| HGNC Family | Sialic acid binding Ig-like lectins (SIGLECs), Immunoglobulin superfamily domain containing |
| Name | sialic acid binding Ig-like lectin 12 (gene/pseudogene) |
| Description | Sialic acid-binding immunoglobulin-like lectins (SIGLECs) are a family of cell surface proteins belonging to the immunoglobulin superfamily. They mediate protein-carbohydrate interactions by selectively binding to different sialic acid moieties present on glycolipids and glycoproteins. This gene encodes a member of the SIGLEC3-like subfamily of SIGLECs. Members of this subfamily are characterized by an extracellular V-set immunoglobulin-like domain followed by two C2-set immunoglobulin-like domains, and the cytoplasmic tyrosine-based motifs ITIM and SLAM-like. The encoded protein, upon tyrosine phosphorylation, has been shown to recruit the Src homology 2 domain-containing protein-tyrosine phosphatases SHP1 and SHP2. It has been suggested that the protein is involved in the negative regulation of macrophage signaling by functioning as an inhibitory receptor. This gene is located in a cluster with other SIGLEC3-like genes on 19q13.4. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013] |
| Summary |
{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSIGLEC12 is a primate gene encoding the Siglec‐XII protein, a member of the CD33‐related Siglec family typically expressed on certain immune cells and various epithelial surfaces. In humans, a fixed missense R122C mutation abolishes its ability to bind sialic acids, and subsequent inactivating mutations – notably a common frameshift allele present in about 58% of individuals – further reduce its functional expression. However, the intact version of SIGLEC12 is retained in a subset of the human population and is particularly expressed on prostate epithelial cells, where its presence is associated with altered regulation of genes linked to carcinoma progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in epithelial biology, SIGLEC12 genetic variation has been implicated in differential responses to pharmacologic interventions. Specifically, the SIGLEC12 single nucleotide polymorphism rs16982743 was found to interact with antihypertensive treatment strategies, where its genotype – when combined with other markers – contributed to a genetic risk score that predicts cardiovascular outcomes. This finding suggests that SIGLEC12 may serve as a useful pharmacogenetic biomarker in personalized cardiovascular therapy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, emerging evidence supports a pro-oncogenic role for Siglec‐XII. Experimental models indicate that expression of the intact protein can drive oncogenic phenotypes, promoting tumor progression in epithelial-derived cancers such as those of the prostate and colorectal regions. Transcriptomic analyses have defined a signature of Siglec‐XII–positive disease, highlighting an association with mismatch-repair defects, inflammation, and specific ethnic predispositions. These findings underscore an evolutionary dynamic whereby the loss of functional SIGLEC12 expression in the majority of humans may have contributed to a decreased susceptibility to certain carcinomas."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Nivedita Mitra, Kalyan Banda, Tasha K Altheide, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SIGLEC12, a human-specific segregating (pseudo)gene, encodes a signaling molecule expressed in prostate carcinomas."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M111.244152"}], "href": "https://doi.org/10.1074/jbc.M111.244152"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21555517"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21555517"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Caitrin W McDonough, Yan Gong, Sandosh Padmanabhan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pharmacogenomic association of nonsynonymous SNPs in SIGLEC12, A1BG, and the selectin region and cardiovascular outcomes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hypertension (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/HYPERTENSIONAHA.111.00823"}], "href": "https://doi.org/10.1161/HYPERTENSIONAHA.111.00823"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23690342"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23690342"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Hector A Cuello, Saptarshi Sinha, Andrea L Verhagen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human-specific elimination of epithelial Siglec-XII suppresses the risk of inflammation-driven colorectal cancers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "JCI Insight (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/jci.insight.181539"}], "href": "https://doi.org/10.1172/jci.insight.181539"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38990656"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38990656"}]}]}]}
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| Synonyms | SLG, S2V, SIGLEC-XII, SIGLECL1 |
| Proteins | SIG12_HUMAN |
| NCBI Gene ID | 89858 |
| API | |
| Download Associations | |
| Predicted Functions |
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| Co-expressed Genes |
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| Expression in Tissues and Cell Lines |
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SIGLEC12 has 1,668 functional associations with biological entities spanning 9 categories (molecular profile, organism, functional term, phrase or reference, disease, phenotype or trait, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 62 datasets.
Click the + buttons to view associations for SIGLEC12 from the datasets below.
