Details for: GABRP

Gene ID: 2568

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: GABRP

Ensembl ID: ENSG00000094755

Description: gamma-aminobutyric acid type A receptor subunit pi

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • acinar cell CL0000622
    CSI 8.53
    rCSI 12.5%
    PRS 97.32
  • duct epithelial cell CL0000068
    CSI 7.18
    rCSI 10.5%
    PRS 96.7
  • tracheal goblet cell CL1000329
    CSI 7.15
    rCSI 15.61%
    PRS 95.41
  • ciliated cell CL0000064
    CSI 6.93
    rCSI 11.23%
    PRS 89.33
  • nasal mucosa goblet cell CL0002480
    CSI 5.65
    rCSI 6.55%
    PRS 94.28
  • pulmonary ionocyte CL0017000
    CSI 4.66
    rCSI 5.67%
    PRS 96.48
  • intestinal tuft cell CL0019032
    CSI 3.94
    rCSI 6.02%
    PRS 95.27
  • secretory cell CL0000151
    CSI 3.84
    rCSI 4%
    PRS 93.71
  • dendritic cell CL0000451
    CSI 3.68
    rCSI 4.54%
    PRS 93.67
  • goblet cell CL0000160
    CSI 3.55
    rCSI 3.35%
    PRS 92.6
  • intrahepatic cholangiocyte CL0002538
    CSI 3.19
    rCSI 7.65%
    PRS 94.09
  • conjunctival epithelial cell CL1000432
    CSI 2.96
    rCSI 4.52%
    PRS 93.6
  • glandular epithelial cell CL0000150
    CSI 2.74
    rCSI 7.21%
    PRS 98.16
  • mammary gland epithelial cell CL0002327
    CSI 2.69
    rCSI 9.44%
    PRS 96.8
  • squamous epithelial cell CL0000076
    CSI 2.68
    rCSI 6.36%
    PRS 91.23
  • respiratory suprabasal cell CL4033048
    CSI 2.67
    rCSI 3.43%
    PRS 95.46
  • mucous neck cell CL0000651
    CSI 2.59
    rCSI 3.73%
    PRS 96.09
  • club cell CL0000158
    CSI 2.44
    rCSI 3.58%
    PRS 91.6
  • ionocyte CL0005006
    CSI 2.36
    rCSI 2.53%
    PRS 95.31
  • epithelial cell CL0000066
    CSI 2.34
    rCSI 3.6%
    PRS 84.32
  • brush cell CL0002204
    CSI 2.25
    rCSI 4.45%
    PRS 95.8
  • multi-ciliated epithelial cell CL0005012
    CSI 2.08
    rCSI 2.08%
    PRS 90.02
  • luminal epithelial cell of mammary gland CL0002326
    CSI 2.06
    rCSI 3.74%
    PRS 97.09
  • respiratory basal cell CL0002633
    CSI 2.01
    rCSI 2.08%
    PRS 95.58
  • kidney loop of Henle thin ascending limb epithelial cell CL1001107
    CSI 1.43
    rCSI 3.69%
    PRS 92.95
  • bronchial goblet cell CL1000312
    CSI 0.87
    rCSI 3.47%
    PRS 96.32
  • basal cell of epithelium of trachea CL1000348
    CSI 0.58
    rCSI 4.12%
    PRS 94.68
  • respiratory goblet cell CL0002370
    CSI 0.34
    rCSI 3.66%
    PRS 96.16
  • epithelial cell of urethra CL1000296
    CSI 0.2
    rCSI 5.02%
    PRS 95.57

