CSF1

Summary

CSF1 (colony stimulating factor 1, HGNC:2432) is a protein-coding gene on chromosome 1p13.3, encoding Macrophage colony-stimulating factor 1 (P09603). Cytokine that plays an essential role in the regulation of survival, proliferation and differentiation of hematopoietic precursor cells, especially mononuclear phagocytes, such as macrophages and monocytes.

The protein encoded by this gene is a cytokine that controls the production, differentiation, and function of macrophages. The active form of the protein is found extracellularly as a disulfide-linked homodimer, and is thought to be produced by proteolytic cleavage of membrane-bound precursors. The encoded protein may be involved in development of the placenta. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 1435 — RefSeq curated summary.

At a glance

• GWAS associations: 25
• Clinical variants (ClinVar): 102 total
• Druggable target: yes
• MANE Select transcript: NM_000757

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2432
Approved symbol	CSF1
Name	colony stimulating factor 1
Location	1p13.3
Locus type	gene with protein product
Status	Approved
Aliases	M-CSF, MCSF, MGC31930
Ensembl gene	ENSG00000184371
Ensembl biotype	protein_coding
OMIM	120420
Entrez	1435

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 16 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000329608, ENST00000357302, ENST00000369801, ENST00000369802, ENST00000420111, ENST00000488198, ENST00000525659, ENST00000526001, ENST00000527192, ENST00000875282, ENST00000875283, ENST00000875284, ENST00000875285, ENST00000875286, ENST00000875287, ENST00000913371, ENST00000958976

RefSeq mRNA: 4 — MANE Select: NM_000757 NM_000757, NM_172210, NM_172211, NM_172212

CCDS: CCDS30797, CCDS816, CCDS817

Canonical transcript exons

ENST00000329608 — 9 exons

Exon	Start	End
ENSE00001291595	109924776	109924828
ENSE00001304095	109915634	109915696
ENSE00001310214	109925147	109925202
ENSE00001321883	109923166	109924190
ENSE00001933966	109910849	109911062
ENSE00001937307	109928852	109930992
ENSE00003576195	109917293	109917463
ENSE00003586257	109921847	109921994
ENSE00003669519	109914259	109914381

Expression profiles

Bgee: expression breadth ubiquitous, 223 present calls, max score 94.58.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.5367 / max 1625.0135, expressed in 1560 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
4462	18.9658	1383
4461	1.8499	1002
4460	1.4640	817
4463	1.1077	608
4459	0.5560	309
4469	0.3023	148
4470	0.1475	52
4465	0.0807	20
4464	0.0627	10

Top tissues by expression

271 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
omental fat pad	UBERON:0010414	94.58	gold quality
peritoneum	UBERON:0002358	94.52	gold quality
adipose tissue of abdominal region	UBERON:0007808	93.68	gold quality
gall bladder	UBERON:0002110	93.05	gold quality
subcutaneous adipose tissue	UBERON:0002190	92.98	gold quality
right coronary artery	UBERON:0001625	92.82	gold quality
apex of heart	UBERON:0002098	92.67	gold quality
left adrenal gland	UBERON:0001234	92.60	gold quality
left coronary artery	UBERON:0001626	92.54	gold quality
cartilage tissue	UBERON:0002418	92.54	gold quality
right adrenal gland	UBERON:0001233	92.43	gold quality
right adrenal gland cortex	UBERON:0035827	92.42	gold quality
left adrenal gland cortex	UBERON:0035825	92.40	gold quality
endometrium epithelium	UBERON:0004811	92.27	silver quality
coronary artery	UBERON:0001621	92.07	gold quality
adrenal cortex	UBERON:0001235	91.77	gold quality
left uterine tube	UBERON:0001303	91.58	gold quality
pancreatic ductal cell	CL:0002079	91.26	silver quality
upper lobe of left lung	UBERON:0008952	91.24	gold quality
spleen	UBERON:0002106	90.82	gold quality
adrenal gland	UBERON:0002369	90.73	gold quality
tibial nerve	UBERON:0001323	90.47	gold quality
adipose tissue	UBERON:0001013	90.41	gold quality
upper lobe of lung	UBERON:0008948	90.37	gold quality
ascending aorta	UBERON:0001496	90.18	gold quality
thoracic aorta	UBERON:0001515	90.14	gold quality
descending thoracic aorta	UBERON:0002345	89.98	gold quality
connective tissue	UBERON:0002384	89.92	gold quality
synovial joint	UBERON:0002217	89.31	gold quality
mucosa of stomach	UBERON:0001199	89.15	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-6	yes	46.66
E-CURD-122	yes	8.69
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
CCL2	Activation
ITGAX	Activation

