Vesicoureteral reflux

disease

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Also known as vesicoureteral reflux (disease)

Summary

Vesicoureteral reflux (MONDO:0006007) is a disease with 10 cohort genes (34 GWAS associations across 4 studies) and 14 clinical trials. Top therapeutic interventions include cefixime, midazolam, and nitrofurantoin.

At a glance

Cohort genes: 10
GWAS associations: 34
ClinVar variants: 10
Clinical trials: 14

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	vesicoureteral reflux
Mondo ID	MONDO:0006007
EFO	EFO:0007536
MeSH	D014718
DOID	DOID:9620
ICD-11	2142055506
SNOMED CT	197811007
UMLS	C0042580
MedGen	21852
Is cancer (heuristic)	no

Also known as: vesicoureteral reflux · vesicoureteral reflux (disease)

Data availability: 10 ClinVar variants · 34 GWAS associations (4 studies) · 1 HPO phenotype.

Disease family

An umbrella term covering 1 Mondo subtype.

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

Related subtypes (7): pyoureter, ureteral obstruction, ureter tuberculosis, ureterolithiasis, ureterocele, ureter neoplasm, ureteritis

Subtypes (1): familial vesicoureteral reflux

Genetics & variants

GWAS landscape

34 GWAS associations across 4 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
rs13013890	2e-09	WDPCP	A	3.65
rs11759064	3e-09	PRKN	T	2.19
rs1154855	4e-09	HMGCLL1 - BMP5	T	0.71
rs10806089	4e-09	LINC02540 - HTR1B	C	2.75
rs189231497	8e-09	DMD - FAM47A	?
rs76292820	3e-08	CSGALNACT1	T	4.71
rs12759898	4e-08	CASQ2	A	1.61
rs4671452	5e-08	EHBP1	G	3.47
rs16838525	7e-08	RNU6-983P - LINC01724	C	6.94
rs79060316	9e-08	ZNF704 - PAG1	T	2.5
rs503022	1e-07	LINC02030 - WNT5A	A	1.81
rs9369289	1e-07	FOXP4-AS1, FOXP4	A	3.91
rs112655681	1e-07	ZNF704	T	2.46
rs13000175	1e-07	WDPCP	A	4.7
rs55754695	2e-07	IL17RB	C	1.85
rs13000344	2e-07	OTX1 - RPL27P5	G	4.34
rs17027651	2e-07	WDPCP	G	3.24
rs11684093	2e-07	WDPCP	C	2.47
rs4493703	3e-07	RPL23AP44 - FTMT	G	0.55
rs2302567	3e-07	EHBP1	G	4.49
rs4976247	4e-07	PITX1-AS1	C	0.78
rs10090061	4e-07	KBTBD11-OT1, ARHGEF10	A	0.6
rs73031356	4e-07	OPCML	C	2.54
rs11583238	5e-07	LINC02781 - LINC02782	A	1.52
rs1841319	5e-07	ZFPM2	A	0.72
rs11666449	5e-07	CATSPERG	T	6.33
rs13023873	6e-07	WDPCP	T	2.39
rs17128665	7e-07	CSGALNACT1	A	3.68
rs6662338	7e-07	PCP4L1	A	3.6
rs7631746	8e-07	LINC02035 - SEMA5B	C	3.49

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST012183	Verbitsky M	2021	1,395	5,366	Copy Number Variant Analysis and Genome-wide Association Study Identify Loci with Large Effect for Vesicoureteral Reflux.
GCST005044	Darlow JM	2017	1,156	1,156	Genome-wide linkage and association study implicates the 10q26 region as a major genetic contributor to primary nonsyndromic vesicoureteric reflux.
GCST005045	Darlow JM	2017	1,147	0	Genome-wide linkage and association study implicates the 10q26 region as a major genetic contributor to primary nonsyndromic vesicoureteric reflux.
GCST90651435	Liu TY	2025	162	202,534	Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	1
Tier 3: regulatory	0
Tier 4: intronic/intergenic	33

MAF distribution

Bucket	Variants
common (>=0.05)	29
low_freq (0.01-0.05)	4
rare (<0.01)	0
unknown	1

