CDH1
cadherin 1, the group of CD molecules|Type I classical cadherins
Basic information
Region (hg38): 16:68737292-68835537
Previous symbols: [ "UVO" ]
Links
Phenotypes
GenCC
Source:
- CDH1-related diffuse gastric and lobular breast cancer syndrome (Strong), mode of inheritance: AD
- hereditary diffuse gastric adenocarcinoma (Definitive), mode of inheritance: AD
- hereditary breast carcinoma (Definitive), mode of inheritance: AD
- blepharocheilodontic syndrome 1 (Moderate), mode of inheritance: AD
- blepharocheilodontic syndrome (Supportive), mode of inheritance: AD
- hereditary diffuse gastric adenocarcinoma (Supportive), mode of inheritance: AD
- cleft soft palate (Moderate), mode of inheritance: AD
- CDH1-related diffuse gastric and lobular breast cancer syndrome (Definitive), mode of inheritance: AD
- blepharocheilodontic syndrome 1 (Definitive), mode of inheritance: AD
- blepharocheilodontic syndrome 1 (Strong), mode of inheritance: AD
- familial ovarian cancer (No Known Disease Relationship), mode of inheritance: AD
- CDH1-related diffuse gastric and lobular breast cancer syndrome (Definitive), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Diffuse gastric and lobular breast cancer syndrome | AD | Oncologic | Surveillance and prophlyactic measures (which may include prophylactic gastrectomy) may allow early diagnosis and treatment (though there is controversy regarding the efficacy of prophlyaxis and surveillance measures), which may potentially be beneficial in the reduction of morbidity and mortality | Craniofacial; Dental; Gastrointestinal; Musculoskeletal; Oncologic | 9751616; 9537325; 10072428; 10477433; 10319582; 11443625; 11968084; 11968083; 12588804; 15235021; 14961571; 16189707; 17660459; 19168852; 20301318; 22020549; 23124477; 23197654; 24037103; 28301459 |
| Variants may also be involved in other malignancies (eg, prostate cancer) either as minor or major risk factors; Variants have also been implicated in the development of facial clefting |
ClinVar
This is a list of variants' phenotypes submitted to
- Hereditary diffuse gastric adenocarcinoma (359 variants)
- Hereditary cancer-predisposing syndrome (167 variants)
- CDH1-related diffuse gastric and lobular breast cancer syndrome (130 variants)
- not provided (65 variants)
- Familial cancer of breast (29 variants)
- 6 conditions (7 variants)
- DIFFUSE GASTRIC AND LOBULAR BREAST CANCER SYNDROME (7 variants)
- Gastric cancer (4 variants)
- CDH1-related disorder (3 variants)
- Malignant tumor of breast (3 variants)
- not specified (2 variants)
- Breast lobular carcinoma (1 variants)
- Diffuse gastric and lobular breast cancer syndrome with cleft lip and with or without cleft palate (1 variants)
- Hereditary diffuse gastric adenocarcinoma;Familial cancer of breast (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the CDH1 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 13 | 769 | 790 | |||
| missense | 1816 | 60 | 27 | 1915 | ||
| nonsense | 111 | 10 | 126 | |||
| start loss | 6 | |||||
| frameshift | 275 | 30 | 311 | |||
| inframe indel | 25 | 28 | ||||
| splice donor/acceptor (+/-2bp) | 24 | 64 | 14 | 102 | ||
| splice region | 4 | 7 | 83 | 108 | 6 | 208 |
| non coding | 123 | 350 | 71 | 545 | ||
| Total | 419 | 116 | 2002 | 1181 | 105 |
Highest pathogenic variant AF is 0.0000842
Variants in CDH1
This is a list of pathogenic ClinVar variants found in the CDH1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 16-68737332-G-A | not specified • Malignant tumor of prostate | Likely benign (Jul 07, 2023) | ||
| 16-68737342-ACTCCAGCCCG-A | Likely benign (Jun 30, 2017) | |||
| 16-68737344-T-C | CDH1-related diffuse gastric and lobular breast cancer syndrome | Uncertain significance (Aug 03, 2023) | ||
| 16-68737345-C-G | Hereditary diffuse gastric adenocarcinoma • not specified • Hereditary cancer-predisposing syndrome • 6 conditions • Malignant tumor of prostate • CDH1-related diffuse gastric and lobular breast cancer syndrome | Benign (Aug 10, 2023) | ||
| 16-68737353-C-A | Hereditary diffuse gastric adenocarcinoma | Conflicting classifications of pathogenicity (Aug 01, 2022) | ||
| 16-68737357-A-AGCCCG | not specified • CDH1-related diffuse gastric and lobular breast cancer syndrome | Uncertain significance (Aug 21, 2023) | ||
| 16-68737359-C-T | Hereditary diffuse gastric adenocarcinoma | Likely benign (May 28, 2019) | ||
| 16-68737362-G-C | Hereditary diffuse gastric adenocarcinoma | Benign/Likely benign (Jul 06, 2023) | ||
| 16-68737363-G-GCCCGA | not specified | Likely benign (Nov 07, 2017) | ||
| 16-68737366-C-G | CDH1-related diffuse gastric and lobular breast cancer syndrome • not specified | Uncertain significance (Aug 21, 2023) | ||
