CDH2

cadherin 2, the group of CD molecules|Type I classical cadherins

Basic information

Region (hg38): 18:27932879-28177946

Previous symbols: [ "NCAD" ]

Links

ENSG00000170558 ∙ NCBI:1000 ∙ OMIM:114020 ∙ HGNC:1759 ∙ Uniprot:P19022 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• arrhythmogenic right ventricular dysplasia, familial, 14 (Moderate), mode of inheritance: AD
• agenesis of corpus callosum, cardiac, ocular, and genital syndrome (Moderate), mode of inheritance: AD
• agenesis of corpus callosum, cardiac, ocular, and genital syndrome (Strong), mode of inheritance: AD
• arrhythmogenic right ventricular dysplasia, familial, 14 (Strong), mode of inheritance: AD
• congenital heart disease (Limited), mode of inheritance: AD
• arrhythmogenic right ventricular cardiomyopathy (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Arrhythmogenic right ventricular dysplasia 14; Agenesis of corpus callosum, cardiac, ocular, and genital syndrome	AD	Cardiovascular	Arrhythmogenic right ventricular dysplasia may involve cardiac sequelae potentially resulting in sudden cardiac death, and awareness may allow early diagnosis and management (such as with ICD placement); Agenesis of corpus callosum, cardiac, ocular, and genital syndrome may involve congenital cardiac and other anomalies, some of which may require surgical intervention	Cardiovascular; Craniofacial; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic	28280076; 34702855

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CDH2 gene.

• Arrhythmogenic right ventricular dysplasia, familial, 14 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CDH2 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			4	192	5	201
missense		3	365	10	3	381
nonsense			4			4
start loss						0
frameshift			10			10
inframe indel			2			2
splice donor/acceptor (+/-2bp)	1	2	4			7
splice region		1	11	25	4	41
non coding			4	72	29	105
Total	1	5	393	274	37

Variants in CDH2

This is a list of pathogenic ClinVar variants found in the CDH2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
18-27952116-G-A			Benign (May 10, 2021)
18-27952145-C-G		CDH2-related disorder	Likely benign (Apr 25, 2022)
18-27952157-T-TC			Uncertain significance (Nov 14, 2023)
18-27952161-C-T			Uncertain significance (Mar 24, 2023)
18-27952162-A-G		Inborn genetic diseases	Likely benign (Mar 21, 2022)
18-27952167-C-T			Uncertain significance (Feb 06, 2023)
18-27952171-A-G		Inborn genetic diseases	Likely benign (Jun 06, 2024)
18-27952177-G-A			Likely benign (Dec 09, 2022)
18-27952187-T-C			Uncertain significance (Feb 16, 2023)
18-27952195-C-A			Likely benign (Apr 04, 2021)
18-27952196-C-T			Uncertain significance (Oct 24, 2022)
18-27952200-G-A			Uncertain significance (May 03, 2022)
18-27952201-C-G			Likely benign (Apr 04, 2021)
18-27952201-C-T			Likely benign (Oct 24, 2022)
18-27952203-C-A		Inborn genetic diseases	Uncertain significance (Mar 01, 2024)
18-27952205-C-A			Uncertain significance (Mar 09, 2022)
18-27952209-C-T		Inborn genetic diseases	Uncertain significance (Nov 16, 2023)
18-27952210-G-A		Inborn genetic diseases	Likely benign (Jan 21, 2024)
18-27952210-G-T		Inborn genetic diseases	Uncertain significance (Dec 01, 2023)
18-27952213-C-T			Likely benign (Apr 04, 2021)
18-27952219-A-G			Likely benign (Mar 23, 2023)
18-27952227-C-T		Inborn genetic diseases	Uncertain significance (May 19, 2024)
18-27952233-C-T		Inborn genetic diseases	Uncertain significance (Apr 07, 2023)
18-27952235-C-G		Inborn genetic diseases	Uncertain significance (Apr 09, 2024)
18-27952239-C-T			Uncertain significance (Oct 18, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CDH2	protein_coding	protein_coding	ENST00000269141	16	226481

