Details for: CDH8

Gene ID: 1006

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: CDH8

Ensembl ID: ENSG00000150394

Description: cadherin 8

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • sst GABAergic cortical interneuron CL4023017
    CSI 39.12
    rCSI 50.43%
    PRS 98.81
  • VIP GABAergic cortical interneuron CL4023016
    CSI 33.94
    rCSI 40.55%
    PRS 98.49
  • sncg GABAergic cortical interneuron CL4023015
    CSI 29.91
    rCSI 48.1%
    PRS 98.36
  • interneuron CL0000099
    CSI 25.09
    rCSI 50.37%
    PRS 99.12
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 24.17
    rCSI 27.91%
    PRS 98.96
  • retinal bipolar neuron CL0000748
    CSI 22.71
    rCSI 42.54%
    PRS 98.56
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 22.62
    rCSI 37.97%
    PRS 98.62
  • inhibitory interneuron CL0000498
    CSI 22.48
    rCSI 51.88%
    PRS 98.64
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 22.16
    rCSI 27.57%
    PRS 98.24
  • L4 intratelencephalic projecting glutamatergic neuron CL4030063
    CSI 21.08
    rCSI 50.42%
    PRS 97.97
  • L2/3 intratelencephalic projecting glutamatergic neuron CL4030059
    CSI 20.22
    rCSI 43.86%
    PRS 97.67
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 20.09
    rCSI 35.48%
    PRS 98.51
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 19.33
    rCSI 46.99%
    PRS 97.92
  • glioblast CL0000030
    CSI 19.24
    rCSI 30.68%
    PRS 98.83
  • ON-bipolar cell CL0000749
    CSI 17.98
    rCSI 26.73%
    PRS 99.19
  • neuron CL0000540
    CSI 17.5
    rCSI 46.61%
    PRS 97.48
  • cerebral cortex neuron CL0010012
    CSI 16.95
    rCSI 69.07%
    PRS 98.53
  • neural cell CL0002319
    CSI 15.81
    rCSI 59.67%
    PRS 97.54
  • amacrine cell CL0000561
    CSI 15.27
    rCSI 44.25%
    PRS 98.65
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 14.31
    rCSI 54.08%
    PRS 98.13
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 13.24
    rCSI 47.64%
    PRS 98.17
  • interstitial cell of Cajal CL0002088
    CSI 12.26
    rCSI 15.61%
    PRS 99.92
  • cerebellar granule cell CL0001031
    CSI 12
    rCSI 17.63%
    PRS 98.82
  • L5/6 near-projecting glutamatergic neuron CL4030067
    CSI 11.92
    rCSI 39.18%
    PRS 97.71
  • L6b glutamatergic cortical neuron CL4023038
    CSI 11.77
    rCSI 36.79%
    PRS 98.48
  • glutamatergic neuron CL0000679
    CSI 11.72
    rCSI 24.09%
    PRS 97.12
  • blood vessel endothelial cell CL0000071
    CSI 11.64
    rCSI 24.15%
    PRS 99.55
  • diffuse bipolar 6 cell CL4033032
    CSI 11.01
    rCSI 57.88%
    PRS 97.52
  • GABAergic amacrine cell CL4030027
    CSI 10.69
    rCSI 36.62%
    PRS 97.77
  • enteric smooth muscle cell CL0002504
    CSI 10.6
    rCSI 15.13%
    PRS 99.75
  • vascular leptomeningeal cell CL4023051
    CSI 10.52
    rCSI 18.44%
    PRS 99.24
  • astrocyte CL0000127
    CSI 10.22
    rCSI 21.78%
    PRS 97.45
  • OFF-bipolar cell CL0000750
    CSI 9.46
    rCSI 12.93%
    PRS 99.13
  • OFFx cell CL4033036
    CSI 9.22
    rCSI 43.37%
    PRS 97.66
  • GABAergic neuron CL0000617
    CSI 9.07
    rCSI 30.39%
    PRS 96.9
  • serotonergic neuron CL0000850
    CSI 8.83
    rCSI 39.45%
    PRS 97.04
  • dopaminergic neuron CL0000700
    CSI 8.57
    rCSI 48.43%
    PRS 98.12
  • peripheral nervous system neuron CL2000032
    CSI 8.35
    rCSI 11.37%
    PRS 99.14
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 8.24
    rCSI 48.54%
    PRS 98.29
  • differentiation-committed oligodendrocyte precursor CL4023059
    CSI 6.85
    rCSI 12.45%
    PRS 98.94
  • glycinergic amacrine cell CL4030028
    CSI 6.8
    rCSI 17.72%
    PRS 98.49
  • macroglial cell CL0000126
    CSI 6.69
    rCSI 17.19%
    PRS 99.22
  • central nervous system neuron CL2000029
    CSI 5.97
    rCSI 43.85%
    PRS 98.76
  • diffuse bipolar 1 cell CL4033027
    CSI 5.52
    rCSI 41.49%
    PRS 97.57
  • retinal ganglion cell CL0000740
    CSI 5.33
    rCSI 11.78%
    PRS 98.46
  • medium spiny neuron CL1001474
    CSI 4.8
    rCSI 41.32%
    PRS 98.62
  • midbrain dopaminergic neuron CL2000097
    CSI 4.15
    rCSI 26.59%
    PRS 98.59
  • ON parasol ganglion cell CL4033052
    CSI 3.45
    rCSI 48.96%
    PRS 98.5
  • GABAergic interneuron CL0011005
    CSI 3.11
    rCSI 49.02%
    PRS 99.42
  • diffuse bipolar 3a cell CL4033029
    CSI 2.92
    rCSI 19.88%
    PRS 97.9
  • direct pathway medium spiny neuron CL4023026
    CSI 2.37
    rCSI 56.7%
    PRS 97.41
  • indirect pathway medium spiny neuron CL4023029
    CSI 2.34
    rCSI 56.52%
    PRS 97.4
  • diffuse bipolar 4 cell CL4033031
    CSI 2.19
    rCSI 25.11%
    PRS 96.55

