Familial juvenile hyperuricemic nephropathy type 2
diseaseOn this page
Also known as ADTKD-RENautosomal dominant tubulointerstitial kidney disease due to mutations in RENfamilial juvenile hyperuricemic nephropathy caused by mutation in RENFJHN type 2HNFJ2hyperuricemic nephropathy, familial juvenile, 2hyperuricemic nephropathy, familial juvenile, type 2REN familial juvenile hyperuricemic nephropathyREN-associated familial juvenile hyperuricemic nephropathyREN-associated FJHNREN-associated kidney diseasetubulointerstitial kidney disease, autosomal dominant, 4
Summary
Familial juvenile hyperuricemic nephropathy type 2 (MONDO:0013128) is a disease caused by REN (GenCC Definitive), with 2 cohort genes.
At a glance
- Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
- Causal gene: REN (GenCC Definitive)
- Cohort genes: 2
- ClinVar variants: 98
Clinical features
Epidemiology
Prevalence records
2 prevalence record(s), Orphanet:
| Type | Class | Value | Geography | Validation |
|---|---|---|---|---|
| Cases/families | 35 | Worldwide | Validated | |
| Point prevalence | <1 / 1 000 000 | Worldwide | Validated |
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | familial juvenile hyperuricemic nephropathy type 2 |
| Mondo ID | MONDO:0013128 |
| MeSH | C567760 |
| OMIM | 613092 |
| Orphanet | 217330 |
| DOID | DOID:0061119 |
| SNOMED CT | 721840000 |
| UMLS | C2751310 |
| MedGen | 414347 |
| GARD | 0013461 |
| Is cancer (heuristic) | no |
Also known as: ADTKD-REN · autosomal dominant tubulointerstitial kidney disease due to mutations in REN · familial juvenile hyperuricemic nephropathy caused by mutation in REN · familial juvenile hyperuricemic nephropathy type 2 · FJHN type 2 · HNFJ2 · hyperuricemic nephropathy, familial juvenile, 2 · hyperuricemic nephropathy, familial juvenile, type 2 · REN familial juvenile hyperuricemic nephropathy · REN-associated familial juvenile hyperuricemic nephropathy · REN-associated FJHN · REN-associated kidney disease · tubulointerstitial kidney disease, autosomal dominant, 4
Data availability: 98 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 › inherited kidney disorder › familial juvenile hyperuricemic nephropathy › familial juvenile hyperuricemic nephropathy type 2
Related subtypes (5): familial juvenile hyperuricemic nephropathy type 1, hyperuricemic nephropathy, familial juvenile type 3, 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
98 retrieved; paginated sample, class counts are floors:
58 uncertain significance, 18 conflicting classifications of pathogenicity, 5 likely pathogenic, 4 pathogenic/likely pathogenic, 4 benign, 4 benign/likely benign, 3 pathogenic, 2 likely benign
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 13125 | NM_000537.4(REN):c.36GCT[3] (p.Leu16del) | LOC107548112 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 13126 | NM_000537.4(REN):c.47T>G (p.Leu16Arg) | LOC107548112 | Pathogenic | no assertion criteria provided |
| 4531376 | NM_000537.4(REN):c.49T>C (p.Trp17Arg) | LOC107548112 | Pathogenic | criteria provided, single submitter |
| 974505 | NM_000537.4(REN):c.58T>C (p.Cys20Arg) | LOC107548112 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1067090 | NM_000537.4(REN):c.249+1G>A | REN | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 13123 | NM_000537.4(REN):c.145C>T (p.Arg49Ter) | REN | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 50210 | NM_000537.4(REN):c.127C>T (p.Arg43Ter) | REN | Pathogenic | criteria provided, single submitter |
| 4074750 | NM_000537.4(REN):c.30G>A (p.Trp10Ter) | LOC107548112 | Likely pathogenic | criteria provided, single submitter |
| 438681 | NM_000537.4(REN):c.47T>A (p.Leu16His) | LOC107548112 | Likely pathogenic | no assertion criteria provided |
| 3384161 | NM_000537.4(REN):c.1079dup (p.Leu361fs) | REN | Likely pathogenic | no assertion criteria provided |
| 3577981 | NM_000537.4(REN):c.1172_1173del (p.Thr391fs) | REN | Likely pathogenic | criteria provided, single submitter |
