Details for: PCDH8

Gene ID: 5100

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: PCDH8

Ensembl ID: ENSG00000136099

Description: protocadherin 8

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • interneuron CL0000099
    CSI 3.76
    rCSI 7.55%
    PRS 82.42
  • radial glial cell CL0000681
    CSI 2.68
    rCSI 3.73%
    PRS 87.57
  • retinal bipolar neuron CL0000748
    CSI 2.59
    rCSI 4.85%
    PRS 79.96
  • sncg GABAergic cortical interneuron CL4023015
    CSI 2.58
    rCSI 4.15%
    PRS 76.24
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 2.33
    rCSI 7.29%
    PRS 78.36
  • VIP GABAergic cortical interneuron CL4023016
    CSI 2.04
    rCSI 2.44%
    PRS 75.19
  • peripheral nervous system neuron CL2000032
    CSI 2.01
    rCSI 2.73%
    PRS 82.38
  • cerebral cortex GABAergic interneuron CL0010011
    CSI 1.98
    rCSI 5.84%
    PRS 89.35
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 1.89
    rCSI 6.81%
    PRS 73.04
  • cerebral cortex neuron CL0010012
    CSI 1.86
    rCSI 7.56%
    PRS 81.66
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.78
    rCSI 3.14%
    PRS 74.6
  • sst GABAergic cortical interneuron CL4023017
    CSI 1.74
    rCSI 2.24%
    PRS 76.26
  • L2/3 intratelencephalic projecting glutamatergic neuron CL4030059
    CSI 1.67
    rCSI 3.61%
    PRS 77.74
  • inhibitory interneuron CL0000498
    CSI 1.49
    rCSI 3.43%
    PRS 79.52
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 0.93
    rCSI 2.27%
    PRS 72.81
  • central nervous system neuron CL2000029
    CSI 0.26
    rCSI 1.95%
    PRS 79.89

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.