Upstream regulators (CollecTRI, top): ABL1, AP1, ATF3, BCL6, CCL2, CEBPA, EGR1, ETS2, FOS, FOXC1, GFI1, HLX, JUN, MITF, MYC, NCOA1, NFIA, NFIC, NFKB1, NFKB, NOTCH1, PHF5A, PPARG, RBPJ, REL, RELA, RUNX1, SMAD1, SMAD4, SMAD5, SMARCB1, SP1, SP3, SPI1, STAT1, TBP, TBX3, TFAP2A, TP63, TXK

miRNA regulators (miRDB)

138 targeting CSF1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805

Literature-anchored findings (GeneRIF, showing 40)

• Macrophage colony-stimulating factor and receptor activator NF-kappaB ligand fail to rescue osteoclast-poor human malignant infantile osteopetrosis in vitro. (PMID:11792569)
• High M-CSF levels may correlate with cellular or organ damage in patients treated with peripheral blood stem cell transplantation for hematologic diseases. (PMID:11843897)
• Opposite effects of different doses of MCSF on ERK phosphorylation and cell proliferation in macrophages. (PMID:12032835)
• CSF-1 and its receptor are regulated by 1,25(OH)(2)D(3) and its analogue tacalcitol in human monocytes which parallels the inhibition of differentiation into dendritic cells without altering survival (PMID:12372416)
• IFN-gamma shifts monocyte differentiation to macrophages rather than DCs through autocrine M-CSF and IL-6 production. (PMID:12393446)
• in human tumor cells, HGF and M-CSF stimulate osteopontin production (which is subsequently used as a substrate for cell adhesion) (PMID:12456016)
• Time-dependent folding events reveal that recombinant MCSF beta molecules pass through both monomeric and dimeric intermediate states, suggesting that the denatured and dimeric bond-reduced protein folds via multiple pathways. (PMID:12501178)
• macrophage colony-stimulating factor increased platelet-activating factor acetylhydrolase secretion by decidual macrophages (PMID:12548211)
• Results suggest that macrophage colony-stimulating factor may autoregulate functional cellular subpopulations of human endometrial stromal cells in an autocrine or a paracrine manner. (PMID:12684699)
• findings directly support the conclusion that membrane-bound colony stimulating factor-1 is functionally active in bone in vivo (PMID:12865350)
• Serum VEGF concentration was increased in arteriosclerosis obliterans (ASO) and thromboangitis obliterans, but increased concentration of M-CSF was seen only in ASO. (PMID:12890905)
• CSF1 has a role in regulating macrophage activation [review] (PMID:12894871)
• Monocytes promote angiogenesis via M-CSF-induced vascular endothelial growth factor production. (PMID:12928417)
• sCSF-1 is a key determinant of bone cell activity in the corticoendosteal envelope (PMID:12929928)
• increased levels of serum macrophage colony stimulating factor markedly precede the development of clinical manifestations of preeclampsia (PMID:14605992)
• Increase in serum M-CSF levels precedes development of preeclampsia. Elevation of serum M-CSF supports M-CSF elevation in placenta. This elevation at 18 weeks of gestation may be related to placental hypoxia, considered cause of preeclampsia. (PMID:14634568)
• findings of co-expression of KIT and/or FMS with their respective ligands implies these receptors might contribute to leukemogenesis in some patients with AML through autocrine, paracrine, or intracrine interactive stimulation. (PMID:14654075)
• The serum M-CSF concentration could be of interest as a tumor marker in squamous cell carcinomas of the head and neck. (PMID:15001836)
• red blood cells from diabetic patients induced an increase in MCSF and VCAM1 expression in HUVEC cells, mediated by AGE-RAGE interaction (PMID:15116247)
