CDH2

Summary

CDH2 (cadherin 2, HGNC:1759) is a protein-coding gene on chromosome 18q12.1, encoding Cadherin-2 (P19022). Calcium-dependent cell adhesion protein; preferentially mediates homotypic cell-cell adhesion by dimerization with a CDH2 chain from another cell.

This gene encodes a classical cadherin and member of the cadherin superfamily. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein is proteolytically processed to generate a calcium-dependent cell adhesion molecule and glycoprotein. This protein plays a role in the establishment of left-right asymmetry, development of the nervous system and the formation of cartilage and bone.

Source: NCBI Gene 1000 — RefSeq curated summary.

At a glance

• Gene–disease (curated): arrhythmogenic right ventricular dysplasia, familial, 14 (Strong, GenCC) — +3 more curated relationships
• GWAS associations: 77
• Clinical variants (ClinVar): 1,156 total — 9 pathogenic, 9 likely-pathogenic
• Phenotypes (HPO): 63
• Druggable target: yes
• MANE Select transcript: NM_001792

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1759
Approved symbol	CDH2
Name	cadherin 2
Location	18q12.1
Locus type	gene with protein product
Status	Approved
Aliases	CDHN, CD325
Ensembl gene	ENSG00000170558
Ensembl biotype	protein_coding
OMIM	114020
Entrez	1000

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 13 protein_coding, 2 retained_intron, 2 nonsense_mediated_decay

ENST00000269141, ENST00000399380, ENST00000413878, ENST00000418492, ENST00000430882, ENST00000674998, ENST00000675173, ENST00000675688, ENST00000675708, ENST00000676041, ENST00000676445, ENST00000876838, ENST00000876839, ENST00000967815, ENST00000967816, ENST00000967818, ENST00000967819

RefSeq mRNA: 2 — MANE Select: NM_001792 NM_001308176, NM_001792

CCDS: CCDS11891, CCDS77172

Canonical transcript exons

ENST00000269141 — 16 exons

Exon	Start	End
ENSE00001103818	28009717	28009872
ENSE00001103869	28011846	28011992
ENSE00001158044	27963357	27963521
ENSE00001158081	27990097	27990350
ENSE00001158160	27985000	27985233
ENSE00001162393	28005849	28005993
ENSE00001169137	28002997	28003169
ENSE00001199798	27982944	27983083
ENSE00001199810	27985528	27985761
ENSE00001199819	27988524	27988666
ENSE00001199832	27992655	27992840
ENSE00001235865	27950966	27952359
ENSE00001235868	28176963	28177130
ENSE00001610614	27993500	27993637
ENSE00003584242	28147673	28147784
ENSE00003649734	28013683	28013909

Expression profiles

Bgee: expression breadth ubiquitous, 233 present calls, max score 99.31.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 38.7118 / max 1034.5312, expressed in 1242 samples.

FANTOM5 promoters (20 alternative TSS)

Promoter ID	TPM avg	Samples expressed
171524	18.2794	1134
171522	8.8597	1097
171528	4.0920	877
171494	3.5513	753
171501	0.7265	323
171527	0.4437	256
171503	0.4273	214
171502	0.4090	155
171495	0.3594	162
171523	0.2976	166

Top tissues by expression

287 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
heart right ventricle	UBERON:0002080	99.31	gold quality
ventricular zone	UBERON:0003053	99.00	gold quality
stromal cell of endometrium	CL:0002255	98.74	gold quality
myocardium	UBERON:0002349	98.55	gold quality
cortical plate	UBERON:0005343	98.40	gold quality
left ventricle myocardium	UBERON:0006566	98.39	gold quality
endothelial cell	CL:0000115	98.13	silver quality
ganglionic eminence	UBERON:0004023	98.01	gold quality
cardiac muscle of right atrium	UBERON:0003379	97.94	gold quality
Brodmann (1909) area 23	UBERON:0013554	97.92	gold quality
middle temporal gyrus	UBERON:0002771	97.77	gold quality
embryo	UBERON:0000922	97.47	gold quality
cardiac ventricle	UBERON:0002082	97.39	gold quality
heart left ventricle	UBERON:0002084	97.32	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	96.99	gold quality
inferior olivary complex	UBERON:0002127	96.44	gold quality
periodontal ligament	UBERON:0008266	96.41	gold quality
heart	UBERON:0000948	96.28	gold quality
cardiac atrium	UBERON:0002081	96.09	gold quality
right atrium auricular region	UBERON:0006631	95.87	gold quality
vena cava	UBERON:0004087	95.64	gold quality
right adrenal gland cortex	UBERON:0035827	95.32	gold quality
right adrenal gland	UBERON:0001233	95.27	gold quality
medial globus pallidus	UBERON:0002477	95.25	gold quality
cranial nerve II	UBERON:0000941	95.24	gold quality
Brodmann (1909) area 10	UBERON:0013541	95.20	gold quality
left adrenal gland	UBERON:0001234	95.02	gold quality
apex of heart	UBERON:0002098	94.95	gold quality
adrenal cortex	UBERON:0001235	94.89	gold quality
frontal pole	UBERON:0002795	94.87	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-10018	yes	265.76
E-CURD-11	yes	91.57
E-HCAD-10	yes	18.72
E-CURD-112	yes	17.37
E-MTAB-9388	yes	11.76
E-GEOD-83139	no	103.80
E-ANND-3	no	5.73
E-MTAB-9543	no	1.22

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, AR, CUX1, EHMT2, GATA3, HNRNPK, JUN, KLF4, KLF8, MARK1, MSX1, MSX2, MTA3, MYC, MZF1, NFKB, NOTCH1, OVOL1, OVOL2, PAWR, PAX6, PPARG, RBPJ, SATB2, SMAD4, SMAD7, SNAI1, SNAI2, SOX4, SOX5, SOX9, SP1, SP3, STAT3, TWIST1, TWIST2, WT1, ZEB1, ZEB2, ZNF77

miRNA regulators (miRDB)

129 targeting CDH2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-221-3P	99.86	71.56	1329
HSA-MIR-222-3P	99.86	71.35	1337
HSA-MIR-548BB-3P	99.86	70.58	4354

Literature-anchored findings (GeneRIF, showing 40)