Functional consequences

Consequence	Count
intron_variant	21
intergenic_variant	11
non_coding_transcript_exon_variant	1
splice_polypyrimidine_tract_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs13013890	2	63426975	G>A	0.124	intron_variant	WDPCP	2e-09	Tier 4: intronic/intergenic
rs11759064	6	162379633	C>G,T	0.13	intron_variant	PRKN	3e-09	Tier 4: intronic/intergenic
rs1154855	6	55747309	G>T	0.478	intergenic_variant	HMGCLL1 - BMP5	4e-09	Tier 4: intronic/intergenic
rs10806089	6	77233340	C>G,T	0.338	intron_variant	LINC02540 - HTR1B	4e-09	Tier 4: intronic/intergenic
rs189231497	X	33638483	G>A,C,T		intergenic_variant	DMD - FAM47A	8e-09	Tier 4: intronic/intergenic
rs76292820	8	19456108	C>T	0.16	intron_variant	CSGALNACT1	3e-08	Tier 4: intronic/intergenic
rs12759898	1	115808763	T>A,C	0.082	intron_variant	CASQ2	4e-08	Tier 4: intronic/intergenic
rs4671452	2	62818853	A>G	0.127	non_coding_transcript_exon_variant	EHBP1	5e-08	Tier 4: intronic/intergenic
rs16838525	1	195540819	T>A,C	0.146	intergenic_variant	RNU6-983P - LINC01724	7e-08	Tier 4: intronic/intergenic
rs79060316	8	80915081	C>T	0.016	intron_variant	ZNF704 - PAG1	9e-08	Tier 4: intronic/intergenic
rs503022	3	55457408	C>A,T	0.134	intergenic_variant	LINC02030 - WNT5A	1e-07	Tier 4: intronic/intergenic
rs9369289	6	41560157	G>A	0.111	intron_variant	FOXP4-AS1, FOXP4	1e-07	Tier 4: intronic/intergenic
rs112655681	8	80800110	A>T	0.016	intron_variant	ZNF704	1e-07	Tier 4: intronic/intergenic
rs13000175	2	63268271	T>A,C	0.134	intron_variant	WDPCP	1e-07	Tier 4: intronic/intergenic
rs55754695	3	53850887	A>C	0.328	intron_variant	IL17RB	2e-07	Tier 4: intronic/intergenic
rs13000344	2	63062599	T>G	0.136	intergenic_variant	OTX1 - RPL27P5	2e-07	Tier 4: intronic/intergenic
rs17027651	2	63164205	A>G	0.129	intron_variant	WDPCP	2e-07	Tier 4: intronic/intergenic
rs11684093	2	63674127	T>C	0.16	intergenic_variant	WDPCP	2e-07	Tier 4: intronic/intergenic
rs4493703	5	121578037	T>C,G	0.344	intergenic_variant	RPL23AP44 - FTMT	3e-07	Tier 4: intronic/intergenic
rs2302567	2	62943786	C>A,G	0.127	splice_polypyrimidine_tract_variant	EHBP1	3e-07	Tier 2: splice/UTR
rs4976247	5	135207369	A>C	0.387	intron_variant	PITX1-AS1	4e-07	Tier 4: intronic/intergenic
rs10090061	8	1824475	G>A,C	0.272	intron_variant	KBTBD11-OT1, ARHGEF10	4e-07	Tier 4: intronic/intergenic
rs73031356	11	133351799	T>C	0.029	intron_variant	OPCML	4e-07	Tier 4: intronic/intergenic
rs11583238	1	5045809	G>A,C,T	0.237	intergenic_variant	LINC02781 - LINC02782	5e-07	Tier 4: intronic/intergenic
rs1841319	8	104799214	C>A	0.173	intergenic_variant	ZFPM2	5e-07	Tier 4: intronic/intergenic
rs11666449	19	38363019	C>G,T	0.185	intron_variant	CATSPERG	5e-07	Tier 4: intronic/intergenic
rs13023873	2	63812433	C>A,T	0.16	intron_variant	WDPCP	6e-07	Tier 4: intronic/intergenic
rs17128665	8	19574687	G>A	0.177	intron_variant	CSGALNACT1	7e-07	Tier 4: intronic/intergenic
rs6662338	1	161259680	G>A	0.022	intron_variant	PCP4L1	7e-07	Tier 4: intronic/intergenic
rs7631746	3	122906409	G>A,C,T	0.195	intergenic_variant	LINC02035 - SEMA5B	8e-07	Tier 4: intronic/intergenic