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.992	0.00829	125736	0	12	125748	0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.09	376	509	0.739	0.0000270	5940
Missense in Polyphen		126	226.95	0.55519		2636
Synonymous	0.170	192	195	0.985	0.0000114	1794
Loss of Function	5.05	6	40.8	0.147	0.00000212	484

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000578	0.0000578
Ashkenazi Jewish	0.000298	0.000298
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000530	0.0000527
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types. Acts as a regulator of neural stem cells quiescence by mediating anchorage of neural stem cells to ependymocytes in the adult subependymal zone: upon cleavage by MMP24, CDH2-mediated anchorage is affected, leading to modulate neural stem cell quiescence. CDH2 may be involved in neuronal recognition mechanism. In hippocampal neurons, may regulate dendritic spine density (By similarity). {ECO:0000250}.
• Pathway: Cell adhesion molecules (CAMs) - Homo sapiens (human);Arrhythmogenic right ventricular cardiomyopathy (ARVC) - Homo sapiens (human);Neural Crest Differentiation;Arrhythmogenic Right Ventricular Cardiomyopathy;Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;Primary Focal Segmental Glomerulosclerosis FSGS;Splicing factor NOVA regulated synaptic proteins;EMT transition in Colorectal Cancer;Developmental Biology;Post-translational protein phosphorylation;Post-translational protein modification;Metabolism of proteins;Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs);CDO in myogenesis;Myogenesis;EGFR1;Posttranslational regulation of adherens junction stability and dissassembly;Cell-cell junction organization;Adherens junctions interactions;Cell junction organization;Cell-Cell communication;N-cadherin signaling events;Signaling events mediated by PTP1B;FGF signaling pathway (Consensus)

Recessive Scores

• pRec: 0.268

Intolerance Scores

• loftool: 0.499
• rvis_EVS: -1.06
• rvis_percentile_EVS: 7.52

Haploinsufficiency Scores

• pHI: 0.943
• hipred: Y
• hipred_score: 0.746
• ghis: 0.566

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.764

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Cdh2
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); embryo 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); 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); muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: cdh2
• Affected structure: neuroepithelial cell
• Phenotype tag: abnormal
• Phenotype quality: apical-basal polarity

Gene ontology

• Biological process: cell morphogenesis;cell-cell junction assembly;cell adhesion;homophilic cell adhesion via plasma membrane adhesion molecules;heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules;synapse assembly;glial cell differentiation;calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules;cell migration;cerebral cortex development;adherens junction organization;positive regulation of MAPK cascade;post-translational protein modification;cellular protein metabolic process;cell-cell adhesion mediated by cadherin;blood vessel morphogenesis;brain morphogenesis;homeostasis of number of cells;regulation of axonogenesis;striated muscle cell differentiation;positive regulation of muscle cell differentiation;regulation of synaptic transmission, glutamatergic;radial glial cell differentiation;neuroepithelial cell differentiation;regulation of oligodendrocyte progenitor proliferation;protein localization to plasma membrane;negative regulation of canonical Wnt signaling pathway;neuroligin clustering involved in postsynaptic membrane assembly;neuronal stem cell population maintenance;cell-cell adhesion;regulation of postsynaptic density protein 95 clustering;positive regulation of synaptic vesicle clustering
• Cellular component: cytoplasm;endoplasmic reticulum lumen;plasma membrane;integral component of plasma membrane;cell-cell junction;cell-cell adherens junction;fascia adherens;focal adhesion;cell surface;postsynaptic density;intercalated disc;basolateral plasma membrane;apical plasma membrane;catenin complex;lamellipodium;cell junction;cortical actin cytoskeleton;sarcolemma;neuron projection;plasma membrane raft;apical part of cell;synapse;collagen-containing extracellular matrix;integral component of presynaptic active zone membrane;integral component of postsynaptic specialization membrane
• Molecular function: calcium ion binding;protein binding;beta-catenin binding;cytoskeletal protein binding;protein kinase binding;protein phosphatase binding;protein homodimerization activity;alpha-catenin binding;gamma-catenin binding;cadherin binding