CSF1 Gene - Colony Stimulating Factor 1
A key cytokine gene regulating macrophage development, bone homeostasis, and innate immunity, with clinical relevance in cancer and inflammatory disorders.
Gene Information Card
| Symbol | CSF1 |
|---|---|
| Full Name | Colony Stimulating Factor 1 |
| Gene Type | Protein Coding |
| Chromosomal Location | 1p13.3 |
| NCBI Gene ID | 1435 ncbi.nlm.nih.gov/gene/1435 |
| Ensembl ID | ENSG00000184371 |
| UniProt ID | P09603 |
| OMIM ID | 120420 |
| HGNC ID | 2432 |
| Aliases | MCSF, M-CSF, CSF-1 |
Description
The CSF1 gene encodes colony stimulating factor 1 (also known as macrophage colony-stimulating factor, M-CSF), a secreted cytokine that controls the survival, proliferation, and differentiation of mononuclear phagocytic cells, primarily macrophages and monocytes. It exerts its effects by binding to its receptor, CSF1R, a tyrosine kinase receptor. CSF1 is crucial for normal development, particularly in bone remodeling (osteoclastogenesis), female reproduction, and innate immune responses. Dysregulation of CSF1 signaling is implicated in various cancers and inflammatory diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Tenosynovial Giant Cell Tumor (TGCT) | Translocation of the CSF1 gene leads to its overexpression, attracting CSF1R-expressing macrophages that form the tumor mass. | OMIM, COSMIC |
| Diffuse-type TGCT (D-TGCT) | CSF1 gene rearrangements (e.g., t(1;2)) cause constitutive overexpression, driving tumor pathology. | OMIM, COSMIC |
| Adult-Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia (ALSP) | While primarily caused by CSF1R mutations, altered CSF1-CSF1R signaling is central to the disease mechanism. | OMIM |
| Osteopetrosis (in animal models) | Loss-of-function mutations in CSF1 lead to severe osteopetrosis due to impaired osteoclast development. | OMIM, NCBI Gene |
| Cancer (various, e.g., breast, ovarian) | CSF1 overexpression in the tumor microenvironment promotes tumor-associated macrophage (TAM) infiltration, which supports tumor growth, angiogenesis, and metastasis. | COSMIC, NCBI Gene |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone Marrow | High | High |
| Spleen | High | High |
| Lung | Medium | Medium |
| Placenta | Medium | Medium |
| Liver | Low | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| THP-1 (Monocytic leukemia) | High | Constitutively expressed; increases upon differentiation to macrophages. |
| U-937 (Histiocytic lymphoma) | High | Expressed in monocytic lineage. |
| MCF7 (Breast adenocarcinoma) | Low | Expression can be induced by inflammatory stimuli. |
| HeLa (Cervical carcinoma) | Low | Basal expression is low. |
| A549 (Lung carcinoma) | Medium | Expression may be modulated by tumor microenvironment. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| CSF1-COL6A3 fusion | Structural variant (translocation) | Rare (specific to TGCT) | Leads to CSF1 overexpression under the COL6A3 promoter, driving tumorigenesis. |
| CSF1-S100A10 fusion | Structural variant (translocation) | Rare (specific to TGCT) | Similar to above, causes CSF1 overexpression. |
| c.1327C>T (p.Arg443Ter) | Nonsense | Very rare (germline) | Predicted to cause loss of function; associated with severe skeletal abnormalities in animal models. |
| c.1054C>T (p.Arg352Trp) | Missense | Very rare (germline) | Uncertain significance; may affect protein function or stability. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in CSF1 are rare in humans but are well-documented in animal models (e.g., op/op mice). They result in severe osteopetrosis, decreased macrophage numbers, and reproductive defects, highlighting the essential role of CSF1 in osteoclast and macrophage biology.
Gain of Function (GOF)
Gain-of-function is primarily achieved through structural rearrangements (e.g., in TGCT) that place the CSF1 gene under the control of a strong, constitutively active promoter. This leads to overexpression of the normal CSF1 protein, which is the key oncogenic driver.
Dominant Negative (DN)
No dominant-negative mutations have been described for CSF1. The protein functions as a secreted ligand, and its effects are mediated through the receptor. Mutations are typically either loss-of-function or gain-of-function via overexpression.
View complete mutation data：
Gene Ontology (GO)
Pathways
• CSF1R Signaling Pathway
• Macrophage differentiation and activation
• Osteoclast differentiation (RANKL/RANK/OPG pathway interplay)
• Innate Immune System
• Cytokine-cytokine receptor interaction
Protein Summary
The CSF1 protein is a homodimeric, glycosylated cytokine that is synthesized as a precursor and proteolytically processed to form a secreted, biologically active molecule. It can also exist as a membrane-bound form. CSF1 binds to its receptor, CSF1R, leading to receptor dimerization and autophosphorylation, which activates downstream signaling cascades including the PI3K/AKT, MAPK/ERK, and JAK/STAT pathways. These pathways regulate the survival, proliferation, and differentiation of monocytes/macrophages. The protein is essential for the development of tissue-resident macrophages, osteoclasts, and microglia.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CSF1 Knockout HEK293 Cell Line | EDJ-KQ636 | Human | 1435 | Details Get a Quote |
| CSF1R Knockout HEK293 Cell Line | EDJ-KQ17808 | Human | 1436 | Details Get a Quote |
| CSF1 Knockout A-549 Cell Line | EDJ-KQ19107 | Human | 1435 | Details Get a Quote |
| CSF1 Knockout HCT 116 Cell Line | EDJ-KQ19108 | Human | 1435 | Details Get a Quote |
| CSF1 Knockout HeLa Cell Line | EDJ-KQ19109 | Human | 1435 | Details Get a Quote |
| CSF1R Knockout HeLa Cell Line | EDJ-KQ52999 | Human | 1436 | Details Get a Quote |
| CSF1R Knockout A-549 Cell Line | EDJ-KQ61465 | Human | 1436 | Details Get a Quote |
| CSF1R Knockout HCT 116 Cell Line | EDJ-KQ69962 | Human | 1436 | Details Get a Quote |
| CSF1R (p.T242=) Point Mutation in HAP1 Cell Line | EDC03445 | Human | 1436 | Details Get a Quote |
| CSF1R (p.P28=) Point Mutation in HAP1 Cell Line | EDC03447 | Human | 1436 | Details Get a Quote |
| CSF1R (c.1626+7C>T )Point Mutation in HAP1 Cell Line | EDC03444 | Human | 1436 | Details Get a Quote |
| CSF1R (c.592+41G>A )Point Mutation in HAP1 Cell Line | EDC03446 | Human | 1436 | Details Get a Quote |
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