ClinVar germline variants

10 retrieved; paginated sample, class counts are floors:

4 pathogenic, 3 likely pathogenic, 2 uncertain significance, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
267883	46;X;inv(X)(p11.4q24)dn		Pathogenic	criteria provided, single submitter
242885	NM_138425.4(C12orf57):c.53-2A>G	C12orf57	Pathogenic	criteria provided, multiple submitters, no conflicts
375502	NM_001375380.1(EBF3):c.280_283del (p.Glu94fs)	EBF3	Pathogenic	no assertion criteria provided
523512	NM_015335.5(MED13L):c.1971del (p.Asp657fs)	MED13L	Pathogenic	criteria provided, single submitter
684663	NM_001272046.2(VWA2):c.1336C>T (p.Arg446Cys)	AFAP1L2	Likely pathogenic	no assertion criteria provided
523499	NM_012330.4(KAT6B):c.3399_3402del (p.Arg1133fs)	KAT6B	Likely pathogenic	criteria provided, single submitter
978555	NM_133433.4(NIPBL):c.1052C>T (p.Pro351Leu)	NIPBL	Likely pathogenic	criteria provided, single submitter
267864	46;XY;t(2;13)(p25.2;q31.3)dn		Uncertain significance	criteria provided, single submitter
1314407	NM_001365276.2(TNXB):c.496A>C (p.Thr166Pro)	TNXB	Uncertain significance	criteria provided, single submitter
523052	NM_022454.4(SOX17):c.456G>C (p.Glu152Asp)	SOX17	Likely benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 14 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TNXB	Orphanet:230839	Classical-like Ehlers-Danlos syndrome type 1
TNXB	Orphanet:289365	Familial vesicoureteral reflux
KAT6B	Orphanet:3047	Blepharophimosis-intellectual disability syndrome, SBBYS type
KAT6B	Orphanet:85201	Genitopatellar syndrome
SOX17	Orphanet:275777	Heritable pulmonary arterial hypertension
SOX17	Orphanet:289365	Familial vesicoureteral reflux
EBF3	Orphanet:658843	Developmental delay-ataxia-hypotonia-facial dysmorphism syndrome
EBF3	Orphanet:96148	Distal deletion 10q syndrome
MED13L	Orphanet:216718	Isolated congenitally uncorrected transposition of the great arteries
MED13L	Orphanet:369891	Developmental delay-facial dysmorphism syndrome due to MED13L deficiency
NIPBL	Orphanet:199	Cornelia de Lange syndrome
NIPBL	Orphanet:329802	5p13 microduplication syndrome
C12orf57	Orphanet:1777	Temtamy syndrome
PRKN	Orphanet:2828	Young-onset Parkinson disease

Cohort genes → proteins

10 cohort genes, 10 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	2
multi_evidence	8

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TNXB	HGNC:11976	ENSG00000168477	P22105	Tenascin-X	clinvar
KAT6B	HGNC:17582	ENSG00000156650	Q8WYB5	Histone acetyltransferase KAT6B	clinvar
SOX17	HGNC:18122	ENSG00000164736	Q9H6I2	Transcription factor SOX-17	clinvar
EBF3	HGNC:19087	ENSG00000108001	Q9H4W6	Transcription factor COE3	clinvar
PACRG	HGNC:19152	ENSG00000112530	Q96M98	Parkin coregulated gene protein	gwas
MED13L	HGNC:22962	ENSG00000123066	Q71F56	Mediator of RNA polymerase II transcription subunit 13-like	clinvar
AFAP1L2	HGNC:25901	ENSG00000169129	Q8N4X5	Actin filament-associated protein 1-like 2	clinvar
NIPBL	HGNC:28862	ENSG00000164190	Q6KC79	Nipped-B-like protein	clinvar
C12orf57	HGNC:29521	ENSG00000111678	Q99622	Protein C10	clinvar
PRKN	HGNC:8607	ENSG00000185345	O60260	E3 ubiquitin-protein ligase parkin	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TNXB	Tenascin-X	Appears to mediate interactions between cells and the extracellular matrix.
KAT6B	Histone acetyltransferase KAT6B	Histone acetyltransferase which may be involved in both positive and negative regulation of transcription.
SOX17	Transcription factor SOX-17	Acts as a transcription regulator that binds target promoter DNA.
EBF3	Transcription factor COE3	Transcriptional activator.
PACRG	Parkin coregulated gene protein	Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating.
MED13L	Mediator of RNA polymerase II transcription subunit 13-like	Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes.
AFAP1L2	Actin filament-associated protein 1-like 2	May play a role in a signaling cascade by enhancing the kinase activity of SRC.
NIPBL	Nipped-B-like protein	Plays an important role in the loading of the cohesin complex on to DNA.
C12orf57	Protein C10	In brain, may be required for corpus callosum development.
PRKN	E3 ubiquitin-protein ligase parkin	Functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins.

