Details for: PLXNA1

Gene ID: 5361

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: PLXNA1

Ensembl ID: ENSG00000114554

Description: plexin A1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • epithelial cell of lower respiratory tract CL0002632
    CSI 3.64
    rCSI 2.82%
    PRS 92.36
  • club cell CL0000158
    CSI 3.52
    rCSI 5.16%
    PRS 85.15
  • duct epithelial cell CL0000068
    CSI 3.27
    rCSI 4.78%
    PRS 93.13
  • melanocyte CL0000148
    CSI 3.16
    rCSI 2.34%
    PRS 85.94
  • epithelial cell of lung CL0000082
    CSI 2.9
    rCSI 2.4%
    PRS 90.56
  • Kupffer cell CL0000091
    CSI 2.88
    rCSI 6.59%
    PRS 90.82
  • secretory cell CL0000151
    CSI 2.81
    rCSI 2.94%
    PRS 88.68
  • sst GABAergic cortical interneuron CL4023017
    CSI 2.74
    rCSI 3.53%
    PRS 77.56
  • lung ciliated cell CL1000271
    CSI 2.49
    rCSI 2.88%
    PRS 84.1
  • stem cell CL0000034
    CSI 2.36
    rCSI 2.27%
    PRS 85.66
  • vascular leptomeningeal cell CL4023051
    CSI 2.15
    rCSI 3.77%
    PRS 86.12
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 2.15
    rCSI 3.79%
    PRS 75.88
  • cerebral cortex neuron CL0010012
    CSI 2.14
    rCSI 8.72%
    PRS 82.59
  • myoepithelial cell CL0000185
    CSI 2.11
    rCSI 5.33%
    PRS 92.41
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 1.93
    rCSI 2.4%
    PRS 74.28
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.62
    rCSI 2.72%
    PRS 76.38
  • peripheral nervous system neuron CL2000032
    CSI 1.59
    rCSI 2.17%
    PRS 83.43
  • placental villous trophoblast CL2000060
    CSI 1.37
    rCSI 2.12%
    PRS 88.1
  • GABAergic neuron CL0000617
    CSI 1.25
    rCSI 4.2%
    PRS 76.2
  • intestinal crypt stem cell of small intestine CL0009017
    CSI 1.17
    rCSI 3.14%
    PRS 91.94
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 1.15
    rCSI 2.8%
    PRS 74.19
  • serotonergic neuron CL0000850
    CSI 1.06
    rCSI 4.76%
    PRS 75.39
  • dopaminergic neuron CL0000700
    CSI 0.83
    rCSI 4.7%
    PRS 79.01
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 0.79
    rCSI 2.48%
    PRS 79.52
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 0.7
    rCSI 2.63%
    PRS 76.66
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.64
    rCSI 2.31%
    PRS 74.31
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 0.38
    rCSI 2.23%
    PRS 76.89

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.