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [CDH8](/details-gene/1006) (Cadherin 8) is a protein-coding gene located on chromosome 16q21 that encodes a type II classical cadherin. As a member of the cadherin superfamily, [CDH8](/details-gene/1006) is a calcium-dependent cell-cell adhesion molecule primarily involved in the formation and maintenance of adherens junctions. Expression data indicates that [CDH8](/details-gene/1006) is a highly significant gene within the central nervous system, showing prominent and specific expression in a diverse array of neuronal subtypes, particularly cortical interneurons. Its function is critical for processes such as synapse organization and homophilic cell adhesion, suggesting a fundamental role in establishing and maintaining neuronal circuits. ## Cellular Roles and Expression Landscape The expression profile of [CDH8](/details-gene/1006) points to a highly specialized role within the nervous system. **Overall**, the gene exhibits its highest significance in various classes of neurons, establishing it as a key marker for neuronal identity and connectivity. The most significant expression is observed in several distinct subtypes of inhibitory interneurons, including [sst GABAergic cortical interneuron](/details-cell/CL4023017) (CSI: 39.12), [VIP GABAergic cortical interneuron](/details-cell/CL4023016) (CSI: 33.94), and [sncg GABAergic cortical interneuron](/details-cell/CL4023015) (CSI: 29.91). This strong enrichment across multiple GABAergic lineages suggests a conserved and critical function in the development or function of inhibitory circuits in the cortex. In addition to interneurons, [CDH8](/details-gene/1006) is also significantly expressed in excitatory neurons, such as [L4 intratelencephalic projecting glutamatergic neuron](/details-cell/CL4030063) (CSI: 21.08) and [L2/3 intratelencephalic projecting glutamatergic neuron](/details-cell/CL4030059) (CSI: 20.22). Its presence in both excitatory and inhibitory populations suggests a role in mediating specific connections between these neuronal types. Furthermore, significant expression is noted in [retinal bipolar neuron](/details-cell/CL0000748) (CSI: 22.71), highlighting its broader importance in mediating cell-cell interactions across different regions of the nervous system, a finding consistent with early studies on cadherin diversity in nervous tissue ([Link](https://doi.org/10.1091/mbc.2.4.261)). ## Pathways and Molecular Function The molecular functions of [CDH8](/details-gene/1006) are intrinsically linked to its role as a cell adhesion molecule. Gene Ontology annotations confirm its involvement in [calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules](/details-cell/GO:0016339) and [homophilic cell adhesion via plasma membrane adhesion molecules](/details-cell/GO:0007156). Its function is structurally dependent on [calcium ion binding](/details-cell/GO:0005509), a hallmark of the cadherin family. Consistent with its high expression in neurons, [CDH8](/details-gene/1006) is implicated in processes vital for neural circuit formation, including [regulation of synapse organization](/details-cell/GO:0050807) and [synaptic transmission, glutamatergic](/details-cell/GO:0035249). At the subcellular level, the protein is localized to the [plasma membrane](/details-cell/GO:0005886) and is a key component of the [adherens junction](/details-cell/GO:0005912), particularly at the [glutamatergic synapse](/details-cell/GO:0098978). Reactome pathway analysis further reinforces this role, placing [CDH8](/details-gene/1006) within the frameworks of [Adherens junctions interactions](/details-pathway/R-HSA-418990) and [Cell-cell communication](/details-pathway/R-HSA-1500931). Its participation in the regulation of type II classical cadherins ([R-HSA-9764260](https://reactome.org/content/detail/R-HSA-9764260)) highlights its integration into the broader network of cadherin-mediated adhesion that governs tissue architecture and cell sorting during development. ## Research Directions The specific and high-level expression of [CDH8](/details-gene/1006) across diverse but specific neuronal populations presents several avenues for future research into the molecular mechanisms of neural circuit assembly and function. **Proposed Hypotheses:** 1. Given its high significance in multiple, distinct GABAergic interneuron subtypes ([sst GABAergic cortical interneuron](/details-cell/CL4023017), [VIP GABAergic cortical interneuron](/details-cell/CL4023016), [pvalb GABAergic cortical interneuron](/details-cell/CL4023018)), [CDH8](/details-gene/1006) may function as a molecular code that dictates the laminar targeting and synaptic partner selection of these inhibitory neurons within cortical columns. 2. The co-expression of [CDH8](/details-gene/1006) in both glutamatergic projection neurons and specific interneurons suggests that [CDH8](/details-gene/1006)-mediated homophilic or heterophilic adhesion is a key mechanism for establishing and maintaining the precise balance of excitatory and inhibitory synapses onto cortical pyramidal cells. Dysregulation of this mechanism could contribute to circuit imbalances seen in neurodevelopmental disorders. **Experimental Approach:** To test the hypothesis that [CDH8](/details-gene/1006) dictates synaptic partner selection for interneurons, a conditional knockout (cKO) mouse model could be employed. By crossing a `Cdh8-floxed` mouse line with a Cre-driver line specific to a major interneuron class (e.g., `Sst-Cre`), [CDH8](/details-gene/1006) can be selectively ablated in somatostatin-positive interneurons. Subsequent analysis using a combination of slice electrophysiology (paired recordings) and high-resolution microscopy (e.g., array tomography or expansion microscopy) would allow for a quantitative assessment of changes in synaptic connectivity, dendritic arborization, and axonal targeting of the affected interneurons compared to control animals. **Therapeutic Potential:** Direct therapeutic targeting of [CDH8](/details-gene/1006) is challenging due to its fundamental role as a structural adhesion molecule in the central nervous system. However, given its specific role in synapse organization and neuronal connectivity, its dysregulation could be a contributing factor to the pathophysiology of neurodevelopmental or psychiatric disorders associated with altered brain wiring, such as autism spectrum disorder or schizophrenia. While not a conventional drug target for inhibition or activation, [CDH8](/details-gene/1006) and its downstream signaling partners could serve as important biomarkers for such conditions or represent nodes in a pathway that could be modulated by more targeted therapeutic strategies.

