Details for: XAGE2

Gene ID: 9502

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: XAGE2

Ensembl ID: ENSG00000155622

Description: X antigen family member 2

Cell Significance Landscape

Associated with

Significant Cells

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

  • extravillous trophoblast CL0008036
    CSI 6.82
    rCSI 8.44%
    PRS 99.59
  • placental villous trophoblast CL2000060
    CSI 6.54
    rCSI 10.1%
    PRS 99.53
  • syncytiotrophoblast cell CL0000525
    CSI 3.9
    rCSI 11.23%
    PRS 98.97

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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  • Node Color (Target Cell CSI, relative to current network):
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  • 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 [XAGE2](/details-gene/9502) is a protein-coding gene located on the X chromosome, identified as a member of the X antigen family. It is best characterized as a cancer/testis (CT) antigen, a class of proteins whose expression is typically restricted to germ cells in the testis but becomes aberrantly re-activated in various malignancies [Link](https://doi.org/10.1002/ijc.10371). Consistent with this restricted expression pattern, expression data shows that in normal tissues, [XAGE2](/details-gene/9502) is a highly significant and specific marker for placental cells, particularly [extravillous trophoblast](/details-cell/CL0008036) and [placental villous trophoblast](/details-cell/CL2000060). Its primary annotated molecular function is protein binding, suggesting it may act as a component of larger protein complexes in these specialized cell types. ## Cellular Roles and Expression Landscape The expression profile of [XAGE2](/details-gene/9502) indicates a highly specialized role in the placenta. **Overall**, the gene exhibits its most significant expression in key cells of the maternal-fetal interface, including [extravillous trophoblast](/details-cell/CL0008036) (CSI: 6.82), [placental villous trophoblast](/details-cell/CL2000060) (CSI: 6.54), and [syncytiotrophoblast cell](/details-cell/CL0000525) (CSI: 3.90). These cells are fundamental for implantation, nutrient exchange, and establishing maternal immunotolerance during pregnancy. This highly restricted expression pattern in the placenta, an immunologically unique organ, aligns with its classification as a cancer/testis antigen [Link](https://pubmed.ncbi.nlm.nih.gov/10197611/). CT antigens are often expressed in immunoprivileged sites, and their re-expression in cancers such as melanoma and Ewing's sarcoma makes them attractive targets for immunotherapy [Link](https://doi.org/10.1002/ijc.10371). The data strongly suggests that the primary physiological role of [XAGE2](/details-gene/9502) in non-pathological contexts is confined to placental development and function. ## Pathways and Molecular Function The functional annotation for [XAGE2](/details-gene/9502) is currently limited, with its primary known molecular function being protein binding ([GO:0005515](https://www.ebi.ac.uk/QuickGO/term/GO:0005515)). This general function suggests that [XAGE2](/details-gene/9502) likely operates not in isolation but as part of a larger protein complex. The specific binding partners and the downstream signaling pathways it regulates, particularly within trophoblasts or tumor cells, are areas requiring further investigation. Elucidating these interactions would be critical to understanding how it contributes to placental biology or the malignant phenotype of cancer cells. ## Research Directions The highly specific expression of [XAGE2](/details-gene/9502) in the placenta and its established identity as a tumor-associated antigen present clear avenues for future research. **Proposed Hypotheses:** 1. Given its high specificity for trophoblasts, [XAGE2](/details-gene/9502) may play a crucial role in placental development or function, potentially mediating cell-cell interactions, invasion, or signaling pathways necessary for successful implantation and pregnancy. 2. As a cancer/testis antigen, the aberrant re-expression of [XAGE2](/details-gene/9502) in tumor cells may confer a selective advantage, possibly by promoting cell proliferation, survival, or by modulating the tumor microenvironment to evade immune surveillance, mimicking functions it might serve in the immunoprivileged placenta. **Key Experimental Approach:** To test the hypothesis that [XAGE2](/details-gene/9502) is critical for placental function (Hypothesis 1), a powerful approach would involve using an *in vitro* human trophoblast stem cell (hTSC) model. By applying CRISPR-Cas9 to knock out [XAGE2](/details-gene/9502) in hTSCs, researchers could then differentiate these cells toward syncytiotrophoblast and extravillous trophoblast lineages. Subsequent analysis using RNA-sequencing would reveal transcriptomic changes, while functional assays, such as Matrigel invasion assays and cell fusion analyses, would directly assess the impact of [XAGE2](/details-gene/9502) loss on key trophoblast behaviors. **Therapeutic Potential:** The restricted expression profile of [XAGE2](/details-gene/9502) makes it an exceptionally promising target for cancer immunotherapy. Because its expression is limited to tumor cells and a single, non-vital adult tissue (testis, not detected in this dataset but known from literature), therapies targeting [XAGE2](/details-gene/9502) would be expected to have a wide therapeutic window with minimal on-target, off-tumor toxicity. It represents a prime candidate for the development of T-cell-based immunotherapies, such as TCR-engineered T cells or cancer vaccines, designed to recognize and eliminate [XAGE2](/details-gene/9502)-expressing tumor cells. The therapeutic strategy would focus on the targeted inhibition or destruction of these malignant cells.

Genular Protein ID: 983416401

Symbol: XAGE2_HUMAN

Name: X antigen family member 2

UniProtKB Accession Codes:

Q96GT9 Q5HYR4

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 7 Ensembl 1 ExpressionAtlas 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 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 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 RefSeq 2 SMART 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 11992404

Title: The XAGE family of cancer/testis-associated genes: alignment and expression profile in normal tissues, melanoma lesions and Ewing's sarcoma.

PubMed ID: 11992404

DOI: 10.1002/ijc.10371

PubMed ID: 15772651

Title: The DNA sequence of the human X chromosome.

PubMed ID: 15772651

DOI: 10.1038/nature03440

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: 10197611

Title: Novel genes in the PAGE and GAGE family of tumor antigens found by homology walking in the dbEST database.

PubMed ID: 10197611

Sequence Information:

  • Length: 111
  • Mass: 12354
  • Checksum: 38C93332C5BA0E14
  • Sequence:
    • MSWRGRSTYR PRPRRSLQPP ELIGAMLEPT DEEPKEEKPP TKSRNPTPDQ KREDDQGAAE 
IQVPDLEADL QELCQTKTGD GCEGGTDVKG KILPKAEHFK MPEAGEGKSQ V