Congenital anomalies of kidney and urinary tract 2

Summary

Congenital anomalies of kidney and urinary tract 2 (MONDO:0027676) is a disease caused by TBX18 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: TBX18 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 21

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital anomalies of kidney and urinary tract 2
Mondo ID	MONDO:0027676
OMIM	143400
DOID	DOID:0080207
UMLS	C5574705
MedGen	1804316
GARD	0025500
Is cancer (heuristic)	no

Also known as: CAKUT2 · congenital anomalies of kidney and urinary tract 2 · congenital anomalies of kidney and urinary tract type 2 · congenital anomaly of kidney and urinary tract caused by mutation in TBX18 · TBX18 congenital anomaly of kidney and urinary tract

Data availability: 21 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › disorder of development or morphogenesis › developmental defect during embryogenesis › congenital anomaly of kidney and urinary tract › congenital anomalies of kidney and urinary tract 2

Related subtypes (2): congenital anomalies of kidney and urinary tract 1, congenital anomalies of kidney and urinary tract 3

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

21 retrieved; paginated sample, class counts are floors:

12 uncertain significance, 3 pathogenic, 2 benign, 1 likely benign, 1 pathogenic/likely pathogenic, 1 conflicting classifications of pathogenicity, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1177415	NM_001080508.3(TBX18):c.692_693insT (p.Glu233fs)	TBX18	Pathogenic	criteria provided, single submitter
208527	NM_001080508.3(TBX18):c.1010del (p.Gly337fs)	TBX18	Pathogenic/Likely pathogenic	no assertion criteria provided
208529	NM_001080508.3(TBX18):c.487A>G (p.Lys163Glu)	TBX18	Pathogenic	no assertion criteria provided
2441800	NM_001080508.3(TBX18):c.1045C>T (p.Arg349Ter)	TBX18	Pathogenic	criteria provided, single submitter
3899978	NM_001080508.3(TBX18):c.1654G>T (p.Gly552Ter)	TBX18	Likely pathogenic	no assertion criteria provided
2282744	NM_001080508.3(TBX18):c.1150G>T (p.Ala384Ser)	TBX18	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1704362	NM_001080508.3(TBX18):c.662G>A (p.Arg221His)	TBX18	Uncertain significance	criteria provided, single submitter
1928628	NM_001080508.3(TBX18):c.1202A>G (p.His401Arg)	TBX18	Uncertain significance	criteria provided, multiple submitters, no conflicts
208528	NM_001080508.3(TBX18):c.1570C>T (p.His524Tyr)	TBX18	Uncertain significance	criteria provided, single submitter
2183211	NM_001080508.3(TBX18):c.205G>A (p.Gly69Arg)	TBX18	Uncertain significance	criteria provided, multiple submitters, no conflicts
2436987	NM_001080508.3(TBX18):c.14G>A (p.Arg5Gln)	TBX18	Uncertain significance	criteria provided, single submitter
3068307	NM_001080508.3(TBX18):c.571A>G (p.Ile191Val)	TBX18	Uncertain significance	criteria provided, single submitter
3377136	NM_001080508.3(TBX18):c.292+2T>G	TBX18	Uncertain significance	criteria provided, single submitter
3393071	NM_001080508.3(TBX18):c.530C>T (p.Ser177Phe)	TBX18	Uncertain significance	criteria provided, multiple submitters, no conflicts
3892606	NM_001080508.3(TBX18):c.1471G>A (p.Gly491Arg)	TBX18	Uncertain significance	criteria provided, single submitter
4080524	NM_001080508.3(TBX18):c.253C>T (p.Pro85Ser)	TBX18	Uncertain significance	criteria provided, single submitter
4526481	NM_001080508.3(TBX18):c.1714G>A (p.Val572Met)	TBX18	Uncertain significance	criteria provided, single submitter
4532037	NM_001080508.3(TBX18):c.653T>C (p.Val218Ala)	TBX18	Uncertain significance	criteria provided, single submitter
1065573	NM_001080508.3(TBX18):c.272A>C (p.Asp91Ala)	TBX18	Likely benign	criteria provided, single submitter
711945	NM_001080508.3(TBX18):c.868G>A (p.Gly290Arg)	TBX18	Benign	criteria provided, multiple submitters, no conflicts
802247	NM_001080508.3(TBX18):c.142G>A (p.Gly48Arg)	TBX18	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 0 · 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
TBX18	Strong	Autosomal dominant	congenital anomalies of kidney and urinary tract 2	4

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
TBX18	HGNC:11595	ENSG00000112837	O95935	T-box transcription factor TBX18	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TBX18	T-box transcription factor TBX18	Acts as a transcriptional repressor involved in developmental processes of a variety of tissues and organs, including the heart and coronary vessels, the ureter and the vertebral column.

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)
TBX18	Transcription factor	no		TF_T-box, p53-like_TF_DNA-bd_sf, TF_T-box_CS

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
popliteal artery	1
right coronary artery	1
tibial artery	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TBX18	162	ubiquitous	marker	right coronary artery, popliteal artery, tibial artery

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TBX18	1,246

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TBX18	O95935	61.09

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
sinoatrial node cell fate commitment	1	16852.0×	9e-04	TBX18
neural plate anterior/posterior regionalization	1	5617.3×	0.001	TBX18
sinoatrial node cell development	1	2808.7×	0.001	TBX18
ureter development	1	2808.7×	0.001	TBX18
regulation of SA node cell action potential	1	2808.7×	0.001	TBX18
sinoatrial node development	1	2106.5×	0.001	TBX18
morphogenesis of embryonic epithelium	1	1532.0×	0.001	TBX18
smooth muscle cell differentiation	1	887.0×	0.002	TBX18
cochlea morphogenesis	1	581.1×	0.003	TBX18
cell fate specification	1	526.6×	0.003	TBX18
somitogenesis	1	374.5×	0.004	TBX18
negative regulation of canonical Wnt signaling pathway	1	117.8×	0.011	TBX18
positive regulation of DNA-templated transcription	1	27.9×	0.041	TBX18
negative regulation of transcription by RNA polymerase II	1	17.7×	0.060	TBX18
regulation of transcription by RNA polymerase II	1	11.7×	0.086	TBX18

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
TBX18	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	TBX18

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)
TBX18	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.