Details for: PCDHA10

Gene ID: 56139

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: PCDHA10

Ensembl ID: ENSG00000250120

Description: protocadherin alpha 10

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 2.46
    rCSI 4.34%
    PRS 99.89

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

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    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
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  • 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 [PCDHA10](/details-gene/56139) is a protein-coding gene located on chromosome 5q31.3 that encodes protocadherin alpha-10, a member of the cadherin superfamily of proteins. As a cell-adhesion molecule, its primary function involves mediating calcium-dependent, homophilic cell-cell recognition, a process crucial for tissue development and morphogenesis ([Link](https://doi.org/10.1016/s0092-8674(00)80789-8)). Consistent with this role, functional annotations implicate [PCDHA10](/details-gene/56139) in nervous system and cardiovascular development. **Overall**, expression data highlight its highly specific and significant role in neuronal subtypes, particularly the [caudal ganglionic eminence derived cortical interneuron](/details-cell/CL4023064), suggesting it is a key determinant of cell identity and connectivity within this lineage. ## Cellular Roles and Expression Landscape The expression profile of [PCDHA10](/details-gene/56139) points to a highly specialized function within the central nervous system. **Overall**, its most significant expression is observed in the [caudal ganglionic eminence derived cortical interneuron](/details-cell/CL4023064) (CSI: 2.46), a specific subtype of GABAergic inhibitory neuron that undergoes long-distance tangential migration during brain development. This high specificity suggests that [PCDHA10](/details-gene/56139) is not a general neuronal marker but rather a key molecule involved in establishing the identity, migration, or synaptic patterning of this particular interneuron population. Its role as a homophilic cell adhesion molecule is consistent with a function in enabling these migrating neurons to recognize each other or navigate their environment to reach their final destination in the cerebral cortex. ## Pathways and Molecular Function The molecular functions of [PCDHA10](/details-gene/56139) are centered on its role as a transmembrane adhesion protein. It is annotated as being integral to the [plasma membrane](/details-ontology/GO:0005886) and active at the [cell-cell contact zone](/details-ontology/GO:0044291). Its function is dependent on [calcium ion binding](/details-ontology/GO:0005509), which is characteristic of the cadherin family and essential for maintaining the structural conformation required for adhesion. This molecular machinery enables its participation in several key biological processes: * **Cell Adhesion:** It directly mediates [homophilic cell adhesion via plasma membrane adhesion molecules](/details-ontology/GO:0007156), allowing cells expressing [PCDHA10](/details-gene/56139) to specifically recognize and bind to one another. * **Nervous System Development:** Its high expression in cortical interneurons strongly supports its annotated role in [nervous system development](/details-ontology/GO:0007399), where precise cell-cell recognition is fundamental for neuronal migration, circuit formation, and synaptic specificity. * **Cardiovascular Development:** Annotations also link it to [aorta development](/details-ontology/GO:0035904) and [aortic valve development](/details-ontology/GO:0003176), indicating that its role in orchestrating cell adhesion extends to tissue morphogenesis outside the nervous system. ## Research Directions The specific expression of [PCDHA10](/details-gene/56139) in a distinct migratory neuronal population offers a clear path for future investigation into the molecular control of brain development. ### Proposed Hypotheses 1. **[PCDHA10](/details-gene/56139) is essential for the tangential migration and proper laminar positioning of CGE-derived interneurons.** Its role in homophilic adhesion may be required for these neurons to migrate collectively or to recognize specific migratory corridors. Disruption of [PCDHA10](/details-gene/56139) function would therefore lead to misplacement of these interneurons within the cortical layers, potentially causing circuit imbalances. 2. **[PCDHA10](/details-gene/56139) mediates target-layer recognition or synaptic partner selection for CGE-derived interneurons.** Beyond migration, the protocadherin code is hypothesized to control synaptic specificity. In this context, [PCDHA10](/details-gene/56139) may be critical for ensuring these interneurons form synapses with the correct neuronal partners in the cortex. ### Key Experimental Approach To test the hypothesis that [PCDHA10](/details-gene/56139) is critical for interneuron migration, a loss-of-function study in a developmental model is warranted. A compelling experiment would involve using *in utero* electroporation in mice to introduce a CRISPR-Cas9 or shRNA construct targeting *Pcdha10* into progenitor cells of the caudal ganglionic eminence (CGE) at embryonic day 13.5. A co-electroporated fluorescent reporter (e.g., GFP) would label the affected cells. The brains would then be analyzed at postnatal day 7 to assess the final positioning of the GFP-labeled interneurons. If the hypothesis is correct, knockdown of *Pcdha10* would result in a significant alteration in the laminar distribution of these interneurons compared to controls. ### Therapeutic Potential Given its highly specific expression and fundamental role in neuronal development, the direct therapeutic potential of targeting [PCDHA10](/details-gene/56139) in adults is likely limited. Its function is structural and developmental, making it a poor candidate for small molecule inhibition or activation in mature circuits. However, if mutations or dysregulation of [PCDHA10](/details-gene/56139) are identified as contributing factors in neurodevelopmental disorders associated with interneuron pathology (e.g., certain forms of epilepsy or schizophrenia), it could serve as a valuable diagnostic marker. Furthermore, understanding the pathways it governs could reveal more druggable downstream targets for correcting circuit imbalances.

