Tubulointerstitial kidney disease, autosomal dominant, 2

Summary

Tubulointerstitial kidney disease, autosomal dominant, 2 (MONDO:0020726) is a disease caused by MUC1 (GenCC Definitive), with 1 cohort gene.

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Causal gene: MUC1 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 25

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	<1 / 1 000 000	0.07	United States	Validated
Point prevalence	1-9 / 1 000 000	0.4	Ireland	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	tubulointerstitial kidney disease, autosomal dominant, 2
Mondo ID	MONDO:0020726
OMIM	174000
Orphanet	88949
DOID	DOID:0061118
NCIT	C123171
UMLS	C1868139
MedGen	358137
GARD	0007002
Is cancer (heuristic)	no

Also known as: ADMCKD1 · ADTKD-MUC1 · autosomal dominant medullary cystic kidney disease without hyperuricemia · autosomal dominant tubulointerstitial kidney disease due to mutations in MUC1 · MCKD1 · medullary cystic kidney disease 1 · medullary cystic kidney disease type 1 · medullary cystic kidney disease, autosomal dominant · MUC1-related autosomal dominant medullary cystic kidney disease · MUCI-related ADTKD

Data availability: 25 ClinVar variants · 5 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 › tubulointerstitial kidney disease, autosomal dominant, 2

Related subtypes (5): familial juvenile hyperuricemic nephropathy type 1, familial juvenile hyperuricemic nephropathy type 2, hyperuricemic nephropathy, familial juvenile type 3, hyperuricemic nephropathy, familial juvenile type 4, 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

25 retrieved; paginated sample, class counts are floors:

10 uncertain significance, 6 likely pathogenic, 5 not provided, 2 pathogenic, 1 conflicting classifications of pathogenicity, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
55830	NC_000001.10:g.(155160963_155162030)insC	MUC1	Pathogenic	no assertion criteria provided
974433	NM_002456.6(MUC1):c.430dup (p.Thr144fs)	MUC1	Pathogenic	criteria provided, single submitter
2506459	NM_001204285.2(MUC1):c.293_296dup (p.Ser100fs)	MUC1	Likely pathogenic	criteria provided, single submitter
3065438	NM_001204285.2(MUC1):c.184del (p.Ser62fs)	MUC1	Likely pathogenic	criteria provided, single submitter
3065546	NM_001204285.2(MUC1):c.1354-1G>A	MUC1	Likely pathogenic	criteria provided, single submitter
3779971	NM_001204286.1(MUC1):c.1078C>T (p.Arg360Ter)	MUC1	Likely pathogenic	criteria provided, single submitter
3900022	NM_001204285.2(MUC1):c.435-27_467del	MUC1	Likely pathogenic	no assertion criteria provided
4292582	NM_001371720.2(MUC1):c.3478C>T (p.Gln1160Ter)	MUC1	Likely pathogenic	criteria provided, single submitter
1031014	NM_001044393.3(MUC1):c.295C>T (p.Arg99Cys)	MUC1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2357056	NM_001204286.1(MUC1):c.379G>A (p.Val127Ile)	MUC1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3068105	NM_002456.6(MUC1):c.717del (p.Ser240fs)	MUC1	Uncertain significance	criteria provided, single submitter
3238849	NM_002456.6(MUC1):c.159+5G>C	MUC1	Uncertain significance	criteria provided, single submitter
3891751	NM_001204286.1(MUC1):c.281A>C (p.Glu94Ala)	MUC1	Uncertain significance	criteria provided, single submitter
3891752	NM_001044391.3(MUC1):c.281C>G (p.Ala94Gly)	MUC1	Uncertain significance	criteria provided, single submitter
3891753	NM_001204286.1(MUC1):c.466G>T (p.Ala156Ser)	MUC1	Uncertain significance	criteria provided, single submitter
3891754	NM_001204286.1(MUC1):c.583T>A (p.Ser195Thr)	MUC1	Uncertain significance	criteria provided, single submitter
3891755	NM_002456.6(MUC1):c.604_607del (p.Cys202fs)	MUC1	Uncertain significance	criteria provided, single submitter
3907663	NM_002456.6(MUC1):c.160-208_160-205dup	MUC1	Uncertain significance	criteria provided, single submitter
4079294	NM_002456.6(MUC1):c.474C>T (p.Ser158=)	MUC1	Uncertain significance	criteria provided, single submitter
1321177	NM_001204286.1(MUC1):c.93G>A (p.Thr31=)	MUC1	Benign	criteria provided, multiple submitters, no conflicts
1301999	NC_000001.10:g.(155160963_155162030)insC		not provided	no classification provided
1302000	NC_000001.10:g.(155160963_155162030)insG		not provided	no classification provided
1302001	NC_000001.10:g.(155160963_155162030)delinsAT		not provided	no classification provided
1302002	NC_000001.10:g.(155160963_155162030)dupGCCGGCCCCGGGTCC		not provided	no classification provided
1301998	NM_002456.6(MUC1):c.253C>T (p.Gln85Ter)	MUC1	not provided	no classification provided

