Blepharocheilodontic syndrome 1

Summary

Blepharocheilodontic syndrome 1 (MONDO:0054740) is a disease caused by CDH1 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: CDH1 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 96

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	blepharocheilodontic syndrome 1
Mondo ID	MONDO:0054740
OMIM	119580
DOID	DOID:0080345
UMLS	C4551988
MedGen	1632198
GARD	0025965
Is cancer (heuristic)	no

Also known as: BCDS1 · blepharo-cheilo-odontic syndrome caused by mutation in CDH1 · blepharocheilodontic syndrome 1 · CDH1 blepharo-cheilo-odontic syndrome

Data availability: 96 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 › autosomal genetic disease › autosomal dominant disease › blepharocheilodontic syndrome › blepharocheilodontic syndrome 1

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

96 retrieved; paginated sample, class counts are floors:

35 uncertain significance, 24 conflicting classifications of pathogenicity, 10 likely benign, 10 pathogenic, 9 benign, 3 likely pathogenic, 3 benign/likely benign, 2 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
132709	NM_004360.5(CDH1):c.715G>A (p.Gly239Arg)	CDH1	Pathogenic	reviewed by expert panel
136055	NM_004360.5(CDH1):c.1003C>T (p.Arg335Ter)	CDH1	Pathogenic	reviewed by expert panel
140781	NM_004360.5(CDH1):c.2064_2065del (p.Cys688_Glu689delinsTer)	CDH1	Pathogenic	reviewed by expert panel
142888	NM_004360.5(CDH1):c.1147C>T (p.Gln383Ter)	CDH1	Pathogenic	reviewed by expert panel
239891	NM_004360.5(CDH1):c.220C>T (p.Arg74Ter)	CDH1	Pathogenic	reviewed by expert panel
265543	NM_004360.5(CDH1):c.1354_1357del (p.Leu452fs)	CDH1	Pathogenic	reviewed by expert panel
3893034	NM_004360.5(CDH1):c.64dup (p.Cys22fs)	CDH1	Pathogenic	criteria provided, single submitter
3893035	NM_004360.5(CDH1):c.661del (p.Asp221fs)	CDH1	Pathogenic	criteria provided, single submitter
438813	NM_004360.5(CDH1):c.760G>T (p.Asp254Tyr)	CDH1	Pathogenic	no assertion criteria provided
486824	NM_004360.5(CDH1):c.382del (p.His128fs)	CDH1	Pathogenic	reviewed by expert panel
492676	NM_004360.5(CDH1):c.1145del (p.Gly382fs)	CDH1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
929048	NM_004360.5(CDH1):c.321C>G (p.Tyr107Ter)	CDH1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1300144	NM_004360.5(CDH1):c.1371_1373del (p.Asn458del)	CDH1	Likely pathogenic	criteria provided, single submitter
265635	NM_004360.5(CDH1):c.1320+1G>C	CDH1	Likely pathogenic	reviewed by expert panel
438812	NM_004360.5(CDH1):c.1320G>T (p.Lys440Asn)	CDH1	Likely pathogenic	criteria provided, single submitter
1215732	NM_004360.5(CDH1):c.1492G>A (p.Asp498Asn)	CDH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
127924	NM_004360.5(CDH1):c.2369C>T (p.Thr790Ile)	CDH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
127929	NM_004360.5(CDH1):c.2644G>A (p.Asp882Asn)	CDH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
133845	NM_004360.5(CDH1):c.1370C>T (p.Thr457Met)	CDH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
133851	NM_004360.5(CDH1):c.322A>G (p.Arg108Gly)	CDH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
140841	NM_004360.5(CDH1):c.2474C>T (p.Pro825Leu)	CDH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
141161	NM_004360.5(CDH1):c.1927A>G (p.Asn643Asp)	CDH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
142357	NM_004360.5(CDH1):c.1501G>A (p.Val501Met)	CDH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
142437	NM_004360.5(CDH1):c.2380G>A (p.Val794Ile)	CDH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
182395	NM_004360.5(CDH1):c.1143G>C (p.Lys381Asn)	CDH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
183867	NM_004360.5(CDH1):c.303C>T (p.Tyr101=)	CDH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
184629	NM_004360.5(CDH1):c.377C>T (p.Pro126Leu)	CDH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
184651	NM_004360.5(CDH1):c.1171G>A (p.Val391Ile)	CDH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
185286	NM_004360.5(CDH1):c.1250A>G (p.Asn417Ser)	CDH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
185969	NM_004360.5(CDH1):c.2371C>T (p.Leu791Phe)	CDH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 15 · Orphanet: 5 · 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
CDH1	Definitive	Autosomal dominant	blepharocheilodontic syndrome 1	15

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CDH1	Orphanet:1331	Familial prostate cancer
CDH1	Orphanet:199306	Cleft lip/palate
CDH1	Orphanet:1997	Blepharo-cheilo-odontic syndrome
CDH1	Orphanet:227535	Hereditary breast cancer
CDH1	Orphanet:26106	Hereditary diffuse gastric cancer

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
CDH1	HGNC:1748	ENSG00000039068	P12830	Cadherin-1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CDH1	Cadherin-1	Cadherins are calcium-dependent cell adhesion proteins.