| 3578102 | NM_000537.4(REN):c.250-1del | REN | Likely pathogenic | criteria provided, single submitter |
| 1963968 | NM_000537.4(REN):c.95A>C (p.Lys32Thr) | LOC107548112 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 873820 | NM_000537.4(REN):c.97C>T (p.Arg33Trp) | LOC107548112 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 874781 | NM_000537.4(REN):c.45G>A (p.Leu15=) | LOC107548112 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 2358379 | NM_000537.4(REN):c.322T>G (p.Ser108Ala) | REN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 294950 | NM_000537.4(REN):c.1076A>T (p.Lys359Ile) | REN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 294951 | NM_000537.4(REN):c.961-12C>A | REN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 294952 | NM_000537.4(REN):c.855C>T (p.Asp285=) | REN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 294954 | NM_000537.4(REN):c.744C>A (p.Asp248Glu) | REN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 294955 | NM_000537.4(REN):c.663G>A (p.Glu221=) | REN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 294957 | NM_000537.4(REN):c.630C>T (p.Phe210=) | REN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 294958 | NM_000537.4(REN):c.492+12C>T | REN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 294960 | NM_000537.4(REN):c.398C>T (p.Ser133Leu) | REN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 294961 | NM_000537.4(REN):c.390C>T (p.Phe130=) | REN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 294962 | NM_000537.4(REN):c.374-13G>A | REN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 3578017 | NM_000537.4(REN):c.710C>T (p.Ser237Leu) | REN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 753683 | NM_000537.4(REN):c.961-5C>A | REN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 876615 | NM_000537.4(REN):c.1118C>T (p.Pro373Leu) | REN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 876616 | NM_000537.4(REN):c.1032G>A (p.Thr344=) | REN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 16 · 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 |
|---|---|---|---|---|
| KCTD11 | Definitive | Autosomal dominant | familial juvenile hyperuricemic nephropathy type 2 | 8 |
| REN | Definitive | Autosomal dominant | familial juvenile hyperuricemic nephropathy type 2 | 8 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| REN | Orphanet:217330 | REN-related autosomal dominant tubulointerstitial kidney disease |
| REN | Orphanet:97369 | Renal tubular dysgenesis of genetic origin |
Cohort genes → proteins
2 cohort genes, 2 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 2 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| KCTD11 | HGNC:21302 | ENSG00000213859 | Q693B1 | BTB/POZ domain-containing protein KCTD11 | gencc,clinvar |
| REN | HGNC:9958 | ENSG00000143839 | P00797 | Renin | gencc,clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| KCTD11 | BTB/POZ domain-containing protein KCTD11 | Plays a role as a marker and a regulator of neuronal differentiation; Up-regulated by a variety of neurogenic signals, such as retinoic acid, epidermal growth factor/EGF and NGFB/nerve growth factor. |
| REN | Renin | Renin is a highly specific endopeptidase, whose only known function is to generate angiotensin I from angiotensinogen in the plasma, initiating a cascade of reactions that produce an elevation of blood pressure and increased sodium retenti… |
Protein-family classification
Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5
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 |
|---|---|---|---|
| Protease | 1 | 18.3× | 0.108 |
| Other/Unknown | 1 | 0.9× | 0.805 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| KCTD11 | Other/Unknown | no | T1-type_BTB, SKP1/BTB/POZ_sf, KCTD11/21_C | |
| REN | Protease | yes | 3.4.23.15 | Aspartic_peptidase_A1, Aspartic_peptidase_AS, Aspartic_peptidase_N |
Expression context
Cohort genes with no expression data: 0.
2 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) | 2 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| esophagus mucosa | 1 |
| lower esophagus mucosa | 1 |
| tibial nerve | 1 |
| adult mammalian kidney | 1 |
| decidua | 1 |
| stromal cell of endometrium | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| KCTD11 | 132 | ubiquitous | marker | lower esophagus mucosa, tibial nerve, esophagus mucosa |
| REN | 126 | tissue_specific | marker | decidua, adult mammalian kidney, stromal cell of endometrium |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| REN | 3,244 |
| KCTD11 | 420 |
Structural data
PDB: 1 · AlphaFold-only: 1 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| REN | P00797 | 91 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| KCTD11 | Q693B1 | 85.00 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 2 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 |
|---|---|---|---|---|
| Metabolism of Angiotensinogen to Angiotensins | 1 | 634.4× | 0.002 | REN |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| response to cGMP | 1 | 4213.0× | 0.003 | REN |
| renin-angiotensin regulation of aldosterone production | 1 | 2808.7× | 0.003 | REN |
| juxtaglomerular apparatus development | 1 | 2808.7× | 0.003 | REN |
| neuroblast differentiation | 1 | 1053.2× | 0.006 | KCTD11 |
| mesonephros development | 1 | 766.0× | 0.006 | REN |
| amyloid-beta metabolic process | 1 | 766.0× | 0.006 | REN |
| angiotensin maturation | 1 | 648.1× | 0.006 | REN |
| negative regulation of neuroblast proliferation | 1 | 601.9× | 0.006 | KCTD11 |
| drinking behavior | 1 | 495.6× | 0.006 | REN |
| response to immobilization stress | 1 | 366.4× | 0.007 | REN |
| response to cAMP | 1 | 255.3× | 0.009 | REN |
| regulation of MAPK cascade | 1 | 227.7× | 0.009 | REN |
| negative regulation of smoothened signaling pathway | 1 | 227.7× | 0.009 | KCTD11 |
| cell maturation | 1 | 221.7× | 0.009 | REN |
| hormone-mediated signaling pathway | 1 | 200.6× | 0.009 | REN |
| neuroblast proliferation | 1 | 183.2× | 0.009 | KCTD11 |
| cellular response to xenobiotic stimulus | 1 | 120.4× | 0.013 | REN |
| regulation of blood pressure | 1 | 110.9× | 0.013 | REN |
| positive regulation of neuron differentiation | 1 | 99.1× | 0.014 | KCTD11 |
| smoothened signaling pathway | 1 | 90.6× | 0.015 | KCTD11 |
| male gonad development | 1 | 78.0× | 0.016 | REN |
| kidney development | 1 | 70.2× | 0.017 | REN |
| response to lipopolysaccharide | 1 | 62.4× | 0.018 | REN |
| protein homooligomerization | 1 | 61.1× | 0.018 | KCTD11 |
| neuron differentiation | 1 | 50.1× | 0.021 | KCTD11 |
| protein ubiquitination | 1 | 20.7× | 0.050 | KCTD11 |
| proteolysis | 1 | 17.1× | 0.058 | REN |
Therapeutics
Drug target analysis
Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 1
Druggability breadth: 2 of 2 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).
Genes with an approved drug
The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.
| Symbol | Example approved molecule |
|---|---|
| REN | CAPTOPRIL |
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| REN | 13 | 4 |
| KCTD11 | 0 | 0 |
Drugs targeting cohort genes (top 30)
| Molecule | Max phase | Targets in cohort |
|---|---|---|
| CAPTOPRIL | 4 | REN |
| ALISKIREN | 4 | REN |
| ALISKIREN FUMARATE | 4 | REN |
| SITOKIREN | 3 | REN |
| ZANKIREN | 2 | REN |
| DITEKIREN | 2 | REN |
| PEPSTATIN | 2 | REN |
| ENALKIREN | 2 | REN |
| REMIKIREN | 2 | REN |
| IMARIKIREN HYDROCHLORIDE | 2 | REN |
| IMARIKIREN | 2 | REN |
| TERLAKIREN | 2 | REN |
| VTP-27999 | 1 | REN |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 1.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| REN | 541 | Binding:472, Functional:68, ADMET:1 |
| KCTD11 | 1 | Binding:1 |
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| REN | 3.4.23.15 | renin |
Cohort genes with high screening signal
≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.
| Symbol | ChEMBL assays |
|---|---|
| REN | 541 |
Pharmacogenomics
Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.
No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).
Chemical tractability of cohort targets
13 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) |
|---|---|---|
| CAPTOPRIL | 4 | REN |
| ALISKIREN | 4 | REN |
| ALISKIREN FUMARATE | 4 | REN |
| SITOKIREN | 3 | REN |
| ZANKIREN | 2 | REN |
| DITEKIREN | 2 | REN |
| PEPSTATIN | 2 | REN |
| ENALKIREN | 2 | REN |
| REMIKIREN | 2 | REN |
| IMARIKIREN HYDROCHLORIDE | 2 | REN |
| IMARIKIREN | 2 | REN |
| TERLAKIREN | 2 | REN |
| VTP-27999 | 1 | REN |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 1 | REN |
| 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 | KCTD11 |
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) |
|---|---|---|
| KCTD11 | 1 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.