Atlas of Genetics and Cytogenetics in Oncology and Haematology


Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

PIK3CA (phosphoinositide-3-kinase, catalytic, alpha polypeptide)

Written2009-04Montserrat Sanchez-Cespedes
Programa d'Epigenetica i Biologia del Cancer-PEBC, Institut d'Investigacions Biomediques Bellvitge (IDIBELL), Hospital Durant i Reynals, Avinguda Gran Via de l'Hospitalet, 199-203 08907-L'Hospitalet de Llobregat-Barcelona, Spain
Updated2018-06Julia Phillips, Enric Domingo
Department of Oncology, University of Oxford, Oxford, United Kingdom / enric.domingo@oncology.ox.ac.uk

Abstract Review on PIK3CA, with data on DNA, on the protein encoded, and where the gene is implicated.

Keywords PIK3CA; Kinase; Cell proliferation; Differentiation

(Note : for Links provided by Atlas : click)

Identity

Alias_namesphosphoinositide-3-kinase, catalytic, alpha polypeptide
phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha
Alias_symbol (synonym)PI3K
Other aliasEC 2.7.1.153
MGC142161
MGC14216
p110-alpha
HGNC (Hugo) PIK3CA
LocusID (NCBI) 5290
Atlas_Id 415
Location 3q26.32  [Link to chromosome band 3q26]
Location_base_pair Starts at 179148523 and ends at 179240093 bp from pter ( according to hg19-Feb_2009)  [Mapping PIK3CA.png]
Local_order centromere-KCNMB2- ZMAT3- LOC101928739-PIK3CA- KCNMB3- ZNF639- MFN1- GNB4- telomere
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
DDX5 (17q23.3) / PIK3CA (3q26.32)FNDC3B (3q26.31) / PIK3CA (3q26.32)PIK3CA (3q26.32) / KCNMB3 (3q26.32)
PPP2CA (5q31.1) / PIK3CA (3q26.32)TAF1D (11q21) / PIK3CA (3q26.32)TBL1XR1 (3q26.32) / PIK3CA (3q26.32)
USP13 (3q26.33) / PIK3CA (3q26.32)

DNA/RNA

 
  Relative size of the 21 exons of PIK3CA. The entire exon 1 is UTR (untranslated region). Exon numeration corresponds to the prevalent transcript (NM-006218).
Description The PIK3CA gene spans a total genomic size of 86,190 bases and is composed of 21 exons, 20 of them coding exons of varying lengths. Putative pseudogenes of PIK3CA have been described on chromosomes 16 (gi 28913054) and 22q11.2 (gi 5931525), the later one in the Cat Eye Syndrome region. These regions are highly homolog to the sequences of exons 9 and 11-13 of the PIK3CA gene.
Transcription The human PIK3CA transcript has an open reading frame of 3,207-bp, predicting a protein of 1,068 amino acid residues.
Pseudogene A pseudogene has been identified in chromosome 20 (LOC100422375) spanning exons 9 to 13 with 95% homology in both exons and introns. A non-specific amplification of PIK3CA could result in a E545A false positive mutation which is the amino-acid most commonly mutated in PIK3CA.

Protein

 
  p110alpha conserved domains. Through its adaptor binding domain p110alpha interacts with the regulatory subunit. C2 domain, protein-kinase-C-homology-2 domain.
Description The PIK3CA gene encodes the p110alpha protein which is a catalytic subunit of the class I PI 3-kinases (PI3K). Class I PI3K are heterodimeric molecules composed of a catalytic subunit, a p110, and a regulatory subunit. There are three possible calatytic subunits p110alpha, beta or delta.
Expression Widely expressed.
Localisation The p110alpha localizes in the cytoplasm.
Function Class I PI 3-kinases (PI3K) are one of the most prevalently dysregulated pathways in human cancer and it is linked to many cellular functions, including cell growth, proliferation, differentiation, motility, survival and intracellular trafficking. PI3K convert PI(4,5)P2 to PI(3,4,5)P3 on the inner leaflet of the plasma membrane. The PI(3,4,)P3 provokes the recruitment to cellular membranes of a variety of signalling proteins, containing PX domain, pleckstrin homology domains (PH domains), FYVE domains and other phosphoinositide-binding domains. One of these is the protein kinase B (PKB/AKT) a very well known protein that is activated as a result of its translocation to the cell membrane where it is then phosphorylated and activated by another kinase, called phosphoinositide dependent kinase 1 (PDK1). The phosphorylation of AKT leads to the activation of the TSC/mTOR pathway. Accordingly, PIK3CA and PTEN genetic alterations are usually alternative events.

Mutations

Epigenetics PIK3CA has a small CpG island in the gene promoter but no methylation has been described.
Somatic Somatic mutations at the PIK3CA gene have been found in tumors and thus, it is a bona fide oncogene (Samuels et al., 2004). Sequencing analyses of pancancer genomes suggests that PIK3CA has at least 19 mutational hotspots (Chang et al, 2016). Most mutations occur in two of the five domains of p110alpha, the helical and kinase domains. However, while there are no frequent hotspot mutations within the Ras-binding domain (RBD), hotspot mutations within the adaptor-binding domain (ABD) and the C2 domain are also frequently found. Hotspots Arg38 and Arg88 are located within the ABD at the interface with the kinase domain. These mutations disrupt hydrogen bonds between the domains which may alter the conformation of the kinase domain and therefore its enzymatic activity. Similarly, hotspots Asn345 and Glu453 within the C2 domain occur at the interface with the iSH2 domain of p85 and are expected to alter the interaction between these domains. Within the helical domain, the most common hotspots Glu542 and Glu545 are usually mutated into lysine and are located at the interface with the nSH2 domain of p85. A structural model of the p110/niSH2 complex suggests that the contacts between these amino acids and the nSH2 domain occur within a region of the nSH2 domain which is also in contact with the kinase domain of p110. These contacts may serve as the mechanism by which the helical domain mutations alter the activity of the enzyme. In the kinase domain, His1047 is frequently mutated to arginine within a helix at the end of the activation loop. Another less frequent kinase mutation of Met1043 occurs within the same helix and likely has similar effects on enzymatic activity. Thr1025 mutations are located near the N-terminus of the catalytic loop which may directly alter the conformation of the catalytic loop as the mechanism by which the mutation alters enzymatic activity (Huang, 2008). Two other hotspot positions, Lys111 and Gly118, are located outside of the five domains in the 81 residue linker between ABD and RBD (Chang, 2016).
The distribution of PIK3CA hotspot mutations can be significantly variable across tumour types in the kinase and helical domain. For example, cervical and bladder cancers share similar distributions of hotspots but they have far fewer H1047R kinase mutations than breast cancer. Similarly, endometrial and colorectal cancers share distribution patterns but display more R88Q mutations than other tumor types, maybe because this change is a target mutation of POLE genomic instability. However, colorectal cancers differ from endometrial cancers in their clonality. In endometrial tumors, both E545 helical domain mutations and H1047 kinase domain mutations are early clonal mutations whereas in colorectal cancer several E545 mutations are subclonal and H1047 mutations clonal (Chang, 2016). The variation in hotspot distributions suggests different functions need to be targeted in different tumour types.
Different domain mutations in PIK3CA have been associated with differential signaling. Kinase domain mutations have higher activation of PI3K complexes and increased G-alpha signaling events. However, some components of the G-alpha signaling pathway such as RHO GTPase complexes have lower activity in the kinase domain mutants relative to other PIK3CA mutants. Additionally, helical domain mutations are associated with lower activation of pathways related to proliferation, such as FOXM1, MYC, and PLK1, in comparison to other PIK3CA mutants. The different patterns of pathway activation associated with mutations of specific PIK3CA domains suggest that kinase domain mutations are more strongly associated with proliferation activity, whereas helical domain mutations are more strongly associated with motility activities. These differences in function across domain specific mutations may drive the varying distribution of mutations seen across cancer types (Yau, 2014).

Implicated in

Note
  
Entity A wide variety of human cancers
Note PIK3CA mutations lead to constitutive activation of p110alpha enzymatic activity, stimulate AKT signaling, and allow growth factor-independent growth (Bader et al., 2005). In addition, when expressed in normal cells, these mutations allow anchorage-independent growth, further attesting to their important role in cancer development (Kang et al., 2005). PIK3CA somatic mutations are frequent in a variety of human primary tumors and cancer cell lines such as, among others, those of the colon, breast, and stomach (Samuels et al., 2004). However, in other tumors, i.e. those of the lung, head and neck, brain, endometrium, ovary, prostate, osteosarcoma and pancreas, hematopoietic malignancies, PIK3CA mutations are not as common (Angulo et al., 2008; Qiu et al., 2006; Muller et al., 2007; Samuels et al., 2004; Schonleben et al., 2006). PIK3CA gene amplification has also been proposed as a mechanism for oncogene activation in some tumors (Angulo et al., 2008).
  
  
Entity Cowden syndrome
Disease Syndrome characterized by multiple noncancerous hamartomas and high predisposition to breast, thyroid and other tumour types. Germline PIK3CA mutations may account for around 10% of cases. Most of these mutations are in different positions to main hotspot somatic PIK3CA mutations. Mutations in the genes from the same pathway PTEN and AKT1 may account for about 25% and 2% of cases respectively.
  

To be noted

Molecular targets: Pan-PI3K inhibitors inhibit all four of the PI3K class I isoforms. However, this broad range of molecular targets results in an increased risk of toxicity and off-target effects. Copanlisib is currently the only pan-PI3K inhibitor that is approved by the FDA for clinical use in treating cancer patients. PI3Kalpha specific inhibitors inhibit the activity of the class I PI3K catalytic subunit alpha isoform and these can be used to target cancers that are dependent on the specific PI3K isoform. The PI3Kalpha isoform is often activated by PIK3CA mutations and initial clinical trials have found greater response to PI3Kalpha inhibitors in PIK3CA mutated cancers than wild type. These specific isoform inhibitors offer greater potential for therapeutic use than nonspecific pan-PI3K inhibitors because they are expected to have fewer off target adverse effects due to the restricted expression of different PI3K isoforms in nonmalignant cells. PI3Kalpha specific inhibitors have yet to be approved for clinical use outside of trials although they have reached the advanced stages of clinical testing (Janku et al, 2018). PI3Kalpha inhibitors seem to result in greater overall response rates and longer progression free survival within patients that possess PIK3CA mutations than without. However, even some patients with PIK3CA mutations have shown short response durations to PI3Kalpha inhibitors (Juric, 2018).
Similarly, aspirin use has been associated with the blocking of the PI3K pathway resulting in suppression of cancer cell growth and induction of apoptosis (Uddin, 2010). A meta-analysis suggests PIK3CA mutations may be predictive of response to aspirin in colorectal cancer although too few studies preclude definitive conclusions (Paleari, 2016). Current trials randomized by aspirin like add-aspiriní might be able to validate these findings.

Bibliography

Expression signatures in lung cancer reveal a profile for EGFR-mutant tumours and identify selective PIK3CA overexpression by gene amplification.
Angulo B, Suarez-Gauthier A, Lopez-Rios F, Medina PP, Conde E, Tang M, Soler G, Lopez-Encuentra A, Cigudosa JC, Sanchez-Cespedes M.
J Pathol. 2008 Feb;214(3):347-56.
PMID 17992665
 
Cancer-specific mutations in PIK3CA are oncogenic in vivo
Bader AG, Kang S, Vogt PK
Proc Natl Acad Sci U S A 2006 Jan 31;103(5):1475-9
PMID 16432179
 
A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer.
Berns K, Horlings HM, Hennessy BT, Madiredjo M, Hijmans EM, Beelen K, Linn SC, Gonzalez-Angulo AM, Stemke-Hale K, Hauptmann M, Beijersbergen RL, Mills GB, van de Vijver MJ, Bernards R.
Cancer Cell. 2007 Oct;12(4):395-402.
PMID 17936563
 
Effects of oncogenic p110alpha subunit mutations on the lipid kinase activity of phosphoinositide 3-kinase
Carson JD, Van Aller G, Lehr R, Sinnamon RH, Kirkpatrick RB, Auger KR, Dhanak D, Copeland RA, Gontarek RR, Tummino PJ, Luo L
Biochem J 2008 Jan 15;409(2):519-24
PMID 17877460
 
Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity
Chang MT, Asthana S, Gao SP, Lee BH, Chapman JS, Kandoth C, Gao J, Socci ND, Solit DB, Olshen AB, Schultz N, Taylor BS
Nat Biotechnol 2016 Feb;34(2):155-63
PMID 26619011
 
Differential pathway activation associated with domain-specific PIK3CA mutations. [abstract].
Christina Yau, Stephen Benz, Charles Vaske, Sam Ng, Josh Stuart, Christopher C. Benz.
Differential pathway activation associated with domain-specific PIK3CA mutations. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4165. doi:10.1158/1538-7445.AM2014-4165
 
Drug discovery approaches targeting the PI3K/Akt pathway in cancer.
Garcia-Echeverria C, Sellers WR.
Oncogene. 2008 Sep 18;27(41):5511-26.
PMID 18794885
 
Insights into the oncogenic effects of PIK3CA mutations from the structure of p110alpha/p85alpha
Huang CH, Mandelker D, Gabelli SB, Amzel LM
Cell Cycle 2008 May 1;7(9):1151-6
PMID 18418043
 
