Details for: POU2AF3

Gene ID: 120376

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: POU2AF3

Ensembl ID: ENSG00000214290

Description: POU class 2 homeobox associating factor 3

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • intestine goblet cell CL0019031
    CSI 4.13
    rCSI 3.67%
    PRS 96.13
  • ciliated epithelial cell CL0000067
    CSI 3.66
    rCSI 3.22%
    PRS 92.94
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 3.44
    rCSI 4.17%
    PRS 83.63
  • astrocyte of the cerebral cortex CL0002605
    CSI 3
    rCSI 6.73%
    PRS 92.23
  • ciliated cell CL0000064
    CSI 3
    rCSI 4.86%
    PRS 93.57
  • suprabasal keratinocyte CL4033013
    CSI 2.7
    rCSI 4.41%
    PRS 79.23
  • basal cell of epidermis CL0002187
    CSI 2.38
    rCSI 4.22%
    PRS 77.73
  • lung ciliated cell CL1000271
    CSI 2.15
    rCSI 2.48%
    PRS 94.61
  • tuft cell of colon CL0009041
    CSI 1.87
    rCSI 4.36%
    PRS 97.04
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 1.67
    rCSI 3.81%
    PRS 92.96

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.

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  • Node Color (Target Cell CSI, relative to current network):
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    • 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 [POU2AF3](/details-gene/120376) is a protein-coding gene that functions as a transcription coactivator. It plays a critical role in cellular transcription by binding to POU domain-containing proteins, thereby modulating gene expression. Expression data indicates that **Overall**, [POU2AF3](/details-gene/120376) is a significant marker in specialized epithelial cell populations, particularly secretory and ciliated lineages. It shows the highest significance in [intestine goblet cell](/details-cell/CL0019031) (CSI: 4.13) and various [ciliated epithelial cell](/details-cell/CL0000067) types. Its function as a coactivator for the transcription factor POU2F3 has been specifically demonstrated in the tuft cell lineage, highlighting its importance in intestinal cell differentiation [Link](https://doi.org/10.1038/s41586-022-04842-7). ## Cellular Roles and Expression Landscape The expression profile of [POU2AF3](/details-gene/120376) suggests a specialized role in the function and maintenance of mucosal and epidermal surfaces. **Overall**, its significance is highest in secretory cells of the gut, such as the [intestine goblet cell](/details-cell/CL0019031), and chemosensory [tuft cell of colon](/details-cell/CL0009041). This is consistent with studies identifying it as a coactivator for POU2F3, a master regulator of the tuft cell lineage [Link](https://doi.org/10.1038/s41586-022-04842-7). A second major functional niche for [POU2AF3](/details-gene/120376) appears to be in cells characterized by motile cilia. High CSI scores are observed in [ciliated epithelial cell](/details-cell/CL0000067) (CSI: 3.66), [ciliated cell](/details-cell/CL0000064) (CSI: 3.00), [lung ciliated cell](/details-cell/CL1000271) (CSI: 2.15), and [ciliated columnar cell of tracheobronchial tree](/details-cell/CL0002145) (CSI: 1.67), suggesting a potential role in ciliogenesis or the regulation of ciliary function. Beyond these roles, [POU2AF3](/details-gene/120376) also shows moderate significance in stratified epithelia, including [suprabasal keratinocyte](/details-cell/CL4033013) and [basal cell of epidermis](/details-cell/CL0002187), as well as in non-epithelial cells like [astrocyte of the cerebral cortex](/details-cell/CL0002605) and [CD8-positive, alpha-beta memory T cell, CD45RO-positive](/details-cell/CL0001203). This indicates that while its primary function may be in specific epithelial lineages, it may also participate in transcriptional regulation in select neural and immune contexts. ## Pathways and Molecular Function Functionally, [POU2AF3](/details-gene/120376) is annotated as a transcriptional coactivator. Its molecular activities include '[dna binding](/details-go/GO:0003677)', '[protein binding](/details-go/GO:0005515)', and specifically '[POU domain binding](/details-go/GO:0070974)'. These functions converge on its primary biological process: the '[positive regulation of dna-templated transcription](/details-go/GO:0045893)'. Consistent with its role as a transcriptional regulator, the protein is localized to both the '[nucleus](/details-go/GO:0005634)' and '[cytoplasm](/details-go/GO:0005737)', suggesting it may shuttle between these compartments to regulate gene expression. Its documented interaction with POU2F3 provides a direct mechanistic link between its molecular function and its observed role in specifying tuft cell identity [Link](https://doi.org/10.1038/s41586-022-04842-7). ## Research Directions The specific expression pattern of [POU2AF3](/details-gene/120376) in specialized intestinal epithelial cells, combined with reports linking variants in its locus to colorectal cancer [Link](https://doi.org/10.1002/ijc.28557), suggests it may play a role in gut homeostasis and pathology. **Testable Hypotheses:** 1. Dysregulation of [POU2AF3](/details-gene/120376) expression or function in intestinal stem cells could alter the balance of secretory cell differentiation (goblet vs. tuft cells), potentially contributing to the initiation or progression of inflammatory bowel disease or colorectal cancer. 2. Given its high expression across multiple ciliated cell types, [POU2AF3](/details-gene/120376) may be a critical upstream regulator of ciliogenesis. Its loss-of-function could lead to defects in mucociliary clearance in the respiratory tract, representing a potential genetic basis for a subset of primary ciliary dyskinesia cases. **Experimental Approach:** To test the first hypothesis, a CRISPR-Cas9 knockout of [POU2AF3](/details-gene/120376) could be generated in human intestinal organoids. The subsequent effects on cellular composition and lineage commitment would be assessed using single-cell RNA sequencing. This would reveal whether [POU2AF3](/details-gene/120376) is required for the proper differentiation of goblet and tuft cells from intestinal stem cell progenitors. Changes in the expression of key lineage markers (e.g., MUC2 for goblet cells, POU2F3 for tuft cells) could be validated by immunofluorescence and qPCR. **Therapeutic Potential:** As an intracellular transcription coactivator, [POU2AF3](/details-gene/120376) presents a challenging direct therapeutic target. However, if its interaction with a DNA-binding partner like POU2F3 is found to be essential for the survival of a specific cancer subtype (e.g., a tuft cell-like carcinoma), developing small molecule inhibitors to disrupt this protein-protein interface could be a viable strategy. Such an approach would require a high degree of specificity to avoid off-target effects, given the gene's expression in multiple healthy epithelial tissues. Therefore, inhibition would be the therapeutic goal, and targeted delivery systems might be necessary to mitigate potential toxicity.

Genular Protein ID: 3296894080

Symbol: OCAT2_HUMAN

Name: Cancer susceptibility candidate protein 13

UniProtKB Accession Codes:

A8K830 E9PMJ8 Q2TBJ3 V5LD62 V5LDI3 V5LDV1 V5LE09 V5LEU3

Database IDs:

AGR 1 AlphaFoldDB 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 8 Ensembl 5 ExpressionAtlas 1 GO 5 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 InterPro 2 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PharmGKB 1 Pharos 1 PhylomeDB 1 Proteomes 1 RNAct 1 RefSeq 6 SMR 1 STRING 1 UCSC 1 VEuPathDB 1 eggNOG 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: 24154973

Title: Identification of genes expressed by immune cells of the colon that are regulated by colorectal cancer-associated variants.

PubMed ID: 24154973

DOI: 10.1002/ijc.28557

PubMed ID: 16554811

Title: Human chromosome 11 DNA sequence and analysis including novel gene identification.

PubMed ID: 16554811

DOI: 10.1038/nature04632

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: 35576971

Title: OCA-T1 and OCA-T2 are coactivators of POU2F3 in the tuft cell lineage.

PubMed ID: 35576971

DOI: 10.1038/s41586-022-04842-7

Sequence Information:

  • Length: 251
  • Mass: 27417
  • Checksum: CDF0D94723FB6CDC
  • Sequence:
    • MSEKPKVYQG VRVKITVKEL LQQRRAHQAA SGGTRSGGSS VHLSDPVAPS SAGLYFEPEP 
ISSTPNYLQR GEFSSCVSCE ENSSCLDQIF DSYLQTEMHP EPLLNSTQSA PHHFPDSFQA 
TPFCFNQSLI PGSPSNSSIL SGSLDYSYSP VQLPSYAPEN YNSPASLDTR TCGYPPEDHS 
YQHLSSHAQY SCFSSATTSI CYCASCEAED LDALQAAEYF YPSTDCVDFA PSAAATSDFY 
KRETNCDICY S