Autosomal dominant medullary cystic kidney disease with or without hyperuricemia

Summary

Autosomal dominant medullary cystic kidney disease with or without hyperuricemia (MONDO:0008264) is a disease with 3 cohort genes and 1 clinical trial.

At a glance

• Cohort genes: 3
• ClinVar variants: 13
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal dominant medullary cystic kidney disease with or without hyperuricemia
Mondo ID	MONDO:0008264
MeSH	C536137
Orphanet	34149
ICD-11	216863438
SNOMED CT	444699000
UMLS	C4511620
MedGen	1377523
GARD	0010801
Is cancer (heuristic)	no

Also known as: ADTKD · autosomal dominant interstitial kidney disease · autosomal dominant medullary cystic kidney disease · autosomal dominant medullary cystic kidney disease with or without hyperuricemia · MCKD · medullary cystic disease · medullary cystic kidney disease

Data availability: 13 ClinVar variants.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal dominant disease › autosomal dominant medullary cystic kidney disease with or without hyperuricemia

Related subtypes (191): autosomal dominant polycystic liver disease, cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1, tuberous sclerosis, Treacher-Collins syndrome, hereditary breast ovarian cancer syndrome, autosomal dominant polycystic kidney disease, Lynch syndrome, branchio-oto-renal syndrome, autosomal dominant Aarskog syndrome, acroosteolysis dominant type, ADULT syndrome, autosomal dominant Alport syndrome, amelogenesis imperfecta type 1B, Townes-Brocks syndrome, nevoid basal cell carcinoma syndrome, blepharophimosis, ptosis, and epicanthus inversus syndrome, autosomal dominant brachyolmia, branchiooculofacial syndrome, pheochromocytoma/paraganglioma syndrome 4, cataract-aberrant oral frenula-growth delay syndrome, cherubism, autosomal dominant chondrodysplasia punctata, autosomal dominant popliteal pterygium syndrome, blepharocheilodontic syndrome, cochleosaccular degeneration-cataract syndrome, renal coloboma syndrome, Beare-Stevenson cutis gyrata syndrome, autosomal dominant vibratory urticaria, neurohypophyseal diabetes insipidus, autosomal dominant Kenny-Caffey syndrome, Rapp-Hodgkin syndrome, Ehlers-Danlos syndrome, classic type, autosomal dominant Ehlers-Danlos syndrome, vascular type, multiple endocrine neoplasia type 1, Coffin-Siris syndrome 1, isolated congenital adermatoglyphia, Flynn-Aird syndrome, Frasier syndrome, hand-foot-genital syndrome, Holt-Oram syndrome, hyperkeratosis-hyperpigmentation syndrome, autosomal dominant ichthyosis vulgaris, hyper-IgE recurrent infection syndrome 1, autosomal dominant, autosomal dominant keratitis, autosomal dominant keratitis-ichthyosis-hearing loss syndrome, LADD syndrome, trichorhinophalangeal syndrome type II, Noonan syndrome with multiple lentigines, microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability, Marfan syndrome, melanoma, cutaneous malignant, susceptibility to, 2, autosomal dominant primary microcephaly, autosomal dominant progressive external ophthalmoplegia, monilethrix, Muir-Torre syndrome, autosomal dominant myoglobinuria, autosomal dominant centronuclear myopathy, nail-patella syndrome, multiple endocrine neoplasia type 2B, autosomal dominant omodysplasia, pheochromocytoma/paraganglioma syndrome 1, Pelger-Huet anomaly, multiple endocrine neoplasia type 2A, piebaldism, generalized juvenile polyposis/juvenile polyposis coli, juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, Peutz-Jeghers syndrome, contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A, autosomal dominant distal renal tubular acidosis, retinoschisis, autosomal dominant, autosomal dominant Robinow syndrome, scapuloperoneal spinal muscular atrophy, autosomal dominant, autosomal dominant sideroblastic anemia, spondyloepiphyseal dysplasia tarda, autosomal dominant, proximal symphalangism, calcaneonavicular coalition, thanatophoric dysplasia type 1, trichorhinophalangeal syndrome type I, Muckle-Wells syndrome, autosomal dominant hypophosphatemic rickets, von Hippel-Lindau disease, Denys-Drash syndrome, autosomal dominant severe congenital neutropenia, Costello syndrome, EEC syndrome, multiple cutaneous and mucosal venous malformations, diffuse nonepidermolytic palmoplantar keratoderma, Timothy syndrome, pheochromocytoma/paraganglioma syndrome 2, spondyloepimetaphyseal dysplasia with multiple dislocations, Brooke-Spiegler