Familial juvenile hyperuricemic nephropathy type 1

Summary

Familial juvenile hyperuricemic nephropathy type 1 (MONDO:0008073) is a disease caused by UMOD (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: UMOD (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 300

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	familial juvenile hyperuricemic nephropathy type 1
Mondo ID	MONDO:0008073
MeSH	C563693
OMIM	162000, 603860, 609886
Orphanet	88950, 209886
DOID	DOID:0061122
NCIT	C123172
SNOMED CT	445503007
UMLS	C4551496
MedGen	1645893
GARD	0010679
NORD	827
Is cancer (heuristic)	no

Also known as: ADMCKD2 · ADTKD-UMOD · autosomal dominant medullary cystic kidney disease type 2 · autosomal dominant medullary cystic kidney disease with hyperuricemia · Autosomal Dominant Tubulo-Interstitial Kidney Disease · autosomal dominant tubulointerstitial kidney disease - UMOD · autosomal dominant tubulointerstitial kidney disease due to mutations in UMOD · familial juvenile gouty nephropathy · familial juvenile hyperuricaemic nephropathy · familial juvenile hyperuricemic nephropathy caused by mutation in UMOD · familial nephropathy with gout · FJHN type 1 · glomerulocystic kidney disease with hyperuricemia and isosthenuria · gouty nephropathy, familial juvenile · HNFJ1 · hyperuricemic nephropathy, familial juvenile · hyperuricemic nephropathy, familial juvenile, 1 · hyperuricemic nephropathy, familial juvenile, type 1 · MCKD2 · medullary cystic kidney disease 2 (+11 more)

Data availability: 300 ClinVar variants · 3 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 1

Related subtypes (5): familial juvenile hyperuricemic nephropathy type 2, 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

300 retrieved; paginated sample, class counts are floors:

148 uncertain significance, 54 likely pathogenic, 37 conflicting classifications of pathogenicity, 27 pathogenic, 9 benign/likely benign, 7 likely benign, 7 benign, 7 pathogenic/likely pathogenic, 4 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
1184610	NM_003361.4(UMOD):c.281G>C (p.Cys94Ser)	UMOD	Pathogenic	no assertion criteria provided
12254	NM_003361.4(UMOD):c.529_555del (p.His177_Arg185del)	UMOD	Pathogenic	criteria provided, multiple submitters, no conflicts
12255	NM_003361.4(UMOD):c.443G>A (p.Cys148Tyr)	UMOD	Pathogenic	criteria provided, single submitter
12256	NM_003361.4(UMOD):c.649T>C (p.Cys217Arg)	UMOD	Pathogenic	no assertion criteria provided
12258	NM_003361.4(UMOD):c.230G>A (p.Cys77Tyr)	UMOD	Pathogenic	no assertion criteria provided
12259	NM_003361.4(UMOD):c.376T>C (p.Cys126Arg)	UMOD	Pathogenic	criteria provided, single submitter
12260	NM_003361.4(UMOD):c.383A>G (p.Asn128Ser)	UMOD	Pathogenic	no assertion criteria provided
12261	NM_003361.4(UMOD):c.764G>A (p.Cys255Tyr)	UMOD	Pathogenic	no assertion criteria provided
12262	NM_003361.4(UMOD):c.898T>G (p.Cys300Gly)	UMOD	Pathogenic	no assertion criteria provided
12263	NM_003361.4(UMOD):c.943T>C (p.Cys315Arg)	UMOD	Pathogenic	no assertion criteria provided
1312491	NM_003361.4(UMOD):c.335G>A (p.Cys112Tyr)	UMOD	Pathogenic	criteria provided, single submitter
242346	NM_003361.4(UMOD):c.278_289delinsCCGCCTCCT (p.Val93_Gly97delinsAlaAlaSerCys)	UMOD	Pathogenic	criteria provided, multiple submitters, no conflicts
2443293	NM_003361.4(UMOD):c.276C>G (p.Cys92Trp)	UMOD	Pathogenic	criteria provided, single submitter
2499669	NM_003361.4(UMOD):c.93G>C (p.Trp31Cys)	UMOD	Pathogenic	no assertion criteria provided
2499670	NM_003361.4(UMOD):c.106C>T (p.His36Tyr)	UMOD	Pathogenic	no assertion criteria provided
287876	NM_003361.4(UMOD):c.744C>G (p.Cys248Trp)	UMOD	Pathogenic	criteria provided, multiple submitters, no conflicts
3255087	NM_003361.4(UMOD):c.707C>G (p.Pro236Arg)	UMOD	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3578735	NM_003361.4(UMOD):c.889T>C (p.Cys297Arg)	UMOD	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3578739	NM_003361.4(UMOD):c.860G>A (p.Cys287Tyr)	UMOD	Pathogenic	criteria provided, single submitter
370029	NM_003361.4(UMOD):c.490G>T (p.Glu164Ter)	UMOD	Pathogenic	no assertion criteria provided
39418	NM_003361.4(UMOD):c.649T>G (p.Cys217Gly)	UMOD	Pathogenic	no assertion criteria provided
4292365	NM_003361.4(UMOD):c.950G>A (p.Cys317Tyr)	UMOD	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
446167	NM_003361.4(UMOD):c.949T>G (p.Cys317Gly)	UMOD	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4813580	NM_003361.4(UMOD):c.163G>A (p.Gly55Ser)	UMOD	Pathogenic	criteria provided, single submitter
488632	NM_003361.4(UMOD):c.358T>G (p.Cys120Gly)	UMOD	Pathogenic	criteria provided, single submitter
521547	NM_003361.4(UMOD):c.707C>T (p.Pro236Leu)	UMOD	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
586922	NM_003361.4(UMOD):c.553C>T (p.Arg185Cys)	UMOD	Pathogenic	criteria provided, multiple submitters, no conflicts
586923	NM_003361.4(UMOD):c.610C>G (p.Arg204Gly)	UMOD	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
64644	NM_003361.4(UMOD):c.743G>C (p.Cys248Ser)	UMOD	Pathogenic	no assertion criteria provided
803225	NM_003361.4(UMOD):c.890G>A (p.Cys297Tyr)	UMOD	Pathogenic	criteria provided, single submitter

