• 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
CDH1 (HGNC:1748) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
cadherin 1
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
UVO
Alias symbols
uvomorulin, CD324
%HI
0.51(Read more about the DECIPHER Haploinsufficiency Index)
pLI
0.15(Read more about gnomAD pLI score)
LOEUF
0.43(Read more about gnomAD LOEUF score)
Cytoband
16q22.1
Genomic Coordinates
GRCh37/hg19: chr16:68771195-68869440 NCBI Ensembl UCSC
GRCh38/hg38: chr16:68737292-68835537 NCBI Ensembl UCSC
MANE Select Transcript
NM_004360.5 ENST00000261769.10 (Read more about MANE Select)
Function
Cadherins are calcium-dependent cell adhesion proteins (PubMed:11976333). They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types. CDH1 is involved in mechanisms regulating cell-cell adhesions, mobility and proliferation of epithelial cells (PubMed:11976333). Has a potent invasive suppressor role. It is a ligand for integrin alpha-E/beta-7. {ECO:0000269|PubMed:11976333, ECO:0000269|PubMed:16... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-8670
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Last Evaluated:
04/10/2020

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
  • hereditary diffuse gastric adenocarcinoma Monarch
HI Evidence:
  • PUBMED: 26182300
    Hansford et al (2015) reported a large series of CDH1 mutation carriers including a new patient with a deletion encompassing exons 1 and 2, and provided a review of CDH1 germline mutations including 126 pathogenic variants (see eTable1). The majority of reported pathogenic alterations in HDGC are loss-of-function-type, including sequence-level alterations (nonsense, frameshift) and larger, exon-level deletions.
  • PUBMED: 24037103
    Yamada et al (2014) detected a 275-kb deletion involving exons 7–16 of CDH1 in a Japanese HDGC family using comparative genomic hybridization (CGH) analysis. The proband (55 year-old female) and her affected son (31 year-old) both carried this deletion.
  • PUBMED: 19168852
    Oliveira et al (2009) reported 5 intragenic (exon-level) deletions of CDH1 in their study of a large cohort of patients (160 families) with hereditary diffuse gastric cancer (HDGC). In sum, CDH1 alterations were identified in 45.6% (73/160) patients.
HI Evidence Comments:
Constitutional (germline) mutation and deletion involving the gene E-cadherin (CDH1) is associated with autosomal dominant hereditary diffuse gastric cancer (HDGC). HDGC is a cancer predisposition syndrome associated with the development of diffuse gastric cancer (DGC) in men and women and lobular breast cancer (LBC) in women. Penetrance estimates vary across studies-see PMIDs 26182300, 20301318. The majority of CDH1 mutations reported in HDGC are loss-of-function-type, including sequence-level mutations (nonsense, frameshift) and intragenic, exon-level deletions. No genotype-phenotype correlations have been reported to date. Germline whole gene deletion of CDH1 has been reported in one individual with Esophagogastric Adenocarcinoma. (PMID: 26556299)

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
TS Evidence Comments:
There is no evidence linking triplosensitivity of CDH1 to clinical phenotypes.

Genomic View

Select assembly: (NC_000016.9) (NC_000016.10)