Diarrhea 9

Summary

Diarrhea 9 (MONDO:0032575) is a disease caused by WNT2B (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: WNT2B (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 7

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	diarrhea 9
Mondo ID	MONDO:0032575
OMIM	618168
UMLS	C4748517
MedGen	1648425
Is cancer (heuristic)	no

Also known as: DIAR9

Data availability: 7 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › digestive system disorder › diarrheal disease › congenital diarrhea › diarrhea 9

Related subtypes (11): congenital malabsorptive diarrhea 4, congenital diarrhea 6, congenital diarrhea 7 with exudative enteropathy, congenital sodium diarrhea, diarrhea 12, with microvillus atrophy, diarrhea 10, protein-losing enteropathy type, diarrhea 11, malabsorptive, congenital, congenital secretory diarrhea, diarrhea 13, diarrhea 14, congenital, diarrhea 15, congenital

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

7 retrieved; paginated sample, class counts are floors:

4 uncertain significance, 2 conflicting classifications of pathogenicity, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
545432	NM_024494.3(WNT2B):c.205C>T (p.Arg69Ter)	WNT2B	Likely pathogenic	criteria provided, single submitter
984423	NM_024494.3(WNT2B):c.423del (p.Phe141fs)	WNT2B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
984424	NM_024494.3(WNT2B):c.722G>A (p.Gly241Asp)	WNT2B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2045490	NM_024494.3(WNT2B):c.457G>A (p.Ala153Thr)	WNT2B	Uncertain significance	criteria provided, multiple submitters, no conflicts
252739	NM_024494.3(WNT2B):c.313C>T (p.Arg105Ter)	WNT2B	Uncertain significance	criteria provided, single submitter
3780806	NM_004185.4(WNT2B):c.125+1del	WNT2B	Uncertain significance	criteria provided, single submitter
4072264	NM_024494.3(WNT2B):c.443C>A (p.Ala148Glu)	WNT2B	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
WNT2B	Strong	Autosomal recessive	diarrhea 9	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
WNT2B	Orphanet:714487	Congenital diarrhea-chronic gastrointestinal inflammation-ocular dysgenesis syndrome

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
WNT2B	HGNC:12781	ENSG00000134245	Q93097	Protein Wnt-2b	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
WNT2B	Protein Wnt-2b	Ligand for members of the frizzled family of seven transmembrane receptors.

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)
WNT2B	Other/Unknown	no		Wnt, Wnt2, Wnt_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
buccal mucosa cell	1
germinal epithelium of ovary	1
parietal pleura	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
WNT2B	231	broad	marker	germinal epithelium of ovary, buccal mucosa cell, parietal pleura

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
WNT2B	1,512

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
WNT2B	Q93097	86.85

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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
WNT ligand biogenesis and trafficking	1	423.0×	0.005	WNT2B
Class B/2 (Secretin family receptors)	1	190.3×	0.005	WNT2B

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
lung induction	1	5617.3×	0.001	WNT2B
mesenchymal-epithelial cell signaling	1	5617.3×	0.001	WNT2B
forebrain regionalization	1	3370.4×	0.001	WNT2B
iris morphogenesis	1	1872.4×	0.002	WNT2B
cornea development in camera-type eye	1	1296.3×	0.002	WNT2B
positive regulation of branching involved in ureteric bud morphogenesis	1	802.5×	0.003	WNT2B
hematopoietic stem cell proliferation	1	648.1×	0.003	WNT2B
lens development in camera-type eye	1	374.5×	0.005	WNT2B
chondrocyte differentiation	1	300.9×	0.005	WNT2B
cell fate commitment	1	295.6×	0.005	WNT2B
cellular response to starvation	1	193.7×	0.007	WNT2B
male gonad development	1	156.0×	0.007	WNT2B
canonical Wnt signaling pathway	1	153.2×	0.007	WNT2B
neuron differentiation	1	100.3×	0.010	WNT2B

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
WNT2B	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	WNT2B

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)
WNT2B	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.