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ASAP1 (ArfGAP with SH3 domain, ankyrin repeat and PH domain 1)

Written2012-02Hisataka Sabe, Yasuhito Onodera, Ari Hashimoto, Shigeru Hashimoto
Hokkaido University Graduate School of Medicine, Department of Molecular Biology, Sapporo, Japan

(Note : for Links provided by Atlas : click)

Identity

Alias_namesbeta 4
DDEF1
Alias_symbol (synonym)PAP
KIAA1249
ZG14P
CENTB4
HGNC (Hugo) ASAP1
LocusID (NCBI) 50807
Atlas_Id 44351
Location 8q24.21  [Link to chromosome band 8q24]
Location_base_pair Starts at 131064351 and ends at 131455906 bp from pter ( according to hg19-Feb_2009)  [Mapping ASAP1.png]
 
  The ASAP1 gene maps on chromosome 8, at 8q24.1-q24.2 according to Entrez Gene (adapted from GeneCards).
Fusion genes
(updated 2016)
ANKS1B (12q23.1) / ASAP1 (8q24.21)ASAP1 (8q24.21) / ASAP1 (8q24.21)ASAP1 (8q24.21) / CLVS1 (8q12.3)
ASAP1 (8q24.21) / FAM19A5 (22q13.32)ASAP1 (8q24.21) / KCNH1 (1q32.2)ASAP1 (8q24.21) / LRRCC1 (8q21.2)
ASAP1 (8q24.21) / MALAT1 (11q13.1)ASAP1 (8q24.21) / MDGA2 (14q21.3)ASAP1 (8q24.21) / P4HA3 (11q13.4)
ASAP1 (8q24.21) / PSMD3 (17q21.1)ASAP1 (8q24.21) / RAD51B (14q24.1)ASAP1 (8q24.21) / ROBO2 (3p12.3)
ASAP1 (8q24.21) / SAMD12 (8q24.12)EFR3A (8q24.22) / ASAP1 (8q24.21)FAM49B (8q24.21) / ASAP1 (8q24.21)
KIAA0430 (16p13.11) / ASAP1 (8q24.21)PNPT1 (2p16.1) / ASAP1 (8q24.21)PVT1 (8q24.21) / ASAP1 (8q24.21)
TRA () / ASAP1 (8q24.21)

DNA/RNA

 
Description The ASAP1 locus spans 391,75 kb, on the minus strand of chromosome 8 from 131456099 to 131064346.
Transcription Transcription produces 16 different mRNAs, 12 alternatively spliced variants and 4 unspliced forms.
There are 9 probable alternative promotors, 6 non overlapping alternative last exons and 5 validated alternative polyadenylation sites. The mRNAs appear to differ by truncation of the 5' end, truncation of the 3' end, presence or absence of 15 cassette exons, overlapping exons with different boundaries (NCBI).

Protein

Expression Epithelial cells, fibroblasts, macrophages, brain (for references see above), and endothelial cells (Hashimoto et al., 2011). Not determined with the other types of cells.
Localisation Intracellular tubulovesicular structures and vesicles, plasma membrane protrusions and leading edges, and invadopodia/podosome structures (Hashimoto et al., 2004; Hashimoto et al., 2005; Onodera et al., 2005).
Function ASAP1 has an ArfGAP zinc-finger domain and exhibits phosphatidylinositol 4,5-bisphosphate-dependent GAP activities for Arf1 and Arf5 but 102- to 103-fold less activity for Arf6 (Brown et al., 1998; Andreev et al., 1999). ASAP1 was shown to enhance cell motility, and this activity was proposed to be mediated by its GAP activity towards Arf1 (Furman et al., 2002). ASAP1 was also shown to associate with focal adhesion kinase (FAK) and contribute to focal adhesion assembly (Liu et al., 2002). Hashimoto et al. (2004 and 2005) have shown that AMAP1 and AMAP2 have the ability to bind stably with GTP-Arf6, but not GDP-Arf6 or other GTP-/GDP-Arf isoforms, in vitro and in vivo. Through this binding, AMAP1 and AMAP2 appear to function as downstream effectors for GTP-Arf6 (Hashimoto et al., 2004; Hashimoto et al., 2005; Onodera et al., 2005). AMAP1 binds to paxillin and cortactin, which are essential components of the invadopodia of MDA-MB-231 breast cancer cells, and acts to recruit these proteins to the sites of Arf6 activation to form invadopodia (Onodera et al., 2005). AMAP1 is hence essential for invasion and metastasis of some breast cancer cells, while AMAP2 is not a component of invadopodia (Onodera et al., 2005; Hashimoto et al., 2006; Nam et al., 2007; Morishige et al., 2008; Sabe et al., 2009). AMAP1 appears to be a useful diagnostic marker as well as therapeutic target of different types of human cancers (see below).

