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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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SIGLEC6
sialic acid binding Ig like lectin 6
Chromosome 19 · 19q13.41
NCBI Gene: 946Ensembl: ENSG00000105492.16HGNC: HGNC:10875UniProt: O43699
26PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingsialic acid bindingcell adhesionplasma membraneFamilial prostate cancerprostate cancerchronic lymphocytic leukemiaacute myeloid leukemia
✦AI Summary

SIGLEC6 is a sialic acid-binding immunoglobulin-like lectin that functions as an adhesion molecule recognizing alpha-2,6-linked sialic acids on cell surfaces 1. The protein is expressed on specific immune cell subsets, including AXL+SIGLEC6+ dendritic cells (ASDCs) that circulate for approximately 2.16 days and are rapidly recruited to inflammatory sites 23. In leukemia, SIGLEC6 is highly expressed on acute myeloid leukemia (AML) blasts and leukemic stem cells but absent from normal hematopoietic stem and progenitor cells, making it an attractive therapeutic target 4. SIGLEC6 CAR T-cell therapy effectively eliminates AML cells by suppressing the SHP2/Src/ERK/IL-3 signaling axis 5. Beyond malignancy, SIGLEC6 engages inhibitory pathways relevant to mast cell silencing in chr19 urticaria treatment 67. In reproduction, embryonic SIGLEC6 interacts with sialylated CD44 in the endometrium to facilitate embryo implantation 1. Clinically, circulating SIGLEC6 levels are markedly elevated (9.5-fold) in preeclampsia and correlate with disease severity, emerging as a potential biomarker 8.

Sources cited
1
SIGLEC6 binds sialylated CD44 in embryonic trophectoderm and facilitates embryo-endometrium attachment during implantation
PMID: 39111624
2
AXL+SIGLEC6+ dendritic cells circulate for ~2.16 days and are rapidly recruited to inflammatory sites with distinctive effector functions
PMID: 39417994
3
AXL+SIGLEC6+ dendritic cells are identified as rare tumor-infiltrating subsets across 33 cancer types with distinct transcriptomic characteristics
PMID: 40742316
4
SIGLEC6 is expressed on AML blasts and leukemic stem cells but absent from normal hematopoietic stem cells, supporting CAR T-cell therapy development
PMID: 34289026
5
SIGLEC6 CAR T cells suppress AML progression by inhibiting SHP2/Src/ERK/IL-3 signaling activation
PMID: 40436895
6
SIGLEC6 agonist monoclonal antibodies (AK006) engage inhibitory receptors to silence mast cell activation in chronic urticaria
PMID: 37605867
7
SIGLEC6 is targeted by novel biologic agents to modulate alternative pathways of mast cell activation in chronic spontaneous urticaria
PMID: 39389712
8
Circulating SIGLEC6 is elevated 9.5-fold in preterm preeclampsia and correlates with disease severity across seven cohorts
PMID: 40737757
Disease Associationsⓘ20
Familial prostate cancerOpen Targets
0.11Weak
prostate cancerOpen Targets
0.11Weak
chronic lymphocytic leukemiaOpen Targets
0.10Weak
acute myeloid leukemiaOpen Targets
0.08Suggestive
preeclampsiaOpen Targets
0.08Suggestive
SplenomegalyOpen Targets
0.08Suggestive
MODYOpen Targets
0.07Suggestive
colorectal carcinomaOpen Targets
0.07Suggestive
maturity-onset diabetes of the young type 3Open Targets
0.06Suggestive
isolated agammaglobulinemiaOpen Targets
0.06Suggestive
X-Linked Combined Immunodeficiency DiseasesOpen Targets
0.05Suggestive
hyperproinsulinemiaOpen Targets
0.05Suggestive
immunodeficiency, common variable, 4Open Targets
0.05Suggestive
maturity-onset diabetes of the young type 10Open Targets
0.05Suggestive
immunodeficiency 88Open Targets
0.05Suggestive
Chronic mucocutaneous candidosisOpen Targets
0.05Suggestive
combined immunodeficiency due to ZAP70 deficiencyOpen Targets
0.04Suggestive
immunodeficiency 11b with atopic dermatitisOpen Targets
0.04Suggestive
primary familial polycythemia due to EPO receptor mutationOpen Targets
0.04Suggestive
eosinophil peroxidase deficiencyOpen Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
LEPProtein interaction96%CCN5Shared pathway67%SIGLEC14Shared pathway50%SIGLEC11Shared pathway50%MUC16Shared pathway50%SIGLEC12Shared pathway50%
Tissue Expression6 tissues
Lung
100%
Bone Marrow
33%
Heart
27%
Liver
6%
Brain
2%
Ovary
0%
Gene Interaction Network
Click a node to explore
SIGLEC6LEPCCN5SIGLEC14SIGLEC11MUC16SIGLEC12
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt O43699
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.98LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.73 [0.55–0.98]
RankingsWhere SIGLEC6 stands among ~20K protein-coding genes
  • #12,874of 20,598
    Most Researched26
  • #9,349of 17,882
    Most Constrained (LOEUF)0.98
Genes detectedSIGLEC6
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Pan-Cancer Analyses Refine the Single-Cell Portrait of Tumor-Infiltrating Dendritic Cells.
PMID: 40742316
Cancer Res · 2025
1.00
2
Chronic Spontaneous Urticaria: Current and Emerging Biologic Agents.
PMID: 39389712
Immunol Allergy Clin North Am · 2024
0.90
3
Mast cell silencing: A novel therapeutic approach for urticaria and other mast cell-mediated diseases.
PMID: 37605867
Allergy · 2024
0.80
4
Siglec-6 is a novel target for CAR T-cell therapy in acute myeloid leukemia.
PMID: 34289026
Blood · 2021
0.70
5
ST6GALNAC1-mediated sialylation in uterine endometrial epithelium facilitates the epithelium-embryo attachment.
PMID: 39111624
J Adv Res · 2025
0.60