CXCR4, C-X-C motif chemokine receptor 4, 7852

N. diseases: 739; N. variants: 23
Disease: WHIM syndrome ×
Source: ALL
Disease Score gda Association Type Type Original DB Sentence supporting the association PMID PMID Year
CUI: C0472817
Disease: WHIM syndrome
WHIM syndrome 		1.000 Biomarker disease BEFREE Importantly, the involvement of CXCR4 in cancer metastasis and WHIM syndrome appears to be due to dysregulation of the receptor leading to enhanced signaling. 17169327 2007
CUI: C0472817
Disease: WHIM syndrome
WHIM syndrome 		1.000 CausalMutation disease CLINVAR Impaired recruitment of Grk6 and beta-Arrestin 2 causes delayed internalization and desensitization of a WHIM syndrome-associated CXCR4 mutant receptor. 19956569 2009
CUI: C0472817
Disease: WHIM syndrome
WHIM syndrome 		1.000 Biomarker disease BEFREE The CXCR4 antagonist plerixafor corrects panleukopenia in patients with WHIM syndrome. 21890643 2011
CUI: C0472817
Disease: WHIM syndrome
WHIM syndrome 		1.000 GeneticVariation disease BEFREE We propose that decreased internalization of WHIM-associated mutated CXCR4 leads to prolongation/enhancement of signaling in response to SDF1 and that this may provide the biochemical basis for the autosomal dominant abnormalities of cell trafficking and function associated with WHIM syndrome. 15781337 2005
CUI: C0472817
Disease: WHIM syndrome
WHIM syndrome 		1.000 GeneticVariation disease BEFREE Stromal-derived factor-1 abolishes constitutive apoptosis of WHIM syndrome neutrophils harbouring a truncating CXCR4 mutation. 16899028 2006
CUI: C0472817
Disease: WHIM syndrome
WHIM syndrome 		1.000 GeneticVariation disease BEFREE We report CXCR4 function in 3 patients with WHIM syndrome carrying heterozygous truncating mutations of CXCR4. 15026312 2004
CUI: C0472817
Disease: WHIM syndrome
WHIM syndrome 		1.000 Biomarker disease MGD Using S1P5(-/-) mice and a new knockin mouse model in which CXCR4 cannot be desensitized (a mouse model of warts, hypogammaglobulinemia, infections, and myelokathexis [WHIM] syndrome), we demonstrate that NK-cell exit from the BM requires both CXCR4 desensitization and S1P5 engagement. 21911833 2011
CUI: C0472817
Disease: WHIM syndrome
WHIM syndrome 		1.000 Biomarker disease BEFREE In competitive mouse bone marrow (BM) transplantation experiments, Cxcr4 haploinsufficiency was sufficient to confer a strong long-term engraftment advantage of donor BM over BM from either wild-type or WHIM syndrome model mice, suggesting a potential mechanism for the patient's cure. 25662009 2015
CUI: C0472817
Disease: WHIM syndrome
WHIM syndrome 		1.000 GeneticVariation disease BEFREE WHIM syndrome (WS), a rare congenital neutropenia due to mutations of the CXCR4 chemokine receptor, is associated with Human Papillomavirus (HPV)-induced Warts, Hypogammaglobulinemia, bacterial Infections and Myelokathexis. 23009155 2012
CUI: C0472817
Disease: WHIM syndrome
WHIM syndrome 		1.000 GeneticVariation disease BEFREE Gain-of-function mutations in CXCR4 affecting receptor desensitization have been reported in the rare immunodeficiency called WHIM syndrome (WS). 27681431 2016
CUI: C0472817
Disease: WHIM syndrome
WHIM syndrome 		1.000 GeneticVariation disease BEFREE Mutations in CXCR4 cause severe leukopenia in myelokathexis or WHIM syndrome. 21835955 2011
CUI: C0472817
Disease: WHIM syndrome
WHIM syndrome 		1.000 Biomarker disease BEFREE The acronym WHIM refers to Warts, Hypogammaglobulinemia, Infections, and Myelokathexis. 10767001 2000
CUI: C0472817
Disease: WHIM syndrome