• Expreeeion of macrophage colony-stimulating factor in human osteoblast-like cells is suppressed by arginine-vasopressin. (PMID:15256272)
• results suggest that nuclear actin plays a role in regulating CSF-1 gene transcription, and this role does not depend on actin polymerization (PMID:15261158)
• In vitro human osteoclastogenesis is dependent on M-CSF and the stimulatory effects of GM-CSF are mediated by M-CSF. (PMID:15358207)
• Crystal structures of HLA-B*3501 in complex with 14-mer macrophage-colony stimulating factor peptide reveal that the antigenic peptide follows the general rules of major histocompatibility complex binding. (PMID:15494511)
• The MGFS mRNA expression in these cell lines and recent studies have demonstrated that HCs can stimulate tumor progression. (PMID:15576295)
• Interferon-gamma stimulates transcription of the CSF-1 gene through this sequence, which binds STAT1 (PMID:15624698)
• A significant serum tumor marker in head and neck squamous cell carcinoma. (PMID:15640942)
• Serum M-CSF levels are markedly increased in Langerhans cell histiocytosis patients who, in addition to bone disease, also show skin or lymph node involvement. (PMID:15728521)
• indicate novel roles of M-CSF in articular cartilage metabolism in collaboration with CTGF/CCN2, particularly during an inflammatory response (PMID:15820145)
• The M-CSF gene was cloned into baculovirus transfer vector pVL1392 under the control of polyhedrin promoter and expressed in the Sf9 cells (Spodoptera frugiperda). (PMID:15866728)
• Uncreased macrophage colony stimulating factor is associated with the process of atherosclerosis in hemodialysis patients (PMID:15919699)
• M-CSF enhances tumor growth in mice by increasing endothelial progenitor cells and activating angiogenesis; the effects of M-CSF are largely based on the induction of systemic VEGF from skeletal muscles. (PMID:15944252)
• catalase has a critical role in CSF-independent survival of human macrophages via regulation of the expression of BCL-2 and BCL-XL (PMID:16204228)
• INI1/hSNF5/BAF47 functions in activation of the colony stimulating factor 1 (CSF1) promoter in HeLa cells. (PMID:16267391)
• MCP-1 and M-CSF, critical for monocyte recruitment, activation, and differentiation, differentially regulate VEGF-A expression and may play an important role in monocyte/macrophage- mediated tumor angiogenesis (PMID:16318581)
• Nurse-like cells are involved in rheumatoid arthritis-induced bone destruction by maintaining osteoclast precursors via production of M-CSF. (PMID:16320327)
• Fusion with COL6A3 overexpresses CSF1, found in some but not all cells in tenosynovial giant-cell tumor and pigmented villonodular synovitis. (PMID:16407111)
• at 35 and 38 weeks, the Macrophage colony-stimulating factor (M-CSF) levels were significantly higher in twin pregnancy than in singleton pregnancy (PMID:16673212)
• three polymorphisms located in the colony stimulating factor 1 (CSF1) gene showed a positive association with aggressive periodontitis (PMID:16844084)
• IL-10 may contribute to the inflammatory process by facilitating monocyte differentiation into TNF-alpha-responsive macrophages in the presence of M-CSF in rheumatoid arthritis. (PMID:16859503)
• Different individual CSF-1 isoforms regulate the frequency of activated macrophages in the kidney during experimental unilateral ureteral obstruction. (PMID:16951369)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	csf1b	ENSDARG00000068263
danio_rerio	csf1a	ENSDARG00000075343
mus_musculus	Csf1	ENSMUSG00000014599
rattus_norvegicus	Csf1	ENSRNOG00000018659

Protein

Protein identifiers

Macrophage colony-stimulating factor 1 — P09603 (reviewed: P09603)

Alternative names: Lanimostim, Proteoglycan macrophage colony-stimulating factor

All UniProt accessions (5): E9PJA2, E9PKP4, E9PQ08, P09603, H7BY18

UniProt curated annotations — full annotation on UniProt →

Function. Cytokine that 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 pro-inflammatory chemokines, 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 development. Required for normal male and female fertility. Promotes reorganization of the actin cytoskeleton, regulates formation of membrane ruffles, cell adhesion and cell migration. Plays a role in lipoprotein clearance.

Subunit / interactions. Homodimer or heterodimer; disulfide-linked. Likely to exist in multiple forms: homodimer consisting of 2 identical 150-200 kDa proteoglycan subunits, heterodimer consisting of a 150-200 kDa proteoglycan subunit and a truncated 43 kDa subunit, and homodimer consisting of 2 identical 43 kDa subunits. Interacts with CSF1R.

Subcellular location. Cell membrane Secreted. Extracellular space.

Post-translational modifications. N-glycosylated. N-glycosylated. N-glycosylated. O-glycosylated; contains chondroitin sulfate. O-glycosylated with core 1 or possibly core 8 glycans. O-glycosylated.

Disease relevance. Aberrant expression of CSF1 or CSF1R can promote cancer cell proliferation, invasion and formation of metastases. Overexpression of CSF1 or CSF1R is observed in a significant percentage of breast, ovarian, prostate, and endometrial cancers. Aberrant expression of CSF1 or CSF1R may play a role in inflammatory diseases, such as rheumatoid arthritis, glomerulonephritis, atherosclerosis, and allograft rejection.

Isoforms (3)

UniProt ID	Names	Canonical?
P09603-1	1	yes
P09603-2	2
P09603-3	3

RefSeq proteins (4): NP_000748, NP_757349, NP_757350, NP_757351 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008001	MCSF-1	Family
IPR009079	4_helix_cytokine-like_core	Homologous_superfamily

Pfam: PF05337

UniProt features (59 total): sequence conflict 9, helix 9, disulfide bond 6, sequence variant 6, glycosylation site 5, compositionally biased region 4, mutagenesis site 4, chain 3, region of interest 3, splice variant 2, topological domain 2, strand 2, signal peptide 1, modified residue 1, transmembrane region 1, turn 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
5LXF	X-RAY DIFFRACTION	2
4FA8	X-RAY DIFFRACTION	2.2
1HMC	X-RAY DIFFRACTION	2.5
3UF2	X-RAY DIFFRACTION	2.75
4WRL	X-RAY DIFFRACTION	2.8
3UEZ	X-RAY DIFFRACTION	3.41
4ADF	X-RAY DIFFRACTION	4.4
4WRM	X-RAY DIFFRACTION	6.85

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P09603-F1	58.62	0.26

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 266

Disulfide bonds (6): 39–122, 63, 80–171, 134–178, 189, 191

Glycosylation sites (5): 154, 172, 309, 363, 365

Mutagenesis-validated functional residues (4):

Position	Phenotype
252	loss of 43 kda subunit.
309	loss of chondroitin sulfate attachment.
444	does not affect production of 150-200 kda subunit.
489–554	produces biologically active protein which is secreted.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-381426	Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-449836	Other interleukin signaling
R-HSA-6783783	Interleukin-10 signaling
R-HSA-8957275	Post-translational protein phosphorylation
R-HSA-9680350	Signaling by CSF1 (M-CSF) in myeloid cells
R-HSA-9856649	Transcriptional and post-translational regulation of MITF-M expression and activity

MSigDB gene sets: 582 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, BERENJENO_ROCK_SIGNALING_NOT_VIA_RHOA_DN, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_MAMMARY_GLAND_MORPHOGENESIS, GOBP_REGULATION_OF_OSTEOCLAST_DIFFERENTIATION, BENPORATH_ES_WITH_H3K27ME3, GOBP_GLAND_MORPHOGENESIS, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CELL_CHEMOTAXIS, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, MODULE_255

GO Biological Process (43): neutrophil homeostasis (GO:0001780), positive regulation of cell-matrix adhesion (GO:0001954), osteoclast proliferation (GO:0002158), response to ischemia (GO:0002931), developmental process involved in reproduction (GO:0003006), inflammatory response (GO:0006954), cell surface receptor protein tyrosine kinase signaling pathway (GO:0007169), Ras protein signal transduction (GO:0007265), positive regulation of cell population proliferation (GO:0008284), positive regulation of gene expression (GO:0010628), regulation of macrophage derived foam cell differentiation (GO:0010743), positive regulation of macrophage derived foam cell differentiation (GO:0010744), positive regulation of macrophage chemotaxis (GO:0010759), monocyte differentiation (GO:0030224), macrophage differentiation (GO:0030225), regulation of ossification (GO:0030278), osteoclast differentiation (GO:0030316), positive regulation of cell migration (GO:0030335), positive regulation of mononuclear cell proliferation (GO:0032946), monocyte homeostasis (GO:0035702), macrophage colony-stimulating factor signaling pathway (GO:0038145), positive regulation of multicellular organism growth (GO:0040018), monocyte activation (GO:0042117), positive regulation of odontogenesis of dentin-containing tooth (GO:0042488), innate immune response (GO:0045087), positive regulation of macrophage differentiation (GO:0045651), positive regulation of monocyte differentiation (GO:0045657), positive regulation of osteoclast differentiation (GO:0045672), positive regulation of Ras protein signal transduction (GO:0046579), homeostasis of number of cells within a tissue (GO:0048873), positive regulation of protein metabolic process (GO:0051247), branching involved in mammary gland duct morphogenesis (GO:0060444), mammary gland fat development (GO:0060611), mammary duct terminal end bud growth (GO:0060763), microglial cell proliferation (GO:0061518), macrophage homeostasis (GO:0061519), myeloid leukocyte migration (GO:0097529), positive regulation of macrophage colony-stimulating factor signaling pathway (GO:1902228), positive regulation of microglial cell migration (GO:1904141), positive regulation of macrophage migration (GO:1905523)

GO Molecular Function (6): cytokine activity (GO:0005125), macrophage colony-stimulating factor receptor binding (GO:0005157), growth factor activity (GO:0008083), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), protein binding (GO:0005515)

GO Cellular Component (8): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), endoplasmic reticulum lumen (GO:0005788), plasma membrane (GO:0005886), membrane (GO:0016020), nuclear body (GO:0016604), perinuclear region of cytoplasm (GO:0048471), CSF1-CSF1R complex (GO:1990682)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Signaling by Interleukins	2
Metabolism of proteins	1
Post-translational protein modification	1
Cytokine Signaling in Immune system	1
MITF-M-regulated melanocyte development	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
myeloid leukocyte differentiation	3
cellular anatomical structure	3
leukocyte homeostasis	2
myeloid cell homeostasis	2
macrophage derived foam cell differentiation	2
mononuclear cell differentiation	2
receptor ligand activity	2
regulation of cell-matrix adhesion	1
cell-matrix adhesion	1
positive regulation of cell-substrate adhesion	1
leukocyte proliferation	1
response to stress	1
reproductive process	1
developmental process	1
defense response	1
enzyme-linked receptor protein signaling pathway	1
small GTPase-mediated signal transduction	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
regulation of cell differentiation	1
regulation of macrophage derived foam cell differentiation	1
positive regulation of cell differentiation	1
positive regulation of leukocyte chemotaxis	1
regulation of macrophage chemotaxis	1
macrophage chemotaxis	1
regulation of granulocyte chemotaxis	1
positive regulation of macrophage migration	1
ossification	1
regulation of multicellular organismal process	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
mononuclear cell proliferation	1
regulation of mononuclear cell proliferation	1
positive regulation of leukocyte proliferation	1
cytokine receptor binding	1

Protein interactions and networks

STRING

3393 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CSF1	CSF1R	P07333	999
CSF1	IL34	Q6ZMJ4	976
CSF1	CSF2	P04141	963
CSF1	EGF	P01133	942
CSF1	CSF3	P09919	932
CSF1	TNFSF11	O14788	909
CSF1	IL3	P08700	899
CSF1	CCR2	P41597	837
CSF1	EGFR	P00533	834
CSF1	IL1A	P01583	808
CSF1	IL6	P05231	806
CSF1	SRC	P12931	804
CSF1	IL1B	P01584	794
CSF1	CCL2	P13500	792
CSF1	IL10	P22301	792

IntAct

67 interactions, top by confidence:

A	B	Type	Score
CSF1	CSF1R	psi-mi:“MI:0407”(direct interaction)	0.920
CSF1R	CSF1	psi-mi:“MI:0407”(direct interaction)	0.920
CSF1	CSF1	psi-mi:“MI:0407”(direct interaction)	0.780
SGTA	CSF1	psi-mi:“MI:0915”(physical association)	0.720
CSF1	SGTA	psi-mi:“MI:0915”(physical association)	0.720
CSF1		psi-mi:“MI:0407”(direct interaction)	0.710

BioGRID (16): FHL3 (Two-hybrid), SGTA (Two-hybrid), NOTCH2NL (Two-hybrid), CSF1 (Affinity Capture-RNA), CSF1 (Affinity Capture-MS), CSF1 (Affinity Capture-RNA), CSF1 (Two-hybrid), CSF1 (Two-hybrid), KRTAP10-8 (Two-hybrid), KRTAP1-1 (Two-hybrid), CYSRT1 (Two-hybrid), CSF1 (Reconstituted Complex), AMIGO1 (Affinity Capture-MS), CBL (Affinity Capture-Western), CSF1 (Reconstituted Complex)

ESM2 similar proteins: A0A1B0GV85, A2ALI5, A2APT9, B0BN44, B1ARY8, B6ZI38, O14836, O35188, O55145, O60279, O60667, P07141, P09603, P0C8S2, P28906, P40225, P40226, P42705, P78423, Q06154, Q08DV9, Q13261, Q1ERP8, Q28270, Q2TB54, Q3UY90, Q4V9H3, Q4W8E7, Q5F267, Q5R770, Q60819, Q64314, Q6PAL1, Q6PCP7, Q6UXB8, Q80XI1, Q8BLK9, Q8CAE9, Q8CBC4, Q8JZQ0

Diamond homologs: P07141, P09603, Q8JZQ0

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
SMARCB1	“up-regulates quantity by expression”	CSF1	“transcriptional regulation”
CSF1	up-regulates	CSF3R	binding
CSF1	“up-regulates activity”	CSF1R	binding
CSF1	up-regulates	M2_polarization
CSF1	up-regulates	CSF2RA	binding

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

102 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	79
Likely benign	7
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

1479 predictions. Top by Δscore:

Variant	Effect	Δscore
1:109911060:ACGGT:A	donor_loss	1.0000
1:109911061:CGGT:C	donor_loss	1.0000
1:109911062:GGT:G	donor_loss	1.0000
1:109911063:GTA:G	donor_loss	1.0000
1:109911064:T:G	donor_loss	1.0000
1:109917287:TTTCA:T	acceptor_loss	1.0000
1:109917290:CA:C	acceptor_loss	1.0000
1:109917291:A:AG	acceptor_gain	1.0000
1:109917292:G:A	acceptor_loss	1.0000
1:109917292:G:GG	acceptor_gain	1.0000
1:109917460:CAAGG:C	donor_loss	1.0000
1:109917461:AAGG:A	donor_loss	1.0000
1:109917462:AGG:A	donor_loss	1.0000
1:109917463:GGT:G	donor_loss	1.0000
1:109917465:T:G	donor_loss	1.0000
1:109921990:CCAAG:C	donor_gain	1.0000
1:109921991:CAAG:C	donor_gain	1.0000
1:109921992:AAG:A	donor_gain	1.0000
1:109921993:AG:A	donor_gain	1.0000
1:109921994:GG:G	donor_gain	1.0000
1:109921995:G:C	donor_loss	1.0000
1:109921995:G:GG	donor_gain	1.0000
1:109924186:GGCGG:G	donor_gain	1.0000
1:109924187:GCGG:G	donor_gain	1.0000
1:109924187:GCGGG:G	donor_gain	1.0000
1:109924190:GGT:G	donor_loss	1.0000
1:109924191:G:GG	donor_gain	1.0000
1:109924191:GT:G	donor_loss	1.0000
1:109911063:G:GG	donor_gain	0.9900
1:109914257:A:AG	acceptor_gain	0.9900

AlphaMissense

3625 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:109917362:T:C	F99L	0.995
1:109917364:C:A	F99L	0.995
1:109917364:C:G	F99L	0.995
1:109917363:T:G	F99C	0.994
1:109921961:T:A	C171S	0.994
1:109921962:G:C	C171S	0.994
1:109914380:T:C	L54P	0.992
1:109915677:T:G	F69C	0.992
1:109917305:T:A	C80S	0.992
1:109917305:T:C	C80R	0.992
1:109917306:G:C	C80S	0.992
1:109917363:T:C	F99S	0.992
1:109915676:T:C	F69L	0.991
1:109915678:T:A	F69L	0.991
1:109915678:T:G	F69L	0.991
1:109921850:T:C	C134R	0.990
1:109921850:T:A	C134S	0.989
1:109921851:G:C	C134S	0.989
1:109921950:T:G	F167C	0.989
1:109915670:T:C	F67L	0.988
1:109915672:T:A	F67L	0.988
1:109915672:T:G	F67L	0.988
1:109917307:C:G	C80W	0.988
1:109921962:G:T	C171F	0.988
1:109917320:G:C	A85P	0.987
1:109921961:T:C	C171R	0.987
1:109921962:G:A	C171Y	0.987
1:109921963:C:G	C171W	0.986
1:109921982:T:A	C178S	0.986
1:109921982:T:C	C178R	0.986

dbSNP variants (sampled 300 via entrez): RS1000070203 (1:109919463 A>G), RS1000229088 (1:109928214 G>A,T), RS1000270428 (1:109922379 C>T), RS1000448778 (1:109909050 A>G), RS1000530365 (1:109928526 T>A), RS1000582076 (1:109915949 A>G,T), RS1000594990 (1:109915898 C>A), RS1000616230 (1:109922052 G>A,C,T), RS1000761284 (1:109922220 T>C), RS1001217216 (1:109928870 C>A,T), RS1001274049 (1:109917166 T>A), RS1001398706 (1:109910569 G>A), RS1001499894 (1:109912370 G>A), RS1001815756 (1:109930242 C>A), RS1001845790 (1:109912627 T>C)

Disease associations

OMIM: gene MIM:120420 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

25 associations (top):

Study	Trait	p-value
GCST000672_4	Paget’s disease	5.000000e-24
GCST001086_6	Paget’s disease	7.000000e-35
GCST001762_441	Obesity-related traits	2.000000e-07
GCST002090_3	Sensory disturbances after bilateral sagittal split ramus osteotomy	3.000000e-06
GCST004610_30	White blood cell count	3.000000e-09
GCST004625_37	Monocyte count	9.000000e-17
GCST005348_54	Total body bone mineral density	2.000000e-10
GCST005989_1	Serum total protein levels	5.000000e-13
GCST005999_1	Aspartate aminotransferase levels	1.000000e-25
GCST006013_6	Lactate dehydrogenase levels	3.000000e-23
GCST006014_1	Creatine kinase levels	1.000000e-40
GCST008839_337	Height	1.000000e-10
GCST009731_16	Blood protein levels in cardiovascular risk	1.000000e-12
GCST010175_1	Adult onset Still’s disease	1.000000e-08
GCST010726_81	Periventricular white matter hyperintensities	1.000000e-07
GCST011348_66	High density lipoprotein cholesterol levels	6.000000e-09
GCST011351_1	Aspartate aminotransferase levels	3.000000e-26
GCST011681_1	Cryptococcosis in HIV infection	3.000000e-07
GCST90002388_621	Lymphocyte count	3.000000e-14
GCST90002393_45	Monocyte count	1.000000e-33
GCST90002394_76	Monocyte percentage of white cells	6.000000e-14
GCST90002400_41	Plateletcrit	1.000000e-15
GCST90002402_486	Platelet count	5.000000e-16
GCST90002407_666	White blood cell count	1.000000e-13
GCST90011899_174	Aspartate aminotransferase levels	2.000000e-64