Implicated in

Note
Entity Breast cancer
Note In primary breast cancers, AMAP1 protein, but not AMAP2 protein, is abnormally overexpressed in their significant population in a manner independent of the transcriptional upregulation of the AMAP1 gene, and levels of AMAP1 protein expression correlates well with the malignant phenotypes (Onodera et al., 2005).
  
Entity Melanoma
Note With the name DDEF1, this gene was identified to be located in an amplified region of chromosome 8q24.12, and the amplification of chromosome 8q in uveal melanomas was found to correlate most strongly with the expression of this gene in melanomas (Ehlers et al., 2005).
  
Entity Colorectal cancer
Note Protein expression of ASAP1 is upregulated in colorectal cancer cells, and this expression correlates with poor metastasis-free survival and prognosis in colorectal cancer patients (Müller et al., 2010). It is worth noting, on the other hand, that a previous study on the copy number changes at 8q11-24 in colorectal carcinomas showed that although the MYC gene, located at 8q24.12-q24.13, is indeed amplified and correlates with the advanced stages of colorectal carcinoma, the DDEF1 gene was not amplified (Buffart et al., 2005).
  
Entity Prostate cancer
Note Additional gene copies of ASAP1 were also detected in a large population of primary prostate cancers, and ASAP1 protein staining was found to be elevated in 80% of primary prostate cancers with substantially higher amounts observed in metastatic lesions compared with benign prostate tissue (Lin et al., 2008).
  
Entity Pancreatic ductal adenocarcinoma
Note DDEF1 gene was found to be frequently amplified, most likely to be oncogenic, in pancreatic ductal adenocarcinomas, accompanied by enhanced expression of this gene (Harada et al., 2009).
  
Entity VEGF- and tumor-induced angiogenesis
Note AMAP1 protein is highly expressed in endothelial cells upon their treatment with vascular endothelial growth factor (VEGF), and an essential component of VEGF- and tumor-induced angiogenesis, and also choroidal neovascularization (Hashimoto et al., 2011).
  

Bibliography

Identification of a new Pyk2 target protein with Arf-GAP activity.
Andreev J, Simon JP, Sabatini DD, Kam J, Plowman G, Randazzo PA, Schlessinger J.
Mol Cell Biol. 1999 Mar;19(3):2338-50.
PMID 10022920
 
ASAP1, a phospholipid-dependent arf GTPase-activating protein that associates with and is phosphorylated by Src.
Brown MT, Andrade J, Radhakrishna H, Donaldson JG, Cooper JA, Randazzo PA.
Mol Cell Biol. 1998 Dec;18(12):7038-51.
PMID 9819391
 
DNA copy number changes at 8q11-24 in metastasized colorectal cancer.
Buffart TE, Coffa J, Hermsen MA, Carvalho B, van der Sijp JR, Ylstra B, Pals G, Schouten JP, Meijer GA.
Cell Oncol. 2005;27(1):57-65.
PMID 15750208
 
DDEF1 is located in an amplified region of chromosome 8q and is overexpressed in uveal melanoma.
Ehlers JP, Worley L, Onken MD, Harbour JW.
Clin Cancer Res. 2005 May 15;11(10):3609-13.
PMID 15897555
 
