Details for: PLEKHS1

Gene ID: 79949

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: PLEKHS1

Ensembl ID: ENSG00000148735

Description: pleckstrin homology domain containing S1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • stem cell CL0000034
    CSI 16.47
    rCSI 15.88%
    PRS 93.88
  • epithelial cell of lower respiratory tract CL0002632
    CSI 8.7
    rCSI 6.74%
    PRS 97.28
  • acinar cell CL0000622
    CSI 7.69
    rCSI 11.28%
    PRS 97.89
  • secretory cell CL0000151
    CSI 7.17
    rCSI 7.48%
    PRS 95.25
  • pulmonary ionocyte CL0017000
    CSI 5.85
    rCSI 7.12%
    PRS 97.29
  • lung secretory cell CL1000272
    CSI 5.7
    rCSI 14.12%
    PRS 96.87
  • ciliated cell CL0000064
    CSI 5.08
    rCSI 8.23%
    PRS 91.06
  • multi-ciliated epithelial cell CL0005012
    CSI 4.99
    rCSI 4.98%
    PRS 92.13
  • nasal mucosa goblet cell CL0002480
    CSI 4.62
    rCSI 5.35%
    PRS 95.42
  • goblet cell CL0000160
    CSI 4.2
    rCSI 3.96%
    PRS 94.27
  • deuterosomal cell CL4033044
    CSI 4.07
    rCSI 13.76%
    PRS 91.22
  • squamous epithelial cell CL0000076
    CSI 3.78
    rCSI 8.98%
    PRS 92.52
  • tracheal goblet cell CL1000329
    CSI 3.68
    rCSI 8.04%
    PRS 96.43
  • ciliated epithelial cell CL0000067
    CSI 3.62
    rCSI 3.18%
    PRS 90.16
  • lung ciliated cell CL1000271
    CSI 3.46
    rCSI 4%
    PRS 92.34
  • duct epithelial cell CL0000068
    CSI 3.45
    rCSI 5.05%
    PRS 97.58
  • respiratory goblet cell CL0002370
    CSI 3.15
    rCSI 34.21%
    PRS 97.17
  • ionocyte CL0005006
    CSI 3.09
    rCSI 3.31%
    PRS 96.42
  • conjunctival epithelial cell CL1000432
    CSI 2.49
    rCSI 3.8%
    PRS 95.05
  • bronchial goblet cell CL1000312
    CSI 2.47
    rCSI 9.89%
    PRS 97.27
  • respiratory suprabasal cell CL4033048
    CSI 2.44
    rCSI 3.13%
    PRS 96.75
  • mucus secreting cell CL0000319
    CSI 2.43
    rCSI 3.86%
    PRS 97.85
  • respiratory basal cell CL0002633
    CSI 2.21
    rCSI 2.29%
    PRS 96.78
  • club cell CL0000158
    CSI 2.06
    rCSI 3.01%
    PRS 93.59
  • intestinal crypt stem cell of small intestine CL0009017
    CSI 1.98
    rCSI 5.33%
    PRS 96.6
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 1.94
    rCSI 4.42%
    PRS 90.48
  • tracheobronchial serous cell CL0019001
    CSI 1.57
    rCSI 6.8%
    PRS 96.81
  • serous secreting cell of bronchus submucosal gland CL4033005
    CSI 0.81
    rCSI 4.63%
    PRS 95.61
  • basal cell of epithelium of trachea CL1000348
    CSI 0.59
    rCSI 4.13%
    PRS 96.05