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 [PLXNA1](/details-gene/5361) encodes Plexin-A1, a transmembrane receptor that is a key component of the semaphorin signaling pathway. Primarily known for its critical role in neuronal development, particularly in axon guidance and neuronal migration, this protein functions as a receptor for class 3 semaphorins. Its involvement is well-documented in pathways such as '[Axon guidance](/details-pathway/R-HSA-422475)' and '[Semaphorin-plexin signaling pathway](/details-go/GO:0071526)'. While its function in the nervous system is well-established, expression data reveals a significant presence in non-neuronal tissues. **Overall**, [PLXNA1](/details-gene/5361) shows high significance in various epithelial cells, most notably in the respiratory tract, suggesting it plays a broader role in tissue morphogenesis, cell migration, and potentially immune regulation. Clinically, variants in [PLXNA1](/details-gene/5361) have been associated with a neurodevelopmental disorder characterized by cerebral and eye anomalies ([OMIM: 601055](https://omim.org/entry/601055)), as reported in a recent study ([Link](https://doi.org/10.1038/s41436-021-01196-9)). ## Cellular Roles and Expression Landscape The expression profile of [PLXNA1](/details-gene/5361) highlights its importance in diverse cellular contexts, extending beyond its classical role in neurogenesis. **Overall**, the gene demonstrates the highest significance in epithelial cell populations of the lung, including [epithelial cell of lower respiratory tract](/details-cell/CL0002632) (CSI: 3.64), [club cell](/details-cell/CL0000158) (CSI: 3.52), and [duct epithelial cell](/details-cell/CL0000068) (CSI: 3.27). This strong expression pattern in secretory and structural cells of the airway suggests a potential role in lung development, homeostasis, or the response to injury. Consistent with its established function, [PLXNA1](/details-gene/5361) is also a significant marker in several neuronal subtypes. These include specialized inhibitory interneurons such as [sst GABAergic cortical interneuron](/details-cell/CL4023017) (CSI: 2.74) and [caudal ganglionic eminence derived cortical interneuron](/details-cell/CL4023064) (CSI: 2.15), as well as broader categories like [cerebral cortex neuron](/details-cell/CL0010012) (CSI: 2.14). This is in line with its function in guiding neuronal migration and forming synaptic connections. Furthermore, the data indicates notable significance in other distinct cell types, such as [melanocyte](/details-cell/CL0000148) (CSI: 3.16), the liver-resident macrophage [Kupffer cell](/details-cell/CL0000091) (CSI: 2.88), and [stem cell](/details-cell/CL0000034) (CSI: 2.36). This diverse expression landscape suggests that [PLXNA1](/details-gene/5361)-mediated signaling may be a conserved mechanism for regulating cell positioning, adhesion, and interaction across multiple tissues. ## Pathways and Molecular Function The functional annotations for [PLXNA1](/details-gene/5361) firmly place it within the semaphorin signaling network, where it acts as a '[Semaphorin receptor activity](/details-go/GO:0017154)'. This activity is central to its role in the nervous system, as evidenced by its association with numerous neurodevelopmental processes. Key Reactome pathways include '[Axon guidance](/details-pathway/R-HSA-422475)', '[Semaphorin interactions](/details-pathway/R-HSA-373755)', and '[Nervous system development](/details-pathway/R-HSA-9675108)'. These are corroborated by Gene Ontology terms like '[Neuron projection guidance](/details-go/GO:0097485)', '[Positive regulation of axonogenesis](/details-go/GO:0050772)', and '[Synapse assembly](/details-go/GO:0007416)'. These functions directly correspond to its significant expression in various [cerebral cortex neuron](/details-cell/CL0010012) subtypes. The signaling cascade often involves the regulation of the cytoskeleton via Rho GTPases, reflected by its link to the '[Signaling by rho gtpases](/details-pathway/R-HSA-194315)' pathway. Beyond the nervous system, its involvement in '[Regulation of cell migration](/details-go/GO:0030334)' and '[Negative regulation of cell adhesion](/details-go/GO:0007162)' provides a molecular basis for its high significance in epithelial and stem cell populations. These processes are fundamental to tissue architecture, wound healing, and morphogenesis. Additionally, its annotation for '[T cell activation via t cell receptor contact with antigen bound to mhc molecule on antigen presenting cell](/details-go/GO:0002291)' suggests a potential immunomodulatory role, which may be relevant in the context of its expression in [Kupffer cell](/details-cell/CL0000091), a key antigen-presenting cell in the liver. ## Research Directions The diverse expression pattern of [PLXNA1](/details-gene/5361), combined with its well-defined signaling functions, opens several avenues for future investigation. Its established link to neurodevelopmental disorders underscores the importance of understanding its function in both neuronal and non-neuronal contexts. **Proposed Hypotheses:** 1. Given its high significance in multiple lung epithelial cell types, such as [club cell](/details-cell/CL0000158), and its role in cell migration, [PLXNA1](/details-gene/5361) may be a critical regulator of epithelial restitution and differentiation during lung tissue repair following injury (e.g., from infection or environmental insults). 2. Based on its expression in [Kupffer cell](/details-cell/CL0000091) and its annotated role in T cell activation, [PLXNA1](/details-gene/5361) signaling could mediate the interaction between resident liver macrophages and lymphocytes, potentially contributing to the liver's unique immune-tolerant environment or its dysregulation in inflammatory liver diseases. **Experimental Approach:** To test the first hypothesis regarding the role of [PLXNA1](/details-gene/5361) in lung epithelial repair, one could utilize an *in vitro* air-liquid interface (ALI) culture model with primary human bronchial epithelial cells. [PLXNA1](/details-gene/5361) expression could be knocked down using CRISPR-Cas9 or shRNA. Following establishment of a differentiated epithelial layer, a mechanical scratch wound would be introduced. The rate of wound closure could be quantified via live-cell imaging. Furthermore, changes in the expression of markers for basal, secretory, and ciliated cells could be assessed by immunofluorescence and quantitative PCR at various time points post-injury to determine if [PLXNA1](/details-gene/5361) is required for both cell migration and proper differentiation during the repair process. **Therapeutic Potential:** As a cell-surface receptor, [PLXNA1](/details-gene/5361) is an accessible drug target. Its strong association with a neurodevelopmental disorder ([Link](https://doi.org/10.1038/s41436-021-01196-9)) suggests that modulating its function could have profound physiological consequences. Therapeutic strategies would likely need to be highly specific. For loss-of-function variants causing disease, a gene therapy approach or the development of small molecule agonists to restore signaling could be explored. Conversely, in pathological contexts where plexin signaling may be hyperactive, such as certain cancers where it can promote invasion, [PLXNA1](/details-gene/5361) could be a target for inhibitory monoclonal antibodies or small molecule antagonists to block its signaling and reduce cell migration.

Genular Protein ID: 2427747163

Symbol: PLXA1_HUMAN

Name: Plexin-A1

UniProtKB Accession Codes:

Q9UIW2

Database IDs:

ABCD 1 AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 6 CORUM 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 3 Ensembl 1 GO 18 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 15 KEGG 1 MANE-Select 1 MIM 3 MINT 1 MalaCards 1 MassIVE 1 MetOSite 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PDB 2 PDBsum 2 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 7 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 Reactome 6 RefSeq 1 SIGNOR 1 SMART 3 SMR 1 STRING 1 SUPFAM 4 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 16641997

Title: The DNA sequence, annotation and analysis of human chromosome 3.

PubMed ID: 16641997

DOI: 10.1038/nature04728

PubMed ID: 8570614

Title: A family of transmembrane proteins with homology to the MET-hepatocyte growth factor receptor.

PubMed ID: 8570614

DOI: 10.1073/pnas.93.2.674

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 19349973

Title: Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins.

PubMed ID: 19349973

DOI: 10.1038/nbt.1532

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 34054129

Title: Biallelic and monoallelic variants in PLXNA1 are implicated in a novel neurodevelopmental disorder with variable cerebral and eye anomalies.

PubMed ID: 34054129

DOI: 10.1038/s41436-021-01196-9

Sequence Information:

  • Length: 1896
  • Mass: 211067
  • Checksum: 76E5C9C0710C7FC1
  • Sequence:
    • MPLPPRSLQV LLLLLLLLLL LPGMWAEAGL PRAGGGSQPP FRTFSASDWG LTHLVVHEQT 
GEVYVGAVNR IYKLSGNLTL LRAHVTGPVE DNEKCYPPPS VQSCPHGLGS TDNVNKLLLL 
DYAANRLLAC GSASQGICQF LRLDDLFKLG EPHHRKEHYL SSVQEAGSMA GVLIAGPPGQ 
GQAKLFVGTP IDGKSEYFPT LSSRRLMANE EDADMFGFVY QDEFVSSQLK IPSDTLSKFP 
AFDIYYVYSF RSEQFVYYLT LQLDTQLTSP DAAGEHFFTS KIVRLCVDDP KFYSYVEFPI 
GCEQAGVEYR LVQDAYLSRP GRALAHQLGL AEDEDVLFTV FAQGQKNRVK PPKESALCLF 
TLRAIKEKIK ERIQSCYRGE GKLSLPWLLN KELGCINSPL QIDDDFCGQD FNQPLGGTVT 
IEGTPLFVDK DDGLTAVAAY DYRGRTVVFA GTRSGRIRKI LVDLSNPGGR PALAYESVVA 
QEGSPILRDL VLSPNHQYLY AMTEKQVTRV PVESCVQYTS CELCLGSRDP HCGWCVLHSI 
CSRRDACERA DEPQRFAADL LQCVQLTVQP RNVSVTMSQV PLVLQAWNVP DLSAGVNCSF 
EDFTESESVL EDGRIHCRSP SAREVAPITR GQGDQRVVKL YLKSKETGKK FASVDFVFYN 
CSVHQSCLSC VNGSFPCHWC KYRHVCTHNV ADCAFLEGRV NVSEDCPQIL PSTQIYVPVG 
VVKPITLAAR NLPQPQSGQR GYECLFHIPG SPARVTALRF NSSSLQCQNS SYSYEGNDVS 
DLPVNLSVVW NGNFVIDNPQ NIQAHLYKCP ALRESCGLCL KADPRFECGW CVAERRCSLR 
HHCAADTPAS WMHARHGSSR CTDPKILKLS PETGPRQGGT RLTITGENLG LRFEDVRLGV 
RVGKVLCSPV ESEYISAEQI VCEIGDASSV RAHDALVEVC VRDCSPHYRA LSPKRFTFVT 
PTFYRVSPSR GPLSGGTWIG IEGSHLNAGS DVAVSVGGRP CSFSWRNSRE IRCLTPPGQS 
PGSAPIIINI NRAQLTNPEV KYNYTEDPTI LRIDPEWSIN SGGTLLTVTG TNLATVREPR 
IRAKYGGIER ENGCLVYNDT TMVCRAPSVA NPVRSPPELG ERPDELGFVM DNVRSLLVLN 
STSFLYYPDP VLEPLSPTGL LELKPSSPLI LKGRNLLPPA PGNSRLNYTV LIGSTPCTLT 
VSETQLLCEA PNLTGQHKVT VRAGGFEFSP GTLQVYSDSL LTLPAIVGIG GGGGLLLLVI 
VAVLIAYKRK SRDADRTLKR LQLQMDNLES RVALECKEAF AELQTDIHEL TNDLDGAGIP 
FLDYRTYAMR VLFPGIEDHP VLKEMEVQAN VEKSLTLFGQ LLTKKHFLLT FIRTLEAQRS 
FSMRDRGNVA SLIMTALQGE MEYATGVLKQ LLSDLIEKNL ESKNHPKLLL RRTESVAEKM 
LTNWFTFLLY KFLKECAGEP LFMLYCAIKQ QMEKGPIDAI TGEARYSLSE DKLIRQQIDY 
KTLTLNCVNP ENENAPEVPV KGLDCDTVTQ AKEKLLDAAY KGVPYSQRPK AADMDLEWRQ 
GRMARIILQD EDVTTKIDND WKRLNTLAHY QVTDGSSVAL VPKQTSAYNI SNSSTFTKSL 
SRYESMLRTA SSPDSLRSRT PMITPDLESG TKLWHLVKNH DHLDQREGDR GSKMVSEIYL 
TRLLATKGTL QKFVDDLFET IFSTAHRGSA LPLAIKYMFD FLDEQADKHQ IHDADVRHTW 
KSNCLPLRFW VNVIKNPQFV FDIHKNSITD ACLSVVAQTF MDSCSTSEHK LGKDSPSNKL 
LYAKDIPNYK SWVERYYADI AKMPAISDQD MSAYLAEQSR LHLSQFNSMS ALHEIYSYIT 
KYKDEILAAL EKDEQARRQR LRSKLEQVVD TMALSS