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 [GABRP](/details-gene/2568) encodes the pi (π) subunit of the gamma-aminobutyric acid type A (GABA-A) receptor, a ligand-gated chloride channel crucial for mediating inhibitory neurotransmission. Functionally, it is annotated with roles in [chloride channel activity](/details-cell/GO:0005254) and [chemical synaptic transmission](/details-cell/GO:0007268). Despite its canonical association with the nervous system, expression data reveals that its most significant and defining roles are in non-neuronal tissues. **Overall**, [GABRP](/details-gene/2568) shows remarkably high significance in a variety of secretory and epithelial cell types, including [acinar cells](/details-cell/CL0000622), [duct epithelial cells](/details-cell/CL0000068), and [tracheal goblet cells](/details-cell/CL1000329). This suggests that the pi subunit has been co-opted for specialized physiological functions in mucosal and glandular tissues, a notion supported by early research identifying its presence in the reproductive system [Link](https://doi.org/10.1074/jbc.272.24.15346). ## Cellular Roles and Expression Landscape The expression profile of [GABRP](/details-gene/2568) highlights its prominent role in epithelial and secretory cell biology, diverging from the typical expression patterns of GABA-A receptor subunits. **Overall**, the gene's significance is highest in cells associated with secretion and mucosal surfaces. It is a top marker for [acinar cells](/details-cell/CL0000622) (CSI: 8.53) of exocrine glands and various epithelial cells lining ducts and tracts, such as [duct epithelial cells](/details-cell/CL0000068) (CSI: 7.18), [tracheal goblet cells](/details-cell/CL1000329) (CSI: 7.15), and [nasal mucosa goblet cells](/details-cell/CL0002480) (CSI: 5.65). Its high significance extends to other specialized epithelial cells, including [ciliated cells](/details-cell/CL0000064), [pulmonary ionocytes](/details-cell/CL0017000), and [intestinal tuft cells](/details-cell/CL0019032). This consistent pattern suggests a fundamental role for [GABRP](/details-gene/2568) in regulating ion flux, fluid secretion, or cellular signaling across diverse mucosal barriers, from the respiratory system to the digestive tract. The presence in [mammary gland epithelial cells](/details-cell/CL0002327) and [intrahepatic cholangiocytes](/details-cell/CL0002538) further underscores its broad importance in glandular tissues. The unexpected but significant expression in [dendritic cells](/details-cell/CL0000451) may indicate a novel, non-canonical role in immune modulation. Notably, despite its functional annotations related to synaptic transmission, canonical neuronal cell types are absent from the list of top-expressing cells. This implies that while the GABRP protein retains its core biochemical function as a chloride channel, its physiological context is predominantly outside the central nervous system. ## Pathways and Molecular Function The molecular functions attributed to [GABRP](/details-gene/2568) are centered on its identity as a component of a neurotransmitter receptor complex. According to Gene Ontology annotations, the protein is an integral part of the [plasma membrane](/details-cell/GO:0005886) and specifically localizes to the [GABA-A receptor complex](/details-cell/GO:1902711) and [chloride channel complex](/details-cell/GO:0034707). Its primary molecular function is [GABA-gated chloride ion channel activity](/details-cell/GO:0022851), which contributes directly to the biological processes of [chloride transmembrane transport](/details-cell/GO:1902476) and the [regulation of membrane potential](/details-cell/GO:0042391). The involvement in [chemical synaptic transmission](/details-cell/GO:0007268) reflects its established role in neuroscience. However, the high expression of [GABRP](/details-gene/2568) in secretory and epithelial cells suggests that these fundamental mechanisms are repurposed in non-neuronal settings. In these contexts, GABA may act as a paracrine signaling molecule to modulate epithelial cell functions like mucus secretion, ion transport, or maintenance of barrier integrity, rather than as a classical neurotransmitter. ## Research Directions The unique, extra-neuronal expression pattern of [GABRP](/details-gene/2568) opens several avenues for future investigation, particularly concerning its role in mucosal physiology and pathology. **Testable Hypotheses:** 1. **[GABRP](/details-gene/2568) modulates mucin secretion and ion transport in airway epithelial cells.** Given its high significance in [tracheal goblet cells](/details-cell/CL1000329) and [pulmonary ionocytes](/details-cell/CL0017000), GABA signaling through GABRP-containing receptors may be a key regulatory pathway for airway surface liquid homeostasis and mucus production. Dysregulation of this pathway could contribute to pathologies like asthma or chronic obstructive pulmonary disease (COPD). 2. **The GABRP subunit confers unique pharmacological properties to GABA-A receptors in epithelial tissues, making them insensitive to classical modulators like benzodiazepines.** Research has previously suggested that the presence of the pi subunit can alter receptor pharmacology [Link](https://doi.org/10.1124/mol.56.3.598). This property could be exploited to develop drugs that target epithelial GABA signaling without causing sedative effects associated with the central nervous system. **Proposed Experiment:** To test the first hypothesis, one could utilize an air-liquid interface (ALI) culture system with primary human bronchial epithelial cells, which differentiates to form a pseudo-stratified epithelium containing both goblet and ciliated cells. - **Method:** [GABRP](/details-gene/2568) expression would be knocked down using lentiviral-delivered shRNA or CRISPR interference (CRISPRi). - **Intervention:** Control and knockdown cultures would be stimulated with GABA or a known secretagogue. - **Readouts:** Changes in mucus secretion could be quantified by measuring MUC5AC protein levels via ELISA. Ion transport function could be assessed using Ussing chamber electrophysiology to measure chloride currents in response to GABAergic agonists and antagonists. A significant reduction in GABA-mediated effects in knockdown cultures would confirm the role of [GABRP](/details-gene/2568) in airway epithelial function. **Therapeutic Potential:** As a cell-surface ion channel highly expressed in specific secretory cell types, [GABRP](/details-gene/2568) represents a potentially attractive therapeutic target. Its tissue-restricted expression outside the CNS suggests that modulators targeting GABRP-containing receptors could offer a favorable safety profile with minimal neurological side effects. In diseases characterized by mucus hypersecretion, such as COPD or cystic fibrosis, a selective **inhibitor** or negative allosteric modulator of GABRP could help reduce airway obstruction. Conversely, in conditions where enhanced epithelial barrier function or fluid secretion is desired, a specific **activator** or positive modulator could prove beneficial.

