Details for: SLAMF9

Gene ID: 89886

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: SLAMF9

Ensembl ID: ENSG00000162723

Description: SLAM family member 9

Cell Significance Landscape

Associated with

Significant Cells

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

  • basal cell of epidermis CL0002187
    CSI 2.17
    rCSI 3.85%
    PRS 93.55
  • suprabasal keratinocyte CL4033013
    CSI 1.45
    rCSI 2.37%
    PRS 95.22

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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    • High
    • Medium
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    • 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 [SLAMF9](/details-gene/89886) (Signaling Lymphocytic Activation Molecule family member 9) is a protein-coding gene located on chromosome 1. It belongs to the SLAM family of type I transmembrane proteins, which are members of the immunoglobulin superfamily known for their roles in regulating immune cell interactions and signaling. Functional annotations consistently link [SLAMF9](/details-gene/89886) to the [immune response](/details-cell/CL0000988) ([GO:0006955](https://www.ebi.ac.uk/QuickGO/term/GO:0006955)), particularly in processes such as [T cell activation](/details-cell/CL0000084) ([GO:0042110](https://www.ebi.ac.uk/QuickGO/term/GO:0042110)). However, expression data indicates its highest significance is in epidermal cells, including [basal cell of epidermis](/details-cell/CL0002187) and [suprabasal keratinocyte](/details-cell/CL4033013). This suggests that in addition to its presumed immunological functions, [SLAMF9](/details-gene/89886) may have a significant and potentially under-characterized role in skin biology and homeostasis. ## Cellular Roles and Expression Landscape **Overall**, the expression profile of [SLAMF9](/details-gene/89886) highlights a prominent role within the epidermis. The gene shows the highest significance in [basal cell of epidermis](/details-cell/CL0002187) (CSI: 2.17), the proliferative layer of the skin, and is also highly significant in differentiating [suprabasal keratinocyte](/details-cell/CL4033013) (CSI: 1.45). This expression pattern is notable given that the SLAM family is primarily associated with hematopoietic cells. Early research identified this gene, under aliases such as CD84-H1 and CD2F-10, in immune cells like dendritic cells ([Link](https://pubmed.ncbi.nlm.nih.gov/11300479/)) and confirmed its membership in the CD2 subset of the immunoglobulin superfamily ([Link](https://doi.org/10.1007/s002510100364)). The discrepancy between its established immune cell context and its high significance in keratinocytes suggests a dual functionality. It may be involved in immune surveillance at the cutaneous barrier or possess a distinct, non-immunological function related to epidermal stratification, cell-cell adhesion, or differentiation. ## Pathways and Molecular Function [SLAMF9](/details-gene/89886) is annotated as an integral membrane protein residing on the [external side of plasma membrane](/details-cell/CL0000589) ([GO:0009897](https://www.ebi.ac.uk/QuickGO/term/GO:0009897)), consistent with its role as a cell-surface receptor. Its involvement in the [immune response](/details-cell/CL0000988) ([GO:0006955](https://www.ebi.ac.uk/QuickGO/term/GO:0006955)) and specifically [T cell activation](/details-cell/CL0000084) ([GO:0042110](https://www.ebi.ac.uk/QuickGO/term/GO:0042110)) is supported by its functional annotations. As a SLAM family member, it likely functions in homophilic or heterophilic cell-cell interactions, transducing signals that modulate cellular activity. While the signaling pathways downstream of [SLAMF9](/details-gene/89886) in immune cells are an area of active research, its molecular function within keratinocytes is largely unexplored. It may participate in signaling cascades that control proliferation in basal cells or the terminal differentiation program in suprabasal layers. ## Research Directions The prominent expression of [SLAMF9](/details-gene/89886) in keratinocytes, contrasted with its immunological annotations, presents compelling avenues for future research. Understanding its role at the interface between the skin barrier and the immune system is of particular interest. ### Testable Hypotheses 1. **[SLAMF9](/details-gene/89886) contributes to epidermal barrier integrity through the regulation of keratinocyte adhesion and differentiation.** Given its high expression in both basal and suprabasal keratinocytes and its nature as a cell-surface protein, it may mediate cell-cell junctions. Dysregulation of [SLAMF9](/details-gene/89886) could therefore compromise barrier function, contributing to the pathology of inflammatory skin diseases like atopic dermatitis. 2. **[SLAMF9](/details-gene/89886) on keratinocytes acts as a sensor or signaling molecule in cutaneous immune surveillance.** It may function as a receptor for pathogen-associated patterns or as a ligand for receptors on skin-resident immune cells, such as Langerhans cells or dermal T cells, thereby modulating local immune tolerance or activation. ### Proposed Experimental Approach To test the hypothesis that [SLAMF9](/details-gene/89886) is critical for epidermal barrier function, a 3D organotypic skin equivalent model could be employed. Primary human keratinocytes with a CRISPR-Cas9-mediated knockout of [SLAMF9](/details-gene/89886) would be cultured to form a stratified epidermis. The integrity of the resulting tissue could be functionally assessed using transepidermal electrical resistance (TEER) measurements and fluorescent dye penetration assays. Furthermore, immunofluorescence microscopy and quantitative PCR could be used to analyze the expression and localization of key structural proteins involved in barrier formation, such as loricrin, filaggrin, and various cadherins, to determine the molecular consequences of [SLAMF9](/details-gene/89886) loss. ### Therapeutic Potential As a cell-surface protein, [SLAMF9](/details-gene/89886) is an accessible target for biologic therapies such as monoclonal antibodies. If it is shown to drive inflammation in diseases like psoriasis, an antagonist antibody could be developed to block its activity. Conversely, if it proves essential for maintaining barrier integrity, an agonist antibody or recombinant ligand might be therapeutically beneficial in conditions like atopic dermatitis. Its apparently high expression in the epidermis suggests that targeted topical therapies could be a viable strategy to maximize efficacy while minimizing potential systemic side effects.

