CSF3R Gene: Structure, Function, and Clinical Significance
A comprehensive guide to the colony-stimulating factor 3 receptor gene, its role in hematopoiesis, associated diseases, and mutation landscape.
Gene Information Card
| Symbol | CSF3R |
|---|---|
| Full Name | colony stimulating factor 3 receptor |
| Gene Type | protein coding |
| Chromosomal Location | 1p34.3 |
| NCBI Gene ID | 1441 ncbi.nlm.nih.gov/gene/1441 |
| Ensembl ID | ENSG00000119535 |
| UniProt ID | Q99062 |
| OMIM ID | 138971 |
| HGNC ID | 2439 |
| Aliases | CD114, GCSFR, SCN7 |
Description
The CSF3R gene encodes the granulocyte colony-stimulating factor receptor (G-CSF-R), a type I transmembrane protein that mediates the effects of granulocyte colony-stimulating factor (G-CSF). This receptor is essential for the proliferation, differentiation, and survival of neutrophil progenitor cells. Mutations in CSF3R are associated with severe congenital neutropenia and acute myeloid leukemia, as well as chronic neutrophilic leukemia.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Severe congenital neutropenia 7 (SCN7) | Loss-of-function mutations impair G-CSF signaling, leading to defective granulopoiesis. | OMIM #617014; ClinVar |
| Acute myeloid leukemia (AML) | Somatic mutations, often truncating, can contribute to leukemogenesis, especially in the context of SCN. | COSMIC; ClinVar |
| Chronic neutrophilic leukemia (CNL) | Gain-of-function mutations (e.g., T618I) in the membrane-proximal region cause constitutive receptor activation. | OMIM #601626; COSMIC; ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone Marrow | 12.5 | High |
| Spleen | 4.2 | Medium |
| Lung | 2.1 | Low |
| Blood | 1.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HL-60 (promyelocytic leukemia) | 15.3 | High expression; used in differentiation studies |
| K-562 (chronic myeloid leukemia) | 8.7 | Moderate expression |
| THP-1 (monocytic leukemia) | 3.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| T618I | Missense | ~80% in CNL | Gain-of-function; constitutive activation of the receptor |
| Q741X | Nonsense | Rare in SCN | Loss-of-function; truncation of cytoplasmic domain |
| C632Y | Missense | Rare in CNL | Gain-of-function; disrupts receptor internalization |
| IVS14+1G>A | Splice site | Reported in SCN | Loss-of-function; aberrant splicing |
Mutation functional classification
Loss of Function (LOF)
Mutations that impair receptor signaling, often truncating or splice-site variants, leading to neutropenia.
Gain of Function (GOF)
Mutations that cause constitutive activation, typically in the membrane-proximal region (e.g., T618I), leading to neutrophilic leukemia.
Dominant Negative (DN)
Some truncating mutations may exert dominant-negative effects by interfering with wild-type receptor function, though this is less well characterized.
View complete mutation data：
Gene Ontology (GO)
| • cytokine receptor activity (GO:0004896) | • signal transducer activity (GO:0004871) |
| • plasma membrane (GO:0005886) | • signal transduction (GO:0007165) |
| • granulocyte colony-stimulating factor signaling pathway (GO:0038151) | • positive regulation of myeloid cell differentiation (GO:0045639) |
Pathways
• G-CSF signaling pathway (Reactome: R-HSA-9674555)
• Cytokine-cytokine receptor interaction (KEGG: hsa04060)
• JAK-STAT signaling pathway (KEGG: hsa04630)
Protein Summary
The CSF3R protein is a 836-amino-acid type I transmembrane receptor with an extracellular domain containing immunoglobulin-like and fibronectin type III domains, a transmembrane domain, and a cytoplasmic domain with conserved motifs for JAK/STAT signaling. It binds G-CSF with high affinity, leading to receptor dimerization and activation of downstream pathways including JAK/STAT, Ras/MAPK, and PI3K/AKT. The receptor is critical for granulopoiesis and is expressed primarily on myeloid progenitors and mature neutrophils.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CSF3R Knockout HEK293 Cell Line | EDJ-KQ17809 | Human | 1441 | Details Get a Quote |
| CSF3R Knockout HeLa Cell Line | EDJ-KQ53004 | Human | 1441 | Details Get a Quote |
| CSF3R Knockout A-549 Cell Line | EDJ-KQ61470 | Human | 1441 | Details Get a Quote |
| CSF3R Knockout HCT 116 Cell Line | EDJ-KQ69967 | Human | 1441 | Details Get a Quote |
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