DEF-1/ASAP1 is a GTPase-activating protein (GAP) for ARF1 that enhances cell motility through a GAP-dependent mechanism.
Furman C, Short SM, Subramanian RR, Zetter BR, Roberts TM.
J Biol Chem. 2002 Mar 8;277(10):7962-9. Epub 2001 Dec 31.
PMID 11773070
 
Genome-wide analysis of pancreatic cancer using microarray-based techniques.
Harada T, Chelala C, Crnogorac-Jurcevic T, Lemoine NR.
Pancreatology. 2009;9(1-2):13-24. Epub 2008 Dec 12. (REVIEW)
PMID 19077451
 
GEP100-Arf6-AMAP1-cortactin pathway frequently used in cancer invasion is activated by VEGFR2 to promote angiogenesis.
Hashimoto A, Hashimoto S, Ando R, Noda K, Ogawa E, Kotani H, Hirose M, Menju T, Morishige M, Manabe T, Toda Y, Ishida S, Sabe H.
PLoS One. 2011;6(8):e23359. Epub 2011 Aug 15.
PMID 21858086
 
Assays and properties of the ArfGAPs, AMAP1 and AMAP2, in Arf6 function.
Hashimoto S, Hashimoto A, Yamada A, Onodera Y, Sabe H.
Methods Enzymol. 2005;404:216-31.
PMID 16413272
 
The ARF Family.
Kahn RA.
ARF Family GTPases, R.A. Kahn ed., Kluwer Acadmic Publishers, 2004.
 
DEF-1, a novel Src SH3 binding protein that promotes adipogenesis in fibroblastic cell lines.
King FJ, Hu E, Harris DF, Sarraf P, Spiegelman BM, Roberts TM.
Mol Cell Biol. 1999 Mar;19(3):2330-7.
PMID 10022919
 
A new paxillin-binding protein, PAG3/Papalpha/KIAA0400, bearing an ADP-ribosylation factor GTPase-activating protein activity, is involved in paxillin recruitment to focal adhesions and cell migration.
Kondo A, Hashimoto S, Yano H, Nagayama K, Mazaki Y, Sabe H.
Mol Biol Cell. 2000 Apr;11(4):1315-27.
PMID 10749932
 
ASAP1, a gene at 8q24, is associated with prostate cancer metastasis.
Lin D, Watahiki A, Bayani J, Zhang F, Liu L, Ling V, Sadar MD, English J, Fazli L, So A, Gout PW, Gleave M, Squire JA, Wang YZ.
Cancer Res. 2008 Jun 1;68(11):4352-9.
PMID 18519696
 
The association of ASAP1, an ADP ribosylation factor-GTPase activating protein, with focal adhesion kinase contributes to the process of focal adhesion assembly.
Liu Y, Loijens JC, Martin KH, Karginov AV, Parsons JT.
Mol Biol Cell. 2002 Jun;13(6):2147-56.
PMID 12058076
 
An ADP-ribosylation factor GTPase-activating protein Git2-short/KIAA0148 is involved in subcellular localization of paxillin and actin cytoskeletal organization.
Mazaki Y, Hashimoto S, Okawa K, Tsubouchi A, Nakamura K, Yagi R, Yano H, Kondo A, Iwamatsu A, Mizoguchi A, Sabe H.
Mol Biol Cell. 2001 Mar;12(3):645-62.
PMID 11251077
 
GEP100 links epidermal growth factor receptor signalling to Arf6 activation to induce breast cancer invasion.
Morishige M, Hashimoto S, Ogawa E, Toda Y, Kotani H, Hirose M, Wei S, Hashimoto A, Yamada A, Yano H, Mazaki Y, Kodama H, Nio Y, Manabe T, Wada H, Kobayashi H, Sabe H.
Nat Cell Biol. 2008 Jan;10(1):85-92. Epub 2007 Dec 16.
PMID 18084281
 
