Details for: MAGEA8

Gene ID: 4107

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: MAGEA8

Ensembl ID: ENSG00000156009

Description: MAGE family member A8

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • placental villous trophoblast CL2000060
    CSI 8.74
    rCSI 13.51%
    PRS 100

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)

Loading network (please wait)...

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 [MAGEA8](/details-gene/4107), or Melanoma-Associated Antigen Family A, Member 8, is a protein-coding gene located on the X chromosome at position Xq28 [Link](https://pubmed.ncbi.nlm.nih.gov/15772651/). As a member of the MAGE cancer-testis antigen family, its expression is highly restricted in healthy adult tissues [Link](https://pubmed.ncbi.nlm.nih.gov/7927540/). Functional annotations suggest [MAGEA8](/details-gene/4107) operates within the [nucleus](/details-cell/GO:0005634) as a transcriptional regulator, where it is implicated in the [negative regulation of transcription by RNA polymerase II](/details-cell/GO:0000122), likely through its ability to bind histone deacetylases ([GO:0042826](https://www.ebi.ac.uk/QuickGO/term/GO:0042826)). **Overall**, its expression profile shows exceptional specificity, with significant expression almost exclusively observed in the '[placental villous trophoblast](/details-cell/CL2000060)', highlighting its specialized role in placental biology. ## Cellular Roles and Expression Landscape The expression landscape of [MAGEA8](/details-gene/4107) is characterized by its remarkable tissue specificity. **Overall**, the gene serves as a highly significant and defining marker for the '[placental villous trophoblast](/details-cell/CL2000060)' (CSI: 8.74), a specialized cell type essential for implantation and nutrient exchange in the placenta. This restricted expression pattern is a hallmark of cancer-testis antigens, which are typically confined to immune-privileged sites like the placenta and germline cells in healthy adults. The high significance of [MAGEA8](/details-gene/4107) in this context suggests it plays a critical, non-redundant role in placental development or in maintaining the unique physiological state of trophoblast cells. The absence of significant expression in other somatic cell types underscores its potential as a highly specific biomarker. ## Pathways and Molecular Function [MAGEA8](/details-gene/4107) functions primarily as a nuclear protein involved in the regulation of gene expression. Its annotation for [negative regulation of transcription by RNA polymerase II](/details-cell/GO:0000122) points to a role as a transcriptional repressor. The molecular mechanism underlying this function is suggested by its capacity for [histone deacetylase binding](/details-cell/GO:0042826). This interaction implies that [MAGEA8](/details-gene/4107) may be part of a larger chromatin-modifying complex that removes acetyl groups from histones, leading to a more compact chromatin structure and the silencing of target genes. This activity within the [nucleus](/details-cell/GO:0005634) is consistent with its proposed role in controlling cellular programs, which in the context of its expression in '[placental villous trophoblast](/details-cell/CL2000060)', could involve silencing genes to maintain cellular identity or regulate placental development. ## Research Directions The highly specific expression of [MAGEA8](/details-gene/4107) in the placenta, combined with the known propensity for MAGE family members to be aberrantly re-expressed in tumors, provides a clear basis for future investigation. While direct comparative data is not provided, the established biology of cancer-testis antigens strongly implies a dichotomy between its physiological role in the placenta and a potential pathological role in cancer. Based on the available data, several testable hypotheses can be proposed: 1. **Role in Placental Development:** [MAGEA8](/details-gene/4107) is essential for maintaining the undifferentiated and proliferative state of '[placental villous trophoblast](/details-cell/CL2000060)' cells by repressing the expression of genes that would otherwise drive terminal differentiation or senescence. 2. **Oncogenic Contribution via Gene Silencing:** Aberrant re-expression of [MAGEA8](/details-gene/4107) in somatic tissues contributes to tumorigenesis by forming repressive complexes that silence key tumor suppressor genes, thereby providing a selective advantage for cancer cell growth and survival. **Experimental Approach to Test Hypothesis 2:** To investigate the oncogenic role of [MAGEA8](/details-gene/4107), one could introduce its expression into a MAGEA8-negative cancer cell line (e.g., melanoma or lung adenocarcinoma). The impact on oncogenic phenotypes such as proliferation, invasion, and resistance to apoptosis could be assessed using standard cell-based assays. To identify its direct downstream targets, a combination of Chromatin Immunoprecipitation sequencing (ChIP-seq) using an antibody against [MAGEA8](/details-gene/4107) and RNA-sequencing (RNA-seq) could be performed. This would reveal the specific genomic loci bound by [MAGEA8](/details-gene/4107) and correlate this binding with changes in gene expression, directly testing the hypothesis that it silences tumor suppressor pathways. **Therapeutic Potential:** Given its extremely restricted expression in normal adult tissues and its identity as a cancer-testis antigen, [MAGEA8](/details-gene/4107) represents a highly attractive target for cancer immunotherapy. The therapeutic strategy would not be to inhibit the protein's function but to target the cancer cells that express it for destruction. Its intracellular location makes it unsuitable for standard antibody-based therapies, but peptides derived from the [MAGEA8](/details-gene/4107) protein can be presented on the surface of cancer cells by HLA molecules, making them ideal targets for T-cell based approaches. This includes the development of therapeutic cancer vaccines to elicit a patient's own T-cell response or adoptive cell transfer therapies using T-cells engineered with high-affinity T-cell receptors (TCRs) specific for MAGEA8-derived peptides.

