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PF4 (platelet factor 4)

Written2014-01Katrien Van Raemdonck, Paul Proost, Jo Van Damme, Sofie Struyf
Laboratory of Molecular Immunology, Rega Institute for Medical Research, Department of Microbiology, Immunology, KU Leuven, Leuven, Belgium

(Note : for Links provided by Atlas : click)


Alias_namesplatelet factor 4
Alias_symbol (synonym)SCYB4
Other aliasPF-4
HGNC (Hugo) PF4
LocusID (NCBI) 5196
Atlas_Id 41693
Location 4q13.3  [Link to chromosome band 4q13]
Location_base_pair Starts at 73980825 and ends at 73982124 bp from pter ( according to hg19-Feb_2009)  [Mapping PF4.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
Note The platelet factor CXCL4 is a rather atypical chemokine because its leukocyte chemoattractant activity is not that prominent. However, CXCL4 influences a large range of processes via interaction with a diversity of cellular receptors. These receptors are expressed on leukocytes, endothelial, epithelial and mesangial cells and also tumor cells and involve classical chemokine receptors as well as glycosaminoglycans (GAG). Its most prominent activity is inhibition of angiogenesis and, consequently, of tumor growth and metastasis.
The general biology of CXCL4 has been reviewed elaborately by different groups (Aidoudi and Bikfalvi, 2010; Kasper and Petersen, 2011; Vandercappellen et al., 2011).


Note The CXCL4 gene is located in the CXC chemokine gene cluster on chromosome 4q, in close proximity of its variant gene PF-4var/PF-4alt/CXCL4L1. The gene and mRNA for CXCL4 are 1300 and 855 bp in length, respectively.
  Figure 1. Structure of the human CXCL4 gene. This figure schematically depicts the structure of the human CXCL4 gene as described in the NCBI database (NM_002619). Lines represent the introns, whereas rectangular exons are coloured blue, yellow and green to represent the non-coding domains, the signal peptide and the mature protein, respectively. Grey numbers indicate the basepair numbering in the CXCL4 mRNA. Red numbers apply to the amino acids encoded.
Description The CXCL4 mRNA is encoded by three exons as depicted in figure 1. Alternative splicing of the gene has not been reported.
Transcription The CXCL4 mRNA is predominantly present in platelets, but has also been detected in monocytes, T cells, T cell clones, human aortic smooth muscle cells, the colorectal adenocarcinoma cell line HCT-8.
Pseudogene None.


Note CXCL4 precursor: 101 amino acids (aa), 10844.9 Da; CXCL4 mature: 70 aa, 7765.2 Da; Alternatively spliced signal peptide CXCL4: 74 aa, 8141.5 Da.
Several NH2-terminally truncated forms.
Description CXCL4 is a member of the CXC chemokine family of chemoattractant cytokines. CXCL4 is a non-ELR CXC chemokine, meaning that it lacks the sequence glutamic acid-leucine-arginine just in front of the two NH2-terminally located conserved cysteine residues.
Expression CXCL4 is stored in secretory granules and released in response to protein kinase C activation. For example, in platelets the CXCL4 protein is stored in the alpha-granules and released upon activation by e.g. thrombin as a homotetramer bound to chrondroitin-4-sulphate on a carrier protein. Therefore, CXCL4 is present at high concentrations in thrombi and concentrations in serum reach levels of 10 µg/ml. CXCL4 protein has also been detected in mast cells by immunohistochemistry, and is released by monocytes (100 ng/ml), activated T cells, cultured microglia (1 ng/ml) and the colorectal adenocarcinoma cell line HCT-8 (0.5 ng/ml). Finally, prostate cancer cell lines DU-145 and PC-3 were shown to express CXCL4.
Localisation Secreted or stored in intracellular granules.
