CSF2
Granulocyte-macrophage colony-stimulating factor
Also known as: CSF2_HUMAN, GM-CSF, GMCSF
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P04141
- Gene
- CSF2
- Ensembl
- ENSG00000164400
- Chromosome
- 5
- Canonical length
- 144 aa
- Protein class
- Cancer-related genes, Predicted secreted proteins
- Subcellular location
- Vesicles
- Secretome location
- Secreted to blood
OverviewNCBI Gene
The protein encoded by this gene is a cytokine that controls the production, differentiation, and function of granulocytes and macrophages. The active form of the protein is found extracellularly as a homodimer. This gene has been localized to a cluster of related genes at chromosome region 5q31, which is known to be associated with interstitial deletions in the 5q- syndrome and acute myelogenous leukemia. Other genes in the cluster include those encoding interleukins 4, 5, and 13. This gene plays a role in promoting tissue inflammation. Elevated levels of cytokines, including the one produced by this gene, have been detected in SARS-CoV-2 infected patients that develop acute respiratory distress syndrome. Mice deficient in this gene or its receptor develop pulmonary alveolar proteinosis. [provided by RefSeq, Aug 2020]
Canonical amino-acid sequenceUniProt
144 residues, UniProt reviewed canonical sequence.
>P04141|CSF2
1 MWLQSLLLLG TVACSISAPA RSPSPSTQPW EHVNAIQEAR RLLNLSRDTA AEMNETVEVI
61 SEMFDLQEPT CLQTRLELYK QGLRGSLTKL KGPLTMMASH YKQHCPPTPE TSCATQIITF
121 ESFKENLKDF LLVIPFDCWE PVQELocalizationUniProt · AlphaFold · HPA
Whether an antibody against CSF2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Secreted
- Secreted
- Yes
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.39
- Highest tissue expression
- 1.9 nTPM
Expression across tissuesHPA
Tissue
- lung: 1.9 nTPM
- urinary bladder: 0.6 nTPM
- bone marrow: 0.4 nTPM
- pancreas: 0.4 nTPM
- gallbladder: 0.3 nTPM
- appendix: 0.2 nTPM
Single-cell type
- innate lymphoid cells: 59 nCPM
- t-cells: 18 nCPM
- alveolar cells type 2: 15 nCPM
- mast cells: 14 nCPM
- nk-cells: 8.1 nCPM
- endometrial secretory cells: 3.6 nCPM
Immune cell
- NK-cell: 6.3 nTPM
- memory CD8 T-cell: 0.5 nTPM
- memory CD4 T-cell: 0.2 nTPM
- basophil: 0 nTPM
- classical monocyte: 0 nTPM
- eosinophil: 0 nTPM
Brain region
- hippocampal formation: 0.6 nTPM
- amygdala: 0.5 nTPM
- cerebral cortex: 0.5 nTPM
- medulla oblongata: 0.5 nTPM
- white matter: 0.5 nTPM
- basal ganglia: 0.3 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about CSF2.
Disease | AutoantibodyPubMed
Conditions in which antibodies against CSF2 are reported. Each links to that disease's full target list.
Showing 5 of 8 — disease pages carrying at least 10 antigens.
ReferencesPubMed · IEDB
Publications for CSF2 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.
Reference: AutoantibodyPubMed
183 publications
- Pulmonary alveolar proteinosis.
2019 · Nat Rev Dis Primers · RCR 12.7 · 292 citations - Anti-granulocyte-macrophage colony-stimulating factor autoantibodies are a risk factor for central nervous system infection by Cryptococcus gattii in otherwise immunocompetent patients.
2014 · mBio · RCR 6.4 · 184 citations - Anti-GM-CSF autoantibodies in patients with cryptococcal meningitis.
2013 · J Immunol · RCR 6.1 · 201 citations - Invasive Nocardiosis: Disease Presentation, Diagnosis and Treatment - Old Questions, New Answers?
2020 · Infect Drug Resist · RCR 4.9 · 65 citations - Gm-CSF regulates pulmonary surfactant homeostasis and alveolar macrophage-mediated innate host defense.
2002 · Annu Rev Physiol · RCR 4.8 · 266 citations
Show 20 more of 183 total
- GM-CSF autoantibodies and neutrophil dysfunction in pulmonary alveolar proteinosis.
2007 · N Engl J Med · RCR 4.7 · 230 citations - Inhaled granulocyte/macrophage-colony stimulating factor as therapy for pulmonary alveolar proteinosis.
2010 · Am J Respir Crit Care Med · RCR 4.1 · 160 citations - Therapeutic efficacy of granulocyte-macrophage colony-stimulating factor in patients with idiopathic acquired alveolar proteinosis.
2001 · Am J Respir Crit Care Med · RCR 4 · 166 citations - The molecular basis of pulmonary alveolar proteinosis.
2010 · Clin Immunol · RCR 4 · 166 citations - The Role of GM-CSF Autoantibodies in Infection and Autoimmune Pulmonary Alveolar Proteinosis: A Concise Review.
