CSF1R Gene: Colony Stimulating Factor 1 Receptor
A key regulator of macrophage development and innate immunity, implicated in neurodegenerative disorders and cancer.
Gene Information Card
| Symbol | CSF1R |
|---|---|
| Full Name | Colony Stimulating Factor 1 Receptor |
| Gene Type | Protein coding |
| Chromosomal Location | 5q32 |
| NCBI Gene ID | 1436 ncbi.nlm.nih.gov/gene/1436 |
| Ensembl ID | ENSG00000182578 |
| UniProt ID | P07333 |
| OMIM ID | 164770 |
| HGNC ID | 2433 |
| Aliases | CD115, C-FMS, FMS, M-CSF-R, CSF-1R, FIM2, HDLS |
Description
The CSF1R gene encodes the colony stimulating factor 1 receptor, a tyrosine-protein kinase that acts as the receptor for colony stimulating factor 1 (CSF1) and interleukin 34 (IL34). It is essential for the proliferation, differentiation, and survival of monocytes, macrophages, and microglia. Mutations in CSF1R are associated with hereditary diffuse leukoencephalopathy with spheroids (HDLS) and adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), as well as various cancers including acute myeloid leukemia and breast cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary diffuse leukoencephalopathy with spheroids (HDLS) / Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) | Loss-of-function mutations in CSF1R impair microglial survival and function, leading to white matter degeneration and axonal spheroids. | OMIM #221820; ClinVar |
| Acute myeloid leukemia (AML) | Gain-of-function mutations (e.g., L301S, Y969C) and chromosomal rearrangements (e.g., FIP1L1-PDGFRA fusion) involving CSF1R lead to constitutive kinase activation and uncontrolled proliferation. | COSMIC; ClinVar |
| Breast cancer | CSF1R overexpression and activation in tumor-associated macrophages promote tumor progression and metastasis via paracrine signaling. | NCBI Gene; PubMed |
| Tenosynovial giant cell tumor (TGCT) | CSF1 overexpression due to translocation (e.g., COL6A3-CSF1) drives CSF1R-dependent recruitment of macrophages, forming tumor masses. | OMIM #159800; ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 0.3 | Low |
| Lung | 2.1 | Medium |
| Liver | 0.5 | Low |
| Spleen | 12.4 | High |
| Bone marrow | 15.8 | High |
| Blood | 8.9 | High |
| Kidney | 1.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| THP-1 (monocytic leukemia) | 18.5 | High expression; model for macrophage differentiation |
| U-937 (histiocytic lymphoma) | 14.2 | High expression; monocytic lineage |
| K-562 (chronic myeloid leukemia) | 0.8 | Low expression |
| HepG2 (hepatocellular carcinoma) | 0.4 | Low expression |
| MCF7 (breast adenocarcinoma) | 2.3 | Moderate expression; associated with tumor microenvironment |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| L301S | Missense | 0.1% (AML) | Gain-of-function; constitutive kinase activation |
| Y969C | Missense | 0.05% (AML) | Gain-of-function; impaired receptor downregulation |
| E633K | Missense | 0.2% (HDLS/ALSP) | Loss-of-function; impaired kinase activity |
| A781T | Missense | 0.15% (HDLS/ALSP) | Loss-of-function; reduced protein stability |
| c.2442-1G>A | Splice site | 0.1% (HDLS/ALSP) | Loss-of-function; exon skipping and frameshift |
Mutation functional classification
Loss of Function (LOF)
Mutations in the kinase domain (e.g., E633K, A781T) or splice-site variants that reduce or abolish CSF1R tyrosine kinase activity, leading to microglial dysfunction and leukoencephalopathy (HDLS/ALSP).
Gain of Function (GOF)
Missense mutations (e.g., L301S, Y969C) that result in constitutive activation of the receptor, associated with acute myeloid leukemia and other myeloid malignancies.
Dominant Negative (DN)
Some CSF1R mutations in HDLS/ALSP may exert dominant-negative effects by forming inactive dimers with wild-type receptors, though this mechanism is less well-characterized.
View complete mutation data：
Gene Ontology (GO)
Pathways
• KEGG: hsa04640 - Hematopoietic cell lineage
• KEGG: hsa04668 - TNF signaling pathway
• KEGG: hsa05140 - Leishmaniasis
• KEGG: hsa05152 - Tuberculosis
• KEGG: hsa05200 - Pathways in cancer
• Reactome: R-HSA-9006934 - Signaling by CSF1 (M-CSF)
• Reactome: R-HSA-9008059 - Interleukin-34 signaling
• Reactome: R-HSA-5673001 - RAF/MAP kinase cascade
Protein Summary
CSF1R (CD115) is a single-pass type I transmembrane receptor tyrosine kinase of the platelet-derived growth factor receptor (PDGFR) family. The mature protein consists of an extracellular domain with five immunoglobulin-like domains, a transmembrane region, and an intracellular tyrosine kinase domain. Upon binding of CSF1 or IL34, the receptor dimerizes and autophosphorylates, activating downstream signaling pathways including MAPK, PI3K/AKT, and JAK/STAT. CSF1R is primarily expressed on monocytes, macrophages, microglia, and osteoclasts, and plays a critical role in innate immunity, bone remodeling, and brain homeostasis. Dysregulation of CSF1R signaling contributes to neurodegenerative diseases and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CSF1R Knockout HEK293 Cell Line | EDJ-KQ17808 | Human | 1436 | 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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