Vesicoureteral reflux 3

Summary

Vesicoureteral reflux 3 (MONDO:0013356) is a disease caused by SOX17 (GenCC Definitive), with 1 cohort gene and 1 clinical trial.

At a glance

• Causal gene: SOX17 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 69
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	vesicoureteral reflux 3
Mondo ID	MONDO:0013356
OMIM	613674
UMLS	C3150927
MedGen	462277
GARD	0018420
Is cancer (heuristic)	no

Also known as: SOX17 vesicoureteral reflux (disease) · vesicoureteral reflux (disease) caused by mutation in SOX17 · vesicoureteral reflux 3 · vesicoureteral reflux type 3 · VUR3

Data availability: 69 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › familial vesicoureteral reflux › vesicoureteral reflux 3

Related subtypes (8): vesicoureteral reflux 1, vesicoureteral reflux, X-linked, vesicoureteral reflux 2, vesicoureteral reflux 4, vesicoureteral reflux 5, vesicoureteral reflux 6, vesicoureteral reflux 7, vesicoureteral reflux 8

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

69 retrieved; paginated sample, class counts are floors:

57 uncertain significance, 3 benign/likely benign, 3 likely benign, 3 conflicting classifications of pathogenicity, 1 benign, 1 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
18415	SOX17, 6-BP INS, NT51	SOX17	Pathogenic	no assertion criteria provided
2683958	NM_022454.4(SOX17):c.245A>G (p.Glu82Gly)	SOX17	Likely pathogenic	criteria provided, single submitter
1651365	NM_022454.4(SOX17):c.57G>C (p.Ala19=)	SOX17	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
18414	NM_022454.4(SOX17):c.532G>T (p.Gly178Cys)	SOX17	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3595653	NM_022454.4(SOX17):c.704C>A (p.Ala235Asp)	SOX17	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1342514	NM_022454.4(SOX17):c.366G>C (p.Glu122Asp)	SOX17	Uncertain significance	criteria provided, single submitter
1923236	NM_022454.4(SOX17):c.625C>G (p.Leu209Val)	SOX17	Uncertain significance	criteria provided, multiple submitters, no conflicts
2355551	NM_022454.4(SOX17):c.982C>G (p.Pro328Ala)	SOX17	Uncertain significance	criteria provided, multiple submitters, no conflicts
2401526	NM_022454.4(SOX17):c.586C>T (p.Pro196Ser)	SOX17	Uncertain significance	criteria provided, multiple submitters, no conflicts
2442628	NM_022454.4(SOX17):c.948_953dup (p.His325_His326insGlnHis)	SOX17	Uncertain significance	criteria provided, multiple submitters, no conflicts
2621863	NM_022454.4(SOX17):c.167C>A (p.Ala56Asp)	SOX17	Uncertain significance	criteria provided, multiple submitters, no conflicts
2886712	NM_022454.4(SOX17):c.566C>A (p.Pro189His)	SOX17	Uncertain significance	criteria provided, multiple submitters, no conflicts
2909246	NM_022454.4(SOX17):c.499C>G (p.Leu167Val)	SOX17	Uncertain significance	criteria provided, multiple submitters, no conflicts
3167742	NM_022454.4(SOX17):c.574C>T (p.Pro192Ser)	SOX17	Uncertain significance	criteria provided, multiple submitters, no conflicts
3447466	NM_022454.4(SOX17):c.913G>A (p.Ala305Thr)	SOX17	Uncertain significance	criteria provided, multiple submitters, no conflicts
3595625	NM_022454.4(SOX17):c.42C>A (p.Ser14Arg)	SOX17	Uncertain significance	criteria provided, single submitter
3595626	NM_022454.4(SOX17):c.89G>A (p.Cys30Tyr)	SOX17	Uncertain significance	criteria provided, single submitter
3595627	NM_022454.4(SOX17):c.100G>A (p.Glu34Lys)	SOX17	Uncertain significance	criteria provided, single submitter
3595628	NM_022454.4(SOX17):c.121G>T (p.Asp41Tyr)	SOX17	Uncertain significance	criteria provided, single submitter
3595629	NM_022454.4(SOX17):c.169G>C (p.Gly57Arg)	SOX17	Uncertain significance	criteria provided, single submitter
3595630	NM_022454.4(SOX17):c.196T>C (p.Ser66Pro)	SOX17	Uncertain significance	criteria provided, single submitter
3595632	NM_022454.4(SOX17):c.251A>G (p.Lys84Arg)	SOX17	Uncertain significance	criteria provided, single submitter
3595633	NM_022454.4(SOX17):c.308-14C>A	SOX17	Uncertain significance	criteria provided, single submitter
3595634	NM_022454.4(SOX17):c.332T>A (p.Leu111Gln)	SOX17	Uncertain significance	criteria provided, single submitter
3595635	NM_022454.4(SOX17):c.353T>C (p.Val118Ala)	SOX17	Uncertain significance	criteria provided, single submitter
3595636	NM_022454.4(SOX17):c.370C>T (p.Leu124=)	SOX17	Uncertain significance	criteria provided, single submitter
3595637	NM_022454.4(SOX17):c.385A>T (p.Met129Leu)	SOX17	Uncertain significance	criteria provided, single submitter
3595638	NM_022454.4(SOX17):c.461G>A (p.Gly154Asp)	SOX17	Uncertain significance	criteria provided, single submitter
3595639	NM_022454.4(SOX17):c.472G>T (p.Gly158Cys)	SOX17	Uncertain significance	criteria provided, single submitter
3595640	NM_022454.4(SOX17):c.478G>A (p.Ala160Thr)	SOX17	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 2 · 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
SOX17	Definitive	Autosomal dominant	vesicoureteral reflux 3	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SOX17	Orphanet:275777	Heritable pulmonary arterial hypertension
SOX17	Orphanet:289365	Familial vesicoureteral reflux

