CXCR4: C-X-C Motif Chemokine Receptor 4
A key regulator of immune cell trafficking, HIV entry, and cancer metastasis
Gene Information Card
| Symbol | CXCR4 |
|---|---|
| Full Name | C-X-C motif chemokine receptor 4 |
| Gene Type | protein-coding |
| Chromosomal Location | 2q22.1 |
| NCBI Gene ID | 7852 ncbi.nlm.nih.gov/gene/7852 |
| Ensembl ID | ENSG00000121966 |
| UniProt ID | P61073 |
| OMIM ID | 162643 |
| HGNC ID | 2561 |
| Aliases | CD184, D2S201E, FB22, HM89, LAP-3, LAP3, LCR1, NPY3R, NPYR, WHIM, WHIMS |
Description
CXCR4 (C-X-C motif chemokine receptor 4) is a G protein-coupled receptor for the chemokine CXCL12 (SDF-1). It plays a critical role in hematopoiesis, immune cell trafficking, and embryonic development. CXCR4 also serves as a co-receptor for HIV-1 entry into T cells. Gain-of-function mutations cause WHIM syndrome (warts, hypogammaglobulinemia, infections, and myelokathexis), while aberrant expression is implicated in cancer metastasis and inflammatory diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| WHIM syndrome | Gain-of-function mutations (e.g., R334X) truncate the C-terminal tail, impairing receptor internalization and leading to enhanced CXCL12 signaling | OMIM #193670; multiple case reports |
| HIV-1 infection | CXCR4 acts as a co-receptor for T-tropic (X4) HIV-1 strains; binding facilitates viral entry into CD4+ T cells | NCBI Gene; reviewed in Berger et al., 1999 |
| Cancer metastasis | CXCR4 overexpression in breast, lung, and other cancers promotes chemotaxis toward CXCL12-rich metastatic sites (e.g., bone, lymph nodes) | Multiple studies; reviewed in Balkwill, 2004 |
| Myelokathexis | Part of WHIM syndrome; impaired neutrophil egress from bone marrow due to CXCR4 gain-of-function | OMIM #193670 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone marrow | 12.5 | High |
| Lymph node | 10.2 | High |
| Spleen | 9.8 | High |
| Thymus | 8.7 | High |
| Lung | 4.3 | Medium |
| Breast | 2.1 | Low |
| Brain | 1.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.3 | High; commonly used for functional studies |
| Jurkat (T cell) | 12.1 | High; endogenous expression |
| MCF-7 (breast cancer) | 8.5 | Medium; associated with metastasis |
| HeLa | 6.2 | Medium |
| K562 (leukemia) | 4.0 | Low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| R334X | Nonsense | Germline; WHIM syndrome | Gain-of-function; C-terminal truncation impairs receptor desensitization |
| S338X | Nonsense | Germline; WHIM syndrome | Gain-of-function; similar mechanism to R334X |
| E343X | Nonsense | Germline; WHIM syndrome | Gain-of-function; truncation of C-terminal tail |
| G336R | Missense | Somatic; rare in cancer | Unknown; reported in COSMIC |
| C28R | Missense | Somatic; rare | Unknown; reported in COSMIC |
Mutation functional classification
Loss of Function (LOF)
Rare; not well characterized in germline; some somatic missense variants may reduce receptor activity
Gain of Function (GOF)
C-terminal truncations (e.g., R334X, S338X, E343X) cause WHIM syndrome; enhanced CXCL12 signaling due to impaired internalization
Dominant Negative (DN)
Not reported for CXCR4
View complete mutation data：
Gene Ontology (GO)
| • GO:0004930 – G protein-coupled receptor activity | • GO:0019957 – C-C chemokine receptor activity |
| • GO:0016493 – C-X-C chemokine receptor activity | • GO:0005886 – plasma membrane |
| • GO:0007165 – signal transduction | • GO:0006935 – chemotaxis |
| • GO:0042119 – neutrophil activation | • GO:0030593 – neutrophil chemotaxis |
| • GO:0002376 – immune system process | • GO:0016032 – viral process |
Pathways
• CXCR4-mediated signaling events (Reactome: R-HSA-418594)
• Chemokine receptors bind chemokines (Reactome: R-HSA-380108)
• HIV infection (Reactome: R-HSA-162906)
• SDF-1/CXCR4 signaling (KEGG: hsa04062)
• Cytokine-cytokine receptor interaction (KEGG: hsa04060)
Protein Summary
CXCR4 is a 352-amino acid G protein-coupled receptor with seven transmembrane domains. It binds exclusively to CXCL12 (SDF-1), activating downstream pathways including PI3K/AKT, MAPK, and calcium mobilization. The receptor is expressed on hematopoietic stem cells, lymphocytes, and various cancer cells. Its C-terminal tail contains serine/threonine residues critical for phosphorylation and internalization; truncating mutations in this region cause WHIM syndrome. CXCR4 is a target for therapeutic blockade in HIV (e.g., plerixafor) and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CXCR4 Knockout HEK293 Cell Line | EDJ-KQ1608 | Human | 7852 | Details Get a Quote |
| CXCR4 Knockout U2OS Cell Line | EDJ-KQ18082 | Human | 7852 | Details Get a Quote |
| CXCR4 Knockout HeLa Cell Line | EDJ-KQ19944 | Human | 7852 | Details Get a Quote |
| CXCR4 Knockout A-549 Cell Line | EDJ-KQ26289 | Human | 7852 | Details Get a Quote |
| CXCR4 Knockout Jurkat Cell Line | EDJ-KZ171 | Human | 7852 | Details Get a Quote |
| CXCR4 Knockout HCT 116 Cell Line | EDJ-KQ71760 | Human | 7852 | Details Get a Quote |
| CXCR4 Knockout HEK293T Cell Line | EDC07548 | Human | 7852 | Details Get a Quote |
| CXCR4 Overexpression HEK293 Stable Cell Line | EDJ-GQ95 | Human | 7852 | Details Get a Quote |
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