syndrome, macrocephaly-autism syndrome, pheochromocytoma/paraganglioma syndrome 3, Duane-radial ray syndrome, PCWH syndrome, heart-hand syndrome, Slovenian type, congenital stationary night blindness autosomal dominant 3, mandibulofacial dysostosis-microcephaly syndrome, multiple endocrine neoplasia type 4, juvenile cataract-microcornea-renal glucosuria syndrome, Crouzon syndrome-acanthosis nigricans syndrome, Birk-Barel syndrome, thrombophilia due to protein S deficiency, autosomal dominant, dyskeratosis congenita, autosomal dominant 2, dyskeratosis congenita, autosomal dominant 3, colorectal cancer, hereditary nonpolyposis, type 6, colorectal cancer, hereditary nonpolyposis, type 7, brain small vessel disease 2A, autosomal dominant, intellectual disability, autosomal dominant 14, intellectual disability, autosomal dominant 15, intellectual disability, autosomal dominant 16, hypopigmentation-punctate palmoplantar keratoderma syndrome, intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency, postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome, intellectual developmental disorder with microcephaly and with or without ocular malformations or hypogonadotropic hypogonadism, intellectual disability, autosomal dominant 29, intellectual disability, autosomal dominant 30, Houge-Janssens syndrome 2, severe achondroplasia-developmental delay-acanthosis nigricans syndrome, dyskeratosis congenita, autosomal dominant 6, epidermolysis bullosa simplex 6, generalized, with scarring and hair loss, autosomal dominant complex spastic paraplegia, early-onset autosomal dominant Alzheimer disease, muscular dystrophy, limb-girdle, autosomal dominant, Feingold syndrome, Carney complex, neuronopathy, distal hereditary motor, autosomal dominant, autosomal dominant coarctation of aorta, autosomal dominant spondylocostal dysostosis, autosomal dominant hypohidrotic ectodermal dysplasia, Cowden disease, autosomal dominant distal myopathy, autosomal dominant rhegmatogenous retinal detachment, palmoplantar keratoderma-spastic paralysis syndrome, Alagille syndrome due to a JAG1 point mutation, PTEN hamartoma tumor syndrome, gastric adenocarcinoma and proximal polyposis of the stomach, autosomal dominant proximal renal tubular acidosis, autosomal dominant spastic ataxia, Waardenburg syndrome, hereditary retinoblastoma, autosomal dominant hypocalcemia, Li-Fraumeni syndrome, Loeys-Dietz syndrome, hereditary hemorrhagic telangiectasia, hereditary inclusion body myopathy-joint contractures-ophthalmoplegia syndrome, microcephalic osteodysplastic dysplasia, Saul-Wilson type, autosomal dominant intermediate Charcot-Marie-Tooth disease, autosomal dominant cutis laxa, autosomal dominant nonsyndromic hearing loss, autosomal dominant optic atrophy, autosomal dominant Emery-Dreifuss muscular dystrophy, autosomal dominant cerebellar ataxia, autosomal dominant osteopetrosis, autosomal dominant epidermolytic ichthyosis, ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome, distal arthrogryposis type 2B1, neurofibromatosis, autosomal dominant cataract, arthrogryposis, distal, type 2B2, arthrogryposis, distal, type 2B3, Charcot-Marie-Tooth disease, demyelinating, type 1G, Delpire-McNeill syndrome, LAMA5-related multisystemic syndrome, autosomal dominant oculocutaneous albinism, Charcot-Marie-tooth disease, axonal, type 2DD, Pilarowski-Bjornsson syndrome, intellectual disability, autosomal dominant, fatty acyl-CoA reductase 1 upregulation, GUCY2D-related dominant retinopathy, RPE65-related dominant retinopathy, autosomal dominant titinopathy, NOG-related symphalangism spectrum disorder, ALPL-related autosomal dominant hypophosphatasia, MYH10-related neurodevelopmental disorder with congenital anomalies, spastic paraplegia 30A, autosomal dominant, TMEM127-related tumor predisposition, MAX-related tumor predisposition, BMPR1A-related juvenile polyposis syndrome, RP1-related dominant retinopathy, Birt-Hogg-Dube syndrome, inclusion body myopathy and brain white matter abnormalities, KINSSHIP syndrome, autosomal dominant nebulin-related myopathy, IMPG1-related dominant retinopathy, PROM1-related dominant retinopathy, PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome, ALG8-related autosomal dominant polycystic kidney and/or liver disease, NOTCH1-related AOS spectrum disorder, FLNB-associated autosomal dominant filamin related bone disorder, familial antiphospholipid syndrome

