SH3BP2 (SH3 Domain Binding Protein 2)
A key regulator of bone homeostasis and inflammation, implicated in cherubism and other skeletal disorders.
Gene Information Card
| Symbol | SH3BP2 |
|---|---|
| Full Name | SH3 domain binding protein 2 |
| Gene Type | protein coding |
| Chromosomal Location | 4p16.3 |
| NCBI Gene ID | 6452 ncbi.nlm.nih.gov/gene/6452 |
| Ensembl ID | ENSG00000087266 |
| UniProt ID | Q9Y2M0 |
| OMIM ID | 602104 |
| HGNC ID | 10825 |
| Aliases | CRBM, 3BP-2, FLJ42079, MGC133155 |
Description
The SH3BP2 gene encodes the SH3 domain-binding protein 2, a cytoplasmic adaptor protein involved in intracellular signaling pathways. It plays a critical role in bone homeostasis by regulating osteoclast differentiation and function. Mutations in SH3BP2 are the primary cause of cherubism, a rare autosomal dominant disorder characterized by bilateral bone resorption and fibrous tissue replacement in the jaw. The protein is also implicated in inflammatory responses and has been studied in the context of cancer and other skeletal diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cherubism | Gain-of-function mutations in the SH3BP2 gene lead to enhanced signaling in myeloid cells, particularly through the SYK and VAV pathways, resulting in increased osteoclast activity and bone resorption in the jaw. | ClinVar, OMIM |
| Periodontitis (potential) | SH3BP2 variants may influence inflammatory responses and bone loss in periodontal tissues, though direct causal evidence is limited. | PubMed (via NCBI) |
| Osteoporosis (potential) | Altered SH3BP2 function could affect bone density, but no direct clinical association has been established. | PubMed (via NCBI) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone Marrow | Not available | High expression in osteoclasts and myeloid cells |
| Lymph Node | Not available | Moderate expression in immune cells |
| Spleen | Not available | Moderate expression |
| Thymus | Not available | Low expression |
| Lung | Not available | Low expression |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| THP-1 (monocyte) | Not available | Monocytic cell line; SH3BP2 expression relevant to myeloid function |
| U937 (histiocytic lymphoma) | Not available | Myeloid lineage; used in studies of SH3BP2 signaling |
| RAW 264.7 (mouse macrophage) | Not available | Murine macrophage cell line; commonly used for SH3BP2 functional studies |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Pro418Thr | Missense | Rare | Gain-of-function; associated with cherubism |
| p.Pro418Arg | Missense | Rare | Gain-of-function; associated with cherubism |
| p.Arg415Gln | Missense | Rare | Gain-of-function; associated with cherubism |
| p.Gly420Arg | Missense | Rare | Gain-of-function; associated with cherubism |
Mutation functional classification
Loss of Function (LOF)
No clear loss-of-function mutations have been reported for SH3BP2; the protein appears essential for normal bone homeostasis.
Gain of Function (GOF)
Most pathogenic mutations in SH3BP2 are missense mutations in the SH3-binding domain that result in gain-of-function, leading to hyperactivation of osteoclasts and cherubism.
Dominant Negative (DN)
No dominant-negative effects have been described for SH3BP2 mutations.
View complete mutation data：
Gene Ontology (GO)
| • protein binding | • signal transduction |
| • regulation of osteoclast differentiation | • positive regulation of protein tyrosine kinase activity |
| • cytokine production | • immune response |
Pathways
• SYK signaling in osteoclasts
• VAV signaling pathway
• Fc gamma receptor signaling
• Toll-like receptor signaling (potential)
Protein Summary
The SH3BP2 protein is a cytoplasmic adaptor that contains an SH3-binding domain, a pleckstrin homology (PH) domain, and a proline-rich region. It interacts with various signaling molecules, including SYK, VAV, and ABL, to modulate intracellular signaling cascades. In osteoclasts, SH3BP2 enhances SYK-dependent signaling, promoting osteoclast differentiation and bone resorption. Mutations in the SH3-binding domain disrupt autoinhibition, leading to constitutive activation and cherubism. The protein is also involved in immune cell signaling, particularly in B cells and macrophages.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SH3BP2 Knockout HEK293 Cell Line | EDJ-KQ3791 | Human | 6452 | Details Get a Quote |
| SH3BP2 Knockout A-549 Cell Line | EDJ-KQ25896 | Human | 6452 | Details Get a Quote |
| SH3BP2 Knockout HCT 116 Cell Line | EDJ-KQ25897 | Human | 6452 | Details Get a Quote |
| SH3BP2 Knockout HeLa Cell Line | EDJ-KQ25898 | Human | 6452 | Details Get a Quote |
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