Function The first extracellular molecules binding CXCL4 were identified to be chrondroitin-sulphate-containing proteoglycans (Figure 2). These GAG mediate the effects of CXCL4 on monocytes and neutrophils and pass intracellular signals to tyrosine kinases of the Src family, members of the MAP kinase family and monomeric GTPases. CXCL4 also has high affinity for heparin and heparan sulphate. Through its ability to bind and neutralize heparin, CXCL4 influences blood coagulation. More so, the interaction of CXCL4 with heparan sulphate proteoglycans on endothelial cells is responsible for the rapid clearance of CXCL4 from the circulation and prevents degradation of the chemokine.
Besides binding to GAG, CXCL4 has also been described to bind several growth factors, such as VEGF and FGF-2, and other chemokines, including CCL2/MCP-1 and possibly CXCL12/SDF-1 (Carlson et al., 2012). This heteromultimerisation, sequestering angiogenic proteins, explains at least in part the anti-angiogenic effect of CXCL4. Heteromer formation of CXCL4 with CCL5/RANTES also affects monocyte recruitment (Koenen et al., 2009), and possibly atherogenesis.
Although proteoglycans are mostly considered to be "co- receptors", the high affinity of CXCL4 for GAG was for a long time thought to mediate most, if not all, of its biological functions since no GPCR for CXCL4 was identified. However, Lasagni et al. identified a splice variant of CXCR3, which was named CXCR3B, as a functional GPCR for CXCL4. Currently, CXCL4 is known to activate both CXCR3A and CXCR3B (Figure 2). In general, proliferative and positive migratory effects are supposed to be mediated by CXCR3A, whereas inhibition of chemotaxis, anti-proliferative and apoptotic effects are postulated to be provoked via CXCR3B.
  Figure 2. Signaling pathways activated by CXCL4. A complex signaling network lies at the basis of the functional diversity of CXCL4. This network integrates several cascades initiated by different cellular receptors, including the G-protein-coupled receptors (GPCR) CXCR3A (Gi) and CXCR3B (Gs). CXCL4 also displays an exceptional high affinity for the glycosaminoglycans chains on membrane-embedded proteoglycans, hypothesized to initiate signaling cascades of their own (Kasper and Petersen, 2011). The schematic network depicted here represents a selection of prominent CXCL4-activated pathways and provides insight into the complexity of CXCL4 signaling, yet does not provide an exhaustive list of all signaling molecules implicated. Target cells for CXCL4 include leukocytes (neutrophils, monocytes, activated T cells, dendritic cells, NK cells and mast cells), endothelial cells, airway epithelial cells, hepatic stellate cells, mesangial cells and vascular pericytes.
Homology CXCL4 is most closely related to its variant CXCL4L1, a non-allelic variant found only in primates. In men, mature proteins only differ in 3 amino acids.


Note CXCL4 appears to behave as a tumor suppressor gene. In multiple myeloma, CXCL4 is frequently silenced as a consequence of promoter hypermethylation (Cheng et al., 2007). Furthermore, a subclass of acute lymphoblastic leukemia patients exhibits a common translocation with a breakpoint distal to the CXCL4 gene (Arthur et al., 1982; Griffin et al., 1987).

Implicated in

Entity Leukemia and myeloma
Prognosis Serum proteome profiling revealed decreased serum levels of CXCL4 as a biomarker for advanced myelodysplastic syndrome (MDS), often progressing to acute myeloid leukemia (AML) (Aivado et al., 2007). Other studies have corroborated involvement of CXCL4 over the course of MDS and AML and have recognized the chemokine as a prognostic, therapy-associated marker indicative of response to therapy, blood count recovery and eventual clinical outcome (Bai et al., 2013; Chen et al., 2010; Kim et al., 2008).
Oncogenesis Evidence in acute lymphoblastic leukemia (ALL), showing a common translocation amongst a subclass of patients, with a breakpoint in 4q21 which was later shown to be distal to the CXCL4 gene, suggested the involvement of CXCL4 in ALL tumorigenesis (Arthur et al., 1982; Griffin et al., 1987). More recently, decreased serum levels of CXCL4 have also been suggested to serve as a marker for pediatric ALL (Shi et al., 2009). In multiple myeloma CXCL4 was effectively identified as a tumor suppressor gene, frequently silenced as a consequence of promoter hypermethylation (Cheng et al., 2007).
Entity Osteosarcoma
Disease The platelet-associated CXCL4 expression was found to be elevated shortly after implantation of human osteosarcoma in mice (Cervi et al., 2008). It has been proposed as a biomarker of early tumor growth. Alternatively, another recent study described plasma levels of CXCL4 to be elevated in pediatric osteosarcoma patients (Li et al., 2011).
Prognosis Not only were plasma levels of CXCL4 in pediatric osteosarcoma patients shown to be significantly higher than those in controls, survival analysis further revealed that higher circulating levels of CXCL4 were associated with a poorer outcome (Li et al., 2011). CXCL4 may prove to be a promising prognostic factor in osteosarcoma patients in the future.
Entity Liposarcoma
Disease The platelet-associated CXCL4 expression, unlike its soluble plasma counterpart, was found to be elevated shortly after implantation of human liposarcoma in mice (Cervi et al., 2008). It has been proposed as a biomarker of early tumor growth.
Entity Mammary adenocarcinoma
Disease The platelet-associated CXCL4 expression, unlike its soluble plasma counterpart, was found to be elevated shortly after implantation of human mammary adenocarcinoma in mice (Cervi et al., 2008). It has been proposed as a biomarker of early tumor growth.
Entity Pancreatic adenocarcinoma
Prognosis Discovery of a cancer-associated reduction of CXCL4 serum concentrations lead to the identification of CXCL4 as a discriminating marker in pancreatic cancer (Fiedler et al., 2009). Potential of CXCL4 as a diagnostic marker was shortly after confirmed (Poruk et al., 2010). Moreover, serum CXCL4 was also identified as a strong independent predictor of survival in this study, where decreased survival is associated with elevated CXCL4 levels. Finally, as a prognostic marker, CXCL4 may prove to be valuable in identifying patients at risk of complications and thus may benefit from prophylactic antithrombotic therapy (Poruk et al., 2010).
Entity Colorectal cancer
Disease Platelet content of CXCL4 in 35 patients with colon cancer was shown to be significantly increased when compared to 84 age-matched healthy controls (Peterson et al., 2012). Though not thought to be clinically relevant, a change in CXCL4 platelet levels was identified as a predictor of colorectal carcinoma which could potentially enable early diagnosis of disease.
Entity Prostate cancer
Prognosis Recent in vitro research has evidenced that particular prostate tumor cells, namely DU-145 and PC-3 cells, exhibit a shift in CXCR3 splice variant presentation (Wu et al., 2012). In combination with the reported elevated tumor CXCL4 expression in vitro, these data suggest CXCL4 might promote in vitro migration and invasiveness of prostate cancer cells marked by a change in their CXCR3 expression pattern. However, CXCL4 levels have been described previously to be significantly decreased in the sera of all metastatic prostate carcinoma patients compared to healthy individuals, as well as compared to localized prostate carcinoma patients (Lam et al., 2005).
Entity Endometriosis-associated ovarian cancer (EAOC)
Oncogenesis Both clear cell and endometrioid types of ovarian cancers occasionally develop on the bases of endometriosis. These endometriosis-associated ovarian cancers (EAOC) are characterized by infiltration of CXCL4-depleted tumor-associated macrophages, whereas in contrast, in pre-existing endometriosis CXCL4 is strongly expressed by CD68+ infiltrating macrophages (Furuya et al., 2012). Macrophage CXCL4 expression is thus associated with EAOC disease state and pre-malignant lesions.
