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SETD2 (SET domain containing 2, histone lysine methyltransferase)

Written2020-07Vivian Wang, Assunta De Rienzo
Division of Thoracic Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, USA; vwang@bwh.harvard.edu; aderienzo@bwh.harvard.edu

Abstract Review of SETD2 and its role in cancer

Keywords SETD2 gene; methyltransferase; cancer

(Note : for Links provided by Atlas : click)

Identity

Alias (NCBI)HBP231
HIF-1
HIP-1
HSPC069
HYPB
KMT3A
LLS
SET2
p231HBP
HGNC (Hugo) SETD2
HGNC Alias symbHYPB
HIF-1
KIAA1732
FLJ23184
KMT3A
HGNC Previous nameSET domain containing 2
LocusID (NCBI) 29072
Atlas_Id 51302
Location 3p21.31  [Link to chromosome band 3p21]
Location_base_pair Starts at 47016408 and ends at 47163977 bp from pter ( according to hg19-Feb_2009)  [Mapping SETD2.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)

DNA/RNA

Description SETD2 gene spans 147 kb. It is composed of 26 exons encoding three mRNA transcript variants ranging from 8,452 to 8,737 nucleotides in length.
Transcription Transcription start is 189 bp for variant 1 and 305 bp for variant 2 upstream of the first ATG of the SETD2 ORF. Variant 2 differs in the 5' UTR and coding sequence compared with variant 1, resulting in a shorter isoform of the SETD2 protein. A third non-coding variant contains an alternate exon compared with variant 1.
Pseