CSF1R (colony stimulating factor 1 receptor)

Gene

• Entrez ID: 1436
• Gene name: Colony stimulating factor 1 receptor
• Gene symbol: CSF1R
• Synonyms: BANDDOS, C-FMS, CD115, CSF-1R, CSFR, FIM2, FMS, HDLS, M-CSF-R
• Chromosome: 5
• Chromosome location: 5q32
• Summary: The protein encoded by this gene is the receptor for colony stimulating factor 1, a cytokine which controls the production, differentiation, and function of macrophages. This receptor mediates most if not all of the biological effects of this cytokine. Ligand binding activates the receptor kinase through a process of oligomerization and transphosphorylation. The encoded protein is a tyrosine kinase transmembrane receptor and member of the CSF1/PDGF receptor family of tyrosine-protein kinases. Mutations in this gene have been associated with a predisposition to myeloid malignancy. The first intron of this gene contains a transcriptionally inactive ribosomal protein L7 processed pseudogene oriented in the opposite direction. Alternative splicing results in multiple transcript variants. Expression of a splice variant from an LTR promoter has been found in Hodgkin lymphoma (HL), HL cell lines and anaplastic large cell lymphoma. [provided by RefSeq, Mar 2017]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs1801271	T>A,C	Likely-pathogenic	Coding sequence variant, non coding transcript variant, missense variant
rs121913390	A>G,T	Likely-pathogenic	Missense variant, coding sequence variant, stop gained, non coding transcript variant
rs121913392	A>C,T	Likely-pathogenic	Stop gained, coding sequence variant, non coding transcript variant
rs121913393	A>G	Likely-pathogenic	Missense variant, coding sequence variant, non coding transcript variant
rs143025739	G>A	Conflicting-interpretations-of-pathogenicity, likely-benign	Non coding transcript variant, missense variant, coding sequence variant, 5 prime UTR variant
rs184499252	G>A,T	Likely-benign, benign, pathogenic	Missense variant, synonymous variant, non coding transcript variant, coding sequence variant
rs281860267	T>C	Pathogenic	Splice acceptor variant
rs281860268	C>T	Pathogenic	Missense variant, coding sequence variant, non coding transcript variant
rs281860269	C>T	Pathogenic	Missense variant, coding sequence variant, non coding transcript variant
rs281860270	A>G	Pathogenic	Missense variant, coding sequence variant, non coding transcript variant
rs281860271	C>G,T	Pathogenic	Missense variant, coding sequence variant, non coding transcript variant
rs281860272	T>C	Pathogenic	Splice acceptor variant
rs281860273	A>T	Pathogenic	Missense variant, coding sequence variant, non coding transcript variant
rs281860274	A>G	Pathogenic	Missense variant, coding sequence variant, non coding transcript variant
rs281860275	C>G	Pathogenic	Intron variant
rs281860276	AGA>-	Pathogenic	Inframe deletion, coding sequence variant, non coding transcript variant
rs281860277	A>G	Pathogenic	Missense variant, coding sequence variant, non coding transcript variant
rs281860278	A>C,G	Pathogenic	Missense variant, coding sequence variant, non coding transcript variant
rs281860279	A>G	Pathogenic	Missense variant, coding sequence variant, non coding transcript variant
rs281860280	G>T	Pathogenic	Missense variant, coding sequence variant, non coding transcript variant
rs281860281	C>A,T	Pathogenic, likely-pathogenic	Missense variant, coding sequence variant, non coding transcript variant
rs387906662	C>A	Pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs397515555	C>T	Pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs397515556	G>A	Pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs397515557	A>G	Pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs587777245	->A	Pathogenic	Coding sequence variant, frameshift variant, intron variant
rs587777246	C>A	Pathogenic	Splice donor variant
rs587777247	G>A,T	Pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs690016546	T>-	Pathogenic	Non coding transcript variant, coding sequence variant, frameshift variant
rs690016547	A>C	Pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs690016548	C>T	Pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs690016549	A>G,T	Pathogenic, likely-pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs690016550	A>G	Pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs690016551	C>G	Pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs690016552	A>G	Pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs690016553	G>A	Pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs690016554	T>C	Pathogenic	Splice acceptor variant
rs690016555	A>T	Pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs690016556	G>A	Pathogenic, likely-pathogenic	Non coding transcript variant, coding sequence variant, stop gained
rs690016557	C>G,T	Pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs690016558	T>A	Pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs690016559	A>G	Pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs690016560	A>G	Pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs690016561	T>G	Pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs690016562	G>A	Pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs690016563	A>G	Pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs690016564	C>T	Pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs690016565	A>T	Pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs690016566	C>T	Pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs917027829	G>A,T	Pathogenic	Non coding transcript variant, coding sequence variant, missense variant, stop gained
rs1057519802	A>C	Likely-pathogenic	Missense variant, coding sequence variant, non coding transcript variant
rs1057520014	C>A	Likely-pathogenic	Missense variant, coding sequence variant, non coding transcript variant
rs1351319114	G>A	Pathogenic	Missense variant, non coding transcript variant, 5 prime UTR variant, coding sequence variant
rs1554101963	TCT>-	Uncertain-significance, pathogenic	Coding sequence variant, inframe deletion, non coding transcript variant
rs1561901881	C>G	Likely-pathogenic	Non coding transcript variant, missense variant, coding sequence variant
rs1561904557	GGAT>TGCC	Pathogenic	Non coding transcript variant, missense variant, coding sequence variant
rs1561905293	G>A	Likely-pathogenic	Non coding transcript variant, missense variant, coding sequence variant
rs1561912628	C>T	Pathogenic	Intron variant
rs1561913526	C>G	Pathogenic	Splice acceptor variant
rs1581280059	G>T	Likely-pathogenic	Missense variant, coding sequence variant, non coding transcript variant
rs1581289103	CT>-	Pathogenic	Intron variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT006103	hsa-miR-155-5p	ELISA, Luciferase reporter assay, qRT-PCR, Western blot	21355095
MIRT006103	hsa-miR-155-5p	Luciferase reporter assay, qRT-PCR	24198819
MIRT438231	hsa-miR-34a-5p	Luciferase reporter assay, qRT-PCR	24198819
MIRT438232	hsa-miR-22-3p	Luciferase reporter assay, qRT-PCR	24198819

Transcription factors

Transcription factor	Regulation	Reference
NR3C1	Unknown	11891846
RUNX1	Unknown	8585955;9209363

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001934	Process	Positive regulation of protein phosphorylation	IMP	20504948
GO:0002244	Process	Hematopoietic progenitor cell differentiation	IBA	21873635
GO:0002931	Process	Response to ischemia	ISS	8922060
GO:0004713	Function	Protein tyrosine kinase activity	TAS	23392676
GO:0004714	Function	Transmembrane receptor protein tyrosine kinase activity	IBA	21873635
GO:0005011	Function	Macrophage colony-stimulating factor receptor activity	IBA	21873635
GO:0005011	Function	Macrophage colony-stimulating factor receptor activity	IMP	7683918, 20504948
GO:0005011	Function	Macrophage colony-stimulating factor receptor activity	ISS
GO:0005515	Function	Protein binding	IPI	22153499, 22483114, 22902366, 23478061, 26235028
GO:0005524	Function	ATP binding	IEA
GO:0005654	Component	Nucleoplasm	IDA
GO:0005886	Component	Plasma membrane	IDA
GO:0005886	Component	Plasma membrane	TAS
GO:0005887	Component	Integral component of plasma membrane	IBA	21873635
GO:0006954	Process	Inflammatory response	TAS	19132917
GO:0007165	Process	Signal transduction	TAS	8981357
GO:0007169	Process	Transmembrane receptor protein tyrosine kinase signaling pathway	IBA	21873635
GO:0007169	Process	Transmembrane receptor protein tyrosine kinase signaling pathway	ISS
GO:0007275	Process	Multicellular organism development	IBA	21873635
GO:0007411	Process	Axon guidance	IEA
GO:0008283	Process	Cell population proliferation	IMP	7683918
GO:0008284	Process	Positive regulation of cell population proliferation	IMP	20504948
GO:0008285	Process	Negative regulation of cell population proliferation	IEA
GO:0008360	Process	Regulation of cell shape	IMP	15117969
GO:0009986	Component	Cell surface	ISS	8922060
GO:0010759	Process	Positive regulation of macrophage chemotaxis	IGI	26754294
GO:0018108	Process	Peptidyl-tyrosine phosphorylation	IDA	20504948
GO:0019221	Process	Cytokine-mediated signaling pathway	IMP	20504948
GO:0019221	Process	Cytokine-mediated signaling pathway	TAS
GO:0019903	Function	Protein phosphatase binding	IEA
GO:0019955	Function	Cytokine binding	IDA	20504948
GO:0019955	Function	Cytokine binding	ISS	19017797
GO:0021772	Process	Olfactory bulb development	IEA
GO:0021879	Process	Forebrain neuron differentiation	IEA
GO:0030097	Process	Hemopoiesis	IMP	7683918
GO:0030224	Process	Monocyte differentiation	TAS	19132917
GO:0030225	Process	Macrophage differentiation	TAS	19132917
GO:0030316	Process	Osteoclast differentiation	IBA	21873635
GO:0030316	Process	Osteoclast differentiation	ISS
GO:0030335	Process	Positive regulation of cell migration	ISS
GO:0031529	Process	Ruffle organization	ISS
GO:0032722	Process	Positive regulation of chemokine production	IMP	20829061
GO:0033674	Process	Positive regulation of kinase activity	IBA	21873635
GO:0036006	Process	Cellular response to macrophage colony-stimulating factor stimulus	IMP	7683918, 20504948
GO:0038145	Process	Macrophage colony-stimulating factor signaling pathway	ISS
GO:0042531	Process	Positive regulation of tyrosine phosphorylation of STAT protein	ISS
GO:0042803	Function	Protein homodimerization activity	ISS	19017797
GO:0043066	Process	Negative regulation of apoptotic process	IEA
GO:0043231	Component	Intracellular membrane-bounded organelle	IDA
GO:0043235	Component	Receptor complex	IBA	21873635
GO:0044794	Process	Positive regulation by host of viral process	IEA
GO:0045087	Process	Innate immune response	IEA
GO:0045124	Process	Regulation of bone resorption	ISS
GO:0045217	Process	Cell-cell junction maintenance	IMP	15117969
GO:0046488	Process	Phosphatidylinositol metabolic process	ISS
GO:0046777	Process	Protein autophosphorylation	IDA	20504948
GO:0048015	Process	Phosphatidylinositol-mediated signaling	ISS
GO:0060603	Process	Mammary gland duct morphogenesis	TAS	15117969
GO:0061098	Process	Positive regulation of protein tyrosine kinase activity	IMP	7681396
GO:0061518	Process	Microglial cell proliferation	IEA
GO:0070374	Process	Positive regulation of ERK1 and ERK2 cascade	ISS
GO:0071345	Process	Cellular response to cytokine stimulus	ISS
GO:0071902	Process	Positive regulation of protein serine/threonine kinase activity	ISS
GO:0120041	Process	Positive regulation of macrophage proliferation	IGI	26754294
GO:1990682	Component	CSF1-CSF1R complex	IBA	21873635
GO:1990682	Component	CSF1-CSF1R complex	ISS	19017797
GO:2000147	Process	Positive regulation of cell motility	IMP	15117969
GO:2000249	Process	Regulation of actin cytoskeleton reorganization	ISS

Other IDs

• MIM: 164770
• HGNC: 2433
• e!Ensembl: ENSG00000182578

Protein

• UniProt ID: P07333
• Protein name: Macrophage colony-stimulating factor 1 receptor (CSF-1 receptor) (CSF-1-R) (CSF-1R) (M-CSF-R) (EC 2.7.10.1) (Proto-oncogene c-Fms) (CD antigen CD115)
• Protein 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, including the ERK1/2 and the JNK pathway (PubMed:20504948, PubMed:30982609). 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. In the central nervous system, may play a role in the development of microglia macrophages (PubMed:30982608).
• PDB: 2I0V, 2I0Y, 2I1M, 2OGV, 3BEA, 3DPK, 3KRJ, 3KRL, 3LCD, 3LCO, 4DKD, 4HW7, 4LIQ, 4R7H, 4R7I, 4WRL, 4WRM, 6IG8, 6N33, 6T2W, 6WXJ
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00047	ig	207 → 293	Immunoglobulin domain	Domain
  PF13927	Ig_3	397 → 489		Domain
  PF07714	PK_Tyr_Ser-Thr	582 → 910	Protein tyrosine and serine/threonine kinase	Domain

• Sequence:

  MGPGVLLLLLVATAWHGQGIPVIEPSVPELVVKPGATVTLRCVGNGSVEWDGPPSPHWTL
  YSDGSSSILSTNNATFQNTGTYRCTEPGDPLGGSAAIHLYVKDPARPWNVLAQEVVVFED
  QDALLPCLLTDPVLEAGVSLVRVRGRPLMRHTNYSFSPWHGFTIHRAKFIQSQDYQCSAL
  MGGRKVMSISIRLKVQKVIPGPPALTLVPAELVRIRGEAAQIVCSASSVDVNFDVFLQHN
  NTKLAIPQQSDFHNNRYQKVLTLNLDQVDFQHAGNYSCVASNVQGKHSTSMFFRVVESAY
  LNLSSEQNLIQEVTVGEGLNLKVMVEAYPGLQGFNWTYLGPFSDHQPEPKLANATTKDTY
  RHTFTLSLPRLKPSEAGRYSFLARNPGGWRALTFELTLRYPPEVSVIWTFINGSGTLLCA
  ASGYPQPNVTWLQCSGHTDRCDEAQVLQVWDDPYPEVLSQEPFHKVTVQSLLTVETLEHN
  QTYECRAHNSVGSGSWAFIPISAGAHTHPPDEFLFTPVVVACMSIMALLLLLLLLLLYKY
  KQKPKYQVRWKIIESYEGNSYTFIDPTQLPYNEKWEFPRNNLQFGKTLGAGAFGKVVEAT
  AFGLGKEDAVLKVAVKMLKSTAHADEKEALMSELKIMSHLGQHENIVNLLGACTHGGPVL
  VITEYCCYGDLLNFLRRKAEAMLGPSLSPGQDPEGGVDYKNIHLEKKYVRRDSGFSSQGV
  DTYVEMRPVSTSSNDSFSEQDLDKEDGRPLELRDLLHFSSQVAQGMAFLASKNCIHRDVA
  ARNVLLTNGHVAKIGDFGLARDIMNDSNYIVKGNARLPVKWMAPESIFDCVYTVQSDVWS
  YGILLWEIFSLGLNPYPGILVNSKFYKLVKDGYQMAQPAFAPKNIYSIMQACWALEPTHR
  PTFQQICSFLQEQAQEDRRERDYTNLPSSSRSGGSGSSSSELEEESSSEHLTCCEQGDIA
  QPLLQPNNYQFC

• Sequence length: 972