Protein-family classification

Druggable: 1 · Difficult: 5 · Unknown: 4 · Druggable fraction: 0.1

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	4	3.3×	0.099
Antibody/Immunoglobulin	1	2.9×	0.589
Scaffold/PPI	1	1.7×	0.599
Other/Unknown	4	0.7×	0.907

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TNXB	Antibody/Immunoglobulin	yes		EGF, Fibrinogen_a/b/g_C_dom, FN3_dom
KAT6B	Transcription factor	no	2.3.1.48	Znf_PHD, HAT_MYST-type, Histone_H1/H5_H15
SOX17	Transcription factor	no		HMG_box_dom, Sox_C, Sox7/17/18_central
EBF3	Transcription factor	no		IPT_dom, Transcription_factor_COE, Ig-like_fold
PACRG	Other/Unknown	no		Parkin_co-regulated_protein
MED13L	Other/Unknown	no		Med13_C, Mediator_Med13_N, MID_MedPIWI
AFAP1L2	Scaffold/PPI	no		PH_domain, PH-like_dom_sf, AFAP
NIPBL	Other/Unknown	no		ARM-like, ARM-type_fold, Nipped-B_C
C12orf57	Other/Unknown	no		Grcc10
PRKN	Transcription factor	no	2.3.2.27	Ubiquitin-like_dom, IBR_dom, Parkin

Expression context

Cohort genes with no expression data: 0.

9 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)	10
unknown	0

Top tissues across cohort

Tissue	Cohort genes
sural nerve	3
calcaneal tendon	2
colonic epithelium	2
male germ line stem cell (sensu Vertebrata) in testis	2
apex of heart	1
right adrenal gland	1
right adrenal gland cortex	1
cortical plate	1
ventricular zone	1
endothelial cell	1
omental fat pad	1
peritoneum	1
subcutaneous adipose tissue	1
tendon of biceps brachii	1
tibialis anterior	1
bronchial epithelial cell	1
epithelium of bronchus	1
right uterine tube	1
tendon	1
left lobe of thyroid gland	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TNXB	134	ubiquitous	marker	apex of heart, right adrenal gland cortex, right adrenal gland
KAT6B	140	ubiquitous	yes	cortical plate, ventricular zone, sural nerve
SOX17	190	broad	marker	endothelial cell, omental fat pad, peritoneum
EBF3	193	broad	marker	tibialis anterior, subcutaneous adipose tissue, tendon of biceps brachii
PACRG	197	broad	marker	bronchial epithelial cell, right uterine tube, epithelium of bronchus
MED13L	297	ubiquitous	marker	calcaneal tendon, colonic epithelium, tendon
AFAP1L2	213	broad	marker	sural nerve, left lobe of thyroid gland, right lobe of thyroid gland
NIPBL	288	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, calcaneal tendon, colonic epithelium
C12orf57	145	ubiquitous	marker	thymus, left ovary, endocervix
PRKN	174	ubiquitous	marker	sural nerve, male germ line stem cell (sensu Vertebrata) in testis, hindlimb stylopod muscle

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PRKN	10,281
NIPBL	3,278
SOX17	2,772
PACRG	2,520
KAT6B	2,214
MED13L	1,606
TNXB	1,335
C12orf57	843
EBF3	655
AFAP1L2	624

Intra-cohort edges

A	B	Sources
PACRG	PRKN	string_interaction

Structural data

PDB: 8 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PRKN	O60260	21
PACRG	Q96M98	5
TNXB	P22105	3
KAT6B	Q8WYB5	3
NIPBL	Q6KC79	3
SOX17	Q9H6I2	2
EBF3	Q9H4W6	2
AFAP1L2	Q8N4X5	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
C12orf57	Q99622	81.41
MED13L	Q71F56	56.79

