Details for: PIRT

Gene ID: 644139

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: PIRT

Ensembl ID: ENSG00000233670

Description: phosphoinositide interacting regulator of transient receptor potential channels

Cell Significance Landscape

Associated with

Significant Cells

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

  • peripheral nervous system neuron CL2000032
    CSI 3.92
    rCSI 5.34%
    PRS 99.44

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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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 [PIRT](/details-gene/644139) (Phosphoinositide Interacting Regulator of Transient Receptor Potential Channels) is a protein-coding gene located on chromosome 17p12, whose full-length cDNA and genomic locus have been previously characterized ([Link](https://doi.org/10.1038/ng1285), [Link](https://doi.org/10.1038/nature04689)). Functionally, [PIRT](/details-gene/644139) is known to bind phosphoinositides at the plasma membrane, where it acts as a regulator of TRP channels. Expression data indicates that [PIRT](/details-gene/644139) is a highly specific and significant marker for [peripheral nervous system neurons](/details-cell/CL2000032), a role that is consistent with its established involvement in the molecular pathways of pain and heat sensation. ## Cellular Roles and Expression Landscape The expression profile of [PIRT](/details-gene/644139) demonstrates a remarkably high degree of cell-type specificity. * **Overall Context:** Analysis of the **Overall** biological context reveals that [PIRT](/details-gene/644139) is most significantly expressed in the [peripheral nervous system neuron](/details-cell/CL2000032) (CSI: 3.92). This high significance suggests that [PIRT](/details-gene/644139) is not just expressed but likely plays a crucial functional role within this cell lineage, which includes sensory neurons responsible for transducing external stimuli into neural signals. The specificity of its expression points towards a specialized role in sensory physiology rather than a general housekeeping function in the nervous system. ## Pathways and Molecular Function Functional annotations for [PIRT](/details-gene/644139) align precisely with its role as a modulator of sensory neuron activity. The protein is localized to the [plasma membrane](/details-cell/GO:0005886) and its molecular function is characterized by binding to phosphoinositides, such as [phosphatidylinositol bisphosphate](/details-cell/GO:1902936) and [phosphatidylinositol-3,4,5-trisphosphate](/details-cell/GO:0005547), as well as to [transmembrane transporters](/details-cell/GO:0044325), which likely include TRP channels. This molecular activity is directly linked to its involvement in key biological processes: * **Sensory Perception:** [PIRT](/details-gene/644139) is implicated in the [regulation of sensory perception of pain](/details-cell/GO:0051930) and the [behavioral response to pain](/details-cell/GO:0048266). * **Thermosensation:** The gene is also involved in the cellular [response to heat](/details-cell/GO:0009408). These functions are consistent with the known role of TRP channels (e.g., TRPV1) in peripheral sensory neurons, which act as primary detectors of noxious heat and inflammatory pain stimuli. The interaction of [PIRT](/details-gene/644139) with these channels may be critical for setting their activation thresholds and modulating sensory signaling. ## Research Directions The highly specific expression and function of [PIRT](/details-gene/644139) in sensory neurons present clear avenues for further investigation, particularly in the context of sensory disorders and pain management. **Proposed Hypotheses:** 1. **Modulation of Pain Hypersensitivity:** Given its role in pain perception, it is hypothesized that the expression level or functional variants of [PIRT](/details-gene/644139) in peripheral sensory neurons directly correlate with individual differences in pain sensitivity. Dysregulation of [PIRT](/details-gene/644139) could be a contributing factor to chronic pain states, such as inflammatory or neuropathic pain, by altering TRP channel sensitization. 2. **Role in Other Sensory Modalities:** As a regulator of TRP channels, which are involved in diverse sensory processes, [PIRT](/details-gene/644139) may play a role beyond pain and heat sensation. It is hypothesized that [PIRT](/details-gene/644139) also modulates the activity of other TRP channels involved in mechanosensation or chemosensation in specific subsets of peripheral neurons. **Experimental Approach:** To test the hypothesis that [PIRT](/details-gene/644139) dysregulation contributes to chronic pain, a conditional knockout mouse model could be generated, specifically deleting *Pirt* in sensory neurons (e.g., using a Nav1.8-Cre driver). These mice could be subjected to models of neuropathic pain (e.g., spared nerve injury) or inflammatory pain (e.g., complete Freund's adjuvant injection). Behavioral assays (e.g., von Frey filaments for mechanical allodynia, Hargreaves test for thermal hyperalgesia) would quantify pain-related behaviors. Subsequently, electrophysiological recordings (e.g., patch-clamp) from isolated dorsal root ganglion neurons from these mice would directly assess changes in the excitability and TRP channel currents in the absence of the gene. **Therapeutic Potential:** [PIRT](/details-gene/644139) represents a promising therapeutic target for the development of novel analgesics. Its specific expression in peripheral sensory neurons suggests that a drug targeting [PIRT](/details-gene/644139) could achieve localized effects on pain signaling with a reduced risk of central nervous system side effects. As a protein that modulates ion channel function, it is an amenable target for small molecule inhibitors. A therapeutic strategy would likely focus on **inhibition**, aiming to disrupt the interaction between [PIRT](/details-gene/644139) and pro-nociceptive TRP channels, thereby dampening their activity and reducing pain hypersensitivity.

Genular Protein ID: 3996025619

Symbol: PIRT_HUMAN

Name: Phosphoinositide-interacting protein

UniProtKB Accession Codes:

P0C851 B7Z648

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 DMDM 1 DNASU 1 EMBL 4 Ensembl 1 GO 6 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 InterPro 1 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 RefSeq 1 SMR 1 STRING 1 TCDB 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16625196

Title: DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage.

PubMed ID: 16625196

DOI: 10.1038/nature04689

Sequence Information:

  • Length: 137
  • Mass: 15334
  • Checksum: 588C1AA13A5BDD05
  • Sequence:
    • MTMETLPKVL EVDEKSPEAK DLLPSQTASS LCISSRSESV WTTTPRSNWE IYRKPIVIMS 
VGGAILLFGV VITCLAYTLK LSDKSLSILK MVGPGFLSLG LMMLVCGLVW VPIIKKKQKH 
RQKSNFLRSL KSFFLTR