Details for: PCDHGC3

Gene ID: 5098

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: PCDHGC3

Ensembl ID: ENSG00000240184

Description: protocadherin gamma subfamily C, 3

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • glioblast CL0000030
    CSI 3.32
    rCSI 5.3%
    PRS 94.85
  • Bergmann glial cell CL0000644
    CSI 3.05
    rCSI 4.18%
    PRS 94.49
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 2.58
    rCSI 2.99%
    PRS 94.71
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 2.57
    rCSI 3.3%
    PRS 96.61
  • stromal cell CL0000499
    CSI 1.33
    rCSI 3.73%
    PRS 96.67

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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  • 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 [PCDHGC3](/details-gene/5098) (Protocadherin Gamma Subfamily C, 3) is a protein-coding gene located on chromosome 5q31.3. As a member of the protocadherin family, a large group of cadherin-related molecules, it functions primarily in calcium-dependent cell-cell adhesion. Functional annotations and expression data strongly suggest a specialized role for [PCDHGC3](/details-gene/5098) in the central nervous system, particularly in mediating homophilic adhesion, organizing synapses, and regulating neuronal apoptosis. **Overall**, its expression is most significant in cell types of neural origin, including [glioblast](/details-cell/CL0000030), [Bergmann glial cell](/details-cell/CL0000644), and [neuroblasts](/details-cell/CL0000338), highlighting its importance in both mature glial cell function and neural development. ## Cellular Roles and Expression Landscape The expression profile of [PCDHGC3](/details-gene/5098) demonstrates a highly specific role within the nervous system. The gene shows its highest significance in [glioblast](/details-cell/CL0000030) (CSI: 3.32), a cell type associated with the most common and aggressive type of primary brain tumor, and [Bergmann glial cell](/details-cell/CL0000644) (CSI: 3.05), a specialized astrocyte critical for cerebellar development and function. Furthermore, [PCDHGC3](/details-gene/5098) is a significant marker for developing neurons, as evidenced by its high scores in both [neuroblast (sensu Nematoda and Protostomia)](/details-cell/CL0000338) (CSI: 2.58) and [neuroblast (sensu Vertebrata)](/details-cell/CL0000031) (CSI: 2.57). This pattern suggests that the gene's function in cell-cell adhesion is fundamental for the migration, differentiation, and survival of neuronal precursors. Its moderate significance in [stromal cell](/details-cell/CL0000499) (CSI: 1.33) may indicate a broader, albeit less prominent, role in tissue architecture outside the CNS. The concentration of high-CSI cells within the neural lineage points to a specialized function in establishing and maintaining the complex cellular organization of the brain. ## Pathways and Molecular Function [PCDHGC3](/details-gene/5098) encodes a transmembrane protein that localizes to the [plasma membrane](/details-go/GO:0005886), where it participates in several key biological processes. Its primary molecular function involves [calcium ion binding](/details-go/GO:0005509), which is essential for its role in '[Calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules](/details-go/GO:0016339)'. This activity is consistent with the general function of protocadherins in the central nervous system, as described in foundational research ([Link](https://doi.org/10.1002/j.1460-2075.1993.tb05878.x)). The gene's involvement in '[Homophilic cell adhesion via plasma membrane adhesion molecules](/details-go/GO:0007156)' is critical for its roles in '[nervous system development](/details-go/GO:0007399)' and '[synapse organization](/details-go/GO:0050808)'. This suggests [PCDHGC3](/details-gene/5098) helps mediate the precise connections between neurons and glial cells required for proper neural circuit formation. Additionally, its participation in the '[negative regulation of neuron apoptotic process](/details-go/GO:0043524)' indicates a pro-survival function, which is consistent with its high expression in progenitor [neuroblasts](/details-cell/CL0000338) that must survive to differentiate and integrate into neural networks. ## Research Directions The specific expression pattern of [PCDHGC3](/details-gene/5098) in neural cells, particularly its high significance in glioblastoma, raises important questions about its role in both normal physiology and brain pathology. Based on the available data, several testable hypotheses can be proposed: 1. **Hypothesis 1:** Given its high expression in [glioblast](/details-cell/CL0000030) and its function in cell adhesion, aberrant expression or function of [PCDHGC3](/details-gene/5098) may disrupt normal cell-cell contacts, contributing to the invasive phenotype of glioblastoma tumors. It might mediate adhesion between tumor cells, promoting collective invasion. 2. **Hypothesis 2:** The role of [PCDHGC3](/details-gene/5098) in preventing neuronal apoptosis and its high expression in [neuroblasts](/details-cell/CL0000338) suggests it is a critical survival factor for neuronal progenitors during corticogenesis. Loss of its function could lead to developmental defects characterized by excessive cell death in the developing brain. A key experiment to test the first hypothesis would be to use CRISPR-Cas9 to knock down or knock out [PCDHGC3](/details-gene/5098) in established glioblastoma cell lines (e.g., U87 or LN-229). The resulting cellular phenotype could be assessed using 3D spheroid invasion assays in a Matrigel matrix, where the extent of single-cell and collective cell migration out of the spheroid would be quantified. Changes in cell-cell junction integrity and expression of other adhesion molecules could be analyzed via immunofluorescence and Western blotting. From a therapeutic standpoint, the high expression of [PCDHGC3](/details-gene/5098) in [glioblast](/details-cell/CL0000030) and its localization on the plasma membrane make it a potentially attractive target. **Inhibition** of its function could be a viable strategy to disrupt tumor cohesion and invasion. Its surface accessibility makes it a candidate for targeted therapies such as antibody-drug conjugates (ADCs) or chimeric antigen receptor (CAR)-T cell therapy, which could specifically target and eliminate glioblastoma cells while potentially sparing other tissues where its expression is lower.

Genular Protein ID: 3982300798

Symbol: PCDGK_HUMAN

Name: Protocadherin gamma-C3

UniProtKB Accession Codes:

Q9UN70 O60622 Q08192 Q9Y5C4

Database IDs:

ABCD 1 AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 1 CTD 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 10 Ensembl 2 ExpressionAtlas 1 GO 9 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 7 KEGG 1 MANE-Select 1 MIM 2 MalaCards 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 4 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 Pumba 1 RNAct 1 RefSeq 2 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 8508762

Title: Protocadherins: a large family of cadherin-related molecules in central nervous system.

PubMed ID: 8508762

DOI: 10.1002/j.1460-2075.1993.tb05878.x

PubMed ID: 9360932

Title: Nonsyndromic deafness DFNA1 associated with mutation of a human homolog of the Drosophila gene diaphanous.

PubMed ID: 9360932

DOI: 10.1126/science.278.5341.1315

PubMed ID: 10380929

Title: A striking organization of a large family of human neural cadherin-like cell adhesion genes.

PubMed ID: 10380929

DOI: 10.1016/s0092-8674(00)80789-8

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: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

Sequence Information:

  • Length: 934
  • Mass: 101077
  • Checksum: 1C8E1EADD485AB10
  • Sequence:
    • MVPEAWRSGL VSTGRVVGVL LLLGALNKAS TVIHYEIPEE REKGFAVGNV VANLGLDLGS 
LSARRFRVVS GASRRFFEVN RETGEMFVND RLDREELCGT LPSCTVTLEL VVENPLELFS 
VEVVIQDIND NNPAFPTQEM KLEISEAVAP GTRFPLESAH DPDVGSNSLQ TYELSRNEYF 
ALRVQTREDS TKYAELVLER ALDREREPSL QLVLTALDGG TPALSASLPI HIKVLDANDN 
APVFNQSLYR ARVLEDAPSG TRVVQVLATD LDEGPNGEII YSFGSHNRAG VRQLFALDLV 
TGMLTIKGRL DFEDTKLHEI YIQAKDKGAN PEGAHCKVLV EVVDVNDNAP EITVTSVYSP 
VPEDAPLGTV IALLSVTDLD AGENGLVTCE VPPGLPFSLT SSLKNYFTLK TSADLDRETV 
PEYNLSITAR DAGTPSLSAL TIVRVQVSDI NDNPPQSSQS SYDVYIEENN LPGAPILNLS 
VWDPDAPQNA RLSFFLLEQG AETGLVGRYF TINRDNGIVS SLVPLDYEDR REFELTAHIS 
DGGTPVLATN ISVNIFVTDR NDNAPQVLYP RPGGSSVEML PRGTSAGHLV SRVVGWDADA 
GHNAWLSYSL LGSPNQSLFA IGLHTGQIST ARPVQDTDSP RQTLTVLIKD NGEPSLSTTA 
TLTVSVTEDS PEARAEFPSG SAPREQKKNL TFYLLLSLIL VSVGFVVTVF GVIIFKVYKW 
KQSRDLYRAP VSSLYRTPGP SLHADAVRGG LMSPHLYHQV YLTTDSRRSD PLLKKPGAAS 
PLASRQNTLR SCDPVFYRQV LGAESAPPGQ QAPPNTDWRF SQAQRPGTSG SQNGDDTGTW 
PNNQFDTEML QAMILASASE AADGSSTLGG GAGTMGLSAR YGPQFTLQHV PDYRQNVYIP 
GSNATLTNAA GKRDGKAPAG GNGNKKKSGK KEKK

Genular Protein ID: 2922955207

Symbol: Q9BR81_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q9BR81

Database IDs:

Antibodypedia 1 Bgee 1 BioGRID-ORCS 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 6 Ensembl 2 GeneTree 1 HGNC 1 HOGENOM 1 IntAct 1 InterPro 1 KEGG 1 NCBI Taxonomy 1 OrthoDB 1 Pfam 2 PharmGKB 1 Proteomes 2 RefSeq 3 SAM 1 UCSC 1 VEuPathDB 1

Citations:

PubMed ID: 11237011

Title: Initial sequencing and analysis of the human genome.

PubMed ID: 11237011

DOI: 10.1038/35057062

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: 15372022

Title: The DNA sequence and comparative analysis of human chromosome 5.

PubMed ID: 15372022

DOI: 10.1038/nature02919

PubMed ID: 15496913

Title: Finishing the euchromatic sequence of the human genome.

PubMed ID: 15496913

DOI: 10.1038/nature03001

Sequence Information:

  • Length: 134
  • Mass: 14071
  • Checksum: 968E142D201C1114
  • Sequence:
    • MVPEAWRSGL QAPPNTDWRF SQAQRPGTSG SQNGDDTGTW PNNQFDTEML QAMILASASE 
AADGSSTLGG GAGTMGLSAR YGPQFTLQHV PDYRQNVYIP GSNATLTNAA GKRDGKAPAG 
GNGNKKKSGK KEKK