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)
CDH1	Other/Unknown	no		Cadherin_Y-type_LIR, Cadherin-like_dom, Cadherin_pro_dom

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
esophagus squamous epithelium	1
gingival epithelium	1
jejunal mucosa	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CDH1	245	broad	marker	jejunal mucosa, esophagus squamous epithelium, gingival epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CDH1	8,738

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CDH1	P12830	22

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 44. 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
Epithelial-Mesenchymal Transition (EMT) during gastrulation	1	1427.5×	0.006	CDH1
InlA-mediated entry of Listeria monocytogenes into host cells	1	1268.9×	0.006	CDH1
Apoptotic cleavage of cell adhesion proteins	1	1038.2×	0.006	CDH1
Listeria monocytogenes entry into host cells	1	1038.2×	0.006	CDH1
Regulation of CDH1 mRNA translation by microRNAs	1	1038.2×	0.006	CDH1
Regulation of CDH1 Function	1	951.7×	0.006	CDH1
Positive Regulation of CDH1 Gene Transcription	1	951.7×	0.006	CDH1
Regulation of MITF-M-dependent genes involved in extracellular matrix, focal adhesion and epithelial-to-mesenchymal transition	1	878.5×	0.006	CDH1
Developmental Lineage of Mammary Stem Cells	1	761.3×	0.006	CDH1
Formation of definitive endoderm	1	713.8×	0.006	CDH1
Developmental Lineage of Mammary Gland Myoepithelial Cells	1	543.8×	0.006	CDH1
SRC activates STAT3 in a quantitative manner, through Cadherin-11 (CDH11), RAC1 and gp130 (IL6ST)	1	496.5×	0.006	CDH1
Apoptotic cleavage of cellular proteins	1	475.8×	0.006	CDH1
Apoptotic execution phase	1	475.8×	0.006	CDH1
Developmental Lineage of Mammary Gland Luminal Epithelial Cells	1	456.8×	0.006	CDH1
RHO GTPases activate IQGAPs	1	346.1×	0.007	CDH1
Regulation of CDH1 posttranslational processing and trafficking to plasma membrane	1	335.9×	0.007	CDH1
Bacterial Infection Pathways	1	335.9×	0.007	CDH1
Gastrulation	1	259.6×	0.008	CDH1
Adherens junctions interactions	1	248.3×	0.008	CDH1
Cell-cell junction organization	1	248.3×	0.008	CDH1
Degradation of CDH1	1	196.9×	0.010	CDH1
Cell junction organization	1	187.2×	0.010	CDH1
MITF-M-dependent gene expression	1	181.3×	0.010	CDH1
Transcriptional and post-translational regulation of MITF-M expression and activity	1	178.4×	0.010	CDH1
Apoptosis	1	167.9×	0.010	CDH1
Activation of STAT3 by cadherin engagement	1	163.1×	0.010	CDH1
Programmed Cell Death	1	146.4×	0.011	CDH1
Cell-Cell communication	1	137.6×	0.011	CDH1
Integrin cell surface interactions	1	134.3×	0.011	CDH1

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
response to heparin	1	5617.3×	0.002	CDH1
regulation of protein catabolic process at postsynapse, modulating synaptic transmission	1	4213.0×	0.002	CDH1
cellular response to indole-3-methanol	1	3370.4×	0.002	CDH1
response to Gram-positive bacterium	1	2808.7×	0.002	CDH1
desmosome assembly	1	2407.4×	0.002	CDH1
positive regulation of protein localization	1	1404.3×	0.003	CDH1
cellular response to lithium ion	1	1123.5×	0.003	CDH1
negative regulation of cell-cell adhesion	1	991.3×	0.003	CDH1
negative regulation of axon extension	1	732.7×	0.004	CDH1
pituitary gland development	1	648.1×	0.004	CDH1
adherens junction organization	1	510.7×	0.004	CDH1
calcium-dependent cell-cell adhesion	1	481.5×	0.004	CDH1
cell-cell junction assembly	1	443.5×	0.004	CDH1
positive regulation of protein import into nucleus	1	421.3×	0.004	CDH1
cell-cell adhesion mediated by cadherin	1	411.0×	0.004	CDH1
synapse assembly	1	230.8×	0.007	CDH1
response to toxic substance	1	210.7×	0.008	CDH1
cell morphogenesis	1	157.5×	0.010	CDH1
homophilic cell-cell adhesion	1	140.4×	0.010	CDH1
neuron projection development	1	122.1×	0.011	CDH1
negative regulation of cell migration	1	111.6×	0.011	CDH1
protein localization to plasma membrane	1	108.7×	0.011	CDH1
cell-cell adhesion	1	101.5×	0.012	CDH1
regulation of gene expression	1	83.4×	0.013	CDH1
response to xenobiotic stimulus	1	69.1×	0.016	CDH1
cell migration	1	61.5×	0.017	CDH1
positive regulation of DNA-templated transcription	1	27.9×	0.036	CDH1

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
CDH1	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
CDH1	18	Binding:18

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	CDH1

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)
CDH1	18	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.