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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 [PCDH8](/details-gene/5100), or protocadherin 8, is a protein-coding gene located on chromosome 13q14.3. It belongs to the protocadherin family, a large group of calcium-dependent cell-adhesion molecules that play critical roles in the establishment and function of neural circuits [Link](https://doi.org/10.1006/geno.1998.5467). Functional annotations link [PCDH8](/details-gene/5100) to processes such as homophilic cell adhesion ([GO:0007156](https://www.ebi.ac.uk/QuickGO/term/GO:0007156)) and the modulation of chemical synaptic transmission ([GO:0050804](https://www.ebi.ac.uk/QuickGO/term/GO:0050804)). Its expression profile is highly specific to the nervous system, with a particularly high significance score in [interneurons](/details-cell/CL0000099), suggesting a key role in regulating neuronal connectivity and synaptic integrity. ## Cellular Roles and Expression Landscape The expression pattern of [PCDH8](/details-gene/5100) strongly indicates a specialized function within the central nervous system. **Overall**, the gene shows its highest significance in various neuronal subtypes. It is a defining marker for [interneurons](/details-cell/CL0000099) (CSI: 3.76), including specific subpopulations such as [sncg GABAergic cortical interneurons](/details-cell/CL4023015) and [chandelier pvalb GABAergic cortical interneurons](/details-cell/CL4023036). This suggests a fundamental role in establishing or maintaining the identity and connectivity of inhibitory circuits in the cortex. Beyond interneurons, [PCDH8](/details-gene/5100) is also highly significant in [radial glial cells](/details-cell/CL0000681) (CSI: 2.68), which are crucial for neuronal guidance during development. High significance is also observed in [retinal bipolar neurons](/details-cell/CL0000748) and various glutamatergic projecting neurons, such as [L5 extratelencephalic projecting glutamatergic cortical neurons](/details-cell/CL4023041). This broad yet specific expression across diverse neuronal populations underscores its importance in the general architecture and function of neural networks. The consistent high expression in these cell types suggests that [PCDH8](/details-gene/5100) functions as a stable molecular component of neuronal and glial cell membranes rather than a dynamically regulated gene. ## Pathways and Molecular Function The molecular functions of [PCDH8](/details-gene/5100) are intrinsically linked to its role as a cell adhesion molecule. Its annotation for calcium ion binding ([GO:0005509](https://www.ebi.ac.uk/QuickGO/term/GO:0005509)) is characteristic of the cadherin superfamily and essential for its adhesive properties. The gene's primary biological processes involve cell-cell interactions, including homophilic cell adhesion ([GO:0007156](https://www.ebi.ac.uk/QuickGO/term/GO:0007156)) and the regulation of synaptic functions ([GO:0007268](https://www.ebi.ac.uk/QuickGO/term/GO:0007268), [GO:0099179](https://www.ebi.ac.uk/QuickGO/term/GO:0099179)). Cellular component analysis localizes the [PCDH8](/details-gene/5100) protein to critical sites of neuronal communication, including the [plasma membrane](/details-cell/GO:0005886), [dendrites](/details-cell/GO:0030425), and both [presynaptic](/details-cell/GO:0042734) and [postsynaptic membranes](/details-cell/GO:0045211). Its specific enrichment in [glutamatergic synapses](/details-cell/GO:0098978) and [Schaffer collateral - ca1 synapses](/details-cell/GO:0098685) is highly consistent with its significant expression in glutamatergic neurons and its proposed role in synaptic organization and transmission. This evidence collectively points to [PCDH8](/details-gene/5100) as a key molecule in mediating the physical connections that underpin the stability and specificity of synaptic contacts in the brain. ## Research Directions The specific enrichment of [PCDH8](/details-gene/5100) in neuronal subtypes, particularly inhibitory [interneurons](/details-cell/CL0000099), coupled with its known role in cell adhesion, suggests that its dysregulation could contribute to neurological or psychiatric disorders characterized by synaptic dysfunction. Prior research has already explored its potential association with schizophrenia [Link](https://doi.org/10.1034/j.1601-183x.2002.10307.x). Based on the available data, several testable hypotheses can be proposed: 1. **Hypothesis 1:** Given its role in homophilic cell adhesion and high expression in GABAergic [interneurons](/details-cell/CL0000099), loss-of-function mutations in [PCDH8](/details-gene/5100) may lead to a reduction in inhibitory synapse density or stability. This could disrupt the excitatory/inhibitory balance in cortical circuits, a key pathological feature in conditions like epilepsy and schizophrenia. 2. **Hypothesis 2:** The high significance of [PCDH8](/details-gene/5100) in [radial glial cells](/details-cell/CL0000681) suggests a role in neurodevelopment. It is plausible that [PCDH8](/details-gene/5100) mediates the adhesion between radial glia and migrating neurons, and its disruption could lead to defects in cortical lamination and neuronal positioning. To test the first hypothesis, a compelling experimental approach would be to use a conditional knockout mouse model. Specifically, one could employ a Cre-Lox system to selectively delete *Pcdh8* in a specific interneuron subpopulation (e.g., parvalbumin-positive interneurons). Subsequent analysis using slice electrophysiology could directly measure changes in inhibitory postsynaptic currents (IPSCs), while super-resolution microscopy could be used to quantify the number and morphology of inhibitory synapses onto pyramidal neurons. Given its fundamental role in maintaining the structural integrity of synapses across many neuronal types, [PCDH8](/details-gene/5100) appears to be a challenging therapeutic target. Direct inhibition could lead to widespread disruption of neural circuits, causing significant off-target effects. Therefore, therapeutic strategies are unlikely to involve direct targeting of the protein. However, a deeper understanding of the signaling pathways regulated by [PCDH8](/details-gene/5100)-mediated adhesion could reveal more druggable downstream effectors that modulate synaptic function.

Genular Protein ID: 1612153933

Symbol: PCDH8_HUMAN

Name: Protocadherin-8

UniProtKB Accession Codes:

O95206 B4DMV7 Q5TAN1 Q5TAN2 Q8IYE9 Q96SF1

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 7 Ensembl 2 ExpressionAtlas 1 GO 15 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 5 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 1 PDBsum 1 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 2 RNAct 1 RefSeq 2 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 9787079

Title: Characterization of two novel protocadherins (PCDH8 and PCDH9) localized on human chromosome 13 and mouse chromosome 14.

PubMed ID: 9787079

DOI: 10.1006/geno.1998.5467

PubMed ID: 11230163

Title: Comparative DNA sequence analysis of mouse and human protocadherin gene clusters.

PubMed ID: 11230163

DOI: 10.1101/gr.167301

PubMed ID: 15057823

Title: The DNA sequence and analysis of human chromosome 13.

PubMed ID: 15057823

DOI: 10.1038/nature02379

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: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 12884975

Title: Screening the human protocadherin 8 (PCDH8) gene in schizophrenia.

PubMed ID: 12884975

DOI: 10.1034/j.1601-183x.2002.10307.x

PubMed ID: 16959974

Title: The consensus coding sequences of human breast and colorectal cancers.

PubMed ID: 16959974

DOI: 10.1126/science.1133427

Sequence Information:

  • Length: 1070
  • Mass: 113019
  • Checksum: CBCCE3C43C0E02D8
  • Sequence:
    • MSPVRRWGSP CLFPLQLFSL CWVLSVAQSK TVRYSTFEED APGTVIGTLA EDLHMKVSGD 
TSFRLMKQFN SSLLRVREGD GQLTVGDAGL DRERLCGQAP QCVLAFDVVS FSQEQFRLVH 
VEVEVRDVND HAPRFPRAQI PVEVSEGAAV GTRIPLEVPV DEDVGANGLQ TVRLAEPHSP 
FRVELQTRAD GAQCADLVLL QELDRESQAA YSLELVAQDG GRPPRSATAA LSVRVLDAND 
HSPAFPQGAV AEVELAEDAP VGSLLLDLDA ADPDEGPNGD VVFAFGARTP PEARRLFRLD 
PRSGRLTLAG PVDYERQDTY ELDVRAQDRG PGPRAATCKV IVRIRDVNDN APDIAITPLA 
APGAPATSPF AAAAAAAALG GADASSPAGA GTPEAGATSL VPEGAARESL VALVSTSDRD 
SGANGQVRCA LYGHEHFRLQ PAYAGSYLVV TAASLDRERI AEYNLTLVAE DRGAPPLRTV 
RPYTVRVGDE NDNAPLFTRP VYEVSVRENN PPGAYLATVA ARDRDLGRNG QVTYRLLEAE 
VGRAGGAVST YVSVDPATGA IYALRSFDYE TLRQLDVRIQ ASDGGSPQLS SSALVQVRVL 
DQNDHAPVLV HPAPANGSLE VAVPGRTAKD TVVARVQARD ADEGANGELA FELQQQEPRE 
AFAIGRRTGE ILLTGDLSQE PPGRVFRALL VISDGGRPPL TTTATVSFVV TAGGGRGPAA 
PASAGSPERS RPPGSRLGVS GSVLQWDTPL IVIIVLAGSC TLLLAAIIAI ATTCNRRKKE 
VRKGGALREE RPGAAGGGAS APGSPEEAAR GAGPRPNMFD VLTFPGTGKA PFGSPAADAP 
PPAVAAAEVP GSEGGSATGE SACHFEGQQR LRGAHAEPYG ASPGFGKEPA PPVAVWKGHS 
FNTISGREAE KFSGKDSGKG DSDFNDSDSD ISGDALKKDL INHMQSGLWA CTAECKILGH 
SDRCWSPSCS GPNAHPSPHP PAQMSTFCKS TSLPRDPLRR DNYYQAQLPK TVGLQSVYEK 
VLHRDYDRTV TLLSPPRPGR LPDLQEIGVP LYQSPPGRYL SPKKGANENV