CSF2

Chr 5

colony stimulating factor 2

Also known as: CSF, GMCSF

NCBI Gene: 1437ENSG00000164400UniProt: P04141

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]

38
ClinVar variants
16
Pathogenic / LP
0.83
pLI score
12
Active trials
Clinical Summary— CSF2
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.83) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
16 Pathogenic / Likely Pathogenic· 12 VUS of 38 total submissions
💊
Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.51LOEUF
pLI 0.835
Z-score 2.26
OE 0.00 (0.00–0.51)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.38Z-score
OE missense 0.88 (0.73–1.07)
70 obs / 79.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.00 (0.00–0.51)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.88 (0.73–1.07)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.93
0≤1.21.6
LoF obs/exp: 0 / 5.9Missense obs/exp: 70 / 79.4Syn Z: 0.32

ClinVar Variant Classifications

38 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic14
Likely Pathogenic2
VUS12
Likely Benign7
Benign3
14
Pathogenic
2
Likely Pathogenic
12
VUS
7
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
14
0
14
Likely Pathogenic
0
0
2
0
2
VUS
0
10
2
0
12
Likely Benign
0
5
1
1
7
Benign
0
0
0
3
3
Total01519438

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CSF2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Single-cell transcriptomics identifies pathogenic T-helper 17.1 cells and pro-inflammatory monocytes in immune checkpoint inhibitor-related pneumonitis.
Franken A et al.·J Immunother Cancer
2022
Tumour-associated macrophages-derived CXCL8 determines immune evasion through autonomous PD-L1 expression in gastric cancer.
Lin C et al.·Gut
2019
Mutant KRAS triggers functional reprogramming of tumor-associated macrophages in colorectal cancer.
Liu H et al.·Signal Transduct Target Ther
2021Functional
Class IIa HDAC inhibition reduces breast tumours and metastases through anti-tumour macrophages.
Guerriero JL et al.·Nature
2017
Regnase-1 downregulation promotes pancreatic cancer through myeloid-derived suppressor cell-mediated evasion of anticancer immunity.
Okabe J et al.·J Exp Clin Cancer Res
2023
Perspectives on the Genetic Associations of Ankylosing Spondylitis.
Wordsworth BP et al.·Front Immunol
2021Review
PAK1 overexpression promotes myxofibrosarcoma angiogenesis through STAT5B-mediated CSF2 transactivation: clinical and therapeutic relevance of amplification and nuclear entry.
Li CF et al.·Int J Biol Sci
2023
Solar urticaria involves rapid mast cell STAT3 activation and neutrophil recruitment, with FcεRI as an upstream regulator.
Rutter KJ et al.·J Allergy Clin Immunol
2024
Therapeutic targeting of the p300/CBP bromodomain enhances the efficacy of immune checkpoint blockade therapy.
Liu J et al.·Oncogene
2025
Csf2 Attenuated Sepsis-Induced Acute Kidney Injury by Promoting Alternative Macrophage Transition.
Li Y et al.·Front Immunol
2020
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Urban particulate matter induces NLRP3/NLRP6 inflammasomes, autophagy, senescence and fibrotic responses by increasing CSF2 signaling in kidney cells.
Su RY et al.·Free Radic Biol Med
2026
Mechanism of Yiqi Huoxue Granule in promoting angiogenesis of skin lesion tissue by increasing CSF2 to reduce mesenchymal stem cell apoptosis.
Shi W et al.·Front Pharmacol
2026🔓 Open AccessFunctional
Histone deacetylase 3 promotes hypoxia-induced human pulmonary arterial smooth muscle cell proliferation by modulating the CSF2-JAK2-STAT5 signaling pathway.
Zhang J et al.·Hum Cell
2026🔓 Open Access
Leptocaramine from Hypecoum erectum inhibits inflammatory responses via CSF2-NF-κB signaling pathway.
Yuan H et al.·Int Immunopharmacol
2026
Transcriptional and post-transcriptional convergence of HES1 and IGF2BP2 sustains CSF2-dependent metabolic adaptability in gastric Cancer.
Du J et al.·Cell Signal
2026
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Lung AdenocarcinomaLung Adenosquamous CarcinomaLung Large Cell Carcinoma

Combination Chemotherapy, Radiation Therapy, and Bevacizumab in Treating Patients With Newly Diagnosed Stage III Non-small Cell Lung Cancer That Cannot Be Removed by Surgery