EFO canonical traits (12, from GWAS)

EFO ID	Trait name
EFO:0004471	insulin sensitivity measurement
EFO:0005324	post-operative sensory disturbance
EFO:0005091	monocyte count
EFO:0004736	aspartate aminotransferase measurement
EFO:0004808	L lactate dehydrogenase measurement
EFO:0004534	creatine kinase measurement
EFO:0005665	white matter hyperintensity measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004587	lymphocyte count
EFO:0007989	monocyte percentage of leukocytes
EFO:0007985	platelet crit
EFO:0004309	platelet count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3989382 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

118 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Lipopolysaccharides	affects cotreatment, increases chemical synthesis, increases reaction, increases activity, increases expression (+3 more)	4
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
Cyclosporine	affects cotreatment, increases expression, decreases expression	3
Cadmium Chloride	decreases expression, increases abundance, increases expression	3
(+)-JQ1 compound	decreases expression	2
Zoledronic Acid	decreases expression, increases expression	2
Fulvestrant	affects cotreatment, increases methylation, increases expression	2
Acetaminophen	increases expression, affects cotreatment	2
Arsenic	affects methylation, affects cotreatment, increases abundance, increases expression	2
Asbestos	increases expression	2
Benzene	increases reaction, decreases expression, increases response to substance, affects cotreatment, increases chemical synthesis	2
Benzo(a)pyrene	affects methylation, increases expression	2
Calcitriol	decreases expression, increases expression, affects cotreatment	2
Chenodeoxycholic Acid	affects cotreatment, increases expression	2
Deoxycholic Acid	affects cotreatment, increases expression	2
Glycochenodeoxycholic Acid	affects cotreatment, increases expression	2
Glycocholic Acid	increases expression, affects cotreatment	2
Glycodeoxycholic Acid	affects cotreatment, increases expression	2
Nickel	increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	decreases expression	2
Triclosan	increases expression	2
Gold Compounds	affects cotreatment, increases expression	2
Particulate Matter	decreases expression, increases abundance	2
aristolochic acid I	increases expression	1
pexidartinib	decreases secretion	1
bisphenol F	decreases methylation	1
2-anisidine	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases methylation	1

Cellosaurus cell lines

15 cell lines: 12 cancer cell line, 3 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_6358	5/9 m a3-18	Transformed cell line	Female
CVCL_A9YZ	NCC-TGCT1-C1	Cancer cell line	Female
CVCL_B8E4	Abcam HCT 116 CSF1 KO	Cancer cell line	Male
CVCL_B9GC	Abcam A-549 CSF1 KO	Cancer cell line	Male
CVCL_D1S0	Abcam U-87MG CSF1 KO	Cancer cell line	Male
CVCL_D2EL	Abcam MCF-7 CSF1 KO	Cancer cell line	Female
CVCL_D7MW	Ubigene A-549 CSF1 KO	Cancer cell line	Male
CVCL_D8JD	Ubigene HCT 116 CSF1 KO	Cancer cell line	Male
CVCL_D9CE	Ubigene HEK293 CSF1 KO	Transformed cell line	Female
CVCL_E0B2	Ubigene HeLa CSF1 KO	Cancer cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.