If available, associations are ranked by standardized value
| Dataset | Summary | |
|---|---|---|
| Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles | tissue samples with high or low expression of SIGLEC12 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset. | |
| Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray | tissue samples with high or low expression of SIGLEC12 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset. | |
| Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles | tissues with high or low expression of SIGLEC12 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset. | |
| BioGPS Human Cell Type and Tissue Gene Expression Profiles | cell types and tissues with high or low expression of SIGLEC12 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset. | |
| CCLE Cell Line Gene CNV Profiles | cell lines with high or low copy number of SIGLEC12 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset. | |
| ChEA Transcription Factor Binding Site Profiles | transcription factor binding site profiles with transcription factor binding evidence at the promoter of SIGLEC12 gene from the CHEA Transcription Factor Binding Site Profiles dataset. | |
| ChEA Transcription Factor Targets | transcription factors binding the promoter of SIGLEC12 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset. | |
| ChEA Transcription Factor Targets 2022 | transcription factors binding the promoter of SIGLEC12 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset. | |
| CM4AI KOLF21J CRISPRi Gene Perturbation Atlas | gene perturbations changing expression of SIGLEC12 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset. | |
| COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 | cellular components co-occuring with SIGLEC12 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset. | |
| COSMIC Cell Line Gene CNV Profiles | cell lines with high or low copy number of SIGLEC12 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset. | |
| COSMIC Cell Line Gene Mutation Profiles | cell lines with SIGLEC12 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset. | |
| DepMap CRISPR Gene Dependency | cell lines with fitness changed by SIGLEC12 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset. | |
| DISEASES Text-mining Gene-Disease Association Evidence Scores 2025 | diseases co-occuring with SIGLEC12 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset. | |
| DisGeNET Gene-Disease Associations | diseases associated with SIGLEC12 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset. | |
| DisGeNET Gene-Phenotype Associations | phenotypes associated with SIGLEC12 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset. | |
| ENCODE Histone Modification Site Profiles | histone modification site profiles with high histone modification abundance at SIGLEC12 gene from the ENCODE Histone Modification Site Profiles dataset. | |
| ENCODE Transcription Factor Binding Site Profiles | transcription factor binding site profiles with transcription factor binding evidence at the promoter of SIGLEC12 gene from the ENCODE Transcription Factor Binding Site Profiles dataset. | |
| ENCODE Transcription Factor Targets | transcription factors binding the promoter of SIGLEC12 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset. | |
| GeneRIF Biological Term Annotations | biological terms co-occuring with SIGLEC12 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset. | |
| GeneSigDB Published Gene Signatures | PubMedIDs of publications reporting gene signatures containing SIGLEC12 from the GeneSigDB Published Gene Signatures dataset. | |
| GEO Signatures of Differentially Expressed Genes for Diseases | disease perturbations changing expression of SIGLEC12 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset. | |
| GEO Signatures of Differentially Expressed Genes for Gene Perturbations | gene perturbations changing expression of SIGLEC12 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset. | |
| GEO Signatures of Differentially Expressed Genes for Kinase Perturbations | kinase perturbations changing expression of SIGLEC12 gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset. | |
| GEO Signatures of Differentially Expressed Genes for Small Molecules | small molecule perturbations changing expression of SIGLEC12 gene from the GEO Signatures of Differentially Expressed Genes for Small Molecules dataset. | |
| GEO Signatures of Differentially Expressed Genes for Viral Infections | virus perturbations changing expression of SIGLEC12 gene from the GEO Signatures of Differentially Expressed Genes for Viral Infections dataset. | |
| GO Biological Process Annotations 2015 | biological processes involving SIGLEC12 gene from the curated GO Biological Process Annotations 2015 dataset. | |
| GO Cellular Component Annotations 2015 | cellular components containing SIGLEC12 protein from the curated GO Cellular Component Annotations 2015 dataset. | |
| GO Molecular Function Annotations 2015 | molecular functions performed by SIGLEC12 gene from the curated GO Molecular Function Annotations 2015 dataset. | |
| GTEx eQTL 2025 | SNPs regulating expression of SIGLEC12 gene from the GTEx eQTL 2025 dataset. | |
| GTEx Tissue Gene Expression Profiles | tissues with high or low expression of SIGLEC12 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles dataset. | |
| GTEx Tissue Gene Expression Profiles 2023 | tissues with high or low expression of SIGLEC12 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles 2023 dataset. | |