ACTIVE NOT RECRUITING
NCT00334815Phase PHASE2National Cancer Institute (NCI)Started 2006-06-15
BevacizumabCisplatinDocetaxel
Lung Non-Small Cell CarcinomaStage IV Lung Cancer AJCC v8

A Multiple Antigen Vaccine (STEMVAC) for the Treatment of Patients With Stage IV Non-Small Cell Lung Cancer

ACTIVE NOT RECRUITING
NCT05242965Phase PHASE2University of WashingtonStarted 2023-03-24
CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope Plasmid DNA VaccineSargramostimComputed Tomography
Low Back Pain

The Prognostic Value of Biomarkers and the Effect of Tolperisone in Acute Low Back Pain and Sciatic Pain "BETA"

ACTIVE NOT RECRUITING
NCT05544656Phase PHASE3Semmelweis UniversityStarted 2019-12-13
Tolperisone HydrochloridePlacebo
LymphomaChemotherapeutic Toxicity

Clonal Hematopoiesis is a Risk Factor for Chemotherapy-Related Complications

RECRUITING
NCT04053439Sunnybrook Health Sciences CentreStarted 2019-08-08
Blood test for determination of CHIP
Chronic Granulomatous Disease (CGD)X-Linked Chronic Granulomatous Disease

Base Editing for Mutation Repair in Hematopoietic Stem & Progenitor Cells for X-Linked Chronic Granulomatous Disease

RECRUITING
NCT06325709Phase PHASE1, PHASE2National Institute of Allergy and Infectious Diseases (NIAID)Started 2024-04-17
PlerixaforFilgrastimPalifermin
Non-Allergic Rhinitis With Eosinophilia Syndrome

Efficacy and Safety of Stapokibart in Non-Allergic Rhinitis With Eosinophilia Syndrome

NOT YET RECRUITING
NCT07240376Phase NAHuazhong University of Science and TechnologyStarted 2025-11-25
Stapokibart (CM310)Placebo
Glioblastoma MultiformeGlioblastoma Multiforme, AdultSupratentorial Glioblastoma

hSTAR GBM (Hematopoetic Stem Cell (HPC) Rescue for GBM)

RECRUITING
NCT05052957Phase PHASE2Leland MethenyStarted 2023-01-20
P140K-MGMTO6-benzylguaninePhoton Based Radiotherapy
AIDS-Related LymphomaAnn Arbor Stage II Diffuse Large B-Cell LymphomaAnn Arbor Stage III Diffuse Large B-Cell Lymphoma

Ibrutinib, Rituximab, Etoposide, Prednisone, Vincristine Sulfate, Cyclophosphamide, and Doxorubicin Hydrochloride in Treating Patients With HIV-Positive Stage II-IV Diffuse Large B-Cell Lymphomas

ACTIVE NOT RECRUITING
NCT03220022Phase PHASE1National Cancer Institute (NCI)Started 2018-03-16
CyclophosphamideDoxorubicin HydrochlorideEtoposide
Endometriosis

Developing a Complex ex Vivo Endometrial Tissue Model to Improve Endometriosis Care

RECRUITING
NCT06331676Phase NAHospices Civils de LyonStarted 2024-06-21
Tissue collectionData collection
High Grade GliomaCNS Tumor

Entrectinib as a Single Agent in Upfront Therapy for Children <3 Years of Age With NTRK1/2/3 or ROS1-FUSED CNS Tumors

RECRUITING
NCT06528691Phase PHASE2St. Jude Children's Research HospitalStarted 2026-03
EntrectinibCyclophosphamideEtoposide
X-linked Severe Combined ImmunodeficiencyX-SCIDXSCID

Base-Edited Hematopoietic Stem/Progenitor Cell X-Linked Severe Combined Immunodeficiency Gene Therapy

ENROLLING BY INVITATION
NCT06851767Phase PHASE1, PHASE2National Institute of Allergy and Infectious Diseases (NIAID)Started 2025-05-09
PlerixaforFilgrastimPalifermin
Solid TumorMelanoma

OH2 Injection in Solid Tumors

RECRUITING
NCT04386967Phase PHASE1, PHASE2Binhui Biopharmaceutical Co., Ltd.Started 2018-11-22
OH2 injectionKeytruda

External Resources

Links to major genomics databases and tools