Browse CSF1R

Summary
SymbolCSF1R
Namecolony stimulating factor 1 receptor
Aliases C-FMS; CSFR; CD115; FMS; McDonough feline sarcoma viral (v-fms) oncogene homolog; CSF-1R; FIM2; HDLS; M-CSF- ......
Chromosomal Location5q32
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Cell membrane; Single-pass type I membrane protein.
Domain PF00047 Immunoglobulin domain
PF07714 Protein tyrosine kinase
Function

Tyrosine-protein kinase that acts as cell-surface receptor for CSF1 and IL34 and plays an essential role in the regulation of survival, proliferation and differentiation of hematopoietic precursor cells, especially mononuclear phagocytes, such as macrophages and monocytes. Promotes the release of proinflammatory chemokines in response to IL34 and CSF1, and thereby plays an important role in innate immunity and in inflammatory processes. Plays an important role in the regulation of osteoclast proliferation and differentiation, the regulation of bone resorption, and is required for normal bone and tooth development. Required for normal male and female fertility, and for normal development of milk ducts and acinar structures in the mammary gland during pregnancy. Promotes reorganization of the actin cytoskeleton, regulates formation of membrane ruffles, cell adhesion and cell migration, and promotes cancer cell invasion. Activates several signaling pathways in response to ligand binding. Phosphorylates PIK3R1, PLCG2, GRB2, SLA2 and CBL. Activation of PLCG2 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate, that then lead to the activation of protein kinase C family members, especially PRKCD. Phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leads to activation of the AKT1 signaling pathway. Activated CSF1R also mediates activation of the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1, and of the SRC family kinases SRC, FYN and YES1. Activated CSF1R transmits signals both via proteins that directly interact with phosphorylated tyrosine residues in its intracellular domain, or via adapter proteins, such as GRB2. Promotes activation of STAT family members STAT3, STAT5A and/or STAT5B. Promotes tyrosine phosphorylation of SHC1 and INPP5D/SHIP-1. Receptor signaling is down-regulated by protein phosphatases, such as INPP5D/SHIP-1, that dephosphorylate the receptor and its downstream effectors, and by rapid internalization of the activated receptor.

> Gene Ontology
 
Biological Process GO:0001819 positive regulation of cytokine production
GO:0001894 tissue homeostasis
GO:0002521 leukocyte differentiation
GO:0002573 myeloid leukocyte differentiation
GO:0006644 phospholipid metabolic process
GO:0006650 glycerophospholipid metabolic process
GO:0007259 JAK-STAT cascade
GO:0007260 tyrosine phosphorylation of STAT protein
GO:0007409 axonogenesis
GO:0007411 axon guidance
GO:0008360 regulation of cell shape
GO:0009306 protein secretion
GO:0018108 peptidyl-tyrosine phosphorylation
GO:0018212 peptidyl-tyrosine modification
GO:0021537 telencephalon development
GO:0021772 olfactory bulb development
GO:0021872 forebrain generation of neurons
GO:0021879 forebrain neuron differentiation
GO:0021953 central nervous system neuron differentiation
GO:0021988 olfactory lobe development
GO:0022604 regulation of cell morphogenesis
GO:0022612 gland morphogenesis
GO:0030099 myeloid cell differentiation
GO:0030224 monocyte differentiation
GO:0030225 macrophage differentiation
GO:0030316 osteoclast differentiation
GO:0030335 positive regulation of cell migration
GO:0030879 mammary gland development
GO:0030900 forebrain development
GO:0031529 ruffle organization
GO:0031532 actin cytoskeleton reorganization
GO:0032602 chemokine production
GO:0032642 regulation of chemokine production
GO:0032722 positive regulation of chemokine production
GO:0032844 regulation of homeostatic process
GO:0032956 regulation of actin cytoskeleton organization
GO:0032970 regulation of actin filament-based process
GO:0033674 positive regulation of kinase activity
GO:0034103 regulation of tissue remodeling
GO:0034330 cell junction organization
GO:0034331 cell junction maintenance
GO:0035239 tube morphogenesis
GO:0036005 response to macrophage colony-stimulating factor
GO:0036006 cellular response to macrophage colony-stimulating factor stimulus
GO:0038145 macrophage colony-stimulating factor signaling pathway
GO:0040017 positive regulation of locomotion
GO:0042503 tyrosine phosphorylation of Stat3 protein
GO:0042509 regulation of tyrosine phosphorylation of STAT protein
GO:0042516 regulation of tyrosine phosphorylation of Stat3 protein
GO:0042517 positive regulation of tyrosine phosphorylation of Stat3 protein
GO:0042531 positive regulation of tyrosine phosphorylation of STAT protein
GO:0043410 positive regulation of MAPK cascade
GO:0043954 cellular component maintenance
GO:0045124 regulation of bone resorption
GO:0045216 cell-cell junction organization
GO:0045217 cell-cell junction maintenance
GO:0045453 bone resorption
GO:0045860 positive regulation of protein kinase activity
GO:0046425 regulation of JAK-STAT cascade
GO:0046427 positive regulation of JAK-STAT cascade
GO:0046486 glycerolipid metabolic process
GO:0046488 phosphatidylinositol metabolic process
GO:0046777 protein autophosphorylation
GO:0046849 bone remodeling
GO:0046850 regulation of bone remodeling
GO:0048015 phosphatidylinositol-mediated signaling
GO:0048017 inositol lipid-mediated signaling
GO:0048667 cell morphogenesis involved in neuron differentiation
GO:0048732 gland development
GO:0048771 tissue remodeling
GO:0048871 multicellular organismal homeostasis
GO:0050663 cytokine secretion
GO:0050707 regulation of cytokine secretion
GO:0050708 regulation of protein secretion
GO:0050714 positive regulation of protein secretion
GO:0050715 positive regulation of cytokine secretion
GO:0050730 regulation of peptidyl-tyrosine phosphorylation
GO:0050731 positive regulation of peptidyl-tyrosine phosphorylation
GO:0051047 positive regulation of secretion
GO:0051222 positive regulation of protein transport
GO:0051272 positive regulation of cellular component movement
GO:0051493 regulation of cytoskeleton organization
GO:0060249 anatomical structure homeostasis
GO:0060443 mammary gland morphogenesis
GO:0060562 epithelial tube morphogenesis
GO:0060603 mammary gland duct morphogenesis
GO:0061097 regulation of protein tyrosine kinase activity
GO:0061098 positive regulation of protein tyrosine kinase activity
GO:0061180 mammary gland epithelium development
GO:0061564 axon development
GO:0070371 ERK1 and ERK2 cascade
GO:0070372 regulation of ERK1 and ERK2 cascade
GO:0070374 positive regulation of ERK1 and ERK2 cascade
GO:0071900 regulation of protein serine/threonine kinase activity
GO:0071902 positive regulation of protein serine/threonine kinase activity
GO:0090195 chemokine secretion
GO:0090196 regulation of chemokine secretion
GO:0090197 positive regulation of chemokine secretion
GO:0097485 neuron projection guidance
GO:0097696 STAT cascade
GO:1903131 mononuclear cell differentiation
GO:1903532 positive regulation of secretion by cell
GO:1904892 regulation of STAT cascade
GO:1904894 positive regulation of STAT cascade
GO:1904951 positive regulation of establishment of protein localization
GO:2000147 positive regulation of cell motility
GO:2000249 regulation of actin cytoskeleton reorganization
Molecular Function GO:0004713 protein tyrosine kinase activity
GO:0004714 transmembrane receptor protein tyrosine kinase activity
GO:0005011 macrophage colony-stimulating factor receptor activity
GO:0019199 transmembrane receptor protein kinase activity
GO:0019902 phosphatase binding
GO:0019903 protein phosphatase binding
GO:0019955 cytokine binding
Cellular Component GO:1990682 CSF1-CSF1R complex
> KEGG and Reactome Pathway
 
KEGG hsa04014 Ras signaling pathway
hsa04015 Rap1 signaling pathway
hsa04060 Cytokine-cytokine receptor interaction
hsa04144 Endocytosis
hsa04151 PI3K-Akt signaling pathway
hsa04380 Osteoclast differentiation
hsa04640 Hematopoietic cell lineage
Reactome R-HSA-1280215: Cytokine Signaling in Immune system
R-HSA-168256: Immune System
R-HSA-449147: Signaling by Interleukins
Summary
SymbolCSF1R
Namecolony stimulating factor 1 receptor
Aliases C-FMS; CSFR; CD115; FMS; McDonough feline sarcoma viral (v-fms) oncogene homolog; CSF-1R; FIM2; HDLS; M-CSF- ......
Chromosomal Location5q32
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between CSF1R and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between CSF1R and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
26957560NeuroblastomaInhibit immunityOur results demonstrate the essential role of CSF-1R signaling during the induction of suppressive myeloid cells and emphasize its clinical potential as an immunotherapy for human cancers.
28536100MesotheliomaInhibit immunityWe show that M-CSFR inhibition using the CSF-1R kinase inhibitor PLX3397 (pexidartinib) effectively reduced numbers of tumor-associated macrophages (TAMs) . TAM depletion could potentially reactivate antitumor immunity.
23418320Prostate CarcinomaInhibit immunity (infiltration)Enhanced macrophage migration induced by conditioned media from irradiated tumor cells was completely blocked by a selective inhibitor of CSF1R. These findings were confirmed in patients with prostate cancer, where serum levels of CSF1 increased after radiotherapy.
29632196Squamous Cell CarcinomaInhibit immunity (infiltration)Our results reveal that a CSF-1R blockade enhances CD8 T cell migration and infiltration into tumor islets.
29436395MelanomaInhibit immunity; immunotherapy targetWe demonstrate in an autochthonous, poorly immunogenic mouse model of melanoma that combination therapy with an agonistic anti-CD40 mAb and CSF-1R inhibitor potently suppressed tumor growth.
24247719MelanomaInhibit immunity; Resistant to immunotherapyInhibition of CSF-1 receptor improves the antitumor efficacy of adoptive cell transfer immunotherapy. In mice receiving the combined treatment, a dramatic reduction of TIMs and a skewing of MHCII(low) to MHCII(hi) macrophages were observed. Furthermore, mice receiving the combined treatment exhibited an increase in tumor-infiltrating lymphocytes (TIL) and T cells, as revealed by real-time imaging in vivo. In conclusion, CSF-1R blockade with PLX3397 improved the efficacy of ACT immunotherapy by inhibiting the intratumoral accumulation of immunosuppressive macrophages.
25082815pancreatic carcinomaInhibit immunityCSF1/CSF1R blockade reprograms tumor-infiltrating macrophages and improves response to T-cell checkpoint immunotherapy in pancreatic cancer models
23221383pancreatic carcinomaInhibit immunityTargeting CCR2 or CSF1R improves chemotherapeutic efficacy, inhibits metastasis, and increases antitumor T-cell responses.
Summary
SymbolCSF1R
Namecolony stimulating factor 1 receptor
Aliases C-FMS; CSFR; CD115; FMS; McDonough feline sarcoma viral (v-fms) oncogene homolog; CSF-1R; FIM2; HDLS; M-CSF- ......
Chromosomal Location5q32
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of CSF1R in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolCSF1R
Namecolony stimulating factor 1 receptor
Aliases C-FMS; CSFR; CD115; FMS; McDonough feline sarcoma viral (v-fms) oncogene homolog; CSF-1R; FIM2; HDLS; M-CSF- ......
Chromosomal Location5q32
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of CSF1R in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.0280.95
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.1960.923
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)870.0940.95
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.3280.487
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.1890.932
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.9870.743
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.2750.576
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.6630.697
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 1112-0.2320.908
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 481.1510.537
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 281.3950.622
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.3110.0708
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of CSF1R in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14177.107.10.452
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 414250250.222
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27733.72.711
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27593.73.40.31
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21174.811.8-70.577
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)86033.3-33.30.165
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13117.707.71
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38272.67.4-4.80.565
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22134.57.7-3.21
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 161407.1-7.10.467
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolCSF1R
Namecolony stimulating factor 1 receptor
Aliases C-FMS; CSFR; CD115; FMS; McDonough feline sarcoma viral (v-fms) oncogene homolog; CSF-1R; FIM2; HDLS; M-CSF- ......
Chromosomal Location5q32
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CSF1R. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolCSF1R
Namecolony stimulating factor 1 receptor
Aliases C-FMS; CSFR; CD115; FMS; McDonough feline sarcoma viral (v-fms) oncogene homolog; CSF-1R; FIM2; HDLS; M-CSF- ......
Chromosomal Location5q32
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CSF1R. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CSF1R.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolCSF1R
Namecolony stimulating factor 1 receptor
Aliases C-FMS; CSFR; CD115; FMS; McDonough feline sarcoma viral (v-fms) oncogene homolog; CSF-1R; FIM2; HDLS; M-CSF- ......
Chromosomal Location5q32
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CSF1R. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolCSF1R
Namecolony stimulating factor 1 receptor
Aliases C-FMS; CSFR; CD115; FMS; McDonough feline sarcoma viral (v-fms) oncogene homolog; CSF-1R; FIM2; HDLS; M-CSF- ......
Chromosomal Location5q32
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of CSF1R expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolCSF1R
Namecolony stimulating factor 1 receptor
Aliases C-FMS; CSFR; CD115; FMS; McDonough feline sarcoma viral (v-fms) oncogene homolog; CSF-1R; FIM2; HDLS; M-CSF- ......
Chromosomal Location5q32
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between CSF1R and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolCSF1R
Namecolony stimulating factor 1 receptor
Aliases C-FMS; CSFR; CD115; FMS; McDonough feline sarcoma viral (v-fms) oncogene homolog; CSF-1R; FIM2; HDLS; M-CSF- ......
Chromosomal Location5q32
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting CSF1R collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting CSF1R.
ID Name Drug Type Targets #Targets
DB00619ImatinibSmall MoleculeABL1, CSF1R, DDR1, KIT, NTRK1, PDGFRA, PDGFRB7
DB01268SunitinibSmall MoleculeCSF1R, FLT1, FLT3, FLT4, KDR, KIT, PDGFRA, PDGFRB8
DB06080ABT-869Small MoleculeCSF1R, FLT1, FLT3, FLT4, KDR, KIT6
DB071675-CYANO-FURAN-2-CARBOXYLIC ACID [5-HYDROXYMETHYL-2-(4-METHYL-PIPERIDIN-1-YL)-PHENYL]-AMIDESmall MoleculeCSF1R1
DB072026-CHLORO-3-(3-METHYLISOXAZOL-5-YL)-4-PHENYLQUINOLIN-2(1H)-ONESmall MoleculeCSF1R1