ASAP1 promotes tumor cell motility and invasiveness, stimulates metastasis formation in vivo, and correlates with poor survival in colorectal cancer patients.
Muller T, Stein U, Poletti A, Garzia L, Rothley M, Plaumann D, Thiele W, Bauer M, Galasso A, Schlag P, Pankratz M, Zollo M, Sleeman JP.
Oncogene. 2010 Apr 22;29(16):2393-403. Epub 2010 Feb 15.
PMID 20154719
 
CIN85, a Cbl-interacting protein, is a component of AMAP1-mediated breast cancer invasion machinery.
Nam JM, Onodera Y, Mazaki Y, Miyoshi H, Hashimoto S, Sabe H.
EMBO J. 2007 Feb 7;26(3):647-56. Epub 2007 Jan 25.
PMID 17255943
 
Expression of AMAP1, an ArfGAP, provides novel targets to inhibit breast cancer invasive activities.
Onodera Y, Hashimoto S, Hashimoto A, Morishige M, Mazaki Y, Yamada A, Ogawa E, Adachi M, Sakurai T, Manabe T, Wada H, Matsuura N, Sabe H.
EMBO J. 2005 Mar 9;24(5):963-73. Epub 2005 Feb 17.
PMID 15719014
 
The EGFR-GEP100-Arf6-AMAP1 signaling pathway specific to breast cancer invasion and metastasis.
Sabe H, Hashimoto S, Morishige M, Ogawa E, Hashimoto A, Nam JM, Miura K, Yano H, Onodera Y.
Traffic. 2009 Aug;10(8):982-93. Epub 2009 Apr 21. (REVIEW)
PMID 19416474
 
ArfGAP family proteins in cell adhesion, migration and tumor invasion.
Sabe H, Onodera Y, Mazaki Y, Hashimoto S.
Curr Opin Cell Biol. 2006 Oct;18(5):558-64. Epub 2006 Aug 9. (REVIEW)
PMID 16904307
 

Citation

This paper should be referenced as such :
Sabe, H ; Onodera, Y ; Hashimoto, A ; Hashimoto, S
ASAP1 (ArfGAP with SH3 domain, ankyrin repeat, PH domain 1)
Atlas Genet Cytogenet Oncol Haematol. 2012;16(7):443-445.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/ASAP1ID44351ch8q24.html