Subtypes (2): familial juvenile hyperuricemic nephropathy type 1, tubulointerstitial kidney disease, autosomal dominant, 2

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

13 retrieved; paginated sample, class counts are floors:

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
12640	NM_000458.4(HNF1B):c.826C>T (p.Arg276Ter)	HNF1B	Pathogenic	criteria provided, multiple submitters, no conflicts
242346	NM_003361.4(UMOD):c.278_289delinsCCGCCTCCT (p.Val93_Gly97delinsAlaAlaSerCys)	UMOD	Pathogenic	criteria provided, multiple submitters, no conflicts
807521	NM_003361.4(UMOD):c.317G>A (p.Cys106Tyr)	UMOD	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
988177	NM_003361.4(UMOD):c.854C>A (p.Ala285Glu)	UMOD	Pathogenic	criteria provided, multiple submitters, no conflicts
1344662	NM_003361.4(UMOD):c.1382C>A (p.Ala461Glu)	UMOD	Likely pathogenic	criteria provided, multiple submitters, no conflicts
988176	NM_003361.4(UMOD):c.272_274del (p.Ser91del)	UMOD	Likely pathogenic	criteria provided, single submitter
988208	NM_003361.4(UMOD):c.411C>G (p.Cys137Trp)	UMOD	Likely pathogenic	no assertion criteria provided
988126	NM_007214.5(SEC63):c.1936-8G>T	SEC63	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1805518	NM_003361.4(UMOD):c.544G>A (p.Glu182Lys)	UMOD	Uncertain significance	criteria provided, single submitter
3068587	NM_003361.4(UMOD):c.518C>A (p.Pro173Gln)	UMOD	Uncertain significance	criteria provided, single submitter
988175	NM_003361.4(UMOD):c.698G>T (p.Gly233Val)	UMOD	Uncertain significance	no assertion criteria provided
988207	NM_003361.4(UMOD):c.768C>G (p.Cys256Trp)	UMOD	Uncertain significance	no assertion criteria provided
988178	NM_003361.4(UMOD):c.1901C>T (p.Thr634Ile)	UMOD	Likely benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 11 · 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
UMOD	Orphanet:88950	UMOD-related autosomal dominant tubulointerstitial kidney disease
SEC63	Orphanet:2924	Isolated polycystic liver disease

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
HNF1B	HGNC:11630	ENSG00000275410	P35680	Hepatocyte nuclear factor 1-beta	clinvar
UMOD	HGNC:12559	ENSG00000169344	P07911	Uromodulin	clinvar
SEC63	HGNC:21082	ENSG00000025796	Q9UGP8	Translocation protein SEC63 homolog	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'.
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…
SEC63	Translocation protein SEC63 homolog	Mediates cotranslational and post-translational transport of certain precursor polypeptides across endoplasmic reticulum (ER).