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
MUC1	Definitive	Autosomal dominant	tubulointerstitial kidney disease, autosomal dominant, 2	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MUC1	Orphanet:88949	MUC1-related autosomal dominant tubulointerstitial kidney disease

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
MUC1	HGNC:7508	ENSG00000185499	P15941	Mucin-1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MUC1	Mucin-1	The alpha subunit has cell adhesive properties.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MUC1	Other/Unknown	no		SEA_dom, SEA_dom_sf

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
nasal cavity epithelium	1
pancreatic ductal cell	1
pylorus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MUC1	247	ubiquitous	marker	pylorus, pancreatic ductal cell, nasal cavity epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MUC1	253

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MUC1	P15941	23

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 21. 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
Defective GALNT3 causes HFTC	1	713.8×	0.007	MUC1
Defective GALNT12 causes CRCS1	1	713.8×	0.007	MUC1
Defective C1GALT1C1 causes TNPS	1	671.8×	0.007	MUC1
Developmental Lineage of Mammary Gland Alveolar Cells	1	634.4×	0.007	MUC1
Termination of O-glycan biosynthesis	1	496.5×	0.007	MUC1
Developmental Lineage of Mammary Gland Luminal Epithelial Cells	1	456.8×	0.007	MUC1
Dectin-2 family	1	423.0×	0.007	MUC1
C-type lectin receptors (CLRs)	1	237.9×	0.011	MUC1
Diseases associated with O-glycosylation of proteins	1	215.5×	0.011	MUC1
O-linked glycosylation of mucins	1	184.2×	0.011	MUC1
O-linked glycosylation	1	144.6×	0.013	MUC1
Diseases of glycosylation	1	131.3×	0.013	MUC1
Interleukin-4 and Interleukin-13 signaling	1	102.9×	0.016	MUC1
Diseases of metabolism	1	80.4×	0.019	MUC1
Signaling by Interleukins	1	64.2×	0.022	MUC1
Cytokine Signaling in Immune system	1	40.8×	0.032	MUC1
Innate Immune System	1	25.5×	0.048	MUC1
Post-translational protein modification	1	19.2×	0.061	MUC1
Disease	1	13.1×	0.081	MUC1
Immune System	1	13.0×	0.081	MUC1
Metabolism of proteins	1	12.4×	0.081	MUC1

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
obsolete negative regulation of transcription by competitive promoter binding	1	1296.3×	0.001	MUC1
negative regulation of cell adhesion mediated by integrin	1	1296.3×	0.001	MUC1
mitotic G1 DNA damage checkpoint signaling	1	1053.2×	0.001	MUC1
negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	1	1053.2×	0.001	MUC1
DNA damage response, signal transduction by p53 class mediator	1	358.6×	0.003	MUC1
positive regulation of transcription by RNA polymerase II	1	14.9×	0.067	MUC1

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
MUC1	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
MUC1	13	Binding:13

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	MUC1

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)
MUC1	13	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.