Entity Metastatic carcinoma
Disease Analysis of platelet content in a heterogeneous group of patients with newly diagnosed metastatic disease (including colorectal cancer, renal cell cancer, malignant fibrous histiocytoma, leiomyosarcoma and peripheral neuroectodermal cancer) a significant reduction in CXCL4 platelet concentrations was observed (Wiesner et al., 2010). Simultaneously, however, CXCL4 was upregulated in cancer patient plasma.
Entity Chemotherapy-induced thrombocytopenia (CIT)
Prognosis CXCL4 may be a useful biomarker predicting the risk of thrombocytopenia developing with chemotherapy (CIT) (Lambert et al., 2012). Patients with low steady-state platelet CXCL4 levels would better tolerate chemotherapy, whereas high concentrations may be an indication for CIT and predict the need for a platelet transfusion.
Entity Hepatitis and liver fibrosis
Disease CXCL4 expression is enhanced in the liver of patients with advanced hepatitis C virus-induced fibrosis or nonalcoholic steatohepatitis and Cxcl4 knock-out mice had significantly reduced histological and biochemical liver damage in an in vivo model for fibrotic liver disease (Zaldivar et al., 2010). In vitro, recombinant mouse CXCL4 stimulated proliferation and chemotaxis of hepatic stellate cells.
Entity Malaria
Disease Acute Plasmodium falciparum infection, causing malaria characterized by especially high morbidity and mortality, leads to elevated plasma levels of platelet-specific proteins, including CXCL4 (Essien and Ebhota, 1983). On the one hand CXCL4 exerts a protective, antimalarial effect. Upon binding of platelets to infected red blood cells, locally released CXCL4 in particular instigates killing of intraerythrocytic P. falciparum parasites (Love et al., 2012; McMorran et al., 2013). The protective function of blood platelets and CXCL4 is dependent on the Duffy-antigen receptor (Fy/DARC) on the erythrocytes. On the other hand, CXCL4 mediates the pathogenesis of cerebral malaria (CM), a serious complication of P. falciparum infection (Wilson et al., 2011). CXCL4 is believed to promote a pro-inflammatory environment and to contribute to disruption of the blood-brain barrier.
Prognosis Wilson et al. have suggested a prominent role for CXCL4 in the pathogenesis of fatal CM and identified this chemokine as a potential prognostic biomarker for CM mortality (Wilson et al., 2011).
Entity Acquired immunodeficiency syndrome (AIDS)
Disease Auerback et al. have identified CXCL4 as a unique broad-spectrum inhibitor of HIV-1 (Auerbach et al., 2012). Through binding of the external viral envelope glycoprotein, gp120, CXCL4 interferes with the earliest events in the viral infectious cycle, namely attachment and entry, and consequently reduces replication of different phenotypic variants of HIV-1 in CD4+ T cells and macrophages. In parallel, another study found activated platelets to release antiviral factors which suppress HIV-1 infection of T cells and confirmed CXCL4 to be a key player in this first line of defense against HIV-1 (Tsegaye et al., 2013).
Prognosis Preliminary results reported by Auerback and colleagues suggest a correlation between higher serum levels of CXCL4 in HIV-1-infected patients and a less advanced clinical stage (Auerbach et al., 2012).
Entity Heparin-induced thrombocytopenia (HIT)
Disease Heparin is widely used as anti-coagulant during invasive vascular surgery and to treat thrombo-embolic pathology. HIT is a rare (1-5%), paradoxal complication of anticoagulant heparin therapy in which patients having developed antibodies against CXCL4/heparin complexes, are at risk for venous as well as arterial thrombosis, despite low platelet counts (Rauova et al., 2010). Heparin is thought to act as an adjuvant integral to immunogenesis, whereas the HIT antibody recognizes antigenic epitopes within CXCL4 and thus the presence of CXCL4 is essential to the clinical manifestations caused by circulating antibodies (Prechel and Walenga, 2013).
Entity Rheumatoid arthritis
Prognosis Increased levels of CXCL4 have been reported in the synovial fluid of patients with rheumatoid arthritis (Erdem et al., 2007). However, especially elevated plasma levels of CXCL4 in particular subsets of patients may be associated with clinical manifestation of rheumatoid arthritis, such as the occurrence of cutaneous vasculitis, and also correlate to a non-response to anti-TNFα therapy (Trocme et al., 2009; Yamamoto et al., 2002).
Entity Proliferative diabetic retinopathy (PDR)
Disease Early on an association was recognized between diabetes and PDR on the one hand and elevated plasma levels of coagulation factors, such as CXCL4, on the other hand (Ek et al., 1982; Roy et al., 1988). Recent clinical studies have not only confirmed elevated CXCL4 levels in the vitreous fluid of PDR patients but also a correlation between vitreous CXCL4 concentration and PDR clinical disease activity (Nawaz et al., 2013). Vitreous levels of CXCL4 are significantly higher both in PDR with active neovascularisation and in PDR without traction retinal detachment.
Entity Inflammatory bowel disease (IBD)
Disease Already in 1987, plasma CXCL4 concentrations were shown to be increased in patients with IBD disease (Simi et al., 1987). CXCL4 was later on identified as a biomarker for IBD using proteomic serum profiling (Meuwis et al., 2007). Though originally controversial, plasma CXCL4 levels were confirmed to be positively correlated to disease activity in Crohn's disease (Vrij et al., 2000).
Prognosis Similar to their predictive role in rheumatoid arthritis, high CXCL4 plasma levels are indicative of non-responsiveness to anti-TNFα antibody (infliximab) treatment in Crohn's disease (Meuwis et al., 2008).
Entity Atherosclerosis
Disease The proatherogenic role of CXCL4 has been established in a variety of mostly preclinical studies (e.g. Sachais et al., 2007). CXCL4, released by activated platelets at injury sites, presumably promotes the progression of atherosclerotic lesions through different mechanisms. These include recruiting and arresting peripheral monocytes at the lesion site and consequently facilitating their differentiation into macrophages and concordant polarization as well as inhibiting degradation of LDL-R while increasing uptake and esterification of ox-LDL in macrophages (Aidoudi and Bikfalvi, 2010; Gleissner, 2012). The histological distribution of CXCL4 was also shown to be associated with the location and grade of vascular lesions (Pitsilos et al., 2003). Staining of macrophages for CXCL4 correlated with symptomatic atherosclerotic disease. Moreover, proinflammatory heteromer formation of CXCL4 with another platelet chemokine CCL5/RANTES has emerged as an additional regulatory mechanism, enhancing monocyte recruitment and thereby contributing to the disease progression (Koenen et al., 2009). Recently, a linkage study described an association between CXCL4 and platelet activation in human patients, thus linking this chemokine to the clinical manifestation of atherosclerosis (Bhatnagar et al., 2012).


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Wiesner T, Bugl S, Mayer F, Hartmann JT, Kopp HG.
Clin Exp Metastasis. 2010 Mar;27(3):141-9. doi: 10.1007/s10585-010-9311-6. Epub 2010 Feb 25.
PMID 20182908
CXCL4 and CXCL10 predict risk of fatal cerebral malaria.
Wilson NO, Jain V, Roberts CE, Lucchi N, Joel PK, Singh MP, Nagpal AC, Dash AP, Udhayakumar V, Singh N, Stiles JK.
Dis Markers. 2011;30(1):39-49. doi: 10.3233/DMA-2011-0763.
PMID 21508508
Altered CXCR3 isoform expression regulates prostate cancer cell migration and invasion.
Wu Q, Dhir R, Wells A.
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PMID 22236567
Elevated plasma levels of beta-thromboglobulin and platelet factor 4 in patients with rheumatic disorders and cutaneous vasculitis.
Yamamoto T, Chikugo T, Tanaka Y.
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This paper should be referenced as such :
Van, Raemdonck K ; Proost, P ; Van, Damme J ; Struyf, S
PF4 (platelet factor 4)
Atlas Genet Cytogenet Oncol Haematol. 2014;18(8):598-604.
Free journal version : [ pdf ]   [ DOI ]
On line version :

External links

HGNC (Hugo)PF4   8861
Entrez_Gene (NCBI)PF4  5196  platelet factor 4
AliasesCXCL4; PF-4; SCYB4
GeneCards (Weizmann)PF4
Ensembl hg19 (Hinxton)ENSG00000163737 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000163737 [Gene_View]  chr4:73980825-73982124 [Contig_View]  PF4 [Vega]
ICGC DataPortalENSG00000163737
TCGA cBioPortalPF4
AceView (NCBI)PF4
Genatlas (Paris)PF4
SOURCE (Princeton)PF4
Genetics Home Reference (NIH)PF4
Genomic and cartography
GoldenPath hg38 (UCSC)PF4  -     chr4:73980825-73982124 -  4q13.3   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)PF4  -     4q13.3   [Description]    (hg19-Feb_2009)
EnsemblPF4 - 4q13.3 [CytoView hg19]  PF4 - 4q13.3 [CytoView hg38]
Mapping of homologs : NCBIPF4 [Mapview hg19]  PF4 [Mapview hg38]
Gene and transcription
Genbank (Entrez)AJ705588 BC093965 BC112093 CR407677 GD143506
RefSeq transcript (Entrez)NM_002619
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)PF4
Cluster EST : UnigeneHs.81564 [ NCBI ]
CGAP (NCI)Hs.81564
Alternative Splicing GalleryENSG00000163737
Gene ExpressionPF4 [ NCBI-GEO ]   PF4 [ EBI - ARRAY_EXPRESS ]   PF4 [ SEEK ]   PF4 [ MEM ]
Gene Expression Viewer (FireBrowse)PF4 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevestigatorExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)5196
GTEX Portal (Tissue expression)PF4
Human Protein AtlasENSG00000163737-PF4 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP02776   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP02776  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP02776
Splice isoforms : SwissVarP02776
Domaine pattern : Prosite (Expaxy)SMALL_CYTOKINES_CXC (PS00471)   
Domains : Interpro (EBI)Chemokine_CXC    Chemokine_CXC_CS    Chemokine_IL8-like_dom    CXC_Chemokine_domain    PF4   
Domain families : Pfam (Sanger)IL8 (PF00048)   
Domain families : Pfam (NCBI)pfam00048   
Domain families : Smart (EMBL)SCY (SM00199)  
Conserved Domain (NCBI)PF4
DMDM Disease mutations5196
Blocks (Seattle)PF4
PDB (SRS)1DN3    1F9Q    1F9R    1F9S    1PFM    1PFN    1RHP    4R9W    4R9Y    4RAU   
PDB (PDBSum)1DN3    1F9Q    1F9R    1F9S    1PFM    1PFN    1RHP    4R9W    4R9Y    4RAU   
PDB (IMB)1DN3    1F9Q    1F9R    1F9S    1PFM    1PFN    1RHP    4R9W    4R9Y    4RAU   
PDB (RSDB)1DN3    1F9Q    1F9R    1F9S    1PFM    1PFN    1RHP    4R9W    4R9Y    4RAU   
Structural Biology KnowledgeBase1DN3    1F9Q    1F9R    1F9S    1PFM    1PFN    1RHP    4R9W    4R9Y    4RAU   
SCOP (Structural Classification of Proteins)1DN3    1F9Q    1F9R    1F9S    1PFM    1PFN    1RHP    4R9W    4R9Y    4RAU   
CATH (Classification of proteins structures)1DN3    1F9Q    1F9R    1F9S    1PFM    1PFN    1RHP    4R9W    4R9Y    4RAU   
Human Protein Atlas [tissue]ENSG00000163737-PF4 [tissue]
Peptide AtlasP02776
Protein Interaction databases
IntAct (EBI)P02776
Ontologies - Pathways
Ontology : AmiGOplatelet degranulation  protein binding  extracellular region  extracellular region  extracellular region  extracellular space  inflammatory response  immune response  G-protein coupled receptor signaling pathway  chemokine activity  heparin binding  positive regulation of gene expression  positive regulation of macrophage derived foam cell differentiation  negative regulation of angiogenesis  cytokine-mediated signaling pathway  platelet activation  leukocyte chemotaxis  positive regulation of cAMP metabolic process  platelet alpha granule lumen  response to lipopolysaccharide  positive regulation of tumor necrosis factor production  regulation of cell proliferation  positive regulation of cAMP-mediated signaling  negative regulation of MHC class II biosynthetic process  positive regulation of macrophage differentiation  negative regulation of megakaryocyte differentiation  negative regulation of cytolysis  positive regulation of transcription from RNA polymerase II promoter  CXCR3 chemokine receptor binding  chemokine-mediated signaling pathway  positive regulation of neutrophil chemotaxis  negative regulation of extrinsic apoptotic signaling pathway in absence of ligand  
Ontology : EGO-EBIplatelet degranulation  protein binding  extracellular region  extracellular region  extracellular region  extracellular space  inflammatory response  immune response  G-protein coupled receptor signaling pathway  chemokine activity  heparin binding  positive regulation of gene expression  positive regulation of macrophage derived foam cell differentiation  negative regulation of angiogenesis  cytokine-mediated signaling pathway  platelet activation  leukocyte chemotaxis  positive regulation of cAMP metabolic process  platelet alpha granule lumen  response to lipopolysaccharide  positive regulation of tumor necrosis factor production  regulation of cell proliferation  positive regulation of cAMP-mediated signaling  negative regulation of MHC class II biosynthetic process  positive regulation of macrophage differentiation  negative regulation of megakaryocyte differentiation  negative regulation of cytolysis  positive regulation of transcription from RNA polymerase II promoter  CXCR3 chemokine receptor binding  chemokine-mediated signaling pathway  positive regulation of neutrophil chemotaxis  negative regulation of extrinsic apoptotic signaling pathway in absence of ligand  
Pathways : KEGGCytokine-cytokine receptor interaction    Leukocyte transendothelial migration   
REACTOMEP02776 [protein]
REACTOME PathwaysR-HSA-418594 [pathway]   
NDEx NetworkPF4
Atlas of Cancer Signalling NetworkPF4
Wikipedia pathwaysPF4
Orthology - Evolution
GeneTree (enSembl)ENSG00000163737
Phylogenetic Trees/Animal Genes : TreeFamPF4
Homologs : HomoloGenePF4
Homology/Alignments : Family Browser (UCSC)PF4
Gene fusions - Rearrangements
Fusion : QuiverPF4
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerPF4 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)PF4
Exome Variant ServerPF4
ExAC (Exome Aggregation Consortium)ENSG00000163737
GNOMAD BrowserENSG00000163737
Genetic variants : HAPMAP5196
Genomic Variants (DGV)PF4 [DGVbeta]
DECIPHERPF4 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisPF4 
ICGC Data PortalPF4 
TCGA Data PortalPF4 
Broad Tumor PortalPF4
OASIS PortalPF4 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICPF4  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDPF4
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch PF4
DgiDB (Drug Gene Interaction Database)PF4
DoCM (Curated mutations)PF4 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)PF4 (select a term)
NCG5 (London)PF4
Cancer3DPF4(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry PF4
NextProtP02776 [Medical]
Target ValidationPF4
Huge Navigator PF4 [HugePedia]
snp3D : Map Gene to Disease5196
BioCentury BCIQPF4
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD5196
Chemical/Pharm GKB GenePA33203
Clinical trialPF4
canSAR (ICR)PF4 (select the gene name)
PubMed165 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Fri Jan 5 12:41:23 CET 2018

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