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 35. Enrichment computed across 10 evidence-associated genes (6 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 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Cohesin Loading onto Chromatin	1	190.3×	0.070	NIPBL
Josephin domain DUBs	1	158.6×	0.070	PRKN
Specification of primordial germ cells	1	146.4×	0.070	SOX17
Formation of definitive endoderm	1	119.0×	0.070	SOX17
Developmental Lineage of Multipotent Pancreatic Progenitor Cells	1	100.2×	0.070	SOX17
Regulation of necroptotic cell death	1	73.2×	0.077	PRKN
PINK1-PRKN Mediated Mitophagy	1	59.5×	0.077	PRKN
Developmental Lineage of Pancreatic Acinar Cells	1	50.1×	0.077	SOX17
Gastrulation	1	43.3×	0.077	SOX17
Aggrephagy	1	41.4×	0.077	PRKN
Deactivation of the beta-catenin transactivating complex	1	38.8×	0.077	SOX17
Developmental Cell Lineages	1	37.3×	0.077	SOX17
Respiratory Syncytial Virus Infection Pathway	1	32.8×	0.078	MED13L
Reproduction	1	31.7×	0.078	SOX17
RSV-host interactions	1	26.1×	0.081	MED13L
Adipogenesis	1	26.1×	0.081	MED13L
ECM proteoglycans	1	25.0×	0.081	TNXB
Regulation of lipid metabolism by PPARalpha	1	23.5×	0.081	MED13L
Transcriptional regulation of white adipocyte differentiation	1	21.6×	0.084	MED13L
TCF dependent signaling in response to WNT	1	19.6×	0.087	SOX17
Signaling by WNT	1	18.7×	0.087	SOX17
Amyloid fiber formation	1	17.1×	0.090	PRKN
PPARA activates gene expression	1	15.7×	0.090	MED13L
Developmental Biology	2	4.8×	0.090	SOX17, MED13L
Chromatin organization	1	13.6×	0.099	KAT6B
HATs acetylate histones	1	13.2×	0.099	KAT6B
Chromatin modifying enzymes	1	12.1×	0.104	KAT6B
Extracellular matrix organization	1	10.5×	0.114	TNXB
Antigen processing: Ubiquitination & Proteasome degradation	1	6.2×	0.182	PRKN
Metabolism of lipids	1	5.3×	0.203	MED13L

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 10 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
gallbladder development	2	1685.2×	7e-05	SOX17, NIPBL
cellular response to unfolded protein	2	198.3×	0.005	PACRG, PRKN
cardiogenic plate morphogenesis	1	1685.2×	0.009	SOX17
external genitalia morphogenesis	1	1685.2×	0.009	NIPBL
positive regulation of neurotransmitter uptake	1	1685.2×	0.009	PRKN
negative regulation of spontaneous neurotransmitter secretion	1	1685.2×	0.009	PRKN
positive regulation of cell fate determination	1	1685.2×	0.009	TNXB
regulation of cardiac cell fate specification	1	1685.2×	0.009	SOX17
metanephros development	2	102.1×	0.009	SOX17, NIPBL
regulation of embryonic development	2	66.1×	0.009	SOX17, NIPBL
outflow tract morphogenesis	2	61.3×	0.009	SOX17, NIPBL
protein destabilization	2	58.1×	0.009	SOX17, PRKN
cognition	2	57.1×	0.009	NIPBL, C12orf57
positive regulation of DNA-templated transcription	4	11.2×	0.009	KAT6B, SOX17, EBF3, AFAP1L2
positive regulation of transcription by RNA polymerase II	5	7.4×	0.009	KAT6B, SOX17, MED13L, NIPBL, PRKN
endodermal cell fate determination	1	842.6×	0.012	SOX17
regulation of developmental growth	1	842.6×	0.012	NIPBL
positive regulation of protein linear polyubiquitination	1	842.6×	0.012	PRKN
negative regulation of endoplasmic reticulum stress-induced neuron intrinsic apoptotic signaling pathway	1	842.6×	0.012	PRKN
response to curcumin	1	842.6×	0.012	PRKN
positive regulation of retrograde transport, endosome to Golgi	1	842.6×	0.012	PRKN
negative regulation of intralumenal vesicle formation	1	842.6×	0.012	PRKN
positive regulation of protein catabolic process	2	40.6×	0.012	SOX17, PRKN
inner cell mass cellular morphogenesis	1	561.7×	0.012	SOX17
rostrocaudal neural tube patterning	1	561.7×	0.012	SOX17
negative regulation of glucokinase activity	1	561.7×	0.012	PRKN
common bile duct development	1	561.7×	0.012	SOX17
endodermal digestive tract morphogenesis	1	561.7×	0.012	SOX17
mitochondrion to lysosome vesicle-mediated transport	1	561.7×	0.012	PRKN
regulation protein catabolic process at presynapse	1	561.7×	0.012	PRKN

