CSF1
protein-codingcolony stimulating factor 1
Gene summary
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. [provided by RefSeq, Sep 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~20.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CSF1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000757.6. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 3 | 3 | ||||
| missense | 82 | 7 | 89 | |||
| nonsense | 0 | |||||
| start loss | 1 | 1 | ||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 84 | 7 | 3 | 94 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000748.4 | 8 | MANE Select | |
| Ensembl | ENSP00000327513.6 | 8 | MANE Select | |
| RefSeq | NP_757349.2 | 9 | Standard | |
| RefSeq | NP_757350.2 | 8 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- PI3K-Akt signaling pathway - Homo sapiens (human)
- TNF signaling pathway - Homo sapiens (human)
- Rap1 signaling pathway - Homo sapiens (human)
- Ras signaling pathway - Homo sapiens (human)
- MAPK signaling pathway - Homo sapiens (human)
Biological Process
- positive regulation of cell-matrix adhesion
- osteoclast proliferation
- developmental process involved in reproduction
- inflammatory response
- transmembrane receptor protein tyrosine kinase signaling pathway
Molecular Function
- cytokine activity
- macrophage colony-stimulating factor receptor binding
- protein binding
- growth factor activity
- identical protein binding
Cellular Component
- extracellular region
- extracellular space
- endoplasmic reticulum lumen
- plasma membrane
- membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000329608
- Coding exons
- 8
- Length
- 20751
- Individuals with no LoFs
- 116733
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 1
- Defined
- 116734
- p
- 0.00000428
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.514 | 285 | 311 | 0.918 | 0.0000170 | 3592 |
| Missense (PolyPhen) | 79 | 104.93 | 0.7529 | 1414 | ||
| Synonymous | -0.969 | 146 | 132 | 1.11 | 0.00000788 | 1140 |
| Loss of Function | 4.04 | 1 | 21.0 | 0.0477 | 9.71e-7 | 247 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.0000095 | 0.0000095 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- 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 proinflammatory 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. {ECO:0000269|PubMed:16337366, ECO:0000269|PubMed:19934330, ECO:0000269|PubMed:20504948, ECO:0000269|PubMed:20829061}.;
- Disease
- DISEASE: Note=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.; DISEASE: Note=Aberrant expression of CSF1 or CSF1R may play a role in inflammatory diseases, such as rheumatoid arthritis, glomerulonephritis, atherosclerosis, and allograft rejection.;
Recessive Scores
- pRec
- 0.607
Intolerance Scores
- LoFtool
- 0.0626
- RVIS EVS
- 0.29
- RVIS percentile EVS
- 71.51
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.955
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |