Details for: PCDHGB5

Gene ID: 56101

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: PCDHGB5

Ensembl ID: ENSG00000276547

Description: protocadherin gamma subfamily B, 5

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • GABAergic neuron CL0000617
    CSI 18.41
    rCSI 61.67%
    PRS 99.79
  • glutamatergic neuron CL0000679
    CSI 17.88
    rCSI 36.75%
    PRS 99.78
  • dopaminergic neuron CL0000700
    CSI 10.49
    rCSI 59.28%
    PRS 99.9
  • serotonergic neuron CL0000850
    CSI 9.03
    rCSI 40.33%
    PRS 99.86
  • basal cell of epidermis CL0002187
    CSI 9.01
    rCSI 15.96%
    PRS 99.91
  • brain vascular cell CL4023072
    CSI 7.02
    rCSI 72.61%
    PRS 99.87
  • cerebellar neuron CL1001611
    CSI 6.65
    rCSI 58.53%
    PRS 99.8

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 [PCDHGB5](/details-gene/56101) is a protein-coding gene that encodes Protocadherin gamma-B5, a member of the large cadherin superfamily of proteins known for mediating calcium-dependent cell-cell adhesion. As part of the protocadherin gamma gene cluster, [PCDHGB5](/details-gene/56101) plays a crucial role in the complex processes of neural circuit formation and synaptic specificity during nervous system development, a function established in foundational research on this gene family [Link](https://doi.org/10.1016/s0092-8674(00)80789-8). Expression data reveals its profound significance across a wide array of neuronal subtypes, including both excitatory and inhibitory neurons, underscoring its fundamental role in establishing and maintaining the intricate architecture of the central nervous system. ## Cellular Roles and Expression Landscape **Overall**, the expression profile of [PCDHGB5](/details-gene/56101) is predominantly concentrated within the nervous system, where it serves as a key marker for multiple neuronal populations. The gene exhibits exceptionally high significance in [GABAergic neuron](/details-cell/CL0000617) (CSI: 18.41) and [glutamatergic neuron](/details-cell/CL0000679) (CSI: 17.88), the primary inhibitory and excitatory neurons in the brain, respectively. This suggests a fundamental role for [PCDHGB5](/details-gene/56101) in establishing the balance and connectivity of core neural circuits. Its high significance extends to more specialized neuronal subtypes, including [dopaminergic neuron](/details-cell/CL0000700) (CSI: 10.49), [serotonergic neuron](/details-cell/CL0000850) (CSI: 9.03), and [cerebellar neuron](/details-cell/CL1001611) (CSI: 6.65), indicating its broad involvement across diverse functional domains of the brain, from motor control and mood regulation to cognition. Beyond its primary neuronal roles, [PCDHGB5](/details-gene/56101) also shows notable significance in non-neuronal cell types such as the [basal cell of epidermis](/details-cell/CL0002187) (CSI: 9.01) and [brain vascular cell](/details-cell/CL4023072) (CSI: 7.02). Its expression in epidermal basal cells suggests a potential function in skin tissue adhesion and stratification, while its presence in brain vascular cells may imply a role in maintaining the integrity of the blood-brain barrier. ## Pathways and Molecular Function The molecular functions attributed to [PCDHGB5](/details-gene/56101) are highly consistent with its observed cellular expression pattern. Its primary annotated roles are in [Cell adhesion](/details-cell/GO:0007155) and, more specifically, [Homophilic cell adhesion via plasma membrane adhesion molecules](/details-cell/GO:0007156). This function is critical for its involvement in [Nervous system development](/details-cell/GO:0007399), where it helps guide neuron-neuron recognition and synapse formation. Mechanistically, its function is dependent on [Calcium ion binding](/details-cell/GO:0005509), a hallmark of the cadherin protein family. As a transmembrane protein, it is localized to the [Plasma membrane](/details-cell/GO:0005886), where it directly mediates intercellular contact. An intriguing annotation is its association with the [Extracellular exosome](/details-cell/GO:0070062), suggesting that [PCDHGB5](/details-gene/56101) or its fragments may be packaged into exosomes, potentially participating in intercellular signaling pathways beyond direct cell-cell contact. ## Research Directions The widespread yet specific expression of [PCDHGB5](/details-gene/56101) across diverse neuronal populations, as well as in non-neuronal tissues, opens up several avenues for future investigation. ### Proposed Hypotheses 1. **Role in Synaptic Specificity:** Given its high expression in both [GABAergic neuron](/details-cell/CL0000617) and [glutamatergic neuron](/details-cell/CL0000679), it is hypothesized that [PCDHGB5](/details-gene/56101) contributes to the specific wiring of inhibitory and excitatory circuits, respectively. Its loss may lead to distinct and measurable defects in synapse formation, pruning, or stability that are circuit-dependent. 2. **Function in Epidermal Integrity:** The significant expression in [basal cell of epidermis](/details-cell/CL0002187) suggests a role beyond the nervous system. We hypothesize that [PCDHGB5](/details-gene/56101) is essential for maintaining cell-cell adhesion at the dermal-epidermal junction and that its disruption could lead to skin blistering or barrier-related pathologies. 3. **Exosome-Mediated Neuronal Communication:** The association with exosomes ([GO:0070062](https://www.ebi.ac.uk/QuickGO/term/GO:0070062)) suggests a non-canonical function. It is hypothesized that fragments of [PCDHGB5](/details-gene/56101) are released in exosomes from neurons and act as signaling molecules that influence the maturation or function of recipient cells, such as glial cells or distal neurons. ### Key Experimental Approach To test the hypothesis regarding its role in synaptic specificity (Hypothesis 1), a powerful approach would be to generate cell-type-specific conditional knockout mice. By crossing a `Pcdhgb5-floxed` mouse with Cre-driver lines specific for either GABAergic neurons (e.g., *Gad2-Cre*) or glutamatergic neurons (e.g., *Vglut2-Cre*), one could selectively delete the gene in either inhibitory or excitatory populations. The resulting phenotypes could be assessed using a combination of techniques: patch-clamp electrophysiology to measure synaptic currents and plasticity, and super-resolution microscopy (e.g., STED or STORM) with synaptic markers to quantify changes in synapse density and morphology in specific brain regions. ### Therapeutic Potential The therapeutic potential of targeting [PCDHGB5](/details-gene/56101) directly is likely limited, as it is a key component of normal neurodevelopment and tissue architecture. Global inhibition or activation could have widespread and detrimental off-target effects. However, its dysregulation is implicated in neurodevelopmental and psychiatric disorders characterized by altered synaptic connectivity. In this context, [PCDHGB5](/details-gene/56101) could serve as a valuable biomarker. Furthermore, for monogenic disorders caused by loss-of-function mutations in this gene, gene therapy aimed at restoring its expression in the appropriate neuronal circuits could represent a viable, albeit challenging, therapeutic strategy.