| GTEx Tissue Sample Gene Expression Profiles | tissue samples with high or low expression of SIGLEC12 gene relative to other tissue samples from the GTEx Tissue Sample Gene Expression Profiles dataset. | |
| GWASdb SNP-Phenotype Associations | phenotypes associated with SIGLEC12 gene in GWAS datasets from the GWASdb SNP-Phenotype Associations dataset. | |
| Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles | cell lines with high or low expression of SIGLEC12 gene relative to other cell lines from the Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles dataset. | |
| HPA Tissue Gene Expression Profiles | tissues with high or low expression of SIGLEC12 gene relative to other tissues from the HPA Tissue Gene Expression Profiles dataset. | |
| HPA Tissue Sample Gene Expression Profiles | tissue samples with high or low expression of SIGLEC12 gene relative to other tissue samples from the HPA Tissue Sample Gene Expression Profiles dataset. | |
| Hub Proteins Protein-Protein Interactions | interacting hub proteins for SIGLEC12 from the curated Hub Proteins Protein-Protein Interactions dataset. | |
| HuGE Navigator Gene-Phenotype Associations | phenotypes associated with SIGLEC12 gene by text-mining GWAS publications from the HuGE Navigator Gene-Phenotype Associations dataset. | |
| IMPC Knockout Mouse Phenotypes | phenotypes of mice caused by SIGLEC12 gene knockout from the IMPC Knockout Mouse Phenotypes dataset. | |
| InterPro Predicted Protein Domain Annotations | protein domains predicted for SIGLEC12 protein from the InterPro Predicted Protein Domain Annotations dataset. | |
| JASPAR Predicted Human Transcription Factor Targets 2025 | transcription factors regulating expression of SIGLEC12 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Human Transcription Factor Targets dataset. | |
| JASPAR Predicted Transcription Factor Targets | transcription factors regulating expression of SIGLEC12 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Transcription Factor Targets dataset. | |
| Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles | cell lines with high or low copy number of SIGLEC12 gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles dataset. | |
| KnockTF Gene Expression Profiles with Transcription Factor Perturbations | transcription factor perturbations changing expression of SIGLEC12 gene from the KnockTF Gene Expression Profiles with Transcription Factor Perturbations dataset. | |
| LOCATE Predicted Protein Localization Annotations | cellular components predicted to contain SIGLEC12 protein from the LOCATE Predicted Protein Localization Annotations dataset. | |
| MotifMap Predicted Transcription Factor Targets | transcription factors regulating expression of SIGLEC12 gene predicted using known transcription factor binding site motifs from the MotifMap Predicted Transcription Factor Targets dataset. | |
| MoTrPAC Rat Endurance Exercise Training | tissue samples with high or low expression of SIGLEC12 gene relative to other tissue samples from the MoTrPAC Rat Endurance Exercise Training dataset. | |
| Pathway Commons Protein-Protein Interactions | interacting proteins for SIGLEC12 from the Pathway Commons Protein-Protein Interactions dataset. | |
| PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations | gene perturbations changing expression of SIGLEC12 gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset. | |
| PerturbAtlas Signatures of Differentially Expressed Genes for Mouse Gene Perturbations | gene perturbations changing expression of SIGLEC12 gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset. | |
| Reactome Pathways 2024 | pathways involving SIGLEC12 protein from the Reactome Pathways 2024 dataset. | |
| Roadmap Epigenomics Histone Modification Site Profiles | histone modification site profiles with high histone modification abundance at SIGLEC12 gene from the Roadmap Epigenomics Histone Modification Site Profiles dataset. | |
| Rummagene Transcription Factor Associations 2026 | transcription factors regulating expression of SIGLEC12 gene from the Rummagene Transcription Factor Associations 2026 dataset. | |
| RummaGEO Drug Perturbation Signatures | drug perturbations changing expression of SIGLEC12 gene from the RummaGEO Drug Perturbation Signatures dataset. | |
| RummaGEO Gene Perturbation Signatures | gene perturbations changing expression of SIGLEC12 gene from the RummaGEO Gene Perturbation Signatures dataset. | |
| Sanger Dependency Map Cancer Cell Line Proteomics | cell lines associated with SIGLEC12 protein from the Sanger Dependency Map Cancer Cell Line Proteomics dataset. | |
| Tabula Sapiens Gene-Cell Associations | cell types with high or low expression of SIGLEC12 gene relative to other cell types from the Tabula Sapiens Gene-Cell Associations dataset. | |
| TargetScan Predicted Nonconserved microRNA Targets | microRNAs regulating expression of SIGLEC12 gene predicted using nonconserved miRNA seed sequences from the TargetScan Predicted Nonconserved microRNA Targets dataset. | |
| TCGA Signatures of Differentially Expressed Genes for Tumors | tissue samples with high or low expression of SIGLEC12 gene relative to other tissue samples from the TCGA Signatures of Differentially Expressed Genes for Tumors dataset. | |
| TISSUES Curated Tissue Protein Expression Evidence Scores 2025 | tissues with high expression of SIGLEC12 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores 2025 dataset. | |
| TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 | tissues co-occuring with SIGLEC12 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 dataset. | |
