CXCL9 (Chemokine (C-X-C Motif) Ligand 9): A Key Mediator of T-Cell Recruitment and Immune Response
Explore the gene, protein, expression, and clinical significance of CXCL9, a chemokine central to immune regulation and disease pathogenesis.
Gene Information Card
| Symbol | CXCL9 |
|---|---|
| Full Name | Chemokine (C-X-C motif) ligand 9 |
| Gene Type | Protein coding |
| Chromosomal Location | 4q21.1 |
| NCBI Gene ID | 4283 ncbi.nlm.nih.gov/gene/4283 |
| Ensembl ID | ENSG00000138755 |
| UniProt ID | Q07325 |
| OMIM ID | 601704 |
| HGNC ID | 7098 |
| Aliases | MIG, CMK, Humig, crg-10, SCYB9 |
Description
CXCL9 (C-X-C motif chemokine ligand 9), also known as Monokine induced by gamma interferon (MIG), is a small cytokine belonging to the CXC chemokine family. It is primarily induced by interferon-gamma (IFN-γ) and functions as a chemoattractant for activated T cells and natural killer (NK) cells by binding to the chemokine receptor CXCR3. CXCL9 plays a critical role in inflammatory responses, immune surveillance, and the pathogenesis of various diseases, including autoimmune disorders, infectious diseases, and cancer. Its expression is tightly regulated and often used as a biomarker for immune activation and disease severity.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Rheumatoid Arthritis | CXCL9 promotes T-cell infiltration into synovial tissue, contributing to chronic inflammation and joint destruction. | Elevated CXCL9 levels in serum and synovial fluid of RA patients; correlation with disease activity (PMID: 23459137). |
| Inflammatory Bowel Disease | CXCL9 recruits CXCR3+ T cells to intestinal mucosa, exacerbating mucosal inflammation. | Increased CXCL9 expression in inflamed colonic tissue from IBD patients (PMID: 22084327). |
| Hepatocellular Carcinoma | CXCL9 may modulate anti-tumor immunity by attracting T cells, but also can promote tumor progression via angiogenesis and immune evasion. | High CXCL9 expression associated with poor prognosis in HCC (PMID: 29467853). |
| Tuberculosis | CXCL9 is induced by IFN-γ during mycobacterial infection and helps recruit effector T cells to the site of infection. | Elevated CXCL9 levels in pleural fluid and serum of TB patients (PMID: 23997055). |
| Graft-versus-Host Disease | CXCL9 contributes to T-cell recruitment to target organs, amplifying alloreactive immune responses. | Increased CXCL9 expression in GVHD target tissues and serum (PMID: 20574438). |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 10.8 | Medium |
| Spleen | 8.9 | Medium |
| Lymph Node | 7.5 | Low |
| Liver | 3.2 | Low |
| Blood | 1.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| THP-1 (monocytic leukemia) | 12.3 | IFN-γ stimulation increases expression |
| A549 (lung carcinoma) | 8.7 | Inducible by IFN-γ |
| HUVEC (endothelial) | 6.5 | Induced by inflammatory cytokines |
| Jurkat (T-cell leukemia) | 2.1 | Low basal expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs2276886 | SNV (intronic) | Allele frequency ~0.3 (G) | May affect splicing or regulatory elements; associated with altered CXCL9 expression in some studies. |
| rs10336 | SNV (3' UTR) | Allele frequency ~0.4 (T) | Potential impact on mRNA stability or miRNA binding; linked to disease susceptibility in autoimmune conditions. |
Mutation functional classification
Loss of Function (LOF)
No well-characterized loss-of-function mutations reported in CXCL9. Gene deletion or epigenetic silencing may reduce expression, impairing T-cell recruitment and immune response.
Gain of Function (GOF)
No activating mutations described; overexpression is typically due to transcriptional upregulation by IFN-γ rather than genetic alterations.
Dominant Negative (DN)
Not applicable; CXCL9 functions as a soluble ligand, and no dominant-negative variants have been identified.
View complete mutation data：
Gene Ontology (GO)
| • chemokine activity | • CXCR3 chemokine receptor binding |
| • immune response | • cell chemotaxis |
| • inflammatory response | • signal transduction |
| • extracellular space |
Pathways
• Chemokine signaling pathway
• Cytokine-cytokine receptor interaction
• T cell receptor signaling pathway
• Inflammatory bowel disease (IBD)
• Rheumatoid arthritis
Protein Summary
CXCL9 is a secreted protein of 126 amino acids (mature form) with a molecular weight of ~14 kDa. It contains the conserved CXC motif (Cys-X-Cys) and is structurally similar to other CXC chemokines. CXCL9 binds specifically to the G protein-coupled receptor CXCR3, which is expressed on activated T cells, NK cells, and some dendritic cells. Upon binding, CXCL9 induces intracellular signaling cascades that promote cell migration, adhesion, and activation. The protein is produced mainly by macrophages, endothelial cells, and fibroblasts in response to IFN-γ. Its expression is regulated at the transcriptional level by STAT1 and IRF1. CXCL9 is also involved in angiogenesis and has both pro- and anti-tumor effects depending on the context.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CXCL9 Knockout HEK293 Cell Line | EDJ-KQ5212 | Human | 4283 | Details Get a Quote |
| CXCL9 Knockout HeLa Cell Line | EDJ-KQ53874 | Human | 4283 | Details Get a Quote |
| CXCL9 Knockout A-549 Cell Line | EDJ-KQ62364 | Human | 4283 | Details Get a Quote |
| CXCL9 Knockout HCT 116 Cell Line | EDJ-KQ70834 | Human | 4283 | Details Get a Quote |
