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

GSKIP (GSK3-beta interaction protein)

Written2016-10Christine Bellanné-Chantelot, Isabelle Plo
Département de Génétique, Hpitaux Universitaires Pitié-Salpétrière-Charles Foix, Paris (CBC); INSERM UMR1170, Institut Gustave Roussy, Villejuif, (CBC, IP), France.;

Abstract GSK3beta interaction protein (GSKIP) is a negative regulator of GSK3B (GSK3 beta) which is a highly conserved serine-threonine kinase involved in many cellular processes including glycogen metabolism, proliferation, differentiation, and development. GSKIP directly interacts with GSK3B through its C-terminal conserved GSK3B -binding domain (GID) and negatively regulates GSK3B in the Wnt/ beta -catenin signaling pathway. The overexpression of GSKIP may result in the activation of the Wnt pathway involved in hematopoietic stem cell homeostasis and normal megakaryopoiesis and in the development of leukemia stem cells in acute myeloid leukemia (AML). In a mouse model, GSK3B allelic deletion results in a myelodysplastic syndrome that, when combined with GSK3A deletion, leads to AML
The germline duplication of ATG2B and GSKIP, both located in 14q32.2, predisposes to the development of familial myeloproliferative neoplasms with autosomal dominant inheritance, in particular essential thrombocythemia progressing to leukemia. Overexpression of ATG2B and GSKIP enhances megakaryocyte progenitor differentiation by increasing progenitor sensitivity to thrombopoietin. Both genes cooperate with somatic JAK2, MPL and CALR mutations and their overexpression provides a growth advantage to hematopoietic cells carrying these driver mutations that may explain the familial aggregation and the progression of essential thrombocythemia to myelofibrosis and leukemia.

Keywords GSKIP; Myeloproliferative neoplasms (MPN); essential thrombocythemia; myelofibrosis; leukemia; predisposition; ATG2B/GSKIP; chromosome 14; CNV; autophagy; Wnt/beta-catenin pathway

(Note : for Links provided by Atlas : click)


chromosome 14 open reading frame 129
Other alias
LocusID (NCBI) 51527
Atlas_Id 64074
Location 14q32.2  [Link to chromosome band 14q32]
Location_base_pair Starts at 96364736 and ends at 96387290 bp from pter ( according to hg19-Feb_2009)  [Mapping GSKIP.png]
Local_order centromere to 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)
Note cooperates with ATG2B, also located in 14q32.2 and included in the 700 kb duplication NC_000014.9:g.96.163.103_96.857.129dup (on Assembly GRCh37)


Description The GSKIP gene consists of 2 non-coding exons and 2 exons, spanning a coding region of 3433 bp.
Transcription There are four transcripts that differ by their 5'UTR and encode the same protein. The longest transcript (NM_001271904) of the GSKIP gene has a total total length of 1050 nucleotides.
Pseudogene Not yet identified.


Description The protein encoded by the GSKIP gene is the GSK3-beta interaction protein of 139 amino acids, with a calculated molecular mass of 15.648 kDa.
Expression Expression of GSKIP has been detected in various normal human tissues (bone marrow, whole blood, thymus, brain, heart, muscle, colon, kidney, liver, lung, pancreas, thyroid, salivary and adrenal glands, skin, ovary, uterus, placenta, prostate and testis). The gene is overexpressed in bone, colon and rectum.
In hematopoietic cells, GSKIP is expressed in CD34+ purified hematopoietic progenitors and CD36+ erythroblasts or CD41+ megakaryocytes derived from CD34+ progenitors cultured in vitro (Saliba et al, 2016)
Localisation GSKIP is localized in the cytoplasm and nucleus.
Function GSKIP belongs to the family of A-kinase anchoring proteins (AKAPs) that bind serine/threonine kinase (PKA). These AKAPs proteins interact with the regulatory domain of PKA and facilitate their phosphorylation. GSKIP directly interacts with GSK3B through its C-terminal conserved GSK3B-binding domain (GID; amino acid 115-139) and negatively regulates GSK3B in the Wnt/beta-catenin signaling pathway (Chou et al, 2006). The overexpression of GSKIP may mimic activation of the Wnt pathway involved in hematopoietic stem cell homeostasis and normal megakaryopoiesis (Li et al, 2008) and in the development of leukemia stem cells in AML (Wang. et al, 2010). It has recently been shown in a mouse model that Gsk3b allelic deletion results in a myelodysplastic syndrome that, when combined with GSK3A deletion, leads to AML (Guezguez et al, 2016).