• Cadherin-mediated cell sorting not determined by binding or adhesion specificity (PMID:11790800)
• Expression of beta1-integrins and N-cadherin in bladder cancer and melanoma cell lines (PMID:11996105)
• expression patterns of E- and N-cadherins in both embryonic and adult (healthy, injured, carious) human teeth (PMID:12057916)
• N-cadherin signal transduction upregulates Bcl-2 (PMID:12095980)
• Protection of the FGFR-1 from fgf-2-induced downregulation by N-cadherin enhances receptor signaling and provides a mechanism by which tumor cells can acquire metastatic properties (PMID:12398894)
• carbohydrate profile of this protein synthesized in human melanoma cell lines. N-glycans of N-cadherin are altered in metastatic melanomas in a way characteristic for invasive tumor cells. (PMID:12545205)
• N-cadherin cleavage by presenilin 1 is regulated by NMDA receptor (PMID:13678586)
• Presenilin-1-mediated delivery of N-cadherin to the plasma membrane is important for N-cadherin to exert its physiological function, and it may control the state of cell-cell contact. (PMID:14515347)
• the comparable region of N-cadherin can substitute for this required region in E-cadherin and is required for suppression by the mutant form of N-cadherin that is capable of suppressing (PMID:14559901)
• In human melanocytic tumors, a causative role of (loss of ) E-cadherin or (gain of ) N-cadherin for melanocytic tumor progression still remains to be proven. (PMID:14675278)
• E- to N-cadherin switching in epithelial carcinomas has a potential impact on metastatic progression. (PMID:15153430)
• N-cadherin may have a role in the epithelial-mesenchymal transition in pancreatic carcinoma (PMID:15217949)
• N-cadherin involved in primary colon cancer progression, promoting tumor invasiveness (PMID:15252840)
• a subset of integrin signaling molecules, namely Fak and paxillin, but not p130 Crk-associated substrate or proline-rich tyrosine kinase 2, participate in processes regulating N-cadherin-based cell-cell adhesion (PMID:15263022)
• Data show that N-cadherin, expressed at the tips of filopodia in colon cancer-derived myofibroblasts invading extracellular matrices in vitro, is upregulated by TGF-beta. (PMID:15331629)
• High expression of N-cadherin is associated with esophageal carcinoma invasiveness (PMID:15355896)
• Decreased expression of N-cadherin correlated with a dramatic increase in invasive behavior of glioma cells (PMID:15527101)
• Sp1/Sp3 and MZF1 are important transcription factors regulating N-cadherin promoter activity and expression in osteoblasts. (PMID:15541732)
• The topics discussed in this review point to N-cadherin as an important player in tumor development and, therefore, a potential target for novel therapeutic approaches. (PMID:15648948)
• regulation of N-cadherin is a crucial event and it has a role in controlling the survival capability of human ovarian surface epithelial cells (PMID:15701645)
• cadherin switching (downregulation of E-cadherin and upregulation of N-cadherin) is necessary for increased motility but is not required for the morphological changes that accompany the epithelium-to-mesenchyme transition (PMID:15713751)
• cleaved by Porphyromonas gingivalis gingipains in endothelial cells (PMID:15731052)
• vascular smooth muscle cell survival is dependent on N-cadherin-mediated cell-cell contacts, which could be important in the context of plaque instability (PMID:15774907)
• Co-localization of ZO-1 with N-cadherin. Zonula occludens protein-1 has role in N-cadherin-based adhesion. (PMID:15855653)
• N-cadherin plays a key role in the transendothelial migration of melanoma cells (PMID:15987741)
• Data suggest that a vimentin-based N-cadherin complex functions together with an actin-based complex to promote strong cell-cell adhesion in fibroblasts. (PMID:16091424)
• ERK activation and p21 and N-cadherin upregulation are required for genistein-induced neuronal differentiation (PMID:16149052)
• demonstrated for the first time that N-cadherin switching occurs in higher grade prostate cancer and correlates significantly with increasing Gleason patterns; N-cadherin may be a useful biomarker of aggressive PC (PMID:16173043)
• N-cadherin is associated with tumor aggressiveness and metastatic potential and may contribute to tumor progression (PMID:16258702)
• The data suggest a novel role for tyrosine phosphorylation of N-cadherin by Src family kinases in the regulation of beta-catenin association during transendothelial migration of melanoma cells. (PMID:16371504)
• N-cadherin up-regulation is associated with recurrent hepatocellular carcinomas (PMID:16596172)
• N-cadherin acts in an invasive mode in bladder cancer, but whether it has a primary role in urothelial neoplastic progression has yet to be investigated. (PMID:16675571)
• beta-catenin is regulated via epsilon-cleavage of N-cadherin (PMID:16707106)
• N-cadherin was selectively expressed on epithelial cells of the thymus, pituitary, pancreas, liver, adrenal, endometrium of the uterus, ovary, and stomach as well as in neuronal tissues. (PMID:16819153)
• N-cadherin and beta3 integrin expression correlates with progression to advanced-stage melanoma. (PMID:16969099)
• These results indicate that N-cadherin may be a critical cell-to-cell adhesion molecule between corneal epithelial stem/progenitor cells and their corresponding niche cells in the limbal epithelium. (PMID:17008425)
• Reduced E-cadherin expression was found in pseudomyxoma peritonei. (PMID:17031402)
• engagement of N-cadherin provides a stop signal for breast carcinoma cell migration (PMID:17171299)
• JNK1 is activated in response to collagen I, which increases tumorigenesis by up-regulating N-cadherin expression and by increasing motility. (PMID:17178870)
• N-cadherin and beta-catenin play role in cell migration via PDGF-Rbeta-mediated signaling through the scaffolding molecule NHERF2 (PMID:17229887)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cdh2	ENSDARG00000018693
mus_musculus	Cdh2	ENSMUSG00000024304
rattus_norvegicus	Cdh2	ENSRNOG00000015602

Paralogs (33): CDH1 (ENSG00000039068), CDH10 (ENSG00000040731), CDH3 (ENSG00000062038), CDH19 (ENSG00000071991), CDHR2 (ENSG00000074276), CDH17 (ENSG00000079112), CDH7 (ENSG00000081138), PCDH11Y (ENSG00000099715), CDHR5 (ENSG00000099834), CDH20 (ENSG00000101542), PCDH11X (ENSG00000102290), CDH23 (ENSG00000107736), CDH9 (ENSG00000113100), CDH6 (ENSG00000113361), CDH26 (ENSG00000124215), CDHR3 (ENSG00000128536), CDH15 (ENSG00000129910), CDH24 (ENSG00000139880), CDH11 (ENSG00000140937), CDH13 (ENSG00000140945), CDH18 (ENSG00000145526), CDHR1 (ENSG00000148600), CDH22 (ENSG00000149654), CDH8 (ENSG00000150394), CDH12 (ENSG00000154162), PCDH1 (ENSG00000156453), DCHS1 (ENSG00000166341), PCDH7 (ENSG00000169851), CDH4 (ENSG00000179242), CDH5 (ENSG00000179776), PCDH9 (ENSG00000184226), DCHS2 (ENSG00000197410), PCDH20 (ENSG00000280165)

Protein

Protein identifiers

Cadherin-2 — P19022 (reviewed: P19022)

Alternative names: CDw325, Neural cadherin

All UniProt accessions (7): P19022, A0A6Q8PF58, A0A6Q8PG20, A0A6Q8PHJ8, C9J126, C9J8J8, C9JMH2

UniProt curated annotations — full annotation on UniProt →

Function. Calcium-dependent cell adhesion protein; preferentially mediates homotypic cell-cell adhesion by dimerization with a CDH2 chain from another cell. 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. Plays a role in cell-to-cell junction formation between pancreatic beta cells and neural crest stem (NCS) cells, promoting the formation of processes by NCS cells. Required for proper neurite branching. Required for pre- and postsynaptic organization. CDH2 may be involved in neuronal recognition mechanism. In hippocampal neurons, may regulate dendritic spine density. May promote axon outgrowth and motor fiber repair via DSP-mediated recruitment to outgrowth tips.

Subunit / interactions. Homodimer (via extracellular region). Can also form heterodimers with other cadherins (via extracellular region). Dimerization occurs in trans, i.e. with a cadherin chain from another cell. Identified in a complex containing at least DSP, JUP, VIM and CDH2; the complex is more abundant following crush injury in regenerating motor neurons and may promote axon outgrowth and motor fiber repair. Interacts with CDCP1. Interacts with PCDH8; this complex may also include TAOK2. The interaction with PCDH8 may lead to internalization through TAOK2/p38 MAPK pathway. Identified in a complex containing FGFR4, NCAM1, CDH2, PLCG1, FRS2, SRC, SHC1, GAP43 and CTTN. May interact with OBSCN (via protein kinase domain 2). Interacts with FBXO45.

Subcellular location. Cell membrane. Sarcolemma. Cell junction. Cell surface. Desmosome. Adherens junction. Cell projection. Axon.

Post-translational modifications. Cleaved by MMP24. Ectodomain cleavage leads to the generation of a soluble 90 kDa N-terminal soluble fragment and a 45 kDa membrane-bound C-terminal fragment 1 (CTF1), which is further cleaved by gamma-secretase into a 35 kDa. Cleavage in neural stem cells by MMP24 affects CDH2-mediated anchorage of neural stem cells to ependymocytes in the adult subependymal zone, leading to modulate neural stem cell quiescence. May be phosphorylated by OBSCN.

Disease relevance. Arrhythmogenic right ventricular dysplasia, familial, 14 (ARVD14) [MIM:618920] A congenital heart disease characterized by infiltration of adipose and fibrous tissue into the right ventricle and loss of myocardial cells, resulting in ventricular and supraventricular arrhythmias. The disease may be caused by variants affecting the gene represented in this entry. Agenesis of corpus callosum, cardiac, ocular, and genital syndrome (ACOGS) [MIM:618929] An autosomal dominant, syndromic neurodevelopmental disorder characterized by global developmental delay and/or intellectual disability, corpus callosum agenesis or hypoplasia, mirror movements, dysmorphic features, and ocular, cardiac, and genital anomalies. The disease is caused by variants affecting the gene represented in this entry. Attention deficit-hyperactivity disorder 8 (ADHD8) [MIM:619957] A form of attention deficit-hyperactivity disorder, a neurobehavioral developmental condition primarily characterized by the coexistence of attentional problems and hyperactivity, with each feature occurring infrequently alone. ADHD8 is an autosomal recessive form with onset in early childhood, usually by age 3 years. ADHD8 patients may manifest mild developmental delay with autism. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. Three calcium ions are usually bound at the interface of each cadherin domain and rigidify the connections, imparting a strong curvature to the full-length ectodomain. Calcium-binding sites are occupied sequentially in the order of site 3, then site 2 and site 1.

Isoforms (2)

UniProt ID	Names	Canonical?
P19022-1	1	yes
P19022-2	2

RefSeq proteins (2): NP_001295105, NP_001783* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000233	Cadherin_Y-type_LIR	Domain
IPR002126	Cadherin-like_dom	Domain
IPR014868	Cadherin_pro_dom	Domain
IPR015919	Cadherin-like_sf	Homologous_superfamily
IPR020894	Cadherin_CS	Conserved_site
IPR027397	Catenin-bd_sf	Homologous_superfamily
IPR039808	Cadherin	Family

Pfam: PF00028, PF01049, PF08758

UniProt features (65 total): sequence variant 19, binding site 15, sequence conflict 8, glycosylation site 7, domain 5, modified residue 2, topological domain 2, signal peptide 1, propeptide 1, region of interest 1, compositionally biased region 1, chain 1, splice variant 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P19022-F1	79.68	0.51

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (15): 170; 170; 226; 228; 228; 259; 260; 261; 262; 262; 263; 293 …

Post-translational modifications (2): 96, 135

Glycosylation sites (7): 190, 273, 325, 402, 572, 651, 692

Function

Pathways and Gene Ontology

Reactome pathways

13 pathways

ID	Pathway
R-HSA-381426	Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-418990	Adherens junctions interactions
R-HSA-525793	Myogenesis
R-HSA-8957275	Post-translational protein phosphorylation
R-HSA-9926550	Regulation of MITF-M-dependent genes involved in extracellular matrix, focal adhesion and epithelial-to-mesenchymal transition
R-HSA-1266738	Developmental Biology
R-HSA-1500931	Cell-Cell communication
R-HSA-392499	Metabolism of proteins
R-HSA-421270	Cell-cell junction organization
R-HSA-446728	Cell junction organization
R-HSA-597592	Post-translational protein modification
R-HSA-9730414	MITF-M-regulated melanocyte development
R-HSA-9856651	MITF-M-dependent gene expression

