Hyperuricemic nephropathy, familial juvenile type 3

Summary

Hyperuricemic nephropathy, familial juvenile type 3 (MONDO:0013643) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hyperuricemic nephropathy, familial juvenile type 3
Mondo ID	MONDO:0013643
OMIM	614227
UMLS	C3280216
MedGen	481846
Is cancer (heuristic)	no

Also known as: HNFJ3 · hyperuricemic nephropathy, familial juvenile, 3

Data availability: 2 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inherited kidney disorder › familial juvenile hyperuricemic nephropathy › hyperuricemic nephropathy, familial juvenile type 3

Related subtypes (5): familial juvenile hyperuricemic nephropathy type 1, familial juvenile hyperuricemic nephropathy type 2, hyperuricemic nephropathy, familial juvenile type 4, tubulointerstitial kidney disease, autosomal dominant, 2, tubulointerstitial kidney disease, autosomal dominant 6

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

2 retrieved; paginated sample, class counts are floors:

1 pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
446150	NM_000458.4(HNF1B):c.230_233del (p.Asp77fs)	HNF1B	Pathogenic	criteria provided, multiple submitters, no conflicts
636234	NM_000458.4(HNF1B):c.458A>G (p.His153Arg)	HNF1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 9 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
HNF1B	Orphanet:1309	Medullary sponge kidney
HNF1B	Orphanet:1331	Familial prostate cancer
HNF1B	Orphanet:2578	Mayer-Rokitansky-Küster-Hauser syndrome type 2
HNF1B	Orphanet:261265	17q12 microdeletion syndrome
HNF1B	Orphanet:93111	HNF1B-related autosomal dominant tubulointerstitial kidney disease
HNF1B	Orphanet:93172	Renal dysplasia, unilateral
HNF1B	Orphanet:93173	Renal dysplasia, bilateral
HNF1B	Orphanet:97363	Unilateral multicystic dysplastic kidney
HNF1B	Orphanet:97364	Bilateral multicystic dysplastic kidney

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
HNF1B	HGNC:11630	ENSG00000275410	P35680	Hepatocyte nuclear factor 1-beta	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
HNF1B	Hepatocyte nuclear factor 1-beta	Transcription factor that binds to the inverted palindrome 5’-GTTAATNATTAAC-3'.

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)
HNF1B	Transcription factor	no		HD, HNF1b_C, HNF-1_N

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
adult mammalian kidney	1
kidney	1
metanephros cortex	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
HNF1B	74	broad	marker	metanephros cortex, adult mammalian kidney, kidney

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HNF1B	1,660

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
HNF1B	P35680	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. 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
Regulation of gene expression in early pancreatic precursor cells	1	1427.5×	0.002	HNF1B
Nephron development	1	878.5×	0.002	HNF1B
Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells	1	713.8×	0.002	HNF1B
Developmental Lineage of Multipotent Pancreatic Progenitor Cells	1	601.0×	0.002	HNF1B
Developmental Lineage of Pancreatic Acinar Cells	1	300.5×	0.004	HNF1B
Developmental Lineage of Pancreatic Ductal Cells	1	228.4×	0.004	HNF1B

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 pronephros size	1	16852.0×	4e-04	HNF1B
pronephric nephron tubule development	1	16852.0×	4e-04	HNF1B
ureteric bud elongation	1	16852.0×	4e-04	HNF1B
obsolete negative regulation of mesenchymal cell apoptotic process involved in mesonephric nephron morphogenesis	1	16852.0×	4e-04	HNF1B
mesenchymal cell apoptotic process involved in metanephros development	1	16852.0×	4e-04	HNF1B
hepatoblast differentiation	1	8426.0×	5e-04	HNF1B
mesonephric duct formation	1	8426.0×	5e-04	HNF1B
regulation of branch elongation involved in ureteric bud branching	1	5617.3×	6e-04	HNF1B
negative regulation of mesenchymal cell apoptotic process involved in metanephros development	1	5617.3×	6e-04	HNF1B
endodermal cell fate specification	1	2808.7×	0.001	HNF1B
inner cell mass cell differentiation	1	2808.7×	0.001	HNF1B
pronephros development	1	2407.4×	0.001	HNF1B
genitalia development	1	1685.2×	0.001	HNF1B
hindbrain development	1	1123.5×	0.002	HNF1B
endocrine pancreas development	1	936.2×	0.002	HNF1B
embryonic digestive tract morphogenesis	1	936.2×	0.002	HNF1B
regulation of Wnt signaling pathway	1	887.0×	0.002	HNF1B
branching morphogenesis of an epithelial tube	1	732.7×	0.002	HNF1B
pancreas development	1	674.1×	0.002	HNF1B
insulin secretion	1	432.1×	0.004	HNF1B
epithelial cell proliferation	1	312.1×	0.005	HNF1B
positive regulation of transcription initiation by RNA polymerase II	1	271.8×	0.005	HNF1B
response to glucose	1	255.3×	0.005	HNF1B
anterior/posterior pattern specification	1	181.2×	0.007	HNF1B
Notch signaling pathway	1	141.6×	0.008	HNF1B
kidney development	1	140.4×	0.008	HNF1B
gene expression	1	79.9×	0.014	HNF1B
positive regulation of gene expression	1	38.7×	0.029	HNF1B
positive regulation of DNA-templated transcription	1	27.9×	0.038	HNF1B
negative regulation of transcription by RNA polymerase II	1	17.7×	0.058	HNF1B

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
HNF1B	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	HNF1B

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)
HNF1B	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.