PIK3CA mutations in patients with advanced cancers treated with PI3K/AKT/mTOR axis inhibitors
Janku F, Tsimberidou AM, Garrido-Laguna I, Wang X, Luthra R, Hong DS, Naing A, Falchook GS, Moroney JW, Piha-Paul SA, Wheler JJ, Moulder SL, Fu S, Kurzrock R
Mol Cancer Ther 2011 Mar;10(3):558-65
PMID 21216929
 
Targeting the PI3K pathway in cancer: are we making headway? Nat Rev Clin Oncol
Janku F, Yap TA, Meric-Bernstam F
2018 May;15(5):273-291 doi: 10
PMID 29508857
 
Phosphatidylinositol 3-Kinase α-Selective Inhibition With Alpelisib (BYL719) in PIK3CA-Altered Solid Tumors: Results From the First-in-Human Study
Juric D, Rodon J, Tabernero J, Janku F, Burris HA, Schellens JHM, Middleton MR, Berlin J, Schuler M, Gil-Martin M, Rugo HS, Seggewiss-Bernhardt R, Huang A, Bootle D, Demanse D, Blumenstein L, Coughlin C, Quadt C, Baselga J
J Clin Oncol 2018 May 1;36(13):1291-1299
PMID 29401002
 
Phosphatidylinositol 3-kinase mutations identified in human cancer are oncogenic.
Kang S, Bader AG, Vogt PK.
Proc Natl Acad Sci U S A. 2005 Jan 18;102(3):802-7. Epub 2005 Jan 12.
PMID 15647370
 
Biochemistry. PI3K charges ahead.
Lee JY, Engelman JA, Cantley LC.
Science. 2007 Jul 13;317(5835):206-7.
PMID 17626872
 
Rare mutations of the PIK3CA gene in malignancies of the hematopoietic system as well as endometrium, ovary, prostate and osteosarcomas, and discovery of a PIK3CA pseudogene
Müller CI, Miller CW, Hofmann WK, Gross ME, Walsh CS, Kawamata N, Luong QT, Koeffler HP
Leuk Res 2007 Jan;31(1):27-32
PMID 16764926
 
Rare mutations of the PIK3CA gene in malignancies of the hematopoietic system as well as endometrium, ovary, prostate and osteosarcomas, and discovery of a PIK3CA pseudogene.
Muller CI, Miller CW, Hofmann WK, Gross ME, Walsh CS, Kawamata N, Luong QT, Koeffler HP.
Leuk Res. 2007 Jan;31(1):27-32. Epub 2006 Jun 9.
PMID 16764926
 
Germline PIK3CA and AKT1 mutations in Cowden and Cowden-like syndromes
Orloff MS, He X, Peterson C, Chen F, Chen JL, Mester JL, Eng C
Am J Hum Genet 2013 Jan 10;92(1):76-80
PMID 23246288
 
PIK3CA Mutation, Aspirin Use after Diagnosis and Survival of Colorectal Cancer
Paleari L, Puntoni M, Clavarezza M, DeCensi M, Cuzick J, DeCensi A
A Systematic Review and Meta-analysis of Epidemiological Studies Clin Oncol (R Coll Radiol)
PMID 26712086
 
PIK3CA mutations in head and neck squamous cell carcinoma.
Qiu W, Schonleben F, Li X, Ho DJ, Close LG, Manolidis S, Bennett BP, Su GH.
Clin Cancer Res. 2006 Mar 1;12(5):1441-6.
PMID 16533766
 
High frequency of mutations of the PIK3CA gene in human cancers.
Samuels Y, Wang Z, Bardelli A, Silliman N, Ptak J, Szabo S, Yan H, Gazdar A, Powell SM, Riggins GJ, Willson JK, Markowitz S, Kinzler KW, Vogelstein B, Velculescu VE.
Science. 2004 Apr 23;304(5670):554. Epub 2004 Mar 11.
PMID 15016963
 
PIK3CA mutations in intraductal papillary mucinous neoplasm/carcinoma of the pancreas.
Schonleben F, Qiu W, Ciau NT, Ho DJ, Li X, Allendorf JD, Remotti HE, Su GH.
Clin Cancer Res. 2006 Jun 15;12(12):3851-5.
PMID 16778113
 
Cyclooxygenase-2 inhibition inhibits PI3K/AKT kinase activity in epithelial ovarian cancer
Uddin S, Ahmed M, Hussain A, Assad L, Al-Dayel F, Bavi P, Al-Kuraya KS, Munkarah A
Int J Cancer 2010 Jan 15;126(2):382-94
PMID 19621391
 