MSigDB gene sets: 571 (showing top): GOBP_SYNAPTIC_VESICLE_LOCALIZATION, MODULE_52, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_EPITHELIUM_DEVELOPMENT, HORIUCHI_WTAP_TARGETS_DN, WALLACE_PROSTATE_CANCER_RACE_UP, GOBP_HETEROPHILIC_CELL_CELL_ADHESION, GOBP_RESPONSE_TO_MUSCLE_STRETCH, DACOSTA_UV_RESPONSE_VIA_ERCC3_XPCS_DN, GOBP_VESICLE_LOCALIZATION, GOBP_SYNAPSE_ASSEMBLY, GOBP_MEMBRANE_BIOGENESIS, GOBP_EPITHELIAL_CELL_DEVELOPMENT, TTTGTAG_MIR520D, GOBP_TYPE_B_PANCREATIC_CELL_DEVELOPMENT

GO Biological Process (32): cell morphogenesis (GO:0000902), type B pancreatic cell development (GO:0003323), cell-cell junction assembly (GO:0007043), cell adhesion (GO:0007155), homophilic cell-cell adhesion (GO:0007156), heterophilic cell-cell adhesion (GO:0007157), synapse assembly (GO:0007416), glial cell differentiation (GO:0010001), neural crest cell development (GO:0014032), calcium-dependent cell-cell adhesion (GO:0016339), cell migration (GO:0016477), cerebral cortex development (GO:0021987), adherens junction organization (GO:0034332), detection of muscle stretch (GO:0035995), positive regulation of MAPK cascade (GO:0043410), cell-cell adhesion mediated by cadherin (GO:0044331), blood vessel morphogenesis (GO:0048514), brain morphogenesis (GO:0048854), homeostasis of number of cells (GO:0048872), striated muscle cell differentiation (GO:0051146), radial glial cell differentiation (GO:0060019), neuroepithelial cell differentiation (GO:0060563), regulation of oligodendrocyte progenitor proliferation (GO:0070445), negative regulation of canonical Wnt signaling pathway (GO:0090090), mesenchymal cell migration (GO:0090497), synaptic vesicle clustering (GO:0097091), neuroligin clustering involved in postsynaptic membrane assembly (GO:0097118), neuronal stem cell population maintenance (GO:0097150), cell-cell adhesion (GO:0098609), regulation of postsynaptic density protein 95 clustering (GO:1902897), positive regulation of synaptic vesicle clustering (GO:2000809), telencephalon development (GO:0021537)

GO Molecular Function (12): RNA binding (GO:0003723), calcium ion binding (GO:0005509), beta-catenin binding (GO:0008013), protein kinase binding (GO:0019901), protein phosphatase binding (GO:0019903), identical protein binding (GO:0042802), alpha-catenin binding (GO:0045294), gamma-catenin binding (GO:0045295), cadherin binding (GO:0045296), protein binding (GO:0005515), enzyme binding (GO:0019899), metal ion binding (GO:0046872)

GO Cellular Component (26): cytoplasm (GO:0005737), endoplasmic reticulum lumen (GO:0005788), plasma membrane (GO:0005886), cell-cell junction (GO:0005911), adherens junction (GO:0005912), fascia adherens (GO:0005916), focal adhesion (GO:0005925), cell surface (GO:0009986), intercalated disc (GO:0014704), basolateral plasma membrane (GO:0016323), apical plasma membrane (GO:0016324), apicolateral plasma membrane (GO:0016327), catenin complex (GO:0016342), lamellipodium (GO:0030027), cell junction (GO:0030054), desmosome (GO:0030057), extracellular matrix (GO:0031012), sarcolemma (GO:0042383), neuron projection (GO:0043005), plasma membrane raft (GO:0044853), apical part of cell (GO:0045177), presynapse (GO:0098793), membrane (GO:0016020), cortical actin cytoskeleton (GO:0030864), synapse (GO:0045202), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Metabolism of proteins	2
Developmental Biology	2
Cell-cell junction organization	1
Post-translational protein modification	1
MITF-M-dependent gene expression	1
Cell junction organization	1
Cell-Cell communication	1
MITF-M-regulated melanocyte development	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	5
cell-cell adhesion	4
plasma membrane region	4
cellular anatomical structure	3
cell-cell junction	3
cell junction assembly	2
cell-cell junction organization	2
plasma membrane bounded cell projection	2
plasma membrane	2
anatomical structure morphogenesis	1
epithelial cell development	1
type B pancreatic cell differentiation	1
cellular process	1
nervous system development	1
synapse organization	1
cell differentiation	1
gliogenesis	1
neural crest cell differentiation	1
stem cell development	1
cell motility	1
pallium development	1
anatomical structure development	1
response to muscle stretch	1
detection of mechanical stimulus	1
MAPK cascade	1
regulation of MAPK cascade	1
positive regulation of intracellular signal transduction	1
blood vessel development	1
tube morphogenesis	1
brain development	1
animal organ morphogenesis	1
multicellular organismal-level homeostasis	1
muscle cell differentiation	1
nucleic acid binding	1
metal ion binding	1
kinase binding	1
phosphatase binding	1
cell adhesion molecule binding	1
binding	1
cation binding	1

Protein interactions and networks

STRING

5348 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDH2	CTNNB1	P35222	999
CDH2	CTNND1	O60716	993
CDH2	CDH1	P12830	983
CDH2	GRIA2	P42262	981
CDH2	NCAM1	P13591	966
CDH2	KLRG1	Q96E93	943
CDH2	GJA1	P17302	941
CDH2	VCL	P18206	934
CDH2	SNAI1	O95863	933
CDH2	PSEN1	P49768	923
CDH2	TJP1	Q07157	903
CDH2	PCDH10	Q9P2E7	897
CDH2	PCDH19	Q8TAB3	896
CDH2	SNAI2	O43623	887
CDH2	FGFR1	P11362	885

IntAct

89 interactions, top by confidence:

A	B	Type	Score
CTNNB1	AXIN1	psi-mi:“MI:0914”(association)	0.940
CDH2	CTNNB1	psi-mi:“MI:0915”(physical association)	0.930
CDH2	CTNNB1	psi-mi:“MI:0914”(association)	0.930
CTNNB1	CDH2	psi-mi:“MI:0915”(physical association)	0.930
TAX1BP3	ARVCF	psi-mi:“MI:0914”(association)	0.690
FCER2	CDH2	psi-mi:“MI:0407”(direct interaction)	0.600
CDH2	FCER2	psi-mi:“MI:0403”(colocalization)	0.600
IGF1R	PIK3R2	psi-mi:“MI:2364”(proximity)	0.590
CDH2	JUP	psi-mi:“MI:0914”(association)	0.560
CTNND1	CDH2	psi-mi:“MI:0915”(physical association)	0.560
JUP	CDH2	psi-mi:“MI:0915”(physical association)	0.560
LGALS1	PODXL	psi-mi:“MI:0914”(association)	0.530
PCDHGB1	FAM171A2	psi-mi:“MI:0914”(association)	0.530
SPSB2	ARHGEF10	psi-mi:“MI:0914”(association)	0.530
CDH2	FAM20C	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
MET	NDUFA4	psi-mi:“MI:2364”(proximity)	0.420
EXOC5	CDH2	psi-mi:“MI:0915”(physical association)	0.370
KSR1	FAM168B	psi-mi:“MI:0914”(association)	0.350
LAMP1	HAX1	psi-mi:“MI:0914”(association)	0.350
CTNNA3	ARVCF	psi-mi:“MI:0914”(association)	0.350
incE	STX7	psi-mi:“MI:0914”(association)	0.350
ZBTB18	DNASE1L1	psi-mi:“MI:0914”(association)	0.350
RYBP	PIPSL	psi-mi:“MI:0914”(association)	0.350
	FAM171A2	psi-mi:“MI:0914”(association)	0.350

BioGRID (186): CDH2 (Affinity Capture-MS), CDH2 (Affinity Capture-Western), FBXO45 (Affinity Capture-Western), CTNNB1 (Affinity Capture-Western), SKP1 (Affinity Capture-Western), CDH2 (Affinity Capture-Western), CCNA2 (Affinity Capture-Western), CDH2 (Affinity Capture-Western), CDH2 (Affinity Capture-Western), CDH2 (Affinity Capture-MS), CDH2 (Affinity Capture-Western), CDH2 (Affinity Capture-Western), EGFR (Affinity Capture-Western), ERBB2 (Affinity Capture-Western), CDH2 (Affinity Capture-Western)

ESM2 similar proteins: B0KW95, B2KI42, B4USZ0, F1PAA9, O02840, O60330, P08641, P09803, P10287, P10288, P12830, P15116, P19022, P19534, P19535, P20310, P22223, P24503, P26009, P33145, P33147, P33148, P33150, P33151, P33152, P39038, P53708, P55283, P55284, P79883, Q08174, Q5DRB7, Q5DRB8, Q5DRC0, Q5DRC2, Q5R9X1, Q5RAX1, Q6R8F2, Q6URK6, Q90275

Diamond homologs: A0A8M2BIB6, B0KW95, B2KI42, B4USZ0, F1PAA9, H2EQR6, O18926, O35902, O55075, O55111, O88277, P08641, P09803, P10287, P10288, P12830, P15116, P19022, P19534, P19535, P20310, P22223, P24503, P30944, P32926, P33145, P33146, P33147, P33148, P33150, P33152, P33545, P39038, P55283, P55290, P55291, P55292, P55849, P55850, P79883

SIGNOR signaling

20 interactions.

A	Effect	B	Mechanism
SRC	down-regulates	CDH2	phosphorylation
CDH2	up-regulates	CDON	binding
CDH2	up-regulates	CDON/SPAG9	binding
CTNND1	“up-regulates quantity by stabilization”	CDH2	binding
ARVCF	“up-regulates quantity by stabilization”	CDH2	binding
CTNND2	“up-regulates quantity by stabilization”	CDH2	binding
calcium(2+)	“up-regulates activity”	CDH2	“chemical activation”
CDH2	“up-regulates activity”	CTNNB1	binding
hsa-mir-494-3p	“down-regulates quantity by repression”	CDH2	“post transcriptional regulation”
hsa-miR-338-3p	“down-regulates quantity by repression”	CDH2	“post transcriptional regulation”
hsa-miR-148a-3p	“down-regulates quantity by repression”	CDH2	“post transcriptional regulation”
TWIST1	“up-regulates quantity by expression”	CDH2	“transcriptional regulation”
CDH2	up-regulates	Epithelial-mesenchymal_transition
LEF1	“up-regulates quantity by expression”	CDH2	“transcriptional regulation”
TCF7	“up-regulates quantity by expression”	CDH2	“transcriptional regulation”
CDH4	“down-regulates quantity by repression”	CDH2
NEXMIF	“up-regulates quantity by expression”	CDH2	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 100 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
protein dephosphorylation	8	20.2×	6e-06
cell surface receptor protein tyrosine kinase signaling pathway	6	11.8×	3e-03
cell-cell adhesion	7	8.1×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

1156 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	9
Likely pathogenic	9
Uncertain significance	608
Likely benign	415
Benign	38

Top pathogenic / likely-pathogenic (18)

Variant ID	HGVS	Classification
3075674	NM_001792.5(CDH2):c.1159-1G>A	Pathogenic
3342458	NM_001792.5(CDH2):c.1344+1G>C	Pathogenic
3769872	NM_001792.5(CDH2):c.1522G>A (p.Glu508Lys)	Pathogenic
804251	NM_001792.5(CDH2):c.2027A>G (p.Tyr676Cys)	Pathogenic
805760	NM_001792.5(CDH2):c.1789G>T (p.Asp597Tyr)	Pathogenic
805761	NM_001792.5(CDH2):c.1802A>C (p.Asn601Thr)	Pathogenic
805762	NM_001792.5(CDH2):c.1839C>G (p.Cys613Trp)	Pathogenic
929497	NM_001792.5(CDH2):c.686A>C (p.Gln229Pro)	Pathogenic
929855	NM_001792.5(CDH2):c.485T>A (p.Val162Asp)	Pathogenic
1695977	NM_001792.5(CDH2):c.448C>T (p.His150Tyr)	Likely pathogenic
1723671	NM_001792.5(CDH2):c.1344+5G>A	Likely pathogenic
2443606	NM_001792.5(CDH2):c.345G>A (p.Trp115Ter)	Likely pathogenic
2446624	NM_001792.5(CDH2):c.172+2T>C	Likely pathogenic
2683877	NM_001792.5(CDH2):c.1805C>G (p.Ala602Gly)	Likely pathogenic
3378101	NM_001792.5(CDH2):c.1321G>T (p.Asp441Tyr)	Likely pathogenic
4755526	NM_001792.5(CDH2):c.1879G>C (p.Asp627His)	Likely pathogenic
545108	NM_001792.5(CDH2):c.2075A>G (p.Asn692Ser)	Likely pathogenic
805758	NM_001792.5(CDH2):c.1057G>A (p.Asp353Asn)	Likely pathogenic

SpliceAI

3429 predictions. Top by Δscore:

Variant	Effect	Δscore
18:27963517:TAGTC:T	acceptor_gain	1.0000
18:27963518:AGTC:A	acceptor_gain	1.0000
18:27963519:GTC:G	acceptor_gain	1.0000
18:27963520:TC:T	acceptor_gain	1.0000
18:27963521:CC:C	acceptor_gain	1.0000
18:27963522:C:CC	acceptor_gain	1.0000
18:27963522:C:T	acceptor_gain	1.0000
18:27963522:CTG:C	acceptor_loss	1.0000
18:27963523:T:C	acceptor_loss	1.0000
18:27982938:GCTCA:G	donor_loss	1.0000
18:27982939:CTCAC:C	donor_loss	1.0000
18:27982940:TCA:T	donor_loss	1.0000
18:27982941:CAC:C	donor_loss	1.0000
18:27982942:A:AC	donor_gain	1.0000
18:27982942:ACC:A	donor_loss	1.0000
18:27982943:C:CC	donor_gain	1.0000
18:27982943:C:T	donor_loss	1.0000
18:27983079:AAGGA:A	acceptor_gain	1.0000
18:27983080:AGGA:A	acceptor_gain	1.0000
18:27983081:GGA:G	acceptor_gain	1.0000
18:27983082:GA:G	acceptor_gain	1.0000
18:27983083:AC:A	acceptor_loss	1.0000
18:27983084:C:CC	acceptor_gain	1.0000
18:27983084:CTA:C	acceptor_loss	1.0000
18:27983088:G:C	acceptor_gain	1.0000
18:27983088:G:GC	acceptor_gain	1.0000
18:27984996:TCA:T	donor_loss	1.0000
18:27984997:CAC:C	donor_loss	1.0000
18:27984998:A:AC	donor_gain	1.0000
18:27984999:C:CT	donor_gain	1.0000

AlphaMissense

5972 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:27952184:A:G	L897P	1.000
18:27952184:A:T	L897H	1.000
18:27952192:G:C	F894L	1.000
18:27952192:G:T	F894L	1.000
18:27952193:A:C	F894C	1.000
18:27952193:A:G	F894S	1.000
18:27952194:A:G	F894L	1.000
18:27952206:A:G	W890R	1.000
18:27952206:A:T	W890R	1.000
18:27952300:A:C	F858L	1.000
18:27952300:A:T	F858L	1.000
18:27952302:A:G	F858L	1.000
18:27952307:A:G	L856S	1.000
18:27952310:A:G	L855P	1.000
18:27952314:A:G	S854P	1.000
18:27952316:T:A	D853V	1.000
18:27952316:T:G	D853A	1.000
18:27952317:C:G	D853H	1.000
18:27952328:G:T	A849D	1.000
18:27952355:A:G	L840P	1.000
18:27963364:A:C	I836S	1.000
18:27963364:A:T	I836N	1.000
18:27963366:G:C	F835L	1.000
18:27963366:G:T	F835L	1.000
18:27963367:A:C	F835C	1.000
18:27963367:A:G	F835S	1.000
18:27963368:A:G	F835L	1.000
18:27963502:A:G	L790P	1.000
18:27963514:T:C	D786G	1.000
18:27982948:T:G	D782A	1.000

dbSNP variants (sampled 300 via entrez): RS1000019970 (18:28001220 G>A,T), RS1000026839 (18:28168887 T>C), RS1000034174 (18:28162418 A>G,T), RS1000054338 (18:28168455 G>A), RS1000065670 (18:28175821 C>A), RS1000090985 (18:28090338 G>A,T), RS1000094603 (18:28151142 T>C), RS1000096265 (18:27988735 T>C), RS1000101656 (18:27995050 C>T), RS1000109234 (18:27943127 T>C), RS1000123319 (18:28051714 A>C), RS1000131633 (18:28094279 G>A), RS1000133527 (18:28008229 G>A,C,T), RS1000137981 (18:28083658 T>A,C), RS1000141570 (18:27950361 T>A,C)

Disease associations

OMIM: gene MIM:114020 | disease phenotypes: MIM:619957, MIM:618920, MIM:618929, MIM:609129, MIM:108010, MIM:217990

GenCC curated gene-disease

Disease	Classification	Inheritance
arrhythmogenic right ventricular dysplasia, familial, 14	Strong	Autosomal dominant
agenesis of corpus callosum, cardiac, ocular, and genital syndrome	Strong	Autosomal dominant
arrhythmogenic right ventricular cardiomyopathy	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
dilated cardiomyopathy	Limited	AD
arrhythmogenic right ventricular cardiomyopathy	Limited	AD

Mondo (9): attention deficit-hyperactivity disorder 8 (MONDO:0859261), arrhythmogenic right ventricular dysplasia, familial, 14 (MONDO:0030062), arrhythmogenic right ventricular cardiomyopathy (MONDO:0016587), agenesis of corpus callosum, cardiac, ocular, and genital syndrome (MONDO:0030065), auditory neuropathy (MONDO:0021944), dilated cardiomyopathy (MONDO:0005021), heart failure (MONDO:0005252), arteriovenous malformations of the brain (MONDO:0007154), corpus callosum, agenesis of (MONDO:0009022)

Orphanet (4): Inherited arrhythmogenic cardiomyopathy (Orphanet:247), Dilated cardiomyopathy (Orphanet:217604), Brain arteriovenous malformation (Orphanet:46724), Isolated corpus callosum agenesis (Orphanet:200)

HPO phenotypes

63 total (30 of 63 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000054	Micropenis
HP:0000218	High palate
HP:0000219	Thin upper lip vermilion
HP:0000256	Macrocephaly
HP:0000307	Pointed chin
HP:0000316	Hypertelorism
HP:0000319	Smooth philtrum
HP:0000322	Short philtrum
HP:0000337	Broad forehead
HP:0000343	Long philtrum
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000391	Thickened helices
HP:0000486	Strabismus
HP:0000490	Deeply set eye
HP:0000494	Downslanted palpebral fissures
HP:0000506	Telecanthus
HP:0000659	Peters anomaly
HP:0000664	Synophrys
HP:0000729	Autistic behavior
HP:0000739	Anxiety
HP:0000912	Sprengel anomaly
HP:0001249	Intellectual disability
HP:0001263	Global developmental delay
HP:0001274	Agenesis of corpus callosum
HP:0001335	Bimanual synkinesia
HP:0001651	Dextrocardia

GWAS associations

77 associations (top):