External links

Nomenclature
HGNC (Hugo)ASAP1   2720
Cards
AtlasASAP1ID44351ch8q24
Entrez_Gene (NCBI)ASAP1  50807  ArfGAP with SH3 domain, ankyrin repeat and PH domain 1
AliasesAMAP1; CENTB4; DDEF1; PAG2; 
PAP; ZG14P
GeneCards (Weizmann)ASAP1
Ensembl hg19 (Hinxton)ENSG00000153317 [Gene_View]  chr8:131064351-131455906 [Contig_View]  ASAP1 [Vega]
Ensembl hg38 (Hinxton)ENSG00000153317 [Gene_View]  chr8:131064351-131455906 [Contig_View]  ASAP1 [Vega]
ICGC DataPortalENSG00000153317
TCGA cBioPortalASAP1
AceView (NCBI)ASAP1
Genatlas (Paris)ASAP1
WikiGenes50807
SOURCE (Princeton)ASAP1
Genetics Home Reference (NIH)ASAP1
Genomic and cartography
GoldenPath hg19 (UCSC)ASAP1  -     chr8:131064351-131455906 -  8q24.1-q24.2   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)ASAP1  -     8q24.1-q24.2   [Description]    (hg38-Dec_2013)
EnsemblASAP1 - 8q24.1-q24.2 [CytoView hg19]  ASAP1 - 8q24.1-q24.2 [CytoView hg38]
Mapping of homologs : NCBIASAP1 [Mapview hg19]  ASAP1 [Mapview hg38]
OMIM605953   
Gene and transcription
Genbank (Entrez)AB033075 AF222859 AI494058 AI656533 AK056811
RefSeq transcript (Entrez)NM_001247996 NM_018482
RefSeq genomic (Entrez)NC_000008 NC_018919 NG_030354 NT_008046 NW_004929340
Consensus coding sequences : CCDS (NCBI)ASAP1
Cluster EST : UnigeneHs.655552 [ NCBI ]
CGAP (NCI)Hs.655552
Alternative Splicing GalleryENSG00000153317
Gene ExpressionASAP1 [ NCBI-GEO ]   ASAP1 [ EBI - ARRAY_EXPRESS ]   ASAP1 [ SEEK ]   ASAP1 [ MEM ]
Gene Expression Viewer (FireBrowse)ASAP1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)50807
GTEX Portal (Tissue expression)ASAP1
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9ULH1   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ9ULH1  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ9ULH1
Splice isoforms : SwissVarQ9ULH1
PhosPhoSitePlusQ9ULH1
Domaine pattern : Prosite (Expaxy)ANK_REP_REGION (PS50297)    ANK_REPEAT (PS50088)    ARFGAP (PS50115)    PH_DOMAIN (PS50003)    SH3 (PS50002)   
Domains : Interpro (EBI)AH/BAR-dom    Ankyrin_rpt    Ankyrin_rpt-contain_dom    ArfGAP    PH_dom-like    PH_domain    SH3_domain   
Domain families : Pfam (Sanger)Ank_2 (PF12796)    ArfGap (PF01412)    PH (PF00169)    SH3_1 (PF00018)   
Domain families : Pfam (NCBI)pfam12796    pfam01412    pfam00169    pfam00018   
Domain families : Smart (EMBL)ANK (SM00248)  ArfGap (SM00105)  PH (SM00233)  SH3 (SM00326)  
Conserved Domain (NCBI)ASAP1
DMDM Disease mutations50807
Blocks (Seattle)ASAP1
PDB (SRS)2D1X    2DA0    2ED1    2RQT    2RQU   
PDB (PDBSum)2D1X    2DA0    2ED1    2RQT    2RQU   
PDB (IMB)2D1X    2DA0    2ED1    2RQT    2RQU   
PDB (RSDB)2D1X    2DA0    2ED1    2RQT    2RQU   
Structural Biology KnowledgeBase2D1X    2DA0    2ED1    2RQT    2RQU   
SCOP (Structural Classification of Proteins)2D1X    2DA0    2ED1    2RQT    2RQU   
CATH (Classification of proteins structures)2D1X    2DA0    2ED1    2RQT    2RQU   
SuperfamilyQ9ULH1
Human Protein AtlasENSG00000153317
Peptide AtlasQ9ULH1
HPRD05809
IPIIPI00873747   IPI00376976   IPI00383062   IPI00020541   IPI00974171   IPI00983032   IPI00985418   IPI01010246   IPI00974332   
Protein Interaction databases
DIP (DOE-UCLA)Q9ULH1
IntAct (EBI)Q9ULH1
FunCoupENSG00000153317
BioGRIDASAP1
STRING (EMBL)ASAP1
ZODIACASAP1
Ontologies - Pathways
QuickGOQ9ULH1
Ontology : AmiGOGTPase activator activity  protein binding  phosphatidylinositol-4,5-bisphosphate binding  phosphatidylinositol-3,4,5-trisphosphate binding  cytosol  membrane  dendritic spine  positive regulation of GTPase activity  metal ion binding  cilium morphogenesis  negative regulation of dendritic spine development  
Ontology : EGO-EBIGTPase activator activity  protein binding  phosphatidylinositol-4,5-bisphosphate binding  phosphatidylinositol-3,4,5-trisphosphate binding  cytosol  membrane  dendritic spine  positive regulation of GTPase activity  metal ion binding  cilium morphogenesis  negative regulation of dendritic spine development  
Pathways : BIOCARTAADP-Ribosylation Factor [Genes]   
Pathways : KEGGEndocytosis    Fc gamma R-mediated phagocytosis   
REACTOMEQ9ULH1 [protein]
REACTOME PathwaysR-HSA-5620916 VxPx cargo-targeting to cilium [pathway]
NDEx NetworkASAP1
Atlas of Cancer Signalling NetworkASAP1
Wikipedia pathwaysASAP1
Orthology - Evolution
OrthoDB50807
GeneTree (enSembl)ENSG00000153317
Phylogenetic Trees/Animal Genes : TreeFamASAP1
HOVERGENQ9ULH1
HOGENOMQ9ULH1
Homologs : HomoloGeneASAP1
Homology/Alignments : Family Browser (UCSC)ASAP1
Gene fusions - Rearrangements
Fusion : MitelmanASAP1/CLVS1 [8q24.21/8q12.3]  
Fusion : MitelmanASAP1/KCNH1 [8q24.21/1q32.2]  [t(1;8)(q32;q24)]  
Fusion : MitelmanASAP1/LRRCC1 [8q24.21/8q21.2]  [t(8;8)(q21;q24)]  
Fusion : MitelmanASAP1/MALAT1 [8q24.21/11q13.1]  [t(8;11)(q24;q13)]  
Fusion : MitelmanASAP1/RAD51B [8q24.21/14q24.1]  [t(8;14)(q24;q24)]  
Fusion : MitelmanASAP1/SAMD12 [8q24.21/8q24.12]  [t(8;8)(q24;q24)]  
Fusion : MitelmanEFR3A/ASAP1 [8q24.22/8q24.21]  [t(8;8)(q24;q24)]  
Fusion : MitelmanFAM49B/ASAP1 [8q24.21/8q24.21]  [t(8;8)(q24;q24)]  
Fusion : MitelmanPVT1/ASAP1 [8q24.21/8q24.21]  [t(8;8)(q24;q24)]  
Fusion: TCGAASAP1 8q24.21 CLVS1 8q12.3 BRCA
Fusion: TCGAASAP1 8q24.21 KCNH1 1q32.2 BRCA
Fusion: TCGAASAP1 8q24.21 LRRCC1 8q21.2 LUAD
Fusion: TCGAASAP1 8q24.21 RAD51B 14q24.1 LUAD
Fusion: TCGAASAP1 8q24.21 SAMD12 8q24.12 LUAD
Fusion: TCGAEFR3A 8q24.22 ASAP1 8q24.21 BRCA
Fusion: TCGAFAM49B 8q24.21 ASAP1 8q24.21 BRCA
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerASAP1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)ASAP1
dbVarASAP1
ClinVarASAP1
1000_GenomesASAP1 
Exome Variant ServerASAP1
ExAC (Exome Aggregation Consortium)ASAP1 (select the gene name)
Genetic variants : HAPMAP50807
Genomic Variants (DGV)ASAP1 [DGVbeta]
DECIPHER (Syndromes)8:131064351-131455906  ENSG00000153317
CONAN: Copy Number AnalysisASAP1 
Mutations
ICGC Data PortalASAP1 
TCGA Data PortalASAP1 
Broad Tumor PortalASAP1
OASIS PortalASAP1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICASAP1  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDASAP1
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 ASAP1
DgiDB (Drug Gene Interaction Database)ASAP1
DoCM (Curated mutations)ASAP1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)ASAP1 (select a term)
intoGenASAP1
NCG5 (London)ASAP1
Cancer3DASAP1(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM605953   
Orphanet
MedgenASAP1
Genetic Testing Registry ASAP1
NextProtQ9ULH1 [Medical]
TSGene50807
GENETestsASAP1
Huge Navigator ASAP1 [HugePedia]
snp3D : Map Gene to Disease50807
BioCentury BCIQASAP1
ClinGenASAP1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD50807
Chemical/Pharm GKB GenePA164716055
Clinical trialASAP1
Miscellaneous
canSAR (ICR)ASAP1 (select the gene name)
Probes
Litterature
PubMed50 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineASAP1
EVEXASAP1
GoPubMedASAP1
iHOPASAP1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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