Protein-family classification

Druggable: 0 · Difficult: 1 · 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
Transcription factor	1	2.8×	0.587
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
HNF1B	Transcription factor	no		HD, HNF1b_C, HNF-1_N
UMOD	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, ZP_dom
SEC63	Other/Unknown	no		DnaJ_domain, Sec63-dom, Ig_E-set

Expression context

Cohort genes with no expression data: 0.

3 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
adult mammalian kidney	2
kidney	1
metanephros cortex	1
adult organism	1
renal medulla	1
body of pancreas	1
colonic epithelium	1
parotid gland	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
UMOD	104	tissue_specific	marker	renal medulla, adult organism, adult mammalian kidney
SEC63	295	ubiquitous	marker	colonic epithelium, body of pancreas, parotid gland

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SEC63	3,355
UMOD	2,084
HNF1B	1,660

Intra-cohort edges

A	B	Sources
HNF1B	UMOD	string_interaction

Structural data

PDB: 2 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
UMOD	P07911	10
HNF1B	P35680	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SEC63	Q9UGP8	77.71

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. Enrichment computed across 3 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
Regulation of gene expression in early pancreatic precursor cells	1	713.8×	0.006	HNF1B
Nephron development	1	439.2×	0.006	HNF1B
Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells	1	356.9×	0.006	HNF1B
Developmental Lineage of Multipotent Pancreatic Progenitor Cells	1	300.5×	0.006	HNF1B
Developmental Lineage of Pancreatic Acinar Cells	1	150.3×	0.009	HNF1B
Developmental Lineage of Pancreatic Ductal Cells	1	114.2×	0.010	HNF1B
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 3 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	5617.3×	0.002	HNF1B
pronephric nephron tubule development	1	5617.3×	0.002	HNF1B
citric acid secretion	1	5617.3×	0.002	UMOD
ureteric bud elongation	1	5617.3×	0.002	HNF1B
obsolete negative regulation of mesenchymal cell apoptotic process involved in mesonephric nephron morphogenesis	1	5617.3×	0.002	HNF1B
mesenchymal cell apoptotic process involved in metanephros development	1	5617.3×	0.002	HNF1B
organ or tissue specific immune response	1	2808.7×	0.002	UMOD
response to water deprivation	1	2808.7×	0.002	UMOD
protein transport into plasma membrane raft	1	2808.7×	0.002	UMOD
hepatoblast differentiation	1	2808.7×	0.002	HNF1B
protein localization to extracellular region	1	2808.7×	0.002	UMOD
nitrogen cycle metabolic process	1	2808.7×	0.002	SEC63
mesonephric duct formation	1	2808.7×	0.002	HNF1B
metanephric thick ascending limb development	1	2808.7×	0.002	UMOD
protein localization to vacuole	1	2808.7×	0.002	UMOD
micturition	1	1872.4×	0.002	UMOD
juxtaglomerular apparatus development	1	1872.4×	0.002	UMOD
regulation of branch elongation involved in ureteric bud branching	1	1872.4×	0.002	HNF1B
renal urate salt excretion	1	1872.4×	0.002	UMOD
negative regulation of mesenchymal cell apoptotic process involved in metanephros development	1	1872.4×	0.002	HNF1B
gene expression	2	53.2×	0.002	HNF1B, UMOD
collecting duct development	1	1404.3×	0.002	UMOD
metanephric ascending thin limb development	1	1404.3×	0.002	UMOD
metanephric distal convoluted tubule development	1	1404.3×	0.002	UMOD
regulation of urine volume	1	1123.5×	0.003	UMOD
urea transmembrane transport	1	1123.5×	0.003	UMOD
endodermal cell fate specification	1	936.2×	0.003	HNF1B
inner cell mass cell differentiation	1	936.2×	0.003	HNF1B
urate transport	1	802.5×	0.003	UMOD
pronephros development	1	802.5×	0.003	HNF1B

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 3 evidence-associated genes (33%) 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
UMOD	0	0
SEC63	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
SEC63	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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	3	HNF1B, UMOD, SEC63

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
HNF1B	0	—
UMOD	0	—
SEC63	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
NCT06065852	Not specified	RECRUITING	National Registry of Rare Kidney Diseases