Citation

This paper should be referenced as such :
Phillips J, Domingo E
PIK3CA (phosphoinositide-3-kinase, catalytic, alpha polypeptide);
Atlas Genet Cytogenet Oncol Haematol. in press
On line version : http://AtlasGeneticsOncology.org/Genes/PIK3CAID415ch3q26.html
History of this paper:
Sanchez-Cespedes, M. PIK3CA (phosphoinositide-3-kinase, catalytic, alpha polypeptide). Atlas Genet Cytogenet Oncol Haematol. 2010;14(3):293-295.
http://documents.irevues.inist.fr/bitstream/handle/2042/44713/04-2009-PIK3CAID415ch3q26.pdf


Other Leukemias implicated (Data extracted from papers in the Atlas) [ 1 ]
  i(3)(q10) in non-Hodgkin's lymphoma (NHL)


Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 15 ]
  Thyroid: Anaplastic (undifferentiated) carcinoma
Colon: Colorectal adenocarcinoma
Breast: Ductal carcinoma
Head and Neck: Epidermoid carcinoma
Male breast cancer
Head and Neck: Oral squamous cell carcinoma
Pancreatic tumors: an overview
Soft tissue tumors: an overview
Lung: Translocations in Adenocarcinoma
inv(3)(q26q26) PIK3CA/KCNMB3
FNDC3B/PIK3CA (3q26)
TBL1XR1/PIK3CA (3q26)
TBL1XR1/PIK3CA (3q26)
USP13/PIK3CA (3q26)
t(3;11)(q26;q21) TAF1D/PIK3CA


