Blepharocheilodontic syndrome 2

Summary

Blepharocheilodontic syndrome 2 (MONDO:0040503) is a disease caused by CTNND1 (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: CTNND1 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 28

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	blepharocheilodontic syndrome 2
Mondo ID	MONDO:0040503
OMIM	617681
DOID	DOID:0080346
UMLS	C4540127
MedGen	1623594
GARD	0016244
Is cancer (heuristic)	no

Also known as: BCDS2 · blepharo-cheilo-odontic syndrome caused by mutation in CTNND1 · CTNND1 blepharo-cheilo-odontic syndrome

Data availability: 28 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal dominant disease › blepharocheilodontic syndrome › blepharocheilodontic syndrome 2

Related subtypes (2): Martinez Monasterio Pinheiro syndrome, blepharocheilodontic syndrome 1

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

28 retrieved; paginated sample, class counts are floors:

10 pathogenic, 10 likely pathogenic, 5 uncertain significance, 1 benign, 1 pathogenic/likely pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
1322171	NM_001085458.2(CTNND1):c.1754del (p.Asn585fs)	CTNND1	Pathogenic	criteria provided, single submitter
2446376	NM_001085458.2(CTNND1):c.566dup (p.Pro190fs)	CTNND1	Pathogenic	no assertion criteria provided
3254974	NM_001085458.2(CTNND1):c.2550+1G>A	CTNND1	Pathogenic	criteria provided, single submitter
3374728	NM_001085458.2(CTNND1):c.2638+2T>G	CTNND1	Pathogenic	criteria provided, single submitter
438815	NM_001085458.2(CTNND1):c.2098C>T (p.Arg700Ter)	CTNND1	Pathogenic	no assertion criteria provided
438816	NM_001085458.2(CTNND1):c.1093C>T (p.Gln365Ter)	CTNND1	Pathogenic	no assertion criteria provided
438817	NM_001085458.2(CTNND1):c.606del (p.Pro203fs)	CTNND1	Pathogenic	criteria provided, single submitter
4532017	NM_001085458.2(CTNND1):c.2720del (p.Pro907fs)	CTNND1	Pathogenic	criteria provided, single submitter
4819058	NM_001085458.2(CTNND1):c.2479C>T (p.Gln827Ter)	CTNND1	Pathogenic	criteria provided, single submitter
1343238	NM_001085458.2(CTNND1):c.1030C>T (p.Arg344Ter)	TMX2-CTNND1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2505972	NM_001085458.2(CTNND1):c.1381C>T (p.Arg461Ter)	TMX2-CTNND1	Pathogenic	criteria provided, multiple submitters, no conflicts
1333575	NM_001085458.2(CTNND1):c.2233G>T (p.Glu745Ter)	CTNND1	Likely pathogenic	criteria provided, single submitter
2412720	NM_001085458.2(CTNND1):c.506C>G (p.Ser169Ter)	CTNND1	Likely pathogenic	criteria provided, single submitter
3775408	NM_001085458.2(CTNND1):c.2737del (p.His913fs)	CTNND1	Likely pathogenic	criteria provided, single submitter
3901930	NM_001085458.2(CTNND1):c.1722+2T>G	CTNND1	Likely pathogenic	criteria provided, single submitter
4081301	NM_001085458.2(CTNND1):c.1350_1351del (p.Cys450_Asp451delinsTer)	CTNND1	Likely pathogenic	criteria provided, single submitter
4291712	NM_001085458.2(CTNND1):c.2076_2077del (p.Ala693fs)	CTNND1	Likely pathogenic	criteria provided, single submitter
4294468	NM_001085458.2(CTNND1):c.2022del (p.Ser675fs)	CTNND1	Likely pathogenic	criteria provided, single submitter
800854	NM_001085458.2(CTNND1):c.2572C>T (p.Arg858Ter)	CTNND1	Likely pathogenic	criteria provided, single submitter
834012	NM_001085458.2(CTNND1):c.1007G>A (p.Trp336Ter)	CTNND1	Likely pathogenic	criteria provided, single submitter
931457	NM_001085458.2(CTNND1):c.1687C>T (p.Gln563Ter)	CTNND1	Likely pathogenic	criteria provided, single submitter
2341411	NM_001085458.2(CTNND1):c.2399A>G (p.Gln800Arg)	CTNND1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1031069	NM_001085458.2(CTNND1):c.1186C>G (p.Arg396Gly)	CTNND1	Uncertain significance	criteria provided, single submitter
1339132	NM_001085458.2(CTNND1):c.2091G>A (p.Thr697=)	CTNND1	Uncertain significance	criteria provided, single submitter
2541896	NM_001085458.2(CTNND1):c.1837C>T (p.Pro613Ser)	CTNND1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3254542	NM_001085458.2(CTNND1):c.1889C>T (p.Ser630Phe)	CTNND1	Uncertain significance	criteria provided, single submitter
3779195	NM_001085458.2(CTNND1):c.1514A>G (p.His505Arg)	CTNND1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1236449	NM_001085458.2(CTNND1):c.483C>T (p.Asp161=)	CTNND1	Benign	criteria provided, multiple submitters, no conflicts