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 [PLEKHS1](/details-gene/79949), or Pleckstrin Homology Domain Containing S1, is a protein-coding gene located on chromosome 10q25.3. Its molecular function is annotated primarily as protein binding, consistent with the presence of a pleckstrin homology (PH) domain, which typically mediates interactions with other proteins and phosphoinositides. **Overall**, expression data reveals a highly specific role for [PLEKHS1](/details-gene/79949), with its most significant expression observed in [stem cell](/details-cell/CL0000034)s and a variety of specialized epithelial and secretory cells, particularly those lining the respiratory tract. This distinct expression pattern suggests a fundamental role in epithelial biology, potentially involving cellular differentiation, maintenance of cell polarity, or secretory functions within mucosal tissues. The gene's initial characterization was part of large-scale cDNA sequencing projects [[Link](https://doi.org/10.1038/ng1285), [Link](https://doi.org/10.1101/gr.2596504)]. ## Cellular Roles and Expression Landscape The expression profile of [PLEKHS1](/details-gene/79949) points to a specialized function in epithelial and progenitor cell populations. The gene's most significant expression is in [stem cell](/details-cell/CL0000034)s (CSI: 16.47), suggesting a potential role in the maintenance of pluripotency or the regulation of lineage commitment. Beyond this progenitor context, [PLEKHS1](/details-gene/79949) demonstrates a profound association with the respiratory system. It is a highly significant marker in multiple cell types critical for airway function, including [epithelial cell of lower respiratory tract](/details-cell/CL0002632) (CSI: 8.70), [pulmonary ionocyte](/details-cell/CL0017000) (CSI: 5.85), and [lung ciliated cell](/details-cell/CL1000271) (CSI: 3.46). This indicates a potential involvement in processes essential for respiratory homeostasis, such as ion transport and mucociliary clearance. Furthermore, [PLEKHS1](/details-gene/79949) is prominently expressed in various secretory cell lineages. These include [acinar cell](/details-cell/CL0000622) (CSI: 7.69), [secretory cell](/details-cell/CL0000151) (CSI: 7.17), [nasal mucosa goblet cell](/details-cell/CL0002480) (CSI: 4.62), and [tracheal goblet cell](/details-cell/CL1000329) (CSI: 3.68). This consistent high expression across different secretory cell types suggests a conserved role in pathways related to synthesis, packaging, or exocytosis of cellular products like mucus. The collective data strongly supports a function for [PLEKHS1](/details-gene/79949) in establishing or maintaining the specialized functions of mucosal and glandular epithelia. ## Pathways and Molecular Function The known molecular function of [PLEKHS1](/details-gene/79949) is linked to protein binding ([GO:0005515](https://www.ebi.ac.uk/QuickGO/term/GO:0005515)). This annotation is supported by its core structural feature, the pleckstrin homology (PH) domain. PH domains are well-characterized modules that mediate protein localization to cellular membranes by binding to phosphoinositides and interacting with other signaling proteins. This function suggests [PLEKHS1](/details-gene/79949) acts as a scaffolding or adaptor protein, recruiting other proteins to specific subcellular locations to orchestrate complex cellular processes. Its high expression in secretory and ciliated cells, which are highly polarized and structurally complex, is consistent with a role in organizing the molecular machinery required for their specialized functions, such as directed secretion or ciliary beating. ## Research Directions The specific and significant expression of [PLEKHS1](/details-gene/79949) in respiratory epithelial progenitors and their differentiated progeny raises several key questions about its role in lung biology and disease. **Proposed Hypotheses:** 1. Given its top significance in [stem cell](/details-cell/CL0000034)s and strong expression across differentiated respiratory lineages (e.g., ciliated, goblet, ionocyte), [PLEKHS1](/details-gene/79949) may be a critical regulator of lung epithelial progenitor cell differentiation, potentially influencing cell fate decisions during tissue homeostasis and repair. 2. The high expression of [PLEKHS1](/details-gene/79949) in multiple secretory cell types, including [acinar cell](/details-cell/CL0000622)s and [goblet cell](/details-cell/CL0000160)s, suggests it may regulate key steps in the secretory pathway, such as vesicle trafficking or fusion with the plasma membrane, thereby controlling mucus production and release. **Experimental Approach:** To test the hypothesis that [PLEKHS1](/details-gene/79949) governs lung epithelial differentiation (Hypothesis 1), a robust experimental model would involve the use of primary human bronchial epithelial stem/progenitor cells cultured at an air-liquid interface (ALI). In this system, one could perform a loss-of-function study using shRNA or CRISPR-Cas9 to knock down or knock out [PLEKHS1](/details-gene/79949). The subsequent impact on cellular differentiation would be assessed over time using single-cell RNA-sequencing (scRNA-seq) to map changes in cell fate trajectories and population frequencies. This could be complemented by immunofluorescence staining for key lineage markers (e.g., FOXJ1 for ciliated cells, MUC5AC for goblet cells) to validate the transcriptomic findings at the protein level. **Therapeutic Potential:** The highly restricted expression of [PLEKHS1](/details-gene/79949) to the respiratory epithelium and its potential role in differentiation and secretion make it an intriguing target for respiratory diseases. In conditions characterized by defective mucociliary clearance, such as cystic fibrosis or chronic obstructive pulmonary disease (COPD), aberrant function or expression of [PLEKHS1](/details-gene/79949) could be a contributing factor. Depending on its precise role, it could be a target for either inhibition or activation. For instance, if its overexpression leads to mucus hypersecretion, inhibitors delivered via inhalation could be therapeutic. Conversely, if it is crucial for epithelial repair, activating its pathway could promote tissue regeneration after injury. As an intracellular scaffolding protein, it may be a challenging drug target for small molecules, but therapeutic strategies using inhaled oligonucleotides (e.g., siRNA, ASOs) to modulate its expression could be a viable approach.

Genular Protein ID: 2765023556

Symbol: PKHS1_HUMAN

Name: Epididymis luminal protein 185

UniProtKB Accession Codes:

Q5SXH7 A8KA02 B3KX00 B6EDE1 Q5SXH8 Q5SXI0 Q6ZQR5 Q8NE42 Q9H5D9

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 3 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 8 Ensembl 4 ExpressionAtlas 1 Gene3D 1 GeneCards 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MassIVE 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 5 RNAct 1 RefSeq 4 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: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15164054

Title: The DNA sequence and comparative analysis of human chromosome 10.

PubMed ID: 15164054

DOI: 10.1038/nature02462

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: 465
  • Mass: 52459
  • Checksum: A9A9C93E5F2B9262
  • Sequence:
    • MAGGKQFTFS YENEVCKQDY FIKSPPSQLF SSVTSWKKRF FILSKAGEKS FSLSYYKDHH 
HRGSIEIDQN SSVEVGISSQ EKMQSVQKMF KCHPDEVMSI RTTNREYFLI GHDREKIKDW 
VSFMSSFRQD IKATQQNTEE ELSLGNKRTL FYSSPLLGPS STSEAVGSSS PRNGLQDKHL 
MEQSSPGFRQ THLQDLSEAT QDVKEENHYL TPRSVLLELD NIIASSDSGE SIETDGPDQV 
SGRIECHYEP MESSFFKETS HESVDSSKEE PQTLPETQDG DLHLQEQGSG IDWCLSPADV 
EAQTTNDQKG NIPDESQVEK LNVFLSPPDV INYLALTEAT GRICVSQWEG PPRLGCIFCH 
GDHLLAVNDL KPQSLEEVSL FLTRSIQKED SFRILSYQVA FGEGTELRDR APGFRTSDRH 
DVAKRACMES DWCRDSKTAP STNLCLSFLF CKIMTNDGAG CWIIK

Genular Protein ID: 1840304716

Symbol: A0A384P5Z2_HUMAN

Name: N/A

UniProtKB Accession Codes:

A0A384P5Z2

Database IDs:

AlphaFoldDB 1 Antibodypedia 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 ExpressionAtlas 1 Gene3D 1 InterPro 3 KEGG 1 NCBI Taxonomy 1 OMA 1 OrthoDB 1 PANTHER 2 PROSITE 2 PeptideAtlas 1 Pfam 1 RefSeq 1 SAM 1 SMART 1 SUPFAM 1 VEuPathDB 1

Sequence Information:

  • Length: 465
  • Mass: 52535
  • Checksum: FDA38999358B350F
  • Sequence:
    • MAGGKQFTFS YENEVCKQDY FIKSPPSQLF SSVTSWKKRF FILSKAGEKS FSLSYYKDHH 
HRGSIEIDQN SSVEVGISSQ EKMQSVQKMF KCHPDEVMSI RTTNREYFLI GHDREKIKDW 
VSFMSSFRQD IKATQQNTEE ELSLGNKRTL FYSSPLLGPS STSEAVGSSS PRNGLQDKHL 
MEQSSPGFRQ THLQDLSEAT QDVKEENHYL TPRSVLLELD NIIASSDSGE SIETDGPDQV 
SGRIECHYEP MESYFFKETS HESVDSSKEE PQTLPETQDG DLHLQEQGSG IDWCLSPADV 
EAQTTNDQKG NIPDESQVEK LNVFLSPPDV INYLALTEAT GRICVSQWEG PPRLGCIFCH 
GDHLLAVNDL KPQSLEEVSL FLTRSIQKED SFRILSYQVA FGEGTELRDR APGFRTSDRH 
DVAKRACMES DWCRDSKTAP STNLCLSFLF CKIMTNDGAG CWIIK