Genular Protein ID: 3367013845

Symbol: GBRP_HUMAN

Name: N/A

UniProtKB Accession Codes:

O00591 A8KA36 D3DQL2 Q32MJ1

Database IDs:

ABCD 1 AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChEBI 1 ChEMBL 1 ChiTaRS 1 DNASU 1 DisGeNET 1 DrugBank 76 DrugCentral 1 EMBL 17 Ensembl 2 ExpressionAtlas 1 GO 11 Gene3D 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 InterPro 10 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 NCBIfam 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRINTS 3 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 RNAct 1 RefSeq 2 Rhea 1 SMR 1 STRING 1 SUPFAM 2 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 9182563

Title: A novel class of GABAA receptor subunit in tissues of the reproductive system.

PubMed ID: 9182563

DOI: 10.1074/jbc.272.24.15346

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

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: 10462548

Title: Incorporation of the pi subunit into functional gamma-aminobutyric Acid(A) receptors.

PubMed ID: 10462548

DOI: 10.1124/mol.56.3.598

PubMed ID: 16959974

Title: The consensus coding sequences of human breast and colorectal cancers.

PubMed ID: 16959974

DOI: 10.1126/science.1133427

Sequence Information:

  • Length: 440
  • Mass: 50640
  • Checksum: 92CA66C264560718
  • Sequence:
    • MNYSLHLAFV CLSLFTERMC IQGSQFNVEV GRSDKLSLPG FENLTAGYNK FLRPNFGGEP 
VQIALTLDIA SISSISESNM DYTATIYLRQ RWMDQRLVFE GNKSFTLDAR LVEFLWVPDT 
YIVESKKSFL HEVTVGNRLI RLFSNGTVLY ALRITTTVAC NMDLSKYPMD TQTCKLQLES 
WGYDGNDVEF TWLRGNDSVR GLEHLRLAQY TIERYFTLVT RSQQETGNYT RLVLQFELRR 
NVLYFILETY VPSTFLVVLS WVSFWISLDS VPARTCIGVT TVLSMTTLMI GSRTSLPNTN 
CFIKAIDVYL GICFSFVFGA LLEYAVAHYS SLQQMAAKDR GTTKEVEEVS ITNIINSSIS 
SFKRKISFAS IEISSDNVDY SDLTMKTSDK FKFVFREKMG RIVDYFTIQN PSNVDHYSKL 
LFPLIFMLAN VFYWAYYMYF

Genular Protein ID: 2462961063

Symbol: B4DTP4_HUMAN

Name: N/A

UniProtKB Accession Codes:

B4DTP4

Database IDs:

ARBA 10 AlphaFoldDB 1 BioGRID-ORCS 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 GO 12 Gene3D 2 InterPro 8 NCBI Taxonomy 1 NCBIfam 1 OrthoDB 1 PANTHER 2 PRINTS 3 PROSITE 1 PeptideAtlas 1 Pfam 2 RefSeq 1 RuleBase 1 SUPFAM 2

Sequence Information:

  • Length: 289
  • Mass: 33419
  • Checksum: 7895927B608BD37F
  • Sequence:
    • MNYSLHLAFV CLSLFTERMC IQGSQFNVEV GRSDKLSLPG FENLTAGYNK FLRPNFGGEP 
VQIALTLDIA SISSISESNM DYTATIYLRQ RWMDQRLVFE GNKSFTLDAR LAEFLWVPDT 
YIVESKKSFL HEVTVGNRLI RLFSNGTVLY ALRITTTVAC NMDLSKYPMD TQTCKLQLES 
WGYDGNDVEF TWLRGNDSVR GLEHLRLAQY TIERYFTLVT RSQQETGNYT RLVLQFELRR 
NVLYFILETY VPSTFLVVLS WVSFWISLDS VPARTCIGDN KGSRRSQYY

Genular Protein ID: 1397251713

Symbol: E7EWG0_HUMAN

Name: N/A

UniProtKB Accession Codes:

E7EWG0

Database IDs:

ARBA 10 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID-ORCS 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 1 Ensembl 2 ExpressionAtlas 1 GO 3 Gene3D 2 GeneTree 1 HGNC 1 HOGENOM 1 InterPro 8 MassIVE 1 NCBI Taxonomy 1 NCBIfam 1 OrthoDB 1 PANTHER 2 PRINTS 3 PROSITE 1 PeptideAtlas 2 Pfam 2 Proteomes 2 RefSeq 1 RuleBase 1 SMR 1 SUPFAM 2 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: 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: 289
  • Mass: 33447
  • Checksum: 5F9BAFC3887A1136
  • Sequence:
    • MNYSLHLAFV CLSLFTERMC IQGSQFNVEV GRSDKLSLPG FENLTAGYNK FLRPNFGGEP 
VQIALTLDIA SISSISESNM DYTATIYLRQ RWMDQRLVFE GNKSFTLDAR LVEFLWVPDT 
YIVESKKSFL HEVTVGNRLI RLFSNGTVLY ALRITTTVAC NMDLSKYPMD TQTCKLQLES 
WGYDGNDVEF TWLRGNDSVR GLEHLRLAQY TIERYFTLVT RSQQETGNYT RLVLQFELRR 
NVLYFILETY VPSTFLVVLS WVSFWISLDS VPARTCIGDN KGSRRSQYY