Genular Protein ID: 3627685327

Symbol: PCDAA_HUMAN

Name: Protocadherin alpha-10

UniProtKB Accession Codes:

Q9Y5I2 A1L493 O75280 Q9NRU2

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 3 CDD 1 CTD 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 5 Ensembl 6 ExpressionAtlas 1 GO 6 Gene3D 1 GeneCards 1 GeneTree 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 2 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 3 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 3 RNAct 1 RefSeq 3 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: 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: 15372022

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

PubMed ID: 15372022

DOI: 10.1038/nature02919

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: 948
  • Mass: 102875
  • Checksum: 8F3C734B05EF4FB8
  • Sequence:
    • MVSRCSCLGV QCLLLSLLLL AAWEVGSGQL HYSVYEEARH GTFVGRIAQD LGLELAELVQ 
RLFRVASKRH GDLLEVNLQN GILFVNSRID REELCGRSVE CSIHLEVIVD RPLQVFHVDV 
EVKDINDNPP RFSVTEQKLS IPESRLLDSR FPLEGASDAD VGENALLTYK LSPNEYFVLD 
IINKKDKDKF PVLVLRKLLD REENPQLKLL LTATDGGKPE FTGSVSLLIL VLDANDNAPI 
FDRPVYEVKM YENQVNQTLV IRLNASDSDE GINKEMMYSF SSLVPPTIRR KFWINERTGE 
IKVNDAIDFE DSNTYEIHVD VTDKGNPPMV GHCTVLVELL DENDNSPEVI VTSLSLPVKE 
DAQVGTVIAL ISVSDHDSGA NGQVTCSLTP HVPFKLVSTY KNYYSLVLDS ALDRERVSAY 
ELVVTARDGG SPPLWATASV SVEVADVNDN APAFAQSEYT VFVKENNPPG CHIFTVSAWD 
ADAQENALVS YSLVERRLGE RSLSSYVSVH AESGKVYALQ PLDHEELELL QFQVSARDGG 
VPPLGSNLTL QVFVLDENDN APALLASPAG SAGGAVSELV LRSVVAGHVV AKVRAVDADS 
GYNAWLSYEL QSAAVGARIP FRVGLYTGEI STTRALDETD SPRQRLLVLV KDHGEPSLTA 
TATVLVSLVE GSQAPKASSR ASVGVAPEVA LVDVNVYLII AICAVSSLLV LTLLLYTALR 
CSAAPTEGAC GPVKPTLVCS SAVGSWSYSQ QRRQRVCSGE GLPKADLMAF SPSLPPCPMV 
DVDGEDQSIG GDHSRKPRQP NPDWRYSASL RAGMHSSVHL EEAGILRAGP GGPDQQWPTV 
SSATPEPEAG EVSPPVGAGV NSNSWTFKYG PGNPKQSGPG ELPDKFIIPG SPAIISIRQE 
PTNSQIDKSD FITFGKKEET KKKKKKKKGN KTQEKKEKGN STTDNSDQ