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
UMOD	Strong	Autosomal dominant	familial juvenile hyperuricemic nephropathy type 1	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
UMOD	Orphanet:88950	UMOD-related autosomal dominant tubulointerstitial kidney disease

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
UMOD	HGNC:12559	ENSG00000169344	P07911	Uromodulin	gencc,clinvar
IGF2BP2	HGNC:28867	ENSG00000073792	Q9Y6M1	Insulin-like growth factor 2 mRNA-binding protein 2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
UMOD	Uromodulin	Functions in biogenesis and organization of the apical membrane of epithelial cells of the thick ascending limb of Henle’s loop (TALH), where it promotes formation of complex filamentous gel-like structure that may play a role in the water…
IGF2BP2	Insulin-like growth factor 2 mRNA-binding protein 2	RNA-binding factor that recruits target transcripts to cytoplasmic protein-RNA complexes (mRNPs).

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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
Other/Unknown	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
UMOD	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, ZP_dom
IGF2BP2	Other/Unknown	no		RRM_dom, KH_dom, KH_dom_type_1

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
adult mammalian kidney	1
adult organism	1
renal medulla	1
adrenal tissue	1
buccal mucosa cell	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
UMOD	104	tissue_specific	marker	renal medulla, adult organism, adult mammalian kidney
IGF2BP2	252	ubiquitous	marker	buccal mucosa cell, adrenal tissue, ventricular zone

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
IGF2BP2	2,594
UMOD	2,084

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
UMOD	P07911	10
IGF2BP2	Q9Y6M1	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Insulin-like Growth Factor-2 mRNA Binding Proteins (IGF2BPs/IMPs/VICKZs) bind RNA	1	1427.5×	0.001	IGF2BP2
Asparagine N-linked glycosylation	1	30.1×	0.033	UMOD

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
citric acid secretion	1	8426.0×	0.002	UMOD
organ or tissue specific immune response	1	4213.0×	0.002	UMOD
response to water deprivation	1	4213.0×	0.002	UMOD
protein transport into plasma membrane raft	1	4213.0×	0.002	UMOD
protein localization to extracellular region	1	4213.0×	0.002	UMOD
metanephric thick ascending limb development	1	4213.0×	0.002	UMOD
protein localization to vacuole	1	4213.0×	0.002	UMOD
micturition	1	2808.7×	0.002	UMOD
juxtaglomerular apparatus development	1	2808.7×	0.002	UMOD
renal urate salt excretion	1	2808.7×	0.002	UMOD
cold-induced thermogenesis	1	2808.7×	0.002	IGF2BP2
collecting duct development	1	2106.5×	0.002	UMOD
metanephric ascending thin limb development	1	2106.5×	0.002	UMOD
metanephric distal convoluted tubule development	1	2106.5×	0.002	UMOD
regulation of urine volume	1	1685.2×	0.002	UMOD
RNA stabilization	1	1685.2×	0.002	IGF2BP2
urea transmembrane transport	1	1685.2×	0.002	UMOD
urate transport	1	1203.7×	0.002	UMOD
connective tissue replacement	1	1203.7×	0.002	UMOD
regulation of protein transport	1	1053.2×	0.003	UMOD
intracellular chloride ion homeostasis	1	842.6×	0.003	UMOD
intracellular phosphate ion homeostasis	1	766.0×	0.003	UMOD
antibacterial innate immune response	1	766.0×	0.003	UMOD
CRD-mediated mRNA stabilization	1	702.2×	0.003	IGF2BP2
neutrophil migration	1	702.2×	0.003	UMOD
multicellular organismal response to stress	1	648.1×	0.003	UMOD
cellular response to unfolded protein	1	495.6×	0.004	UMOD
renal sodium ion absorption	1	495.6×	0.004	UMOD
glomerular filtration	1	468.1×	0.004	UMOD
intracellular sodium ion homeostasis	1	383.0×	0.005	UMOD

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
UMOD	0	0
IGF2BP2	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
IGF2BP2	3	Binding:3

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

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	2	UMOD, IGF2BP2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
UMOD	0	—
IGF2BP2	3	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.