WHIM syndrome 		1.000 GeneticVariation disease BEFREE The CXCR4 mutations in WHIM syndrome impair the stability of the T-cell immunologic synapse. 23794067 2013
CUI: C0472817
Disease: WHIM syndrome
WHIM syndrome 		1.000 GeneticVariation disease BEFREE These results suggest that WHIM-mutant CXCR4 may lead to spontaneous aberrant B-cell activation, via CXCL12-mediated costimulation, impairing B-cell survival and thus possibly contributing to the WHIM syndrome defects in adaptive immunity. 28928741 2017
CUI: C0472817
Disease: WHIM syndrome
WHIM syndrome 		1.000 Biomarker disease GENOMICS_ENGLAND We propose that the sustained CXCR4 activity in patient cells accounts for the immune-hematologic clinical manifestations and the profusion of warts characteristic of the WHIM syndrome. 15536153 2005
CUI: C0472817
Disease: WHIM syndrome
WHIM syndrome 		1.000 Biomarker disease BEFREE We propose that FLNA interaction with ICL3 is central for endocytosis and signaling of WT and WHIM-like CXCR4 receptors. 25355818 2015
CUI: C0472817
Disease: WHIM syndrome
WHIM syndrome 		1.000 GeneticVariation disease BEFREE Thus, disease allele deletion resulting in Cxcr4 haploinsufficiency was superior to disease allele repair in a mouse model of gene therapy for WHIM syndrome, allowing correction of leukopenia without recipient conditioning. 29715199 2018
CUI: C0472817
Disease: WHIM syndrome
WHIM syndrome 		1.000 GeneticVariation disease BEFREE Finding two patients with WHIM who do not have detectable mutations of CXCR4 but whose cells are hyperresponsive to CXCL12 raises the possibility that there is more than one genetic basis for WHIM. 19057201 2009
CUI: C0472817
Disease: WHIM syndrome
WHIM syndrome 		1.000 Biomarker disease BEFREE Together, these studies demonstrate the role Ser-346/7 plays in arrestin recruitment and initiation of receptor desensitization and provide insight into the dysregulation of CXCR4 observed in patients with various forms of WHIM syndrome. 28331048 2017
CUI: C0472817
Disease: WHIM syndrome
WHIM syndrome 		1.000 GeneticVariation disease CLINVAR
CUI: C0472817
Disease: WHIM syndrome
WHIM syndrome 		1.000 GeneticVariation disease BEFREE WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome is a genetic autoimmune disorder that results from gain-of-function mutations in the gene encoding chemokine receptor CXCR4. 29939159 2018
CUI: C0472817
Disease: WHIM syndrome
WHIM syndrome 		1.000 Biomarker disease GENOMICS_ENGLAND The identification of mutations in CXCR4 in individuals with WHIM syndrome represents the first example of aberrant chemokine receptor function causing human disease and suggests that the receptor may be important in cell-mediated immunity to HPV infection. 12692554 2003
CUI: C0472817
Disease: WHIM syndrome
WHIM syndrome 		1.000 Biomarker disease BEFREE Alteration in Cxcr4 desensitization resulted in decrease of circulating HSPCs in five patients with WS. 28550161 2017
CUI: C0472817
Disease: WHIM syndrome
WHIM syndrome 		1.000 AlteredExpression disease BEFREE We propose that the sustained CXCR4 activity in patient cells accounts for the immune-hematologic clinical manifestations and the profusion of warts characteristic of the WHIM syndrome. 15536153 2005
CUI: C0472817
Disease: WHIM syndrome
WHIM syndrome 		1.000 Biomarker disease MGD These mice provide a model to decipher the role of CXCR4 desensitization in the homeostasis of B and T cells and to investigate which manifestations of patients with WHIM syndrome may be overcome by dampening the gain of CXCR4 function. 22438253 2012