SIGLEC10 (Sialic Acid Binding Ig Like Lectin 10): Immune Checkpoint and Disease Implications
A comprehensive biomedical overview of SIGLEC10, including gene structure, expression, disease associations, mutations, and functional pathways.
Gene Information Card
| Symbol | SIGLEC10 |
|---|---|
| Full Name | sialic acid binding Ig like lectin 10 |
| Gene Type | protein coding |
| Chromosomal Location | 19q13.41 |
| NCBI Gene ID | 89790 ncbi.nlm.nih.gov/gene/89790 |
| Ensembl ID | ENSG00000142512 |
| UniProt ID | Q96LC7 |
| OMIM ID | 606091 |
| HGNC ID | 15624 |
| Aliases | SLG2, SIGLEC-10, PRO940, Siglec10 |
Description
SIGLEC10 (sialic acid binding Ig like lectin 10) is a member of the CD33-related Siglec family of immunomodulatory receptors. It is a type I transmembrane protein with an extracellular domain that binds sialic acid-containing glycans, and an intracellular tail containing immunoreceptor tyrosine-based inhibitory motifs (ITIMs). Upon ligand binding, SIGLEC10 recruits phosphatases such as SHP-1 and SHP-2, leading to inhibition of immune cell activation. It is expressed predominantly on immune cells, including B cells, natural killer (NK) cells, and subsets of T cells and dendritic cells. SIGLEC10 plays a role in immune homeostasis, and its dysregulation has been implicated in cancer, autoimmune diseases, and inflammatory conditions. It is also a target for cancer immunotherapy, as its blockade can enhance anti-tumor immune responses.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | SIGLEC10 is overexpressed on tumor-associated immune cells and tumor cells, contributing to immune evasion by inhibiting anti-tumor immunity. Its interaction with sialylated ligands on tumor cells suppresses NK and T cell activity. | Multiple studies, including those in NCBI and COSMIC, report elevated SIGLEC10 expression in tumor microenvironments and its association with poor prognosis in several cancers. |
| Autoimmune diseases (e.g., systemic lupus erythematosus) | SIGLEC10 may modulate B cell receptor signaling and autoantibody production. Reduced SIGLEC10 function could lead to hyperactive immune responses. | Evidence from OMIM and literature suggests genetic variants and altered expression of SIGLEC10 are associated with autoimmune susceptibility. |
| Inflammatory diseases (e.g., asthma, allergic inflammation) | SIGLEC10 on eosinophils and mast cells may regulate inflammatory responses. Its engagement can dampen allergic reactions. | Studies referenced in NCBI and UniProt indicate a role in modulating inflammation. |
| Infectious diseases (e.g., HIV, influenza) | SIGLEC10 can be exploited by pathogens to suppress immune responses. Some viruses use sialic acid mimicry to engage SIGLEC10 and evade immunity. | Research articles and databases like NCBI and UniProt document interactions with pathogens. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Spleen | High | High expression in immune-rich tissues. |
| Lymph node | High | High expression in immune-rich tissues. |
| Bone marrow | Medium | Moderate expression in hematopoietic tissues. |
| Blood | Medium | Expression in leukocytes. |
| Lung | Low | Low expression, mainly in immune cells. |
| Liver | Low | Low expression, possibly in Kupffer cells. |
| Brain | Low | Low expression, in microglia. |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| B cells (e.g., Ramos) | High | High expression on B lymphocytes. |
| NK cells (e.g., NK-92) | Medium | Moderate expression on NK cells. |
| Monocytes (e.g., THP-1) | Medium | Moderate expression on monocytes. |
| T cells (e.g., Jurkat) | Low | Low expression on T cells. |
| Dendritic cells (e.g., Mo-DC) | Medium | Moderate expression on dendritic cells. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs1126618 (missense variant) | SNP | Frequency varies by population (e.g., ~30% in some cohorts) | May affect ligand binding or protein stability; clinical significance uncertain. |
| rs2072269 (missense variant) | SNP | Frequency varies; ~20% in some populations | Potential impact on immune signaling; associated with autoimmune risk in some studies. |
| Copy number variations (CNVs) | CNV | Rare | Altered gene dosage may influence immune regulation; not well characterized. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in SIGLEC10 could lead to reduced inhibitory signaling, resulting in hyperactive immune responses and increased susceptibility to autoimmune diseases. However, such mutations are rare and not well documented in major databases.
Gain of Function (GOF)
Gain-of-function mutations that enhance SIGLEC10 expression or signaling could promote immune evasion in cancer, but specific activating mutations have not been extensively reported.
Dominant Negative (DN)
Dominant-negative effects are possible if a mutant allele interferes with wild-type SIGLEC10 function, but no such mutations have been clearly identified.
View complete mutation data：
Gene Ontology (GO)
| • carbohydrate binding | • protein binding |
| • sialic acid binding | • cell surface receptor signaling pathway |
| • negative regulation of immune response | • immune system process |
| • signal transduction | • plasma membrane |
| • integral component of membrane |
Pathways
• Immune system (Reactome: R-HSA-168256)
• Signaling by SHP2 (Reactome: R-HSA-112409)
• CD22-mediated B cell receptor regulation (Reactome: R-HSA-5690714)
• Innate Immune System (Reactome: R-HSA-168249)
Protein Summary
SIGLEC10 is a type I transmembrane protein of 697 amino acids (UniProt Q96LC7). It consists of an N-terminal V-set immunoglobulin-like domain that binds sialic acid, followed by two C2-set Ig-like domains, a transmembrane region, and a cytoplasmic tail containing two ITIM-like motifs. The protein is heavily glycosylated. Upon ligand engagement, the ITIMs become phosphorylated by Src family kinases, recruiting SHP-1 and SHP-2 phosphatases, which dephosphorylate signaling molecules and attenuate immune cell activation. SIGLEC10 is expressed on various immune cells and functions as an inhibitory receptor. Its molecular weight is approximately 75-80 kDa (unmodified), but glycosylation increases it to ~100-120 kDa. The protein is involved in cell-cell interactions and immune homeostasis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SIGLEC10 Knockout HEK293 Cell Line | EDJ-KQ17766 | Human | 89790 | Details Get a Quote |
| SIGLEC10 Knockout HeLa Cell Line | EDJ-KQ57738 | Human | 89790 | Details Get a Quote |
| SIGLEC10 Knockout A-549 Cell Line | EDJ-KQ66234 | Human | 89790 | Details Get a Quote |
| SIGLEC10 Knockout HCT 116 Cell Line | EDJ-KQ74655 | Human | 89790 | Details Get a Quote |
