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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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SIGLEC7
sialic acid binding Ig like lectin 7
Chromosome 19 · 19q13.41
NCBI Gene: 27036Ensembl: ENSG00000168995.14HGNC: HGNC:10876UniProt: Q9Y286
56PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingsialic acid bindingcell adhesionplasma membraneneurodegenerative diseaseneoplasmposterior cortical atrophybreast cancer
✦AI Summary

SIGLEC7 encodes a sialic acid-binding immunoglobulin-like lectin that functions as an inhibitory immune checkpoint receptor primarily expressed on natural killer (NK) cells and macrophages. The protein mediates sialic acid-dependent binding to cells, preferentially recognizing α-2,3- and α-2,6-linked sialic acids and disialogangliosides including GD2 and GD3 12. Upon ligand binding, SIGLEC7 recruits cytoplasmic phosphatases via SH2 domains to inhibit immune cell activation through dephosphorylation of signaling molecules 3. In cancer contexts, tumor cells exploit SIGLEC7 for immune evasion by expressing sialic acid ligands that suppress NK cell cytotoxicity and macrophage phagocytosis 14. The receptor binds to MYC-driven disialyl-T glycans, functioning as a 'don't eat me' signal that prevents cancer cell clearance 5. SIGLEC7 expression correlates with poor prognosis in multiple cancer types including prostate and pancreatic cancers, where sialylated glycans on both tumor cells and cancer-associated fibroblasts engage SIGLEC7 to promote immunosuppressive macrophage differentiation 67. Therapeutically, blocking SIGLEC7-ligand interactions enhances anti-tumor immunity, making it a promising target for cancer immunotherapy combinations 14.

Sources cited
1
SIGLEC7 binds GD2 disialoganglioside and interruption of this interaction enhances anti-tumor immunity
PMID: 35027753
2
SIGLEC7 expression correlates with poor prognosis in prostate cancer and blocking interactions inhibits tumor growth
PMID: 39436703
3
SIGLEC7 on NK cells negatively regulates immune function through sialic acid-containing ligand interactions
PMID: 32322597
4
Pancreatic cancer-associated fibroblasts express sialic acids that serve as SIGLEC7 ligands to modulate macrophage differentiation
PMID: 38594506
5
Sialic acids in pancreatic cancer cells drive tumor-associated macrophage differentiation via SIGLEC7
PMID: 33627655
6
SIGLEC7 on NK cells binds gangliosides GD3 and GD2 to inhibit immune signaling
PMID: 36701102
7
MYC-driven disialyl-T glycans function as SIGLEC7 ligands serving as 'don't eat me' signals
PMID: 36897988
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.20Weak
neoplasmOpen Targets
0.11Weak
posterior cortical atrophyOpen Targets
0.09Suggestive
breast cancerOpen Targets
0.09Suggestive
gliomaOpen Targets
0.08Suggestive
chronic lymphocytic leukemiaOpen Targets
0.08Suggestive
neutrophil immunodeficiency syndromeOpen Targets
0.08Suggestive
Miyoshi myopathyOpen Targets
0.08Suggestive
non-alcoholic fatty liver diseaseOpen Targets
0.07Suggestive
immunodeficiency 86Open Targets
0.06Suggestive
cancerOpen Targets
0.06Suggestive
type 2 diabetes mellitusOpen Targets
0.06Suggestive
Recurrent infection due to specific granule deficiencyOpen Targets
0.05Suggestive
Alzheimer diseaseOpen Targets
0.05Suggestive
diabetes mellitusOpen Targets
0.05Suggestive
Autosomal recessive hyper-IgE syndromeOpen Targets
0.05Suggestive
Autosomal recessive hyper-IgE syndrome due to TYK2 deficiencyOpen Targets
0.05Suggestive
immunodeficiency 35Open Targets
0.05Suggestive
acute myeloid leukemiaOpen Targets
0.05Suggestive
immunodeficiency 81Open Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
ISLRShared pathway100%LGALS4Shared pathway100%LY6DShared pathway100%SIGLEC5Shared pathway100%PSTPIP1Shared pathway100%TROAPShared pathway100%
Tissue Expression6 tissues
Bone Marrow
100%
Liver
88%
Lung
86%
Heart
16%
Brain
15%
Ovary
9%
Gene Interaction Network
Click a node to explore
SIGLEC7ISLRLGALS4LY6DSIGLEC5PSTPIP1TROAP
PROTEIN STRUCTURE
Preparing viewer…
PDB1NKO · 1.45 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.03LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.77 [0.58–1.03]
RankingsWhere SIGLEC7 stands among ~20K protein-coding genes
  • #8,134of 20,598
    Most Researched56
  • #10,169of 17,882
    Most Constrained (LOEUF)1.03
Genes detectedSIGLEC7
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Anti-GD2 synergizes with CD47 blockade to mediate tumor eradication.
PMID: 35027753
Nat Med · 2022
1.00
2
Sialylated glycoproteins suppress immune cell killing by binding to Siglec-7 and Siglec-9 in prostate cancer.
PMID: 39436703
J Clin Invest · 2024
0.90
3
Pancreatic cancer-associated fibroblasts modulate macrophage differentiation via sialic acid-Siglec interactions.
PMID: 38594506
Commun Biol · 2024
0.80
4
The Roles of Siglec7 and Siglec9 on Natural Killer Cells in Virus Infection and Tumour Progression.
PMID: 32322597
J Immunol Res · 2020
0.70
5
Sialic acids in pancreatic cancer cells drive tumour-associated macrophage differentiation via the Siglec receptors Siglec-7 and Siglec-9.
PMID: 33627655
Nat Commun · 2021
0.60