Genular Protein ID: 2200582934

Symbol: SLAF9_HUMAN

Name: SLAM family member 9

UniProtKB Accession Codes:

Q96A28 Q5JRQ9 Q5JRR0 Q6UWG1

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 5 Ensembl 2 GO 3 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 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 PeptideAtlas 1 PharmGKB 1 Pharos 1 PhylomeDB 1 Proteomes 1 RNAct 1 RefSeq 3 SMR 1 STRING 1 SUPFAM 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 neXtProt 1

Citations:

PubMed ID: 11300479

Title: Genetic approach to insight into the immunobiology of human dendritic cells and identification of CD84-H1, a novel CD84 homologue.

PubMed ID: 11300479

PubMed ID: 11685473

Title: CD2F-10: a new member of the CD2 subset of the immunoglobulin superfamily.

PubMed ID: 11685473

DOI: 10.1007/s002510100364

PubMed ID: 12975309

Title: The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment.

PubMed ID: 12975309

DOI: 10.1101/gr.1293003

PubMed ID: 16710414

Title: The DNA sequence and biological annotation of human chromosome 1.

PubMed ID: 16710414

DOI: 10.1038/nature04727

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: 289
  • Mass: 32436
  • Checksum: 2BA22CBAC2E7F275
  • Sequence:
    • MCAFPWLLLL LLLQEGSQRR LWRWCGSEEV VAVLQESISL PLEIPPDEEV ENIIWSSHKS 
LATVVPGKEG HPATIMVTNP HYQGQVSFLD PSYSLHISNL SWEDSGLYQA QVNLRTSQIS 
TMQQYNICVY RWLSEPQITV NFESSGEGAC SMSLVCSVEK AGMDMTYSWL SRGDSTYTFH 
EGPVLSTSWR PGDSALSYTC RANNPISNVS SCPIPDGPFY ADPNYASEKP STAFCLLAKG 
LLIFLLLVIL AMGLWVIRVQ KRHKMPRMKK LMRNRMKLRK EAKPGSSPA

Genular Protein ID: 1642681519

Symbol: Q6NSE6_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q6NSE6

Database IDs:

AlphaFoldDB 1 BioGRID-ORCS 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 2 NCBI Taxonomy 1 OrthoDB 1 PharmGKB 1 RefSeq 1

Citations:

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: 38
  • Mass: 4576
  • Checksum: 41942446D0FD5917
  • Sequence:
    • MGLWVIRVQK RHKMPRMKKL MRNRMKLRKE AKPGSSPA