CDH1

cadherin 1, the group of CD molecules|Type I classical cadherins

Basic information

Region (hg38): 16:68737291-68835537

Previous symbols: [ "UVO" ]

Links

ENSG00000039068 ∙ NCBI:999 ∙ OMIM:192090 ∙ HGNC:1748 ∙ Uniprot:P12830 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 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: CGD

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 ClinVar and linked to the CDH1 gene.

• Hereditary diffuse gastric adenocarcinoma (3164 variants)
• Hereditary cancer-predisposing syndrome (2397 variants)
• not provided (791 variants)
• not specified (525 variants)
• CDH1-related diffuse gastric and lobular breast cancer syndrome (314 variants)
• Familial cancer of breast (190 variants)
• Breast and/or ovarian cancer (75 variants)
• Malignant tumor of breast (62 variants)
• 6 conditions (37 variants)
• Malignant tumor of prostate (36 variants)
• CDH1-related condition (20 variants)
• Blepharocheilodontic syndrome 1 (15 variants)
• Hereditary breast ovarian cancer syndrome (11 variants)
• Gastric cancer (7 variants)
• Inborn genetic diseases (6 variants)
• Ovarian cancer (6 variants)
• Hereditary cancer (4 variants)
• Endometrial carcinoma (4 variants)
• Familial cancer of breast;Hereditary diffuse gastric adenocarcinoma (3 variants)
• Neoplasm of stomach (3 variants)
• Carcinoma of colon (3 variants)
• Cleft lip with or without cleft palate (3 variants)
• Breast lobular carcinoma (2 variants)
• Orofacial cleft (1 variants)
• Breast carcinoma (1 variants)
• Colon cancer (1 variants)
• Hereditary diffuse gastric adenocarcinoma;Malignant tumor of breast (1 variants)
• Spinocerebellar ataxia 45 (1 variants)
• Hereditary diffuse gastric adenocarcinoma;Blepharocheilodontic syndrome 1;Familial cancer of breast;Malignant tumor of prostate (1 variants)
• Diffuse midline glioma, H3 K27-altered (1 variants)
• Gastric cancer, familial diffuse, and cleft lip with or without cleft palate (1 variants)
• Gastric adenocarcinoma (1 variants)
• Anophthalmia-microphthalmia syndrome (1 variants)
• Hereditary diffuse gastric adenocarcinoma;Breast lobular carcinoma (1 variants)
• Cleft lip/palate (1 variants)
• Hereditary diffuse gastric adenocarcinoma;Familial cancer of breast (1 variants)
• Neoplasm of ovary (1 variants)
• Breast neoplasm (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		1	14	728	7	750
missense	2	10	1753	52	24	1841
nonsense	110	10	3			123
start loss	6					6
frameshift	270	29	6			305
inframe indel		1	24	2		27
splice donor/acceptor (+/-2bp)	18	69	11			98
splice region	3	7	82	99	5	196
non coding			114	320	70	504
Total	406	120	1925	1102	101

Highest pathogenic variant AF is 0.00000657

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	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: gnomAD

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: dbNSFP

• 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