Germinal A germline 14q32.2 head-to-tail duplication of 700 kb has been associated with familial myeloid malignancies (Saliba et al , 2015). The germline duplication includes the genes TCL1A, GSKIP, ATG2B, BDKRB1, BDKRB2 and the first exon of AK7. The overexpression of ATG2B and GSKIP that are expressed in myeloid cells, enhances hematopoietic progenitor differentiation, particularly of megacaryocytes. The development of myeloid malignancies required the cooperation of both genes with the myeloproliferative neoplasms (MPN) driver JAK2 Val617Phe mutation, MPL or CALR mutations. The mechanism of cooperation between ATG2B and GSKIP with MPN driver mutations remains unknown.
The germline duplication with the same distal and proximal breakpoints has only been identified in MPN families originated from West Indies (Martinique) suggesting a founder effect.

Implicated in

Entity Familial myeloproliferative neoplasms (MPN)
Disease Familial MPN originated from West-indies (Martinique) and in particular, essential thrombocythemia progressing to myelofibrosis and/or acute myeloid leukemia and primary myelofibrosis may be linked to ATG2B/GSKIP germline duplication. The predisposition is highly penetrant (80%) and is characterized by an earlier age of MPN onset in comparison to sporadic cases (41 years versus > 60 years). The spectrum of acquired driver mutations (JAK2 Val617Phe , MPL and CALR mutations) is similar to the spectrum of mutations in sporadic MPN cases.
Prognosis The percentage of transformation is close to 50% in these familial MPN cases and is related to the detection of mutations affecting epigenetic regulator genes such as TET2 IDH1 or IDH2.
Entity Acute myeloid leukemia (AML)
Disease AML originated from West-indies (Martinique) may be linked to ATG2B/GSKIP germline duplication.
Prognosis The prognosis of the disease is also linked to the detection of acquired mutations in TET2, IDH1 or in IDH2. No TP53 mutation was found, contrary to what was observed in AML evolving from MPN, suggesting a different pathway for leukemic transformation.


GSKIP is homologous to the Axin GSK3beta interaction domain and functions as a negative regulator of GSK3beta
Chou HY, Howng SL, Cheng TS, Hsiao YL, Lieu AS, Loh JK, Hwang SL, Lin CC, Hsu CM, Wang C, Lee CI, Lu PJ, Chou CK, Huang CY, Hong YR
Biochemistry. 2006;45:11379-89
PMID 16981698
Deficiencies in Hematopoietic Stem Cells Initiate Pre-neoplastic State that Is Predictive of Clinical Outcomes of Human Acute Leukemia.
Guezguez B, Almakadi M, Benoit YD, Shapovalova Z, Rahmig S, Fiebig-Comyn A, Casado FL, Tanasijevic B, Bresolin S, Masetti R, Doble BW, Bhatia M
Cancer Cell. 2016;29:61-74
PMID 26766591
GSK3beta is a negative regulator of platelet function and thrombosis.
Li D, August S, Woulfe DS
Blood 2008;111:3522-30
PMID 18218855
Germline duplication of ATG2B and GSKIP predisposes to familial myeloid malignancies
Saliba J, Saint-Martin C, Di Stefano A, Lenglet G, Marty C, Keren B, Pasquier F, Valle VD, Secardin L, Leroy G, Mahfoudhi E, Grosjean S, Droin N, Diop M, Dessen P, Charrier S, Palazzo A, Merlevede J, Meniane JC, Delaunay-Darivon C, Fuseau P, Isnard F, Casadevall N, Solary E, Debili N, Bernard OA, Raslova H, Najman A, Vainchenker W, Bellanné-Chantelot C, Plo I
Nat Genet. 2015;47:1131-40
PMID 26280900
The Wnt/beta-catenin pathway is required for the development of leukemia stem cells in AML
Wang Y, Krivtsov AV, Sinha AU, North TE, Goessling W, Feng Z, Zon LI, Armstrong SA.
Science. 2010;327(5973):1650-3
PMID 20339075


This paper should be referenced as such :
Christine Bellann-Chantelot, Isabelle Plo
GSKIP (GSK3-beta interaction protein)
Atlas Genet Cytogenet Oncol Haematol. 2017;21(6):197-199.
Free journal version : [ pdf ]   [ DOI ]
On line version :

Other Cancer prone implicated (Data extracted from papers in the Atlas) [ 1 ]
  Familial Myeloproliferative Disorders

External links

HGNC (Hugo)GSKIP   20343
Entrez_Gene (NCBI)GSKIP  51527  GSK3B interacting protein
AliasesC14orf129; HSPC210
GeneCards (Weizmann)GSKIP
Ensembl hg19 (Hinxton)ENSG00000100744 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000100744 [Gene_View]  ENSG00000100744 [Sequence]  chr14:96364736-96387290 [Contig_View]  GSKIP [Vega]
ICGC DataPortalENSG00000100744
Genatlas (Paris)GSKIP
Genetics Home Reference (NIH)GSKIP
Genomic and cartography
GoldenPath hg38 (UCSC)GSKIP  -     chr14:96364736-96387290 +  14q32.2   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)GSKIP  -     14q32.2   [Description]    (hg19-Feb_2009)
GSKIP - 14q32.2 [CytoView hg19]  GSKIP - 14q32.2 [CytoView hg38]
Mapping of homologs : NCBIGSKIP [Mapview hg19]  GSKIP [Mapview hg38]
Gene and transcription
Genbank (Entrez)AF151044 AK000796 AK094654 AK314423 BC004818
RefSeq transcript (Entrez)NM_001271904 NM_001271905 NM_001271906 NM_016472
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)GSKIP
Cluster EST : UnigeneHs.745067 [ NCBI ]
CGAP (NCI)Hs.745067
Alternative Splicing GalleryENSG00000100744
Gene Expression Viewer (FireBrowse)GSKIP [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevestigatorExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)51527
GTEX Portal (Tissue expression)GSKIP
Human Protein AtlasENSG00000100744-GSKIP [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9P0R6   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ9P0R6  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ9P0R6
Splice isoforms : SwissVarQ9P0R6
Domains : Interpro (EBI)DUF727    GSKIP_dom   
Domain families : Pfam (Sanger)DUF727 (PF05303)   
Domain families : Pfam (NCBI)pfam05303   
Domain structure : Prodom (Prabi Lyon)DUF727 (PD080843)   
Conserved Domain (NCBI)GSKIP
DMDM Disease mutations51527
Blocks (Seattle)GSKIP
PDB Europe1SGO   
Structural Biology KnowledgeBase1SGO   
SCOP (Structural Classification of Proteins)1SGO   
CATH (Classification of proteins structures)1SGO   
Human Protein Atlas [tissue]ENSG00000100744-GSKIP [tissue]
Peptide AtlasQ9P0R6
IPIIPI00009374   IPI01026185   IPI01026069   
Protein Interaction databases
IntAct (EBI)Q9P0R6
Ontologies - Pathways
Ontology : AmiGOcytoplasm  
Ontology : EGO-EBIcytoplasm  
Atlas of Cancer Signalling NetworkGSKIP
Wikipedia pathwaysGSKIP
Orthology - Evolution
GeneTree (enSembl)ENSG00000100744
Phylogenetic Trees/Animal Genes : TreeFamGSKIP
Homologs : HomoloGeneGSKIP
Homology/Alignments : Family Browser (UCSC)GSKIP
Gene fusions - Rearrangements
Fusion : QuiverGSKIP
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerGSKIP [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)GSKIP
Exome Variant ServerGSKIP
ExAC (Exome Aggregation Consortium)ENSG00000100744
GNOMAD BrowserENSG00000100744
Varsome BrowserGSKIP
Genetic variants : HAPMAP51527
Genomic Variants (DGV)GSKIP [DGVbeta]
DECIPHERGSKIP [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisGSKIP 
ICGC Data PortalGSKIP 
TCGA Data PortalGSKIP 
Broad Tumor PortalGSKIP
OASIS PortalGSKIP [ Somatic mutations - Copy number]
Mutations and Diseases : HGMDGSKIP
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch GSKIP
DgiDB (Drug Gene Interaction Database)GSKIP
DoCM (Curated mutations)GSKIP (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)GSKIP (select a term)
Cancer3DGSKIP(select the gene name)
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry GSKIP
NextProtQ9P0R6 [Medical]
Target ValidationGSKIP
Huge Navigator GSKIP [HugePedia]
snp3D : Map Gene to Disease51527
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD51527
Chemical/Pharm GKB GenePA134987554
Clinical trialGSKIP
canSAR (ICR)GSKIP (select the gene name)
DataMed IndexGSKIP
PubMed17 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
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 : Tue Apr 30 14:40:21 CEST 2019

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

For comments and suggestions or contributions, please contact us