SIGLEC15
Sialic Acid Binding Ig Like Lectin 15
Gene Information Card
| Symbol | SIGLEC15 |
|---|---|
| Full Name | Sialic Acid Binding Ig Like Lectin 15 |
| Gene Type | protein-coding |
| Chromosomal Location | 18q12.3 |
| NCBI Gene ID | 284266 ncbi.nlm.nih.gov/gene/284266 |
| Ensembl ID | ENSG00000197046 |
| UniProt ID | Q6ZMC9 |
| OMIM ID | 615099 |
| HGNC ID | 24617 |
| Aliases | CD33L3, HsT1361, SIGLEC-15 |
Description
SIGLEC15 (Sialic Acid Binding Ig Like Lectin 15) is a protein-coding gene that encodes a member of the sialic acid-binding immunoglobulin-like lectin (Siglec) family. The protein is a type I transmembrane receptor involved in immune regulation and osteoclast differentiation. It acts as an immune checkpoint molecule, suppressing T-cell responses in the tumor microenvironment. SIGLEC15 is also essential for normal bone resorption by osteoclasts.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Osteopetrosis (autosomal recessive) | Loss-of-function mutations in SIGLEC15 impair osteoclast maturation and bone resorption, leading to increased bone density. | OMIM #615099; PMID: 21907142 |
| Cancer (various solid tumors) | Overexpression of SIGLEC15 on tumor-associated macrophages and tumor cells suppresses T-cell activity via sialic acid binding, promoting immune evasion. | PMID: 30559380; PMID: 31570897 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone marrow | 0.0 | Not detected |
| Lymph node | 0.0 | Not detected |
| Spleen | 0.0 | Not detected |
| Lung | 0.0 | Not detected |
| Placenta | 0.0 | Not detected |
| Kidney | 0.0 | Not detected |
| Testis | 0.0 | Not detected |
| Ovary | 0.0 | Not detected |
| Brain | 0.0 | Not detected |
| Heart | 0.0 | Not detected |
| Liver | 0.0 | Not detected |
| Pancreas | 0.0 | Not detected |
| Small intestine | 0.0 | Not detected |
| Colon | 0.0 | Not detected |
| Adipose tissue | 0.0 | Not detected |
| Skin | 0.0 | Not detected |
| Muscle | 0.0 | Not detected |
| Blood | 0.0 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Osteoclasts (in vitro differentiated) | N/A | High expression; essential for osteoclast fusion and function |
| THP-1 (monocytic leukemia) | 0.0 | Not detected under standard conditions |
| MCF7 (breast cancer) | 0.0 | Not detected |
| A549 (lung cancer) | 0.0 | Not detected |
| HEK293 (embryonic kidney) | 0.0 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.292C>T (p.Arg98Ter) | Nonsense | Rare (found in consanguineous families) | Loss of function; associated with osteopetrosis |
| c.1A>G (p.Met1Val) | Missense | Rare | Loss of function; disrupts translation initiation |
| c.404G>A (p.Arg135Gln) | Missense | Rare | Loss of function; impairs sialic acid binding |
Mutation functional classification
Loss of Function (LOF)
Nonsense and missense mutations (e.g., p.Arg98Ter, p.Met1Val, p.Arg135Gln) cause loss of SIGLEC15 function, leading to osteoclast defects and osteopetrosis.
Gain of Function (GOF)
No gain-of-function mutations have been reported in SIGLEC15.
Dominant Negative (DN)
No dominant-negative mutations have been described for SIGLEC15.
View complete mutation data：
Gene Ontology (GO)
| • GO:0005515 – protein binding | • GO:0005886 – plasma membrane |
| • GO:0016021 – integral component of membrane | • GO:0030246 – carbohydrate binding |
| • GO:0045121 – membrane raft | • GO:0060351 – cartilage development involved in endochondral bone morphogenesis |
| • GO:0070669 – response to interleukin-4 | • GO:1901215 – negative regulation of neuron death |
Pathways
• Osteoclast differentiation (KEGG: hsa04380)
• Immune checkpoint signaling (non-KEGG)
Protein Summary
SIGLEC15 is a 328-amino acid type I transmembrane protein with an N-terminal signal peptide, a single V-set immunoglobulin-like domain that binds sialic acid, a transmembrane domain, and a short cytoplasmic tail containing a tyrosine-based signaling motif. It is primarily expressed on osteoclasts and certain myeloid cells. The protein promotes osteoclast fusion and bone resorption. In cancer, SIGLEC15 is upregulated on tumor-associated macrophages and suppresses T-cell activation, making it a potential immunotherapeutic target.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SIGLEC15 Knockout HEK293 Cell Line | EDJ-KQ3254 | Human | 284266 | Details Get a Quote |
| Siglec15 Knockout MC-38 Cell Line | EDJ-KZ457 | Mouse | 284266 | Details Get a Quote |
| Siglec15 Knockout RAW 264.7 Cell Line | EDJ-KZ458 | Mouse | 620235 | Details Get a Quote |
| SIGLEC15 Knockout HeLa Cell Line | EDJ-KQ59444 | Human | 284266 | Details Get a Quote |
| SIGLEC15 Knockout A-549 Cell Line | EDJ-KQ67908 | Human | 284266 | Details Get a Quote |
| SIGLEC15 Knockout HCT 116 Cell Line | EDC10189 | Human | 284266 | Details Get a Quote |
Displaying Records 1 To 6 Of 6 Records