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
CTNND1	Definitive	Autosomal dominant	blepharocheilodontic syndrome 2	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CTNND1	Orphanet:1997	Blepharo-cheilo-odontic syndrome

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CTNND1	HGNC:2515	ENSG00000198561	O60716	Catenin delta-1	gencc,clinvar
TMX2-CTNND1	HGNC:41992	ENSG00000254462		TMX2-CTNND1 readthrough (NMD candidate)	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CTNND1	Catenin delta-1	Key regulator of cell-cell adhesion that associates with and regulates the cell adhesion properties of both C-, E- and N-cadherins, being critical for their surface stability.

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)
CTNND1	Other/Unknown	no		Armadillo, ARM-like, ARM-type_fold
TMX2-CTNND1	Other/Unknown	no

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	1

Top tissues across cohort

Tissue	Cohort genes
esophagus mucosa	1
lower esophagus mucosa	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CTNND1	134	ubiquitous	marker	ventricular zone, esophagus mucosa, lower esophagus mucosa
TMX2-CTNND1		ubiquitous	yes

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CTNND1	2,883
TMX2-CTNND1	0

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CTNND1	O60716	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 10. Enrichment computed across 2 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
CDH11 homotypic and heterotypic interactions	1	1631.4×	0.002	CTNND1
Regulation of CDH19 Expression and Function	1	1427.5×	0.002	CTNND1
InlA-mediated entry of Listeria monocytogenes into host cells	1	1268.9×	0.002	CTNND1
Regulation of CDH11 function	1	1038.2×	0.002	CTNND1
Regulation of CDH1 Function	1	951.7×	0.002	CTNND1
SRC activates STAT3 in a quantitative manner, through Cadherin-11 (CDH11), RAC1 and gp130 (IL6ST)	1	496.5×	0.003	CTNND1
VEGFR2 mediated vascular permeability	1	407.9×	0.004	CTNND1
Adherens junctions interactions	1	248.3×	0.005	CTNND1
Degradation of CDH1	1	196.9×	0.006	CTNND1
Activation of STAT3 by cadherin engagement	1	163.1×	0.006	CTNND1

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
negative regulation of blood vessel branching	1	16852.0×	7e-04	CTNND1
positive regulation of protein localization to cell-cell junction	1	5617.3×	1e-03	CTNND1
negative regulation of D-glucose transmembrane transport	1	3370.4×	0.001	CTNND1
negative regulation of intracellular signal transduction	1	2106.5×	0.001	CTNND1
cell migration involved in sprouting angiogenesis	1	648.1×	0.003	CTNND1
regulation of postsynaptic membrane neurotransmitter receptor levels	1	495.6×	0.004	CTNND1
cell-cell adhesion mediated by cadherin	1	411.0×	0.004	CTNND1
cell-cell adhesion	1	101.5×	0.012	CTNND1
Wnt signaling pathway	1	99.7×	0.012	CTNND1
protein stabilization	1	66.9×	0.016	CTNND1
negative regulation of transcription by RNA polymerase II	1	17.7×	0.056	CTNND1

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
CTNND1	0	0
TMX2-CTNND1	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
CTNND1	1	Binding:1

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	2	CTNND1, TMX2-CTNND1

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)
CTNND1	1	—
TMX2-CTNND1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.