Atlas of Genetics and Cytogenetics in Oncology and Haematology

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ATG2B (Autophagy-related 2B)

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

Abstract Autophagy is a cellular process involved in the sequestration of cytosolic components and their degradation by lysosomes. Autophagy has been involved in physiological responses to stress or aging and in the development of many human diseases including solid and haematological cancers. In humans, 16 autophagy-related genes are known. The ATG2B protein is involved in the late steps of the autophagy process i.e. the formation of autophagosomes that fuse with lysosomes before degradation. Loss-of -function (frameshift) acquired mutations of ATG2B have been identified in gastric and colorectal carcinomas with high microsatellite instability. Both pharmacologic and genetic evidence indicate that autophagy plays pleiotropic functions in hematopoietic cell homeostasis and leukemogeneis. Autophagy could exert two opposite roles (cell death and survival) depending on the nature of the hematopoietic malignancy.
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 ATG2B; 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)


Alias (NCBI)C14orf103
HGNC Alias symbFLJ10242
HGNC Previous nameC14orf103
HGNC Previous namechromosome 14 open reading frame 103
 ATG2 autophagy related 2 homolog B (S. cerevisiae)
LocusID (NCBI) 55102
Atlas_Id 55326
Location 14q32.2  [Link to chromosome band 14q32]
Location_base_pair Starts at 96279195 and ends at 96363341 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping ATG2B.png]
Local_order telomere to centromere.
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
ATG2B (14q32.2) / SLC22A17 (14q11.2)
Note cooperates with GSKIP, 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 ATG2B gene consists of 42 exons spanning a region of 82.08 kb.
Transcription A single mRNA transcript (NM_018036.6) of the ATG2B gene, with a total length of 6234 nucleotides, has been annotated.
Pseudogene Not yet identified.


Description The protein encoded by the ATG2B gene is the autophagy-related protein 2 homolog B of 2078 amino acids, with a calculated molecular mass of 232.8 kDa
Expression Expression of ATG2B 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).
In hematopoietic cells, ATG2B 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 ATG2B is mainly localized in the nucleus.
Function Autophagy is an intracellular degradation system by which cytoplasmic materials are enclosed by the autophagosomes and transferred to lysosomes before degradation. The autophagy process has been extensively studied in yeast; 35 autophagy-related genes (ATG) have been identified, of which 16 are currently known in humans . This cellular process is a highly conserved among species. In humans, two ATG2 proteins, ATG2A and ATG2B, have redundant functions and are required for autophagosome formation (Velikkakath AK et al , 2012).
Homology 44.5% of human ATG2B residues are identical to those of human ATG2A.


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.
Somatic A loss-of-function somatic mutation (c.3120delA, p.Lys1040fs) in gastric carcinomas (15.6%) and in colorectal carcinomas (11.6%) (Klionsky DJ, 2009).

Implicated in

Entity Familial myeloproliferative neoplasms (MPN)
Disease Familial MPN, in particular, essential thrombocythemia progressing to myelofibrosis and/or acute myeloid leukemia and primary myelofibrosis, with autosomal dominant inheritance and originated from West-indies (Martinique) 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.
Entity Gastric carcinoma
Note Loss-of-functions somatic mutations in ATG genes (ATG2B, ATG5, ATG9B and ATG12) are identified in 28% of gastric carcinomas with high microsatellite instability. These mutations may contribute to cancer development by deregulating the autophagy process (Kang et al, 2009).
Entity Colorectal cancer
Note Loss-of-functions somatic mutations in ATG genes (ATG2B, ATG5, ATG9B and ATG12) are identified in 28% of colorectal carcinomas with high microsatellite instability. These mutations may contribute to cancer development by deregulating the autophagy process (Kang et al, 2009).


Frameshift mutations of autophagy-related genes ATG2B, ATG5, ATG9B and ATG12 in gastric and colorectal cancers with microsatellite instability.
Kang MR, Kim MS, Oh JE, Kim YR, Song SY, Kim SS, Ahn CH, Yoo NJ, Lee SH
J Pathol; 2009;217:702-6
PMID 19197948
Autophagy: from phenomenology to molecular understanding in less than a decade.
Klionsky DJ.
Nat Rev Mol Cell Biol 2007;8:931-937.
PMID 17712358
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
Autophagy: from phenomenology to molecular understanding in less than a decade.
Velikkakath AK, Nishimura T, Oita E, Ishihara N, Mizushima N.
Mol Biol Cell. 201;23:896-909.
PMID 22219374


This paper should be referenced as such :
Christine Bellann-Chantelot, Isabelle Plo
ATG2B (Autophagy-related 2B)
Atlas Genet Cytogenet Oncol Haematol. 2017;21(6):205-207.
Free journal version : [ pdf ]   [ DOI ]

Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 1 ]
  t(14;14)(q11;q32) ATG2B/SLC22A17

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

External links

HGNC (Hugo)ATG2B   20187
Entrez_Gene (NCBI)ATG2B    autophagy related 2B
GeneCards (Weizmann)ATG2B
Ensembl hg19 (Hinxton)ENSG00000066739 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000066739 [Gene_View]  ENSG00000066739 [Sequence]  chr14:96279195-96363341 [Contig_View]  ATG2B [Vega]
ICGC DataPortalENSG00000066739
TCGA cBioPortalATG2B
Genatlas (Paris)ATG2B
SOURCE (Princeton)ATG2B
Genetics Home Reference (NIH)ATG2B
Genomic and cartography
GoldenPath hg38 (UCSC)ATG2B  -     chr14:96279195-96363341 -  14q32.2   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)ATG2B  -     14q32.2   [Description]    (hg19-Feb_2009)
GoldenPathATG2B - 14q32.2 [CytoView hg19]  ATG2B - 14q32.2 [CytoView hg38]
genome Data Viewer NCBIATG2B [Mapview hg19]  
Gene and transcription
Genbank (Entrez)AK001104 AK055200 AK123451 AK128275 AK302641
RefSeq transcript (Entrez)NM_018036
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)ATG2B
Alternative Splicing GalleryENSG00000066739
Gene ExpressionATG2B [ NCBI-GEO ]   ATG2B [ EBI - ARRAY_EXPRESS ]   ATG2B [ SEEK ]   ATG2B [ MEM ]
Gene Expression Viewer (FireBrowse)ATG2B [ Firebrowse - Broad ]
GenevisibleExpression of ATG2B in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)55102
GTEX Portal (Tissue expression)ATG2B
Human Protein AtlasENSG00000066739-ATG2B [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ96BY7   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ96BY7  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ96BY7
Splice isoforms : SwissVarQ96BY7
Domains : Interpro (EBI)ATG2    Autophagy-rel_C    VPS13_N   
Domain families : Pfam (Sanger)ATG_C (PF09333)    Chorein_N (PF12624)   
Domain families : Pfam (NCBI)pfam09333    pfam12624   
Conserved Domain (NCBI)ATG2B
Blocks (Seattle)ATG2B
Human Protein Atlas [tissue]ENSG00000066739-ATG2B [tissue]
Peptide AtlasQ96BY7
Protein Interaction databases
IntAct (EBI)Q96BY7
Ontologies - Pathways
Ontology : AmiGOautophagosome assembly  phagophore assembly site  autophagy of mitochondrion  nucleoplasm  lipid droplet  extrinsic component of membrane  phagophore assembly site membrane  autophagy of nucleus  
Ontology : EGO-EBIautophagosome assembly  phagophore assembly site  autophagy of mitochondrion  nucleoplasm  lipid droplet  extrinsic component of membrane  phagophore assembly site membrane  autophagy of nucleus  
NDEx NetworkATG2B
Atlas of Cancer Signalling NetworkATG2B
Wikipedia pathwaysATG2B
Orthology - Evolution
GeneTree (enSembl)ENSG00000066739
Phylogenetic Trees/Animal Genes : TreeFamATG2B
Homologs : HomoloGeneATG2B
Homology/Alignments : Family Browser (UCSC)ATG2B
Gene fusions - Rearrangements
Fusion : MitelmanATG2B/SLC22A17 [14q32.2/14q11.2]  
Fusion PortalATG2B 14q32.2 SLC22A17 14q11.2 BLCA
Fusion : Fusion_HubATAD2B--ATG2B    ATG2B--APPL2    ATG2B--CALD1    ATG2B--CCNL1    ATG2B--CD46    ATG2B--COPS3    ATG2B--D2HGDH    ATG2B--DDX24    ATG2B--GGNBP2    ATG2B--SETD3    ATG2B--SLC22A17    ATG2B--TANK    ATG2B--TDRD9    ATG2B--UBE4B    ATG2B--UBR7   
ATG2B--ZNF236    CLPX--ATG2B    DYNC1H1--ATG2B    FTL--ATG2B    PAPOLA--ATG2B    SPAG16--ATG2B    SYNE2--ATG2B    VAPA--ATG2B    ZNF22--ATG2B   
Fusion : QuiverATG2B
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerATG2B [hg38]
Exome Variant ServerATG2B
GNOMAD BrowserENSG00000066739
Varsome BrowserATG2B
Genomic Variants (DGV)ATG2B [DGVbeta]
DECIPHERATG2B [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisATG2B 
ICGC Data PortalATG2B 
TCGA Data PortalATG2B 
Broad Tumor PortalATG2B
OASIS PortalATG2B [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICATG2B  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DATG2B
Mutations and Diseases : HGMDATG2B
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 ATG2B
DgiDB (Drug Gene Interaction Database)ATG2B
DoCM (Curated mutations)ATG2B (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)ATG2B (select a term)
NCG6 (London) select ATG2B
Cancer3DATG2B(select the gene name)
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry ATG2B
NextProtQ96BY7 [Medical]
Target ValidationATG2B
Huge Navigator ATG2B [HugePedia]
Clinical trials, drugs, therapy
Protein Interactions : CTD
Pharm GKB GenePA162377102
Clinical trialATG2B
canSAR (ICR)ATG2B (select the gene name)
DataMed IndexATG2B
PubMed32 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 1 18:46:55 CET 2021

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