Genular Protein ID: 1744458349

Symbol: PCDGH_HUMAN

Name: Protocadherin gamma-B5

UniProtKB Accession Codes:

Q9Y5G0 Q52LK8 Q9Y5C6

Database IDs:

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 5 Ensembl 2 GO 6 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyConnect 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 7 KEGG 1 MANE-Select 1 MIM 2 MINT 1 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 RNAct 1 RefSeq 2 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 SwissPalm 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

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

Sequence Information:

  • Length: 923
  • Mass: 99875
  • Checksum: 2CC42DDF7D80CC60
  • Sequence:
    • MGSGAGELGR AERLPVLFLF LLSLFCPALC EQIRYRIPEE MPKGSVVGNL ATDLGFSVQE 
LPTRKLRVSS EKPYFTVSAE SGELLVSSRL DREEICGKKP ACALEFEAVA ENPLNFYHVN 
VEIEDINDHT PKFTQNSFEL QISESAQPGT RFILEVAEDA DIGLNSLQKY KLSLNPSFSL 
IIKEKQDGSK YPELALEKTL DREQQSYHRL VLTALDGGHP PLSGTTELRI QVTDANDNPP 
VFNRDVYRVS LRENVPPGTT VLQVSATDQD EGINSEITYS FYRTGQIFSL NSKSGEITTQ 
KKLDFEETKE YSMVVEGRDG GGLVAQCTVE INIQDENDNS PEVTFHSLLE MILENAVPGT 
LIALIKIHDQ DSGENGEVNC QLQGEVPFKI ISSSKNSYKL VTDGTLDREQ TPEYNVTITA 
TDRGKPPLSS SISVILHIRD VNDNAPVFHQ ASYLVSVPEN NPPGASIAQV CASDLDLGLN 
GQVSYSIMAS DLEPLALASY VSMSAQSGVV FAQRAFDYEQ LRTFELTLQA RDQGSPALSA 
NVSLRVLVGD RNDNAPRVLY PALGPDGSAL FDMVPRAAEP GYLVTKVVAV DADSGHNAWL 
SYHVLQASEP GLFSLGLRTG EVRTARALGD RDAARQRLLV AVRDGGQPPL SATATLHLVF 
ADSLQEVLPD ITDRPVPSDP QAELQFYLVV ALALISVLFL LAVILAVALR LRRSSSPAAW 
SCFQPGLCVK SGPVVPPNYS QGTLPYSYNL CVAHTGKTEF NFLKCSEQLS SGQDILCGDS 
SGALFPLCNS SESTSHPELQ APPNTDWRFS QAQRPGTSGS QNGDDTGTWP NNQFDTEMLQ 
AMILASASEA ADGSSTLGGG AGTMGLSARY GPQFTLQHVP DYRQNVYIPG SNATLTNAAG 
KRDGKAPAGG NGNKKKSGKK EKK