Therapeutics

Drugs indicated for this disease

0 approved, 1 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Alginic Acid	Phase 3 (in late-stage trials)

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 10

Druggability breadth: 2 of 10 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
TNXB	0	0
KAT6B	0	0
SOX17	0	0
EBF3	0	0
PACRG	0	0
MED13L	0	0
AFAP1L2	0	0
NIPBL	0	0
C12orf57	0	0
PRKN	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
KAT6B	22	Binding:20, Functional:2
SOX17	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
KAT6B	2.3.1.48	histone acetyltransferase
PRKN	2.3.2.27, 2.3.2.31	RING-type E3 ubiquitin transferase, RBR-type E3 ubiquitin transferase

Pharmacogenomics

Cohort genes with a PharmGKB record: 10; 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	1	TNXB
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	9	KAT6B, SOX17, EBF3, PACRG, MED13L, AFAP1L2, NIPBL, C12orf57, PRKN

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
TNXB	0	—
KAT6B	22	—
SOX17	1	—
EBF3	0	—
PACRG	0	—
MED13L	0	—
AFAP1L2	0	—
NIPBL	0	—
C12orf57	0	—
PRKN	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 14.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	10
PHASE3	3
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00004487	PHASE3	UNKNOWN	Phase III Study of Chondrocyte Alginate Gel Suspension in Pediatric Patients With Vesicoureteral Reflux
NCT00405704	PHASE3	COMPLETED	Randomized Intervention for Children With Vesicoureteral Reflux (RIVUR)
NCT02021006	PHASE3	UNKNOWN	Antibiotic Prophylaxis and Renal Damage In Congenital Abnormalities of the Kidney and Urinary Tract
NCT02786810	PHASE2	COMPLETED	Contrast Enhanced Ultrasound for Evaluation of Reflux Nephropathy
NCT00186199	Not specified	COMPLETED	Determination of Voiding Patterns of Children With Vesicoureteral Reflux
NCT00815334	Not specified	COMPLETED	Efficacy of Endoscopic Subureteral Injection for Vesicoureteral Reflux in Adults With Decreased Bladder Compliance
NCT00830479	Not specified	WITHDRAWN	Study of Endoscopic Versus Open Surgery for Urinary Reflux
NCT00894465	Not specified	TERMINATED	Midazolam Effect in Children Undergoing Voiding Cystourethrogram (VCUG)
NCT01137929	Not specified	WITHDRAWN	Bacterial and Host Genetic Risk Factors in Acute Pyelonephritis
NCT01373385	Not specified	COMPLETED	Prospective Pediatric Vesicoureteral Reflux Surgery Database
NCT01483105	Not specified	COMPLETED	DVD-Based Training Program in Self-Hypnosis for Children
NCT01578291	Not specified	TERMINATED	Parent Education and Medical Play: A Comparison of Psychological Preparation Strategies for Voiding Cystourethrogram
NCT01780493	Not specified	COMPLETED	The Long Term Follow-Up Results Of The Direct Nipple Ureteroneocystostomy Technique
NCT01926353	Not specified	COMPLETED	Polyacrylate Polyalcohol Copolymer for Vesicoureteral Reflux

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CEFIXIME	4	1
MIDAZOLAM	4	1
NITROFURANTOIN	4	1
SULFAMETHOXAZOLE	4	1
TRIMETHOPRIM	4	1

Cohort genes: TNXB, KAT6B, SOX17, EBF3, PACRG, MED13L, AFAP1L2, NIPBL, C12orf57, PRKN
Drugs: Cefixime, Midazolam, Nitrofurantoin, Sulfamethoxazole, Trimethoprim