External links

Nomenclature
HGNC (Hugo)PIK3CA   8975
LRG (Locus Reference Genomic)LRG_310
Cards
AtlasPIK3CAID415ch3q26
Entrez_Gene (NCBI)PIK3CA  5290  phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha
AliasesCLOVE; CWS5; MCAP; MCM; 
MCMTC; PI3K; PI3K-alpha; p110-alpha
GeneCards (Weizmann)PIK3CA
Ensembl hg19 (Hinxton)ENSG00000121879 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000121879 [Gene_View]  ENSG00000121879 [Sequence]  chr3:179148523-179240093 [Contig_View]  PIK3CA [Vega]
ICGC DataPortalENSG00000121879
TCGA cBioPortalPIK3CA
AceView (NCBI)PIK3CA
Genatlas (Paris)PIK3CA
WikiGenes5290
SOURCE (Princeton)PIK3CA
Genetics Home Reference (NIH)PIK3CA
Genomic and cartography
GoldenPath hg38 (UCSC)PIK3CA  -     chr3:179148523-179240093 +  3q26.32   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)PIK3CA  -     3q26.32   [Description]    (hg19-Feb_2009)
EnsemblPIK3CA - 3q26.32 [CytoView hg19]  PIK3CA - 3q26.32 [CytoView hg38]
Mapping of homologs : NCBIPIK3CA [Mapview hg19]  PIK3CA [Mapview hg38]
OMIM114480   114500   114550   162900   167000   171834   182000   211980   602501   612918   613659   615108   
Gene and transcription
Genbank (Entrez)AB210020 AI379480 AK021510 AK292940 AK297203
RefSeq transcript (Entrez)NM_006218
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)PIK3CA
Cluster EST : UnigeneHs.732394 [ NCBI ]
CGAP (NCI)Hs.732394
Alternative Splicing GalleryENSG00000121879
Gene ExpressionPIK3CA [ NCBI-GEO ]   PIK3CA [ EBI - ARRAY_EXPRESS ]   PIK3CA [ SEEK ]   PIK3CA [ MEM ]
Gene Expression Viewer (FireBrowse)PIK3CA [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevestigatorExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)5290
GTEX Portal (Tissue expression)PIK3CA
Human Protein AtlasENSG00000121879-PIK3CA [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP42336   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP42336  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP42336
Splice isoforms : SwissVarP42336
PhosPhoSitePlusP42336
Domaine pattern : Prosite (Expaxy)PI3_4_KINASE_1 (PS00915)    PI3_4_KINASE_2 (PS00916)    PI3_4_KINASE_3 (PS50290)    PI3K_ABD (PS51544)    PI3K_C2 (PS51547)    PI3K_RBD (PS51546)    PIK_HELICAL (PS51545)   
Domains : Interpro (EBI)ARM-type_fold    Kinase-like_dom_sf    PI3/4_kinase_cat_dom    PI3/4_kinase_cat_sf    PI3/4_kinase_CS    PI3K_adapt-bd_dom    PI3K_C2_dom    PI3K_Ras-bd_dom    PI3K_Vps34    PI3Kalpha_dom    PI_Kinase    PInositide-3_kin_accessory_dom    Ubiquitin-like_domsf   
Domain families : Pfam (Sanger)PI3_PI4_kinase (PF00454)    PI3K_C2 (PF00792)    PI3K_p85B (PF02192)    PI3K_rbd (PF00794)    PI3Ka (PF00613)   
Domain families : Pfam (NCBI)pfam00454    pfam00792    pfam02192    pfam00794    pfam00613   
Domain families : Smart (EMBL)PI3K_C2 (SM00142)  PI3K_p85B (SM00143)  PI3K_rbd (SM00144)  PI3Ka (SM00145)  PI3Kc (SM00146)  
Conserved Domain (NCBI)PIK3CA
DMDM Disease mutations5290
Blocks (Seattle)PIK3CA
PDB (SRS)2ENQ    2RD0    3HHM    3HIZ    3ZIM    4JPS    4L1B    4L23    4L2Y    4OVU    4OVV    4TUU    4TV3    4WAF    4YKN    4ZOP    5DXH    5DXT    5FI4    5ITD    5SW8    5SWG    5SWO    5SWP    5SWR    5SWT    5SX8    5SX9    5SXA    5SXB    5SXC    5SXD    5SXE    5SXF    5SXI    5SXJ    5SXK    5UBR    5UK8    5UKJ    5UL1   
PDB (PDBSum)2ENQ    2RD0    3HHM    3HIZ    3ZIM    4JPS    4L1B    4L23    4L2Y    4OVU    4OVV    4TUU    4TV3    4WAF    4YKN    4ZOP    5DXH    5DXT    5FI4    5ITD    5SW8    5SWG    5SWO    5SWP    5SWR    5SWT    5SX8    5SX9    5SXA    5SXB    5SXC    5SXD    5SXE    5SXF    5SXI    5SXJ    5SXK    5UBR    5UK8    5UKJ    5UL1   
PDB (IMB)2ENQ    2RD0    3HHM    3HIZ    3ZIM    4JPS    4L1B    4L23    4L2Y    4OVU    4OVV    4TUU    4TV3    4WAF    4YKN    4ZOP    5DXH    5DXT    5FI4    5ITD    5SW8    5SWG    5SWO    5SWP    5SWR    5SWT    5SX8    5SX9    5SXA    5SXB    5SXC    5SXD    5SXE    5SXF    5SXI    5SXJ    5SXK    5UBR    5UK8    5UKJ    5UL1   
PDB (RSDB)2ENQ    2RD0    3HHM    3HIZ    3ZIM    4JPS    4L1B    4L23    4L2Y    4OVU    4OVV    4TUU    4TV3    4WAF    4YKN    4ZOP    5DXH    5DXT    5FI4    5ITD    5SW8    5SWG    5SWO    5SWP    5SWR    5SWT    5SX8    5SX9    5SXA    5SXB    5SXC    5SXD    5SXE    5SXF    5SXI    5SXJ    5SXK    5UBR    5UK8    5UKJ    5UL1   
Structural Biology KnowledgeBase2ENQ    2RD0    3HHM    3HIZ    3ZIM    4JPS    4L1B    4L23    4L2Y    4OVU    4OVV    4TUU    4TV3    4WAF    4YKN    4ZOP    5DXH    5DXT    5FI4    5ITD    5SW8    5SWG    5SWO    5SWP    5SWR    5SWT    5SX8    5SX9    5SXA    5SXB    5SXC    5SXD    5SXE    5SXF    5SXI    5SXJ    5SXK    5UBR    5UK8    5UKJ    5UL1   
