CDH1 |
- 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)