Study	Trait	p-value
GCST001188_6	vWF and FVIII levels	6.000000e-06
GCST001419_12	Temperament (bipolar disorder)	5.000000e-06
GCST001762_397	Obesity-related traits	8.000000e-06
GCST002162_8	Lung function (FVC)	5.000000e-06
GCST002312_1	Periodontal disease-related phenotype (Socransky)	9.000000e-06
GCST003818_7	Resting heart rate	6.000000e-10
GCST005076_15	Breast cancer (estrogen-receptor negative)	3.000000e-07
GCST005077_4	Breast cancer	1.000000e-08
GCST005316_220	Intelligence (MTAG)	1.000000e-08
GCST005606_9	Response to hepatitis B vaccine	7.000000e-06
GCST008114_12	Type 2 diabetes	8.000000e-06
GCST008792_7	Urinary albumin-to-creatinine ratio in diabetes	1.000000e-08
GCST009391_1307	Metabolite levels	7.000000e-06
GCST009462_70	Optic disc size	4.000000e-12
GCST009524_91	Household income (MTAG)	2.000000e-08
GCST010002_135	Refractive error	2.000000e-15
GCST010320_73	PR interval	2.000000e-07
GCST010321_60	PR interval	4.000000e-08
GCST010796_2042	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-09
GCST010796_2043	Electrocardiogram morphology (amplitude at temporal datapoints)	5.000000e-08
GCST010796_2044	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST010796_2045	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-08
GCST010796_2046	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST010796_2047	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-09
GCST010796_2048	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST010796_2049	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-08
GCST010796_2050	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-08
GCST010796_3001	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-20
GCST010796_3002	Electrocardiogram morphology (amplitude at temporal datapoints)	8.000000e-19
GCST010796_3003	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-18

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0004365	personality trait
EFO:0004730	hormone measurement
EFO:0004312	vital capacity
EFO:0004337	intelligence
EFO:0004645	response to vaccine
EFO:0007778	urinary albumin to creatinine ratio
EFO:0010517	oxalate measurement
EFO:0009695	household income
EFO:0004462	PR interval
EFO:0004327	electrocardiography
EFO:0007828	daytime rest measurement

MeSH disease descriptors (6)

Descriptor	Name	Tree numbers
D061085	Agenesis of Corpus Callosum	C10.500.034; C16.131.666.034; C23.300.008
D019571	Arrhythmogenic Right Ventricular Dysplasia	C14.240.400.145; C14.280.238.028; C14.280.400.145; C16.131.240.400.145
D002311	Cardiomyopathy, Dilated	C14.280.195.160; C14.280.238.070; C16.320.488.750
D006333	Heart Failure	C14.280.434
D002538	Intracranial Arteriovenous Malformations	C10.228.140.300.520; C10.500.190.500; C14.240.850.750.295; C14.240.850.875.500; C14.907.150.295; C14.907.253.560.400; C16.131.240.850.750.295; C16.131.240.850.875.500; C16.131.666.190.500
C538268	Auditory neuropathy (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1697669 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs17446819	Efficacy	3	methadone
rs8094439	Efficacy	3	methadone

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs8094439	CDH2	3	2.25	1	methadone
rs17446819	CDH2	3	2.25	1	methadone
rs1944294	CDH2		0.00	0

ChEMBL bioactivities

1 potent at pChembl≥5 of 1 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.30	IC50	5000	nM	CHEMBL1689350

PubChem BioAssay actives

1 with measured affinity, of 7 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[(4R,7S,10S,13S,16S,19R)-19-acetamido-4-carbamoyl-16-(1H-imidazol-5-ylmethyl)-13-methyl-6,9,12,15,18-pentaoxo-10-propan-2-yl-1,2-dithia-5,8,11,14,17-pentazacycloicos-7-yl]acetic acid	587333: Antagonist activity at N-cadherin	ic50	5.0000	uM

CTD chemical–gene interactions

229 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases reaction, increases expression, affects localization, decreases expression, increases methylation (+2 more)	14
sodium arsenite	increases abundance, increases expression, decreases expression, increases reaction, affects reaction (+1 more)	10
Cadmium Chloride	affects localization, increases abundance, increases expression	6
Particulate Matter	decreases reaction, increases expression, increases abundance	6
Fulvestrant	increases expression, decreases reaction	5
Quercetin	affects expression, decreases expression, increases expression, decreases reaction, affects reaction	5
Valproic Acid	decreases expression, decreases methylation, affects cotreatment	5
Resveratrol	decreases expression, decreases reaction, increases expression, affects cotreatment	4
Arsenic Trioxide	decreases expression, increases expression, increases reaction, affects reaction, decreases reaction	4
Cadmium	decreases reaction, increases abundance, increases expression	4
Doxorubicin	affects expression, affects cotreatment, decreases expression, increases response to substance	4
Estradiol	decreases reaction, increases expression, affects cotreatment	4
Tobacco Smoke Pollution	decreases reaction, increases expression, increases reaction, decreases expression	4
trichostatin A	affects cotreatment, decreases expression	3
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	decreases expression, decreases reaction, increases expression, increases abundance	3
bisphenol S	increases expression, decreases reaction, affects reaction	3
Arsenic	decreases reaction, increases abundance, increases expression, affects expression, affects response to substance	3
Benzo(a)pyrene	affects cotreatment, increases expression, decreases methylation	3
Cisplatin	affects cotreatment, decreases expression, decreases response to substance, increases expression	3
Tamoxifen	affects expression, affects reaction, affects cotreatment, increases expression, decreases expression	3
Tretinoin	affects expression, decreases expression, increases expression, decreases reaction	3
Cyclosporine	decreases expression	3
Lithium Chloride	decreases reaction, increases expression, decreases expression	3
aristolochic acid I	decreases expression, increases expression	2
thymoquinone	increases reaction, decreases expression, decreases reaction	2
arsenite	increases abundance, increases expression, increases methylation, affects reaction	2
cobaltous chloride	decreases expression, increases expression	2
dictamnine	decreases reaction, increases expression, affects expression, increases reaction, affects cotreatment (+1 more)	2
andrographolide	decreases reaction, increases expression, decreases expression, increases reaction	2
cordycepin	decreases expression, affects cotreatment, increases reaction	2

ChEMBL screening assays

4 unique, capped per target: 3 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1694377	Functional	Antagonist activity at N-cadherin	Tripeptide motifs in biology: targets for peptidomimetic design. — J Med Chem
CHEMBL3822107	Binding	Inhibition of recombinant N-cadherin-Fc chimeric protein (unknown origin) homodimerization at 10 uM preincubated for 30 mins followed by N-cadherin-Fc addition by surface plasmon resonance analysis relative to control	Crystal Structure of Human E-Cadherin-EC1EC2 in Complex with a Peptidomimetic Competitive Inhibitor of Cadherin Homophilic Interaction. — J Med Chem

Cellosaurus cell lines

4 cell lines: 3 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2TY	Abcam HEK293T CDH2 KO	Transformed cell line	Female
CVCL_F0XP	BT-20N	Cancer cell line	Female
CVCL_SI14	HAP1 CDH2 (-) 1	Cancer cell line	Male
CVCL_XM67	HAP1 CDH2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

285 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00374465	PHASE4	UNKNOWN	Therapy With Verapamil or Carvedilol in Chronic Heart Failure
NCT01293903	PHASE4	COMPLETED	Study of Qiliqiangxin Capsule to Treat Dilated Cardiomyopathy
NCT01557140	PHASE4	COMPLETED	A Randomized Trial of Carvedilol in Chronic Chagas Cardiomyopathy
NCT01917149	PHASE4	COMPLETED	Supramaximal Titrated Inhibition of RAAS in Dilated Cardiomyopathy
NCT02115581	PHASE4	COMPLETED	Coenzyme Q10 Supplementation in Children With Idiopathic Dilated Cardiomyopathy
NCT06236022	PHASE4	RECRUITING	The Effects of Sirolimus in Patients With Dilated Cardiomyopathy Infected With Kaposi Sarcoma-associated Virus
NCT00083772	PHASE4	TERMINATED	Use of Nesiritide in the Management of Acute Diastolic Heart Failure
NCT00146848	PHASE4	COMPLETED	PEGASUS CRT Study: Atrial Support Study in Cardiac Resynchronization Therapy
NCT00154115	PHASE4	COMPLETED	Levosimendan in High Risk Heart Valve Surgery
NCT00170313	PHASE4	TERMINATED	CORE: Study to Evaluate the Conducted AF-Response-Algorithm in Patients Suffering From Heart Failure and Atrial Fibrillation
NCT00180596	PHASE4	COMPLETED	PACMAN - PAcing for CardioMyopathies, a EuropeAN Study
NCT00187200	PHASE4	COMPLETED	Response of Cardiac Resynchronization Therapy Optimization With Ventricle to Ventricle Timing in Heart Failure Patients
NCT00206232	PHASE4	COMPLETED	Novel Treatment for Diastolic Heart Failure in Women
NCT00206856	PHASE4	TERMINATED	Rapid Assessment of Bedside BNP In Treatment of Heart Failure (RABBIT)
NCT00219388	PHASE4	COMPLETED	Efficacy and Safety of Treatment With Simdax® Versus Dobutrex® in Decompensated Heart Failure Patients.
NCT00288587	PHASE4	COMPLETED	Extracorporeal Ultrafiltration (UF) vs. Usual and Customary Care for Patients With Severe Heart Failure (HF)
NCT00305526	PHASE4	TERMINATED	REBEAT Resynchronisation and Beta-Blocker European Trial
NCT00324766	PHASE4	COMPLETED	Levosimendan in Acute Heart Failure Following Acute Myocardial Infarction.
NCT00347087	PHASE4	COMPLETED	Effect of Irbesartan on Insulin Sensitivity in Chronic Heart Failure
NCT00371085	PHASE4	COMPLETED	Congestive Heart Failure Outreach Program
NCT00384566	PHASE4	WITHDRAWN	A Comparison of the Effect of Carvedilol and Metoprolol on Airways Tone in Patients With Heart Failure
NCT00391846	PHASE4	COMPLETED	Evaluation of Heart Failure Treatment Guided by N-terminal Pro B-type Natriuretic Peptide (NTproBNP) vs Clinical Symptoms and Signs Alone
NCT00400582	PHASE4	COMPLETED	A Pharmacogenomic Study of Candesartan in Heart Failure
NCT00402376	PHASE4	TERMINATED	Evaluation of Myocardial Improvement in Patients Supported by Ventricular Assist Device Under Optimal Pharmacological Therapy
NCT00418119	PHASE4	UNKNOWN	Erythropoietin Treatment in Patients With Systolic Left Ventricular Dysfunction, Mild Anemia and Normal Renal Function
NCT00422318	PHASE4	COMPLETED	Treatment of Hyperuricemia in Patients With Heart Failure
NCT00477789	PHASE4	COMPLETED	Effects of Allopurinol on Diastolic Function in Chronic Heart Failure Patients
NCT00480077	PHASE4	TERMINATED	Diagnostic Outcome Trial in Heart Failure (DOT-HF Trial)
NCT00489177	PHASE4	COMPLETED	Optimal Programming to Improve Mechanical Indices, Symptoms and Exercise in Cardiac Resynchronization Therapy.
NCT00491907	PHASE4	TERMINATED	Effect of Folic Acid on Endothelial and Baroreceptor Function in Patients With Heart Failure
NCT00497900	PHASE4	COMPLETED	The Effect of Calcium and Vitamin D in Patients With Heart Failure
NCT00498472	PHASE4	COMPLETED	NT-proBNP in the Optimization of Treatment After Recent Acute Heart Failure Trial
NCT00512759	PHASE4	COMPLETED	Goal-directed Afterload Reduction in Acute Congestive Cardiac Decompensation Study
NCT00517426	PHASE4	COMPLETED	Effects of Acetazolamide and CO2 Inhalation on Exercise-induced Periodic Breathing in Heart Failure
NCT00517725	PHASE4	COMPLETED	Nebivolol Versus Bisoprolol Versus Carvedilol in Heart Failure
NCT00527059	PHASE4	UNKNOWN	Renal Effects of Levosimendan in Patients Admitted With Acute Decompensated Heart Failure
NCT00551499	PHASE4	COMPLETED	Cardiac Resynchronisation Therapy in Combination With Overdrive Pacing in the Treatment of Central Sleep Apnea in CHF
NCT00552851	PHASE4	UNKNOWN	Changes of Left Ventricular Mass and Cardiac Function in Patients With Active Acromegaly During Treatment With the Growth Hormone Receptor Antagonist Pegvisomant
NCT00574119	PHASE4	COMPLETED	Effect of Aldosterone on Energy Starvation in Heart Failure
NCT00613964	PHASE4	TERMINATED	The Effects of Carperitide on Short and Long-term Prognosis in Patients With Both Cardiac and Renal Failure