Genular Protein ID: 4066201777

Symbol: CADH8_HUMAN

Name: Cadherin-8

UniProtKB Accession Codes:

P55286 B3KWC1 Q14DC6 Q9ULB2

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 4 Ensembl 1 ExpressionAtlas 1 GO 22 Gene3D 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 6 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRINTS 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 2 RefSeq 1 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TopDownProteomics 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 10861224

Title: Identification of three human type-II classic cadherins and frequent heterophilic interactions between different subclasses of type-II classic cadherins.

PubMed ID: 10861224

DOI: 10.1042/0264-6021:3490159

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 7982033

Title: Cloning of five human cadherins clarifies characteristic features of cadherin extracellular domain and provides further evidence for two structurally different types of cadherin.

PubMed ID: 7982033

DOI: 10.3109/15419069409014199

PubMed ID: 2059658

Title: Diversity of the cadherin family: evidence for eight new cadherins in nervous tissue.

PubMed ID: 2059658

DOI: 10.1091/mbc.2.4.261

Sequence Information:

  • Length: 799
  • Mass: 88253
  • Checksum: 9B119B86039C6A0A
  • Sequence:
    • MPERLAEMLL DLWTPLIILW ITLPPCIYMA PMNQSQVLMS GSPLELNSLG EEQRILNRSK 
RGWVWNQMFV LEEFSGPEPI LVGRLHTDLD PGSKKIKYIL SGDGAGTIFQ INDVTGDIHA 
IKRLDREEKA EYTLTAQAVD WETSKPLEPP SEFIIKVQDI NDNAPEFLNG PYHATVPEMS 
ILGTSVTNVT ATDADDPVYG NSAKLVYSIL EGQPYFSIEP ETAIIKTALP NMDREAKEEY 
LVVIQAKDMG GHSGGLSGTT TLTVTLTDVN DNPPKFAQSL YHFSVPEDVV LGTAIGRVKA 
NDQDIGENAQ SSYDIIDGDG TALFEITSDA QAQDGIIRLR KPLDFETKKS YTLKVEAANV 
HIDPRFSGRG PFKDTATVKI VVEDADEPPV FSSPTYLLEV HENAALNSVI GQVTARDPDI 
TSSPIRFSID RHTDLERQFN INADDGKITL ATPLDRELSV WHNITIIATE IRNHSQISRV 
PVAIKVLDVN DNAPEFASEY EAFLCENGKP GQVIQTVSAM DKDDPKNGHY FLYSLLPEMV 
NNPNFTIKKN EDNSLSILAK HNGFNRQKQE VYLLPIIISD SGNPPLSSTS TLTIRVCGCS 
NDGVVQSCNV EAYVLPIGLS MGALIAILAC IILLLVIVVL FVTLRRHKNE PLIIKDDEDV 
RENIIRYDDE GGGEEDTEAF DIATLQNPDG INGFLPRKDI KPDLQFMPRQ GLAPVPNGVD 
VDEFINVRLH EADNDPTAPP YDSIQIYGYE GRGSVAGSLS SLESTTSDSD QNFDYLSDWG 
PRFKRLGELY SVGESDKET