SCOP (Structural Classification of Proteins)2ENQ    2RD0    3HHM    3HIZ    3ZIM    4JPS    4L1B    4L23    4L2Y    4OVU    4OVV    4TUU    4TV3    4WAF    4YKN    4ZOP    5DXH    5DXT    5FI4    5ITD    5SW8    5SWG    5SWO    5SWP    5SWR    5SWT    5SX8    5SX9    5SXA    5SXB    5SXC    5SXD    5SXE    5SXF    5SXI    5SXJ    5SXK    5UBR    5UK8    5UKJ    5UL1   
CATH (Classification of proteins structures)2ENQ    2RD0    3HHM    3HIZ    3ZIM    4JPS    4L1B    4L23    4L2Y    4OVU    4OVV    4TUU    4TV3    4WAF    4YKN    4ZOP    5DXH    5DXT    5FI4    5ITD    5SW8    5SWG    5SWO    5SWP    5SWR    5SWT    5SX8    5SX9    5SXA    5SXB    5SXC    5SXD    5SXE    5SXF    5SXI    5SXJ    5SXK    5UBR    5UK8    5UKJ    5UL1   
SuperfamilyP42336
Human Protein Atlas [tissue]ENSG00000121879-PIK3CA [tissue]
Peptide AtlasP42336
HPRD01382
IPIIPI00031386   IPI00784619   IPI00946104   IPI00946100   
Protein Interaction databases
DIP (DOE-UCLA)P42336
IntAct (EBI)P42336
FunCoupENSG00000121879
BioGRIDPIK3CA
STRING (EMBL)PIK3CA
ZODIACPIK3CA
Ontologies - Pathways
QuickGOP42336
Ontology : AmiGOangiogenesis  liver development  vasculature development  protein serine/threonine kinase activity  protein binding  ATP binding  cytoplasm  cytosol  plasma membrane  phosphatidylinositol 3-kinase complex  phosphatidylinositol 3-kinase complex  phosphatidylinositol 3-kinase complex, class IA  phosphatidylinositol 3-kinase complex, class IA  glucose metabolic process  protein phosphorylation  epidermal growth factor receptor signaling pathway  G-protein coupled receptor signaling pathway  axon guidance  regulation of gene expression  phosphatidylinositol 3-kinase signaling  membrane  negative regulation of macroautophagy  kinase activity  kinase activity  1-phosphatidylinositol-3-kinase activity  1-phosphatidylinositol-3-kinase activity  1-phosphatidylinositol-3-kinase activity  phosphorylation  cell migration  cytokine-mediated signaling pathway  lamellipodium  platelet activation  platelet activation  protein kinase activator activity  T cell costimulation  positive regulation of TOR signaling  activation of protein kinase activity  positive regulation of peptidyl-serine phosphorylation  phosphatidylinositol 3-kinase activity  phosphatidylinositol 3-kinase activity  1-phosphatidylinositol-4-phosphate 3-kinase activity  phosphatidylinositol-3-phosphate biosynthetic process  phosphatidylinositol-3-phosphate biosynthetic process  insulin receptor signaling pathway via phosphatidylinositol 3-kinase  Fc-epsilon receptor signaling pathway  Fc-gamma receptor signaling pathway involved in phagocytosis  ERBB2 signaling pathway  regulation of multicellular organism growth  anoikis  regulation of cellular respiration  protein kinase B signaling  negative regulation of neuron apoptotic process  endothelial cell migration  insulin receptor substrate binding  hypomethylation of CpG island  phosphatidylinositol phosphorylation  phosphatidylinositol phosphorylation  phosphatidylinositol-4,5-bisphosphate 3-kinase activity  phosphatidylinositol-4,5-bisphosphate 3-kinase activity  vascular endothelial growth factor receptor signaling pathway  phosphatidylinositol-mediated signaling  phosphatidylinositol-mediated signaling  T cell receptor signaling pathway  leukocyte migration  positive regulation of protein kinase B signaling  phosphatidylinositol kinase activity  cardiac muscle contraction  adipose tissue development  cellular response to glucose stimulus  energy homeostasis  negative regulation of fibroblast apoptotic process  regulation of genetic imprinting  negative regulation of anoikis  
Ontology : EGO-EBIangiogenesis  liver development  vasculature development  protein serine/threonine kinase activity  protein binding  ATP binding  cytoplasm  cytosol  plasma membrane  phosphatidylinositol 3-kinase complex  phosphatidylinositol 3-kinase complex  phosphatidylinositol 3-kinase complex, class IA  phosphatidylinositol 3-kinase complex, class IA  glucose metabolic process  protein phosphorylation  epidermal growth factor receptor signaling pathway  G-protein coupled receptor signaling pathway  axon guidance  regulation of gene expression  phosphatidylinositol 3-kinase signaling  membrane  negative regulation of macroautophagy  kinase activity  kinase activity  1-phosphatidylinositol-3-kinase activity  1-phosphatidylinositol-3-kinase activity  1-phosphatidylinositol-3-kinase activity  phosphorylation  cell migration  cytokine-mediated signaling pathway  lamellipodium  platelet activation  platelet activation  protein kinase activator activity  T cell costimulation  positive regulation of TOR signaling  activation of protein kinase activity  positive regulation of peptidyl-serine phosphorylation  phosphatidylinositol 3-kinase activity  phosphatidylinositol 3-kinase activity  1-phosphatidylinositol-4-phosphate 3-kinase activity  phosphatidylinositol-3-phosphate biosynthetic process  phosphatidylinositol-3-phosphate biosynthetic process  insulin receptor signaling pathway via phosphatidylinositol 3-kinase  Fc-epsilon receptor signaling pathway  Fc-gamma receptor signaling pathway involved in phagocytosis  ERBB2 signaling pathway  regulation of multicellular organism growth  anoikis  regulation of cellular respiration  protein kinase B signaling  negative regulation of neuron apoptotic process  endothelial cell migration  insulin receptor substrate binding  hypomethylation of CpG island  phosphatidylinositol phosphorylation  phosphatidylinositol phosphorylation  phosphatidylinositol-4,5-bisphosphate 3-kinase activity  phosphatidylinositol-4,5-bisphosphate 3-kinase activity  vascular endothelial growth factor receptor signaling pathway  phosphatidylinositol-mediated signaling  phosphatidylinositol-mediated signaling  T cell receptor signaling pathway  leukocyte migration  positive regulation of protein kinase B signaling  phosphatidylinositol kinase activity  cardiac muscle contraction  adipose tissue development  cellular response to glucose stimulus  energy homeostasis  negative regulation of fibroblast apoptotic process  regulation of genetic imprinting  negative regulation of anoikis  
Pathways : KEGG   
REACTOMEP42336 [protein]
REACTOME PathwaysR-HSA-912631 [pathway]   
NDEx NetworkPIK3CA
Atlas of Cancer Signalling NetworkPIK3CA
Wikipedia pathwaysPIK3CA
Orthology - Evolution
OrthoDB5290
GeneTree (enSembl)ENSG00000121879
Phylogenetic Trees/Animal Genes : TreeFamPIK3CA
HOVERGENP42336
HOGENOMP42336
Homologs : HomoloGenePIK3CA
Homology/Alignments : Family Browser (UCSC)PIK3CA
Gene fusions - Rearrangements
Fusion : MitelmanPIK3CA/KCNMB3 [3q26.32/3q26.32]  
Fusion : MitelmanTBL1XR1/PIK3CA [3q26.32/3q26.32]  [t(3;3)(q26;q26)]  
Fusion : MitelmanUSP13/PIK3CA [3q26.33/3q26.32]  [t(3;3)(q26;q26)]  
Fusion PortalTBL1XR1 3q26.32 PIK3CA 3q26.32 BRCA
Fusion PortalUSP13 3q26.33 PIK3CA 3q26.32 BRCA
Fusion : QuiverPIK3CA
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerPIK3CA [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)PIK3CA
dbVarPIK3CA
ClinVarPIK3CA
1000_GenomesPIK3CA 
Exome Variant ServerPIK3CA
ExAC (Exome Aggregation Consortium)ENSG00000121879
GNOMAD BrowserENSG00000121879
Varsome BrowserPIK3CA
Genetic variants : HAPMAP5290
Genomic Variants (DGV)PIK3CA [DGVbeta]
DECIPHERPIK3CA [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisPIK3CA 
Mutations
ICGC Data PortalPIK3CA 
TCGA Data PortalPIK3CA 
Broad Tumor PortalPIK3CA
OASIS PortalPIK3CA [ Somatic mutations - Copy number]
Cancer Gene: CensusPIK3CA 
Somatic Mutations in Cancer : COSMICPIK3CA  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDPIK3CA
intOGen PortalPIK3CA
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)Mendelian genes
LOVD (Leiden Open Variation Database)MSeqDR-LSDB Mitochondrial Disease Locus Specific Database
BioMutasearch PIK3CA
DgiDB (Drug Gene Interaction Database)PIK3CA
DoCM (Curated mutations)PIK3CA (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)PIK3CA (select a term)
intoGenPIK3CA
NCG5 (London)PIK3CA
Cancer3DPIK3CA(select the gene name)
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM114480    114500    114550    162900    167000    171834    182000    211980    602501    612918    613659    615108   
Orphanet243    17004    20370    3245    21511    21064    21066    10805    14375   
DisGeNETPIK3CA
MedgenPIK3CA
Genetic Testing Registry PIK3CA
NextProtP42336 [Medical]
TSGene5290
GENETestsPIK3CA
Target ValidationPIK3CA
Huge Navigator PIK3CA [HugePedia]
snp3D : Map Gene to Disease5290
BioCentury BCIQPIK3CA
ClinGenPIK3CA (curated)
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD5290
Chemical/Pharm GKB GenePA33308
Drug Sensitivity PIK3CA
Clinical trialPIK3CA
Miscellaneous
canSAR (ICR)PIK3CA (select the gene name)
Other databasehttp://cancergenome.broadinstitute.org/index.php?tgene=PIK3CA
Probes
Litterature
PubMed499 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMinePIK3CA
EVEXPIK3CA
GoPubMedPIK3CA
iHOPPIK3CA
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

Search in all EBI   NCBI

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Mon Sep 3 16:01:55 CEST 2018

Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us

jlhuret@AtlasGeneticsOncology.org.