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
SOX17	HGNC:18122	ENSG00000164736	Q9H6I2	Transcription factor SOX-17	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SOX17	Transcription factor SOX-17	Acts as a transcription regulator that binds target promoter DNA.

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)
SOX17	Transcription factor	no		HMG_box_dom, Sox_C, Sox7/17/18_central

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
endothelial cell	1
omental fat pad	1
peritoneum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SOX17	190	broad	marker	endothelial cell, omental fat pad, peritoneum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SOX17	2,772

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SOX17	Q9H6I2	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 12. 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
Specification of primordial germ cells	1	878.5×	0.007	SOX17
Formation of definitive endoderm	1	713.8×	0.007	SOX17
Developmental Lineage of Multipotent Pancreatic Progenitor Cells	1	601.0×	0.007	SOX17
Developmental Lineage of Pancreatic Acinar Cells	1	300.5×	0.008	SOX17
Gastrulation	1	259.6×	0.008	SOX17
Deactivation of the beta-catenin transactivating complex	1	233.1×	0.008	SOX17
Developmental Cell Lineages	1	223.9×	0.008	SOX17
Reproduction	1	190.3×	0.008	SOX17
TCF dependent signaling in response to WNT	1	117.7×	0.011	SOX17
Signaling by WNT	1	112.0×	0.011	SOX17
Developmental Biology	1	14.5×	0.075	SOX17
Signal Transduction	1	10.2×	0.098	SOX17

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
cardiogenic plate morphogenesis	1	16852.0×	9e-04	SOX17
regulation of cardiac cell fate specification	1	16852.0×	9e-04	SOX17
endodermal cell fate determination	1	8426.0×	9e-04	SOX17
gallbladder development	1	8426.0×	9e-04	SOX17
inner cell mass cellular morphogenesis	1	5617.3×	9e-04	SOX17
rostrocaudal neural tube patterning	1	5617.3×	9e-04	SOX17
common bile duct development	1	5617.3×	9e-04	SOX17
endodermal digestive tract morphogenesis	1	5617.3×	9e-04	SOX17
positive regulation of endodermal cell differentiation	1	5617.3×	9e-04	SOX17
stem cell fate specification	1	4213.0×	9e-04	SOX17
endocardium formation	1	4213.0×	9e-04	SOX17
cardiac cell fate determination	1	4213.0×	9e-04	SOX17
heart formation	1	3370.4×	0.001	SOX17
endodermal cell fate specification	1	2808.7×	0.001	SOX17
endocardial cell differentiation	1	2808.7×	0.001	SOX17
ureter development	1	2808.7×	0.001	SOX17
embryonic heart tube morphogenesis	1	1872.4×	0.001	SOX17
embryonic foregut morphogenesis	1	1685.2×	0.001	SOX17
cell migration involved in gastrulation	1	1532.0×	0.001	SOX17
response to alkaloid	1	1532.0×	0.001	SOX17
endoderm formation	1	1404.3×	0.001	SOX17
regulation of stem cell proliferation	1	1404.3×	0.001	SOX17
regulation of stem cell division	1	1404.3×	0.001	SOX17
positive regulation of stem cell differentiation	1	1296.3×	0.002	SOX17
embryonic heart tube development	1	766.0×	0.002	SOX17
signal transduction involved in regulation of gene expression	1	702.2×	0.003	SOX17
metanephros development	1	510.7×	0.003	SOX17
regulation of embryonic development	1	330.4×	0.005	SOX17
outflow tract morphogenesis	1	306.4×	0.005	SOX17
protein destabilization	1	290.6×	0.005	SOX17

Therapeutics

Drug target analysis

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

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
SOX17	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SOX17	1	Binding: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

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	SOX17

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)
SOX17	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05319067	Not specified	RECRUITING	Study of Gut Microbiota Diversity in Children Aged 1-3 Years on Prolonged Antibiotic Prophylaxis for Grade 3 or Higher Vesicoureteral Reflux Compared With 2 Age-matched Control Groups