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Symbol CDH2 contributors: shn/pgu - updated : 19-11-2019
HGNC name cadherin 2, type 1, N-cadherin (neuronal)
HGNC id 1759
TYPE functioning gene
STRUCTURE 244.25 kb     16 Exon(s)
10 Kb 5' upstream gene genomic sequence study
text structure a CCG repeat in 5'utr
MAPPING cloned Y linked N status confirmed
Map cen - D18S478 - D18S1151 - CDH2 - D18S847 - D18S463 - qter
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
16 - 4016 97 906 - 2018 30242148
15 - 3908 - 875 - 2018 30242148
Type widely
   expressed in (based on citations)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart   predominantly Homo sapiens
Digestiveintestinesmall intestine   
Endocrineadrenal gland   highly
 neuroendocrinepituitary  highly
Nervousbraindiencephalonamygdala   Mus musculus
 brainlimbic systemhippocampus   Mus musculus
 braindiencephalonhypothalamus   Mus musculus
Reproductivemale systemtestis  highly
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Muscularsmoothvessel   Homo sapiens
cell lineage
cell lines
physiological period embryo
Text expressed at the time of gastrulation and neurulation
  • a N terminal hydrophobic domain, large N-terminal extracellular domain composed of five tandem repeat domains, termed cadherin repeats that contain four Ca2+-binding sites, and are involved in homotypic protein–protein interactions
  • a transmembrane (1TM) segment and a highly conserved cytoplasmic tail
  • cytoplasmic domain containing two main binding regions, the C-terminal domain (CTD) and the juxtamembrane domain (JMD)
  • secondary structure a cadherin pro-region, five EC repeats of about 110 residues, each of which fold into seven anti-parallel beta strands arranged into two beta sandwich folds, a transmembrane region and a cytoplasmic tail
    conjugated GlycoP , RiboP
    interspecies ortholog to Cdh2, Mus musculus
    ortholog to Cdh2, Rattus norvegicus
    ortholog to cdh2, Danio rerio
    ortholog to CDH2, Pan troglodytes
  • cadherin superfamily
  • CATEGORY adhesion
    SUBCELLULAR LOCALIZATION     plasma membrane,junction,tight
    plasma membrane,junction,adherens
    intracellular,cytoplasm,organelle,endoplasmic reticulum
  • observed in the cytoplasm, was actively internalized by endocytosis
  • basic FUNCTION
  • N-cadherin plays a critical role in early heart development as well as in other morphogenetic processes
  • putatively involved in synaptic adhesion, axon outgrowth
  • and guidance
  • cell-cell or cell-ECM interactions
  • required for establishment of left-right asymmetry during gastrulation
  • maybe involved in establishment of embryonic left-right asymetry
  • regulates dendritic spine morphogenesis and related synaptic functions, presumably cooperating with cadherin-independent adhesive mechanisms to maintain spine-axon contacts
  • mediates apical adhesion between retina epithelial cells
  • calcium-dependent cell adhesion molecule that is associated with invasive tumors in breast cancer
  • modifies KCNA5 activity and is thus a novel candidate signaling molecule participating in the regulation of a variety of functions including cardiac action potential and vascular tone
  • plays a pivotal role in the maintenance of the progenitor phenotype in cultured limbal epithelial cells
  • cell adhesion molecules that interacts in a homophilic Ca2+-dependent manner through its extracellular ectodomains
  • having specific function in the maintenance of dendrite arbors
  • CDH2 and CDH11 are crucial regulators of postnatal skeletal growth and bone mass maintenance, serving overlapping, yet distinct, functions in the osteogenic lineage
  • with NLGN1, cooperate to control vesicle clustering at nascent synapses
  • intimately involved in neuronal cell adhesion, signaling, differentiation and synapse function
  • acts by postsynaptically accumulating neuroligin-1 and activating its function via the scaffolding molecule MAGI2, leading, in turn, to presynaptic vesicle clustering
  • in neurons, is required to enable neuroligin-1 to exert its vesicle cluster-inducing effect
  • key cell adhesion molecule implicated in chondrogenic differentiation
  • PCDH19 and CDH2 function together to regulate cell adhesion and to mediate morphogenetic movements during brain development
  • important role during dendrite arborization, axon guidance, and synaptogenesis
  • ATP-sensitive protein that is associated with altered Huntington disease CAG striatal cell adhesion and neuritogenesis
  • integrator of adhesion and cytoskeletal signaling required for proper neuronal cell development and synaptic function
  • important for multipolar neurons to polarize their migration toward the cortical plate
  • regulates the proliferation of DA (dopaminergic) progenitors and the differentiation of DA neurons through canonical WNT-CTNNB1 signaling in the ventral midbrain (vMB)
  • is a cell adhesion molecule which is enriched at synapses
  • relocalizes from the periphery to the center of the synapse after transient synaptic stimulation in hippocampal neurons
  • regulates molecular organization of excitatory and inhibitory synaptic circuits in adult hippocampus
  • functional role of CDH2 adherens junctions (AJ) in vasomotor regulation
  • plays a vital role in cell adhesion, making it a biologically plausible candidate gene in ARVC pathogenesis (PMID
  • regulates signaling mechanisms required for lens fiber cell elongation and lens morphogenesis
  • important role in neurulation, brain development and regulation of synaptic function
  • importance of CDH2 in angiogenesis
  • CDH2-mediated interactions are necessary for migration and survival during the postmitotic phase of interneuron development
  • essential roles in neural development include neuronal migration and axon pathfinding
    a component
  • constituent of transmembrane glycoprotein component of adherens junction
  • forms a molecular complex with axin1 and LRP5 involving the LRP5 cytoplasmic tail domain
  • functionally interacts with LRP6 and axin1 in osteoblasts
    small molecule
  • forms heterodimers R-cadherins
  • protein tyrosine phosphatase, non-receptor type 1, PTPN1
  • in retinoblastoma and normal retina N-cadherin associated with alpha-catenin and beta-catenin
  • glutamate receptor 6, GLUR6
  • Presenilin1, PS1
  • RICS-beta-catenin complex
  • cell adhesion molecule-related/down-regulated by oncogenes; surface glycoprotein, Ig superfamily member, CDO and Boc homolog (mouse), BOC
  • cadherin-11, alpha- and beta-catenin, plakoglobin (proportions variable among species), p120ctn and vinculin
  • hemophilic, calcium dependent interactions
  • interacting by its C terminus with the cytoskeleton via beta-catenin
  • Wnt coreceptor LRP5 and regulates canonical Wnt/beta-catenin signaling in osteoblasts
  • CDH2-axin1-LRP5 interaction negatively regulates Wnt/beta-catenin signaling and is critical in the regulation of osteoblast function, bone formation, and bone mass
  • CDCP1
  • cleaved specifically by the disintegrin and metalloproteinase ADAM10 in its ectodomain
  • on GRIA2, B3GAT1 regulates cell surface stability of GRIA2 by modulating the interaction with CDH2
  • N-cadherins form homophilic interactions with N-cadherins on opposing membranes and these molecular interactions mediate the effect of neuronal activity on promoting dendrite growth, an important aspect of coordinated neural circuit development
  • mechanistic link among the cell adhesion molecule, CDH2, the actin-binding scaffold protein, CTTN, and KCNA5 remodeling in the heart
  • its expression facilitates cis-dimerization of APP (
  • SHROOM3 and CDH2 function cooperatively downstream of PITX2 to directly regulate cell shape changes necessary for early gut tube morphogenesis
  • adhesion by the PCDH19-CDH2 complex was unaffected by mutations that disrupt CDH2 homophilic binding but was inhibited by a mutation in PCDH19
  • CDH2 engagement mediates neuronal cell survival by enhancing the MAP kinase pathway and down-regulating the pro-apoptotic protein BCL2L11
  • BEX2 promoted the progression of glioma by promoting cell migration and invasion, and these effects might be mediated by CDH2 and MMP2
  • CEACAM1 inhibit cell-matrix adhesion and promote cell motility and CDH2 is a crucial protein involved in the processes
  • CDH2 specifically interacts with FBXO45 through two consensus motifs overlapping the site of calcium-binding and dimerization of the cadherin molecule
  • function of desmoplakin in motor nerve regeneration by linking CDH2 to intermediate filaments in regenerating motor axons
  • CDH2 and CDH11 act as regulators of stem cell fate decisions
  • CDON promotes neural crest migration by regulating CDH2 localization
  • CD82 regulates bone marrow homing of acute myeloid leukemia by modulating the molecular organization of CDH2
  • new role for CTNND1 bound to the CDH2 precursor ensuring its trafficking through the biosynthetic pathway towards the cell surface
  • AMOTL1 is an essential effector of the CDH2 mediated endothelial/pericyte junctional complex
  • EXOC4 regulates CDH2 expression by controlling SMAD3 and SMAD4 expression at the basal transcriptional level, thereby modulating cell migration and adhesion
  • periodic expression of PCDH8 in the anterior presomitic mesoderm (PSM) triggers rhythmic endocytosis of CDH2, allowing for segmental de-adhesion and individualization of somites
  • RELN transiently (and not persistently) promotes CDH2-mediated neuronal aggregation
  • INVS could upregulate the expression of CDH2, VIM, MMP2, and MMP9
  • PKD1 enhances the stability of CDH2 on cell membrane and promotes synapse morphogenesis and synaptic plasticity in an activity-dependent manner
  • CDH2 promotes neurite branching and it is required for three synaptic organizers, NLGN1, leucine-rich repeat transmembrane protein 2 (LRRTM2), and CADM1 to stimulate presynaptic differentiation
  • interaction of NECTIN2 with CDH2
  • GJA1 controls neural crest cell migration by directly regulating CDH2 transcription
  • CDH2-signaling via TRIO assembles adherens junctions to restrict endothelial permeability
  • cell & other
    Other regulated by PSEN1 (PSEN1-mediated delivery of CDH2 to the plasma membrane is important for exerting its physiological function, and control of the state of cell-cell contact)
    cleaved by ADAM10 (cleavage of N-cadherin is essential for chondrocyte differentiation)
    upregulated by RAP1 (
    corresponding disease(s) ACOGS , ARVC14
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in ductal carcinomas, decreased levels in primary tumors correlate with local recurrence and death in long-term follow-up of patients
    of either CDH2 or LIN7C disrupts neural tube formation
    loss of CDH2 alters the actin cytoskeleton, leading to a decrease in the cortical actin-binding protein, CTTN, which associates with KCNA5 channel and regulates its function in the heart
    tumoral     --low  
    by promoter methylation in colorectal cancer patients
    constitutional     --over  
    partially attenuated nucleus pulposus (NP) cell senescence, decreased ROS content and inhibited the activation of the NFKB1 pathway under the high glucose condition
    Variant & Polymorphism
    Candidate gene
    Therapy target
    diabetetype 2 
    is a potential therapeutic target to slow Diabetes-mediated disc nucleus pulposus (NP) degeneration
  • Homozygous N-cadherin mutant embryos die by Day 10 of gestation
  • in adult mice loss of N-cadherin in osteolineage cells favors bone formation