CXCR4
Chr 2ADC-X-C motif chemokine receptor 4
Also known as: CD184, D2S201E, FB22, HM89, HSY3RR, LCR1, LESTR, NPY3R
The protein is a seven-transmembrane chemokine receptor that binds CXCL12/SDF-1 and signals through G-protein coupled pathways to regulate cell migration, hematopoiesis, and vascular development. Mutations cause WHIM syndrome (warts, hypogammaglobulinemia, infections, and myelokathexis), a primary immunodeficiency affecting neutrophil trafficking and immune function. Inheritance is autosomal dominant.
Definitive — sufficient evidence for diagnostic panels
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Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function, dominant-negative and loss-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
CXCR4 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
New Preclinical and Clinical Approaches to Mesothelioma
RECRUITINGPrognostic Value of Circulating Tumoral DNA After the First 6 Months of Treatment in Patients With Waldenström Macroglobulinemia
RECRUITINGMotixafortide for MRD Sensitization in AML
NOT YET RECRUITINGU69-CART-Cells For R/R T-ALL
RECRUITINGIbrutinib Followed by BR (Bendamustine and Rituximab) as a Time-Limited Therapy for Waldenström Macroglobulinemia
NOT YET RECRUITINGPrognostic Analyses on a Validation Series of Patients With Waldenström's Disease
RECRUITINGDecitabine in Treating Patients With Myelofibrosis
ACTIVE NOT RECRUITINGGenetic Polymorphism Associated With Coronary Heart Disease Susceptibility and Variability of Clopidogrel Response
ACTIVE NOT RECRUITINGBiomoleculars Markers of Sensitivity to Pre- and Post-operative Chemotherapy of Gastric and Cardia Adenocarcinomas: a Pilot Study
RECRUITINGRelevance of [68Ga]Ga -PentixaFor-PET for Initial Staging and Therapeutic Evaluation of Multiple Myeloma
ACTIVE NOT RECRUITINGNo open access results found
External Resources
Links to major genomics databases and tools