| 16-68737366-C-T | CDH1-related diffuse gastric and lobular breast cancer syndrome | Uncertain significance (Aug 21, 2023) | ||
| 16-68737367-G-T | Hereditary diffuse gastric adenocarcinoma • not specified | Benign/Likely benign (Aug 15, 2023) | ||
| 16-68737369-C-T | not specified | Likely benign (Aug 07, 2017) | ||
| 16-68737371-C-T | CDH1-related diffuse gastric and lobular breast cancer syndrome | Uncertain significance (Aug 21, 2023) | ||
| 16-68737372-G-A | Hereditary diffuse gastric adenocarcinoma | Uncertain significance (Aug 01, 2022) | ||
| 16-68737375-C-A | not specified • Hereditary diffuse gastric adenocarcinoma | Conflicting classifications of pathogenicity (Jan 12, 2018) | ||
| 16-68737376-G-A | not specified | Likely benign (Aug 09, 2017) | ||
| 16-68737377-C-T | not specified | Likely benign (May 02, 2016) | ||
| 16-68737379-C-A | not specified | Likely benign (Jul 27, 2015) | ||
| 16-68737380-C-T | Uncertain significance (Jan 04, 2016) | |||
| 16-68737383-G-T | not specified | Likely benign (May 22, 2017) | ||
| 16-68737384-C-G | not specified | Likely benign (Jun 02, 2017) | ||
| 16-68737387-C-G | not specified • Hereditary diffuse gastric adenocarcinoma | Conflicting classifications of pathogenicity (Aug 01, 2022) | ||
| 16-68737390-C-T | not specified | Likely benign (May 18, 2015) | ||
| 16-68737392-C-G | not specified | Likely benign (Oct 29, 2014) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| CDH1 | protein_coding | protein_coding | ENST00000261769 | 16 | 98324 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.146 | 0.854 | 125732 | 0 | 15 | 125747 | 0.0000596 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.706 | 448 | 492 | 0.910 | 0.0000299 | 5775 |
| Missense in Polyphen | 147 | 200.96 | 0.73149 | 2347 | ||
| Synonymous | 0.0918 | 200 | 202 | 0.992 | 0.0000143 | 1789 |
| Loss of Function | 4.22 | 9 | 36.5 | 0.246 | 0.00000202 | 432 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000239 | 0.000239 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000528 | 0.0000527 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000980 | 0.0000980 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- 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:16417575}.;
- Disease
- DISEASE: Hereditary diffuse gastric cancer (HDGC) [MIM:137215]: A cancer predisposition syndrome with increased susceptibility to diffuse gastric cancer. Diffuse gastric cancer is a malignant disease characterized by poorly differentiated infiltrating lesions resulting in thickening of the stomach. Malignant tumors start in the stomach, can spread to the esophagus or the small intestine, and can extend through the stomach wall to nearby lymph nodes and organs. It also can metastasize to other parts of the body. {ECO:0000269|PubMed:10319582, ECO:0000269|PubMed:12216071}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. Heterozygous CDH1 germline mutations are responsible for familial cases of diffuse gastric cancer. Somatic mutations has also been found in patients with sporadic diffuse gastric cancer and lobular breast cancer.; DISEASE: Endometrial cancer (ENDMC) [MIM:608089]: A malignancy of endometrium, the mucous lining of the uterus. Most endometrial cancers are adenocarcinomas, cancers that begin in cells that make and release mucus and other fluids. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Ovarian cancer (OC) [MIM:167000]: The term ovarian cancer defines malignancies originating from ovarian tissue. Although many histologic types of ovarian tumors have been described, epithelial ovarian carcinoma is the most common form. Ovarian cancers are often asymptomatic and the recognized signs and symptoms, even of late-stage disease, are vague. Consequently, most patients are diagnosed with advanced disease. {ECO:0000269|PubMed:8075649}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Breast cancer, lobular (LBC) [MIM:137215]: A type of breast cancer that begins in the milk-producing glands (lobules) of the breast. {ECO:0000269|PubMed:17660459}. Note=The gene represented in this entry may be involved in disease pathogenesis.; DISEASE: Blepharocheilodontic syndrome 1 (BCDS1) [MIM:119580]: A form of blepharocheilodontic syndrome, a rare autosomal dominant disorder. It is characterized by lower eyelid ectropion, upper eyelid distichiasis, euryblepharon, bilateral cleft lip and palate, and features of ectodermal dysplasia, including hair anomalies, conical teeth and tooth agenesis. An additional rare manifestation is imperforate anus. There is considerable phenotypic variability among affected individuals. {ECO:0000269|PubMed:28301459}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Cell adhesion molecules (CAMs) - Homo sapiens (human);Gastric cancer - Homo sapiens (human);Adherens junction - Homo sapiens (human);Melanoma - Homo sapiens (human);Bladder cancer - Homo sapiens (human);Hippo signaling pathway - Homo sapiens (human);Apelin signaling pathway - Homo sapiens (human);Rap1 signaling pathway - Homo sapiens (human);Bacterial invasion of epithelial cells - Homo sapiens (human);Pathogenic Escherichia coli infection - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Thyroid cancer - Homo sapiens (human);Endometrial cancer - Homo sapiens (human);Cell Cycle;Integrated Breast Cancer Pathway;Neural Crest Differentiation;Pathogenic Escherichia coli infection;Mammary gland development pathway - Involution (Stage 4 of 4);Bladder Cancer;Preimplantation Embryo;H19 action Rb-E2F1 signaling and CDK-β-catenin activity;Endometrial cancer;EMT transition in Colorectal Cancer;Disease;Signal Transduction;downregulated of mta-3 in er-negative breast tumors;Integrin cell surface interactions;Extracellular matrix organization;Infectious disease;Apoptotic cleavage of cell adhesion proteins;Apoptotic cleavage of cellular proteins;Immune System;Apoptotic execution phase;Apoptosis;Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell;Programmed Cell Death;Adaptive Immune System;Fibroblast growth factor-1;sumoylation as a mechanism to modulate ctbp-dependent gene responses;RHO GTPases activate IQGAPs;RHO GTPase Effectors;Signaling by Rho GTPases;EGFR1;tgf beta signaling pathway;Degradation of the extracellular matrix;E-cadherin signaling in keratinocytes;Posttranslational regulation of adherens junction stability and dissassembly;a6b1 and a6b4 Integrin signaling;Arf6 trafficking events;AlphaE beta7 integrin cell surface interactions;Wnt;Cell-cell junction organization;Adherens junctions interactions;Cell junction organization;Cell-Cell communication;Regulation of nuclear beta catenin signaling and target gene transcription;Stabilization and expansion of the E-cadherin adherens junction;RAC1 signaling pathway;Nectin adhesion pathway;CDC42 signaling events;Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met);FGF signaling pathway;E-cadherin signaling in the nascent adherens junction;InlA-mediated entry of Listeria monocytogenes into host cells;Listeria monocytogenes entry into host cells
(Consensus)
Recessive Scores
- pRec
- 0.934
Intolerance Scores
- loftool
- 0.329
- rvis_EVS
- -1.06
- rvis_percentile_EVS
- 7.52
Haploinsufficiency Scores
- pHI
- 0.825
- hipred
- Y
- hipred_score
- 0.655
- ghis
- 0.639
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.897
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Cdh1
- Phenotype
- digestive/alimentary phenotype; immune system phenotype; embryo phenotype; neoplasm; reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype;
Zebrafish Information Network
- Gene name
- cdh1
- Affected structure
- Rohon-Beard neuron
- Phenotype tag
- abnormal
- Phenotype quality
- mislocalised
Gene ontology
- Biological process
- cell morphogenesis;cell-cell junction assembly;homophilic cell adhesion via plasma membrane adhesion molecules;synapse assembly;response to toxic substance;regulation of gene expression;calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules;pituitary gland development;negative regulation of cell-cell adhesion;extracellular matrix organization;negative regulation of cell migration;neuron projection development;adherens junction organization;entry of bacterium into host cell;positive regulation of protein import into nucleus;cell-cell adhesion mediated by cadherin;positive regulation of transcription, DNA-templated;cellular response to lithium ion;cellular response to indole-3-methanol;protein localization to plasma membrane;cell-cell adhesion;regulation of protein catabolic process at postsynapse, modulating synaptic transmission
- Cellular component
- extracellular region;cytoplasm;endosome;trans-Golgi network;plasma membrane;cell-cell adherens junction;cytoplasmic side of plasma membrane;cell surface;actin cytoskeleton;integral component of membrane;lateral plasma membrane;catenin complex;flotillin complex;lamellipodium;cell junction;cortical actin cytoskeleton;apical junction complex;perinuclear region of cytoplasm;extracellular exosome;postsynapse;glutamatergic synapse
- Molecular function
- calcium ion binding;protein binding;beta-catenin binding;cytoskeletal protein binding;ankyrin binding;GTPase activating protein binding;identical protein binding;protein homodimerization activity;gamma-catenin binding;cadherin binding;cell adhesion molecule binding