Genular Protein ID: 1432001321

Symbol: MAGA8_HUMAN

Name: Melanoma-associated antigen 8

UniProtKB Accession Codes:

P43361 Q9BUN9

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 6 EMDB 1 Ensembl 3 GO 3 Gene3D 2 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 5 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 1 PDBsum 1 PIR 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 RefSeq 4 SMART 2 SMR 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

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: 7927540

Title: Structure, chromosomal localization, and expression of 12 genes of the MAGE family.

PubMed ID: 7927540

DOI: 10.1007/bf01246677

Sequence Information:

  • Length: 318
  • Mass: 35215
  • Checksum: EA02C1FB42F6C080
  • Sequence:
    • MLLGQKSQRY KAEEGLQAQG EAPGLMDVQI PTAEEQKAAS SSSTLIMGTL EEVTDSGSPS 
PPQSPEGASS SLTVTDSTLW SQSDEGSSSN EEEGPSTSPD PAHLESLFRE ALDEKVAELV 
RFLLRKYQIK EPVTKAEMLE SVIKNYKNHF PDIFSKASEC MQVIFGIDVK EVDPAGHSYI 
LVTCLGLSYD GLLGDDQSTP KTGLLIIVLG MILMEGSRAP EEAIWEALSV MGLYDGREHS 
VYWKLRKLLT QEWVQENYLE YRQAPGSDPV RYEFLWGPRA LAETSYVKVL EHVVRVNARV 
RISYPSLHEE ALGEEKGV

Genular Protein ID: 1347493561

Symbol: B2R9W4_HUMAN

Name: N/A

UniProtKB Accession Codes:

B2R9W4

Database IDs:

AlphaFoldDB 1 BioGRID-ORCS 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 Gene3D 2 InterPro 5 KEGG 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PROSITE 2 PeptideAtlas 1 Pfam 2 PharmGKB 1 RefSeq 3 SAM 1 SMART 2

Sequence Information:

  • Length: 318
  • Mass: 35157
  • Checksum: ACD9ACBDA69887DD
  • Sequence:
    • MLLGQKSQRY KAEEGLQAQG EAPGLMDVQI PTAEEQKAAS SSSTLIMGTL EEVTDSGSPS 
PPQSPEGASS SLTVTDSTLW SQSGEGSSSN EEEGPSTSPD PAHLESLFRE ALDEKVAELV 
RFLLRKYQIK EPVTKAEMLE SVIKNYKNHF PDIFSKASEC MQVIFGIDVK EVDPAGHSYI 
LVTCLGLSYD GLLGDDQSTP KTGLLIIVLG MILMEGSRAP EEAIWEALSV MGLYDGREHS 
VYWKLRKLLT QEWVQENYLE YRQAPGSDPV RYEFLWGPRA LAETSYVKVL EHVVRVNARV 
RISYPSLHEE ALGEEKGV