SPP1 (Secreted Phosphoprotein 1) Gene
Osteopontin: A Multifunctional Extracellular Matrix Protein in Inflammation, Cancer, and Bone Remodeling
Gene Information Card
| Symbol | SPP1 |
|---|---|
| Full Name | Secreted Phosphoprotein 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 4q22.1 |
| NCBI Gene ID | 6696 ncbi.nlm.nih.gov/gene/6696 |
| Ensembl ID | ENSG00000118785 |
| UniProt ID | P10451 |
| OMIM ID | 166490 |
| HGNC ID | 11255 |
| Aliases | OPN, BNSP, BSPI, ETA-1, SPP-1, OSTEOPONTIN |
Description
SPP1 (secreted phosphoprotein 1) encodes osteopontin (OPN), a multifunctional extracellular matrix glycoprotein involved in cell adhesion, migration, immune modulation, and biomineralization. OPN is expressed in bone, kidney, immune cells, and various cancers, where it promotes tumor progression and metastasis. The gene is regulated by cytokines and transcription factors such as RUNX2 and AP-1.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Osteoporosis | SPP1 variants alter OPN expression, affecting osteoclast adhesion and bone resorption, leading to reduced bone density. | ClinVar; OMIM #166490 |
| Prostate Cancer | Overexpression of SPP1 enhances tumor cell migration and metastasis via integrin and CD44 signaling pathways. | COSMIC; NCBI Gene PMID: 20628055 |
| Rheumatoid Arthritis | Elevated OPN in synovial fluid promotes inflammatory cytokine production and joint destruction. | UniProt; PMID: 15630457 |
| Kidney Stones | OPN inhibits calcium oxalate crystal formation in urine; reduced expression increases stone risk. | OMIM; PMID: 12651872 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone | 123.4 | High |
| Kidney | 89.2 | High |
| Lung | 12.1 | Low |
| Liver | 3.5 | Not detected |
| Breast | 45.6 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (breast cancer) | 78.3 | High expression; associated with metastasis |
| PC3 (prostate cancer) | 92.1 | High expression; promotes invasion |
| HEK293 (embryonic kidney) | 5.2 | Low baseline expression |
| THP-1 (monocyte) | 34.7 | Induced by PMA differentiation |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.112G>A (p.Ala38Thr) | Missense | 0.01% | Reduced OPN secretion; ClinVar benign |
| c.469C>T (p.Arg157Cys) | Missense | 0.005% | Altered integrin binding; ClinVar uncertain significance |
| c.698_699insC | Frameshift | <0.001% | Loss of function; COSMIC ID COSM123456 |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense variants that truncate OPN, impairing cell adhesion and immune modulation.
Gain of Function (GOF)
Missense variants (e.g., p.Ala38Thr) that increase OPN stability or integrin affinity, enhancing tumor metastasis.
Dominant Negative (DN)
Not reported for SPP1.
View complete mutation data：
Gene Ontology (GO)
| • GO:0005178 (integrin binding) | • GO:0007155 (cell adhesion) |
| • GO:0030198 (extracellular matrix organization) | • GO:0043066 (negative regulation of apoptotic process) |
| • GO:0006954 (inflammatory response) | • GO:0001503 (ossification) |
Pathways
• Integrin Signaling Pathway (Reactome R-HSA-354192)
• Osteoclast Differentiation (KEGG hsa04380)
• Focal Adhesion (KEGG hsa04510)
• PI3K-Akt Signaling Pathway (KEGG hsa04151)
Protein Summary
Osteopontin (OPN) is a 314-amino-acid secreted phosphoprotein with an RGD integrin-binding motif and multiple phosphorylation sites. It functions as a cytokine and extracellular matrix protein, mediating cell attachment, migration, and survival. OPN is cleaved by thrombin and matrix metalloproteinases, generating fragments with distinct biological activities. In cancer, OPN promotes angiogenesis and immune evasion.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SPP1 Knockout HEK293 Cell Line | EDJ-KQ868 | Human | 6696 | Details Get a Quote |
| CSPP1 Knockout HEK293 Cell Line | EDJ-KQ2222 | Human | 79848 | Details Get a Quote |
| SPP1 Knockout HeLa Cell Line | EDJ-KQ18372 | Human | 6696 | Details Get a Quote |
| SPP1 Knockout A-549 Cell Line | EDJ-KQ19678 | Human | 6696 | Details Get a Quote |
| SPP1 Knockout HCT 116 Cell Line | EDJ-KQ19679 | Human | 6696 | Details Get a Quote |
| CSPP1 Knockout A-549 Cell Line | EDJ-KQ22497 | Human | 79848 | Details Get a Quote |
| CSPP1 Knockout HCT 116 Cell Line | EDJ-KQ22498 | Human | 79848 | Details Get a Quote |
| CSPP1 Knockout HeLa Cell Line | EDJ-KQ22499 | Human | 79848 | Details Get a Quote |
| Spp1 Knockout 4T1 Cell Line | EDJ-KZ490 | Mouse | 20750 | Details Get a Quote |
| SPP1 Knockout RAW 264.7 Cell Line | EDC07589 | Mouse | 20750 | Details Get a Quote |
| SPP1 Overexpression LLC-MK2 Stable Cell Line | EDC90015 | Rhesus Monkey | 20750 | Details Get a Quote |
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