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CXCL12 (chemokine (C-X-C motif) ligand 12)

Written2015-08Giulia Gentile, Maria Guarnaccia, Sebastiano Cavallaro
Functional Genomics Unit, Institute of Neurogical Sciences, National Research Council, Catania, Italy

Abstract Review on CXCL12, with data on DNA, on the protein encoded, and where the gene is implicated.

Keywords CXCL12; Lung cancer; Breast cancer; Human Immunodeficiency Virus-type 1 (HIV-1) infection; WHIM Syndrome; Autoimmune Diseases

(Note : for Links provided by Atlas : click)

Identity

Alias_namesSDF1A
SDF1B
SDF1
stromal cell-derived factor 1
chemokine (C-X-C motif) ligand 12
Alias_symbol (synonym)SCYB12
SDF-1a
SDF-1b
PBSF
TLSF-a
TLSF-b
TPAR1
Other alias|FONTCOMOR=#900060>SDF-1
TLSF
SDF-1A
SDF-1B
IRH
HGNC (Hugo) CXCL12
LocusID (NCBI) 6387
Atlas_Id 40219
Location 10q11.21  [Link to chromosome band 10q11]
Location_base_pair Starts at 44370153 and ends at 44385097 bp from pter ( according to hg19-Feb_2009)  [Mapping CXCL12.png]
Local_order Molecular Location: Chromosome 10; base pairs 44,865,601-44,880,545 reverse strand, in the February 2009 hg19 human assembly (GRCh37). According to UCSC Genome Browser on Human Feb. 2009 assembly (GRCh37/hg19), genes flanking CXCL12 on 10q11.21, in centromere to telomere direction, are ZNF32 (zinc finger protein 32), HNRNPA3P1 (heterogeneous nuclear ribonucleoprotein A3 pseudogene 1), CXCL12, THEM72 (transmembrane protein 72), RASSF4 (Ras association (RalGDS/AF-6) domain family member 4).
Fusion genes
(updated 2016)
ANGPT1 (8q23.1) / CXCL12 (10q11.21)CXCL12 (10q11.21) / CXCL12 (10q11.21)CXCL12 (10q11.21) / NKAIN3 (8q12.3)
ECD (10q22.1) / CXCL12 (10q11.21)IPMK (10q21.1) / CXCL12 (10q11.21)
Note Synonyms: Stromal cell-derived factor 1, Pre-B cell growth-stimulating factor, Intercrine reduced in hepatomas.

DNA/RNA

 
  Figure 1 Schematic structure of the four exons of human CXCL12 (exon1: 153bp; exon2: 118bp; exon3: 87bp; exon4: 3191bp). Two of them are made up not only of coding regions (in green color) but also of non-coding ones (in red color).
Description The CXCL12 gene consists of 4 exons spanning 14.94 kb on the chromosome 10 at band q11.21 (reverse strand) (Figure 1).
Transcription Alternative splicing results in eight transcript variants (Table 1), as shown in Ensembl database. Among them, six correspond to as many protein isoforms (Yu et al., 2006).
Pseudogene No known pseudogenes.

Protein

 
Description CXCL12 gene encodes a stromal cell-derived alpha chemokine, also known as SDF1, a member of the intercrine family. This family is defined by the location of the first two cysteine residues in the sequence, which are separated by one amino acid (C-X-C chemokine)(Hromas, 1997). Six protein isoforms have been identified in human: Alpha, Beta, Gamma, Delta, Epsilon and Theta (Table 2; Figure 2), produced by alternative splicing events (Yu et al., 2006). In particular Alpha and Beta isoforms, secreted as full-length molecules, undergo to post-translational modifications by a proteolytic cleavage, becoming respectively processed forms SDF-1-alpha(3-67) and SDF-1-beta(3-72)(De la Luz Sierra et al., 2004). The Beta isoform has been chosen as the canonical sequence and, together with Alpha isoform, is ubiquitously expressed in liver, pancreas and spleen. The Gamma Isoform is mainly expressed in heart, while the isoforms Delta, Epsilon and Theta are mainly expressed in pancreas. In the developmental stage, the isoform Alpha is ubiquitously expressed in fetal tissues, Beta and Delta isoforms in fetal spleen and liver, while Gamma and Theta isoforms are weakly detected in fetal kidney (Yu et al., 2006).
 
  Figure 2 The figure shows (A)the molecule processing of CXCL12 beta isoform sequence, in which the potential signal peptide is marked in red color while the polypeptide chain in blue color (data obtained from UniProtKB database);(B) the multiple sequence alignment of the six CXCL12 isoforms. For each isoform, after the 88 identical positions there are a certain number of different residues, highlighted in light blue color. (Alignment produced by CLC Sequence Viewer 7.0 from CLCbio - QIAGEN Company, using Clustal Omega multiple alignment program). SDF-1-alpha(3-67) and SDF-1-beta(3-72), processed by post-translational proteolytic cleavage, are marked by yellow and orange boxes respectively (data on both sequences belong to UniProtKB database).
Expression CXCL12 is widely expressed in a variety of tissue types, such as heart, liver, spleen, kidney, brain, skeletal muscle, endothelium, epithelium, lymphoid organs, stem cells as well as overexpressed in cancer cells (Kryczek et al., 2007; Teicher and Fricker, 2010).
Localisation Extracellular region.
Function The CXCL12 protein functions as a ligand for two seven-transmembrane receptors (7-TMRs). The first one is the chemokine (C-X-C motif) receptor 4 (CXCR4), a monogamous receptor that signals through heterotrimeric G proteins and beta-arrestin; the second one is the chemokine (C-X-C motif) receptor 7 (CXCR7), a non-monogamous receptor that does not activate G-protein-mediated signal transduction but signals only through beta-arrestin (Oberlin et al., 1996; Rajagopal et al., 2010; Sun et al., 2010; Zhu et al., 2012; Sanchez-Martin et al., 2013). In particular, CXCL12 has a higher affinity of binding to CXCR7 than to CXCR4 (Zhu et al., 2012), even if its affinity to CXCR7 seems to be reduced by the expression of CXCR4 at the membrane (Sanchez-Martin et al., 2013). CXCL12 is secreted in the extracellular space as monomeric and dimeric forms, which can trigger different effects on cell signaling (Ray et al., 2012). In fact, whereas CXCR4 binds both monomeric and dimeric forms, CXCR7 binds preferentially the dimeric one (Sanchez-Martin et al., 2013). For example, dimeric CXCL12 form induces calcium mobilization but fails to promote chemotaxis, which is induced by the monomer-based interactions (Ray et al., 2012; Sanchez-Martin et al., 2013). Many others cellular functions depend on CXCL12 activity, including embryogenesis, apoptosis and survival, immune response, tissue homeostasis, angiogenesis, calcium ion homeostasis, clathrin-mediated endocytosis, cytoskeletal rearrangement, cell proliferation and migration, tumor growth and metastasis (Vlahakis et al., 2002; Goda et al., 2006; Petit et al., 2007; Khan et al., 2008; Agle et al., 2010; Drury et al.,2010; Karin, 2010; Kremer, 2010; Sun et al., 2010; Zhu et al., 2012).
Homology The CXCL12 Gene Tree shows a great evolutionary conservation across species (Figure 3). The internal nodes of the phylogenetic tree are annotated for duplication (red boxes) and speciation (blue boxes) events, which correspond to paralogs and orthologs homologous genes respectively.
 
  Figure 3 The CXCL12 Gene Tree shows the maximum likelihood phylogenetic tree representing the evolutionary history of the CXCL12 gene, constructed using the alignment of a CXCL12 representative protein for each species (green bars). The Gene tree has been generated by Ensembl (GeneTree ENSGT00390000014056 - August 2015) using the Gene Orthology/Paralogy prediction method pipeline (Vilella et al., 2009).

Mutations

Note NOTE It has been suggested that a single nucleotide polymorphism (SNP)in the 3' untranslated region of SDF-1-beta transcript is associated not only with a delayed onset (Winkler et al., 1998) and a modest protective effect against infection and progression of AIDS (Modi et al., 2005), but also with the early onset of type 1 diabetes (Dubois-Laforgue et al., 2001) and with an increased likelihood of developing several cancers (as lung, breast, colorectal and prostate)(Ma et al., 2012; Shi et al., 2013). This could be explained by an increased level and stability of SDF-1-beta transcript as effect of this mutation (Garcia-Moruja et al., 2009).
Somatic A SNP consisting of a G-to-A transition at position 801, counting from the ATG start codon in the 3' UTR of the Genbank reference sequence L36033, was represented in the SDF-1-beta transcript but not in the SDF-1-alpha transcript (Winkler et al., 1998). The mutation CXCL12-G801A-3 Prime UTR, also known as SDF1-3-prime-A, located at chromosome 10 position 44873550 on Assembly GRCh37, has been classified as pathogenic variant (dbSNP: rs387906400)related to the phenotype Human immunodeficiency virus type 1, resistance to (OMIM: 600835.0001).

Implicated in

Note
  
Entity Lung cancer
Note The CXCL12 expression showed an increase in lung cancer cell lines (small cell lung cancers and non-small cell lung cancers) compared to non-malignant human bronchial epithelial cell ones. This overexpression was positively but weakly correlated with those of CXCR4 or CXCR7, suggesting that CXCL12 may differentially interact with its receptors depending on the cellular context (Imai et al., 2010). Furthermore, different evidences support the involvement of the CXCL12/CXCR4 axis, but not CXCL12/CXCR7, in the metastatic behavior of non-small cell lung cancer, suggesting their potential use as prognostic markers and drug targets (Paratore et al., 2011; Cavallaro, 2013; Choi et al., 2014).
  
  
Entity Breast cancer
Note The CXCL12 expression has been shown to stimulate breast cancer cells proliferation and promote tumor growth (Allinen et al., 2004; Duda et al., 2011). Moreover, a CXCL12 gene variant CXCL12-A (CXCL12-G801A, a single nucleotide polymorphism in the 3' untranslated region) was associated with an increased susceptibility to breast cancer (Dimberg et al., 2007). The interactions of CXCL12/CXCR4 seems to have a critical role in determining the metastatic destination of breast cancer metastasis (Muller et al., 2001; Hinton et al., 2011), while the CXCR7 expression has been linked to the ability of tumor cells to produce lung and brain metastasis (Sun et al., 2010). In a recent study, the expression profiles of the six CXCL12 isoforms and both receptors have been investigated in a large clinical cohort and common breast cancer cell lines. As result, isoform-specific differences in expression and breast cancer outcomes have been established, while CXCR4 and CXCR7 showed an opposite pattern in cancer as compared with normal and further differences between hormone receptor status and molecular subtypes (Zhao et al., 2014).
  
  
Entity Other malignancies
Note The importance of CXCL12 pathways in the proliferation, growth and metastasis processes has been assessed for many other types of tumors, among which prostate cancer (Vaday et. al., 2004; Zhang et al., 2008; Sun et al., 2010; Duda et al., 2011), pancreatic adenocarcinoma (Shen et al., 2013; Wu et al., 2013), neuroblastoma (Zagozdzon et al.,2008; Liberman et al., 2012), glioblastoma (Gatti et al., 2013; Wurth et al., 2014; Yao et al., 2015), colorectal cancer (Brand et al., 2005; Akishima-Fukasawa et al., 2009; Drury et al., 2010), melanoma (Scala et al., 2005; Toyozawa et al.,2012; Mitchell et al., 2014), bladder cancer (Retz et al., 2005; Shen et al., 2013), esophageal cancer (Sasaki et al., 2008; Wang et al., 2009; Tachezy et al., 2013), renal cancer (Pan et al., 2006; Ieran et al., 2014) and ovarian cancer (Popple et al., 2012).
  
  
Entity Human Immunodeficiency Virus-type 1 (HIV-1) infection
Note Since the discovery of the leukocyte-derived seven-transmembrane domain receptor (LESTR) twenty years ago (Loetscher et al., 1994) and of its function of co-receptor (termed fusin) for lymphocyte-tropic HIV-1 strains, the role of this chemokine receptor in modulating cell permissiveness to the infection was delineated in few years(Feng et al., 1996). At the same time, was reported the identification of the SDF-1 human chemokine as the natural ligand for LESTR/fusin protein, so named CXCR4, and its function of infection inhibitor by lymphocyte-tropic HIV-1 strains (Bleul et al., 1996 ; Oberlin et al., 1996). It was clarified that the HIV-1 infection requires expression of CD4, as primary receptor, and the CXCR4 as entry co-factor at the target cell surface; the engagement of these receptors by the HIV-1 envelope glycoprotein is essential for membrane fusion and, HIV infection can be prevented by HIV co-receptor antagonists (Davis et al., 1997). The HIV suppressive activity of SDF-1, by inhibition of HIV replication, was explained by a SDF-1 alpha-dependent internalization of the CXCR4 (Amara et al., 1997). Furthermore, as previously described in the mutations section, the SDF-1-beta chemokine gene variant in the homozygous state (SDF1-3'A/3'A), has been correlate to a delay of the AIDS onset (Winkler et al., 1998). During these years, different CXCR4 antagonists have reached later stage clinical trials but no one is currently underway (Henrich and Kuritzkes, 2013).
  
  
Entity WHIM Syndrome
Note WHIM is an acronym for an immunodeficiency disorder characterized by (w)arts, (h)ypogammaglobulinemia, (i)nfections and (m)yelokathexis symptoms. In most cases, it is caused by an inherited mutation affecting the CXCR4 gene (Hernandez et al., 2003; Liu et al., 2012).
  
  
Entity Autoimmune Diseases
Note CXCL12 functions as an anti-inflammatory chemokine during autoimmune inflammatory responses suggesting the use of CXCL12-based therapies for autoimmune inflammatory diseases (Karin, 2010; Villalvilla et al., 2014).
  

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Winkler C, Modi W, Smith MW, Nelson GW, Wu X, Carrington M, Dean M, Honjo T, Tashiro K, Yabe D, Buchbinder S, Vittinghoff E, Goedert JJ, O'Brien TR, Jacobson LP, Detels R, Donfield S, Willoughby A, Gomperts E, Vlahov D, Phair J, O'Brien SJ
ALIVE Study, Hemophilia Growth and Development Study (HGDS), Multicenter AIDS Cohort Study (MACS), Multicenter Hemophilia Cohort Study (MHCS), San Francisco City Cohort (SFCC) Science
PMID 9430590
 
Role of CXCL12/CXCR4 signaling axis in pancreatic cancer
Wu PF, Lu ZP, Cai BB, Tian L, Zou C, Jiang KR, Miao Y
Chin Med J (Engl) 2013;126(17):3371-4
PMID 24033967
 
CXCL12/CXCR4 Axis Upregulates Twist to Induce EMT in Human Glioblastoma
Yao C, Li P, Song H, Song F, Qu Y, Ma X, Shi R, Wu J
Mol Neurobiol 2015 Jul 16
PMID 26179613
 
Identification and expression of novel isoforms of human stromal cell-derived factor 1
Yu L, Cecil J, Peng SB, Schrementi J, Kovacevic S, Paul D, Su EW, Wang J
Gene 2006 Jun 7;374:174-9
PMID 16626895
 
Csk homologous kinase inhibits CXCL12-CXCR4 signaling in neuroblastoma
Zagozdzon R, Fu Y, Avraham HK
Int J Oncol 2008 Mar;32(3):619-23
PMID 18292939
 
Chemokine CXCL12 and its receptor CXCR4 expression are associated with perineural invasion of prostate cancer
Zhang S, Qi L, Li M, Zhang D, Xu S, Wang N, Sun B
J Exp Clin Cancer Res 2008 Nov 4;27:62
PMID 18983683
 
A Comprehensive Analysis of CXCL12 Isoforms in Breast Cancer(1,2
Zhao S, Chang SL, Linderman JJ, Feng FY, Luker GD
) Transl Oncol
PMID 24836649
 
CXCL12 enhances human neural progenitor cell survival through a CXCR7- and CXCR4-mediated endocytotic signaling pathway
Zhu B, Xu D, Deng X, Chen Q, Huang Y, Peng H, Li Y, Jia B, Thoreson WB, Ding W, Ding J, Zhao L, Wang Y, Wavrin KL, Duan S, Zheng J
Stem Cells 2012 Nov;30(11):2571-83
PMID 22987307
 
Homeostatic chemokine receptors and organ-specific metastasis
Zlotnik A, Burkhardt AM, Homey B
Nat Rev Immunol 2011 Aug 25;11(9):597-606
PMID 21866172
 

Citation

This paper should be referenced as such :
Gentile G, Guarnaccia M, Cavallaro S
CXCL12 (chemokine (C-X-C motif) ligand 12);
Atlas Genet Cytogenet Oncol Haematol. in press
On line version : http://AtlasGeneticsOncology.org/Genes/CXCL12ID40219ch10q11.html


Other Leukemias implicated (Data extracted from papers in the Atlas) [ 2 ]
  Chronic myelogenous leukaemia (CML)
Multiple Myeloma


Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 1 ]
  Lung: Translocations in Squamous Cell Carcinoma


External links

Nomenclature
HGNC (Hugo)CXCL12   10672
Cards
AtlasCXCL12ID40219ch10q11
Entrez_Gene (NCBI)CXCL12  6387  C-X-C motif chemokine ligand 12
AliasesIRH; PBSF; SCYB12; SDF1; 
TLSF; TPAR1
GeneCards (Weizmann)CXCL12
Ensembl hg19 (Hinxton)ENSG00000107562 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000107562 [Gene_View]  chr10:44370153-44385097 [Contig_View]  CXCL12 [Vega]
ICGC DataPortalENSG00000107562
TCGA cBioPortalCXCL12
AceView (NCBI)CXCL12
Genatlas (Paris)CXCL12
WikiGenes6387
SOURCE (Princeton)CXCL12
Genetics Home Reference (NIH)CXCL12
Genomic and cartography
GoldenPath hg38 (UCSC)CXCL12  -     chr10:44370153-44385097 -  10q11.21   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)CXCL12  -     10q11.21   [Description]    (hg19-Feb_2009)
EnsemblCXCL12 - 10q11.21 [CytoView hg19]  CXCL12 - 10q11.21 [CytoView hg38]
Mapping of homologs : NCBICXCL12 [Mapview hg19]  CXCL12 [Mapview hg38]
OMIM600835   609423   
Gene and transcription
Genbank (Entrez)AI092156 AJ227905 AK090482 AK124641 AK292628
RefSeq transcript (Entrez)NM_000609 NM_001033886 NM_001178134 NM_001277990 NM_199168
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)CXCL12
Cluster EST : UnigeneHs.522891 [ NCBI ]
CGAP (NCI)Hs.522891
Alternative Splicing GalleryENSG00000107562
Gene ExpressionCXCL12 [ NCBI-GEO ]   CXCL12 [ EBI - ARRAY_EXPRESS ]   CXCL12 [ SEEK ]   CXCL12 [ MEM ]
Gene Expression Viewer (FireBrowse)CXCL12 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)6387
GTEX Portal (Tissue expression)CXCL12
Protein : pattern, domain, 3D structure
UniProt/SwissProtP48061   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP48061  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP48061
Splice isoforms : SwissVarP48061
PhosPhoSitePlusP48061
Domains : Interpro (EBI)Chemokine_IL8-like_dom    CXC_Chemokine_domain   
Domain families : Pfam (Sanger)IL8 (PF00048)   
Domain families : Pfam (NCBI)pfam00048   
Domain families : Smart (EMBL)SCY (SM00199)  
Conserved Domain (NCBI)CXCL12
DMDM Disease mutations6387
Blocks (Seattle)CXCL12
PDB (SRS)1A15    1QG7    1SDF    1VMC    2J7Z    2K01    2K03    2K04    2K05    2KEC    2KED    2KEE    2KOL    2N55    2NWG    2SDF    3GV3    3HP3    4LMQ    4UAI   
PDB (PDBSum)1A15    1QG7    1SDF    1VMC    2J7Z    2K01    2K03    2K04    2K05    2KEC    2KED    2KEE    2KOL    2N55    2NWG    2SDF    3GV3    3HP3    4LMQ    4UAI   
PDB (IMB)1A15    1QG7    1SDF    1VMC    2J7Z    2K01    2K03    2K04    2K05    2KEC    2KED    2KEE    2KOL    2N55    2NWG    2SDF    3GV3    3HP3    4LMQ    4UAI   
PDB (RSDB)1A15    1QG7    1SDF    1VMC    2J7Z    2K01    2K03    2K04    2K05    2KEC    2KED    2KEE    2KOL    2N55    2NWG    2SDF    3GV3    3HP3    4LMQ    4UAI   
Structural Biology KnowledgeBase1A15    1QG7    1SDF    1VMC    2J7Z    2K01    2K03    2K04    2K05    2KEC    2KED    2KEE    2KOL    2N55    2NWG    2SDF    3GV3    3HP3    4LMQ    4UAI   
SCOP (Structural Classification of Proteins)1A15    1QG7    1SDF    1VMC    2J7Z    2K01    2K03    2K04    2K05    2KEC    2KED    2KEE    2KOL    2N55    2NWG    2SDF    3GV3    3HP3    4LMQ    4UAI   
CATH (Classification of proteins structures)1A15    1QG7    1SDF    1VMC    2J7Z    2K01    2K03    2K04    2K05    2KEC    2KED    2KEE    2KOL    2N55    2NWG    2SDF    3GV3    3HP3    4LMQ    4UAI   
SuperfamilyP48061
Human Protein AtlasENSG00000107562
Peptide AtlasP48061
HPRD02904
IPIIPI00848299   IPI00413781   IPI00651692   IPI01011188   IPI00386173   IPI00719836   IPI00945655   
Protein Interaction databases
DIP (DOE-UCLA)P48061
IntAct (EBI)P48061
FunCoupENSG00000107562
BioGRIDCXCL12
STRING (EMBL)CXCL12
ZODIACCXCL12
Ontologies - Pathways
QuickGOP48061
Ontology : AmiGOresponse to hypoxia  neuron migration  positive regulation of endothelial cell proliferation  receptor binding  extracellular region  extracellular space  cytoplasm  cellular calcium ion homeostasis  chemotaxis  defense response  immune response  cell adhesion  signal transduction  G-protein coupled receptor signaling pathway  axon guidance  chemokine activity  chemokine activity  blood circulation  regulation of actin polymerization or depolymerization  growth factor activity  adult locomotory behavior  response to radiation  response to heat  response to virus  external side of plasma membrane  telencephalon cell migration  animal organ regeneration  positive regulation of dopamine secretion  chemoattractant activity  chemokine receptor binding  response to peptide hormone  CXCR chemokine receptor binding  positive regulation of cell adhesion  positive regulation of axon extension involved in axon guidance  positive chemotaxis  induction of positive chemotaxis  cell chemotaxis  extracellular exosome  chemokine-mediated signaling pathway  positive regulation of monocyte chemotaxis  positive regulation of calcium ion import  negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage  negative regulation of leukocyte tethering or rolling  response to ultrasound  negative regulation of leukocyte apoptotic process  positive regulation of T cell migration  
Ontology : EGO-EBIresponse to hypoxia  neuron migration  positive regulation of endothelial cell proliferation  receptor binding  extracellular region  extracellular space  cytoplasm  cellular calcium ion homeostasis  chemotaxis  defense response  immune response  cell adhesion  signal transduction  G-protein coupled receptor signaling pathway  axon guidance  chemokine activity  chemokine activity  blood circulation  regulation of actin polymerization or depolymerization  growth factor activity  adult locomotory behavior  response to radiation  response to heat  response to virus  external side of plasma membrane  telencephalon cell migration  animal organ regeneration  positive regulation of dopamine secretion  chemoattractant activity  chemokine receptor binding  response to peptide hormone  CXCR chemokine receptor binding  positive regulation of cell adhesion  positive regulation of axon extension involved in axon guidance  positive chemotaxis  induction of positive chemotaxis  cell chemotaxis  extracellular exosome  chemokine-mediated signaling pathway  positive regulation of monocyte chemotaxis  positive regulation of calcium ion import  negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage  negative regulation of leukocyte tethering or rolling  response to ultrasound  negative regulation of leukocyte apoptotic process  positive regulation of T cell migration  
Pathways : BIOCARTACXCR4 Signaling Pathway [Genes]    Pertussis toxin-insensitive CCR5 Signaling in Macrophage [Genes]   
Pathways : KEGG   
REACTOMEP48061 [protein]
REACTOME PathwaysR-HSA-418594 [pathway]   
NDEx NetworkCXCL12
Atlas of Cancer Signalling NetworkCXCL12
Wikipedia pathwaysCXCL12
Orthology - Evolution
OrthoDB6387
GeneTree (enSembl)ENSG00000107562
Phylogenetic Trees/Animal Genes : TreeFamCXCL12
HOVERGENP48061
HOGENOMP48061
Homologs : HomoloGeneCXCL12
Homology/Alignments : Family Browser (UCSC)CXCL12
Gene fusions - Rearrangements
Fusion : MitelmanANGPT1/CXCL12 [8q23.1/10q11.21]  [t(8;10)(q23;q11)]  
Fusion : MitelmanECD/CXCL12 [10q22.1/10q11.21]  [t(10;10)(q11;q22)]  
Fusion : MitelmanIPMK/CXCL12 [10q21.1/10q11.21]  [t(10;10)(q11;q21)]  
Fusion: TCGAECD 10q22.1 CXCL12 10q11.21 BRCA
Fusion: TCGAIPMK 10q21.1 CXCL12 10q11.21 LUAD
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerCXCL12 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)CXCL12
dbVarCXCL12
ClinVarCXCL12
1000_GenomesCXCL12 
Exome Variant ServerCXCL12
ExAC (Exome Aggregation Consortium)CXCL12 (select the gene name)
Genetic variants : HAPMAP6387
Genomic Variants (DGV)CXCL12 [DGVbeta]
DECIPHERCXCL12 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisCXCL12 
Mutations
ICGC Data PortalCXCL12 
TCGA Data PortalCXCL12 
Broad Tumor PortalCXCL12
OASIS PortalCXCL12 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICCXCL12  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDCXCL12
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
LOVD (Leiden Open Variation Database)TBsLVD Tuberculosis susceptibility Locus Variation Database
BioMutasearch CXCL12
DgiDB (Drug Gene Interaction Database)CXCL12
DoCM (Curated mutations)CXCL12 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)CXCL12 (select a term)
intoGenCXCL12
NCG5 (London)CXCL12
Cancer3DCXCL12(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM600835    609423   
Orphanet
MedgenCXCL12
Genetic Testing Registry CXCL12
NextProtP48061 [Medical]
TSGene6387
GENETestsCXCL12
Target ValidationCXCL12
Huge Navigator CXCL12 [HugePedia]
snp3D : Map Gene to Disease6387
BioCentury BCIQCXCL12
ClinGenCXCL12
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD6387
Chemical/Pharm GKB GenePA35602
Clinical trialCXCL12
Miscellaneous
canSAR (ICR)CXCL12 (select the gene name)
Probes
Litterature
PubMed499 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineCXCL12
EVEXCXCL12
GoPubMedCXCL12
iHOPCXCL12
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Mon Sep 18 17:00:31 CEST 2017

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