2021 · Front Immunol · RCR 3.7 · 53 citations - Cryptococcus gattii Species Complex as an Opportunistic Pathogen: Underlying Medical Conditions Associated with the Infection.
2021 · mBio · RCR 3.6 · 44 citations - Anti-GM-CSF autoantibodies predict outcome of cryptococcal meningitis in patients not infected with HIV: A cohort study.
2024 · Clin Microbiol Infect · RCR 3.5 · 16 citations - Prevalence and healthcare burden of pulmonary alveolar proteinosis.
2018 · Orphanet J Rare Dis · RCR 3.4 · 74 citations - High-affinity autoantibodies specifically eliminate granulocyte-macrophage colony-stimulating factor activity in the lungs of patients with idiopathic pulmonary alveolar proteinosis.
2004 · Blood · RCR 3.4 · 176 citations - Standardized serum GM-CSF autoantibody testing for the routine clinical diagnosis of autoimmune pulmonary alveolar proteinosis.
2014 · J Immunol Methods · RCR 3.3 · 90 citations - Pulmonary alveolar proteinosis: new insights from a single-center cohort of 70 patients.
2011 · Respir Med · RCR 3.1 · 95 citations - Pathogenesis-driven treatment of primary pulmonary alveolar proteinosis.
2024 · Eur Respir Rev · RCR 3.1 · 11 citations - Granulocyte/macrophage-colony-stimulating factor autoantibodies and myeloid cell immune functions in healthy subjects.
2009 · Blood · RCR 3 · 120 citations - Pulmonary alveolar proteinosis caused by deletion of the GM-CSFRalpha gene in the X chromosome pseudoautosomal region 1.
2008 · J Exp Med · RCR 3 · 135 citations - Hereditary pulmonary alveolar proteinosis: pathogenesis, presentation, diagnosis, and therapy.
2010 · Am J Respir Crit Care Med · RCR 3 · 123 citations - Anti-GM-CSF Neutralizing Autoantibodies in Colombian Patients with Disseminated Cryptococcosis.
2023 · J Clin Immunol · RCR 2.9 · 23 citations - Nocardia-induced granulocyte macrophage colony-stimulating factor is neutralized by autoantibodies in disseminated/extrapulmonary nocardiosis.
2015 · Clin Infect Dis · RCR 2.8 · 76 citations - Antibody to granulocyte-macrophage colony-stimulating factor is a dominant anti-cytokine activity in human IgG preparations.
1998 · Blood · RCR 2.7 · 108 citations - Human GM-CSF autoantibodies and reproduction of pulmonary alveolar proteinosis.
2009 · N Engl J Med · RCR 2.7 · 119 citations - Pulmonary alveolar proteinosis, a primary immunodeficiency of impaired GM-CSF stimulation of macrophages.
2009 · Curr Opin Immunol · RCR 2.6 · 118 citations
Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.51
- gnomAD pLI
- 0.83
- gnomAD missense Z
- 0.38
- DepMap mean gene effect
- -0.04
- DepMap dependency class
- none
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 2% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- cell population proliferation
- cell surface receptor signaling pathway via JAK-STAT
- cell surface receptor signaling pathway via STAT
- cellular response to granulocyte macrophage colony-stimulating factor stimulus
- cellular response to lipopolysaccharide
- dendritic cell differentiation
- embryonic placenta development
- epithelial fluid transport
- granulocyte-macrophage colony-stimulating factor signaling pathway
- histamine secretion
- immune response
- macrophage differentiation
- monocyte differentiation
- myeloid cell differentiation
- myeloid dendritic cell differentiation
- negative regulation of DNA-templated transcription
- negative regulation of extrinsic apoptotic signaling pathway in absence of ligand
- neutrophil differentiation
- positive regulation of cell migration
- positive regulation of cell population proliferation
- positive regulation of gene expression
- positive regulation of interleukin-23 production
- positive regulation of leukocyte proliferation
- positive regulation of macrophage derived foam cell differentiation
- positive regulation of podosome assembly
- regulation of circadian sleep/wake cycle, sleep
- response to fluid shear stress
- response to silicon dioxide
Molecular functions
- cytokine activity
- growth factor activity
- granulocyte macrophage colony-stimulating factor receptor binding
Cellular components
Protein domainsUniProt · Pfam · InterPro
- Four-helical cytokine-like, core
- Granulocyte-macrophage colony-stimulating factor
- Granulocyte-macrophage colony-stimulating factor
KeywordsUniProt
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads CSF2 as an antibody target. Whether an autoantibody or antibody against CSF2 could matter depends on whether native CSF2 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
CSF2 is annotated as secreted, so native CSF2 circulates and is directly accessible to antibodies. Secreted and cell-surface proteins are the autoantibody targets most likely to act like drugs, blocking or depleting the native protein.
Annotation status
The present source text does not explicitly label CSF2 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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