NCT06867263	Not specified	NOT_YET_RECRUITING	Outcomes of Posterior Urethral Valve Fulguration
NCT01537601	Not specified	COMPLETED	CIRCumcision and Urinary Tract Infections in Boys With Posterior Urethral Valves
NCT03116217	Not specified	UNKNOWN	Validation of a Fetal Urine Peptidome-based Classifier to Predict Post-natal Renal Function in Posterior Urethral Valves
NCT05168358	Not specified	UNKNOWN	Overnight Bladder Drainage and Posterior Urethral Valve Sequelae

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
OXYBUTYNIN	4	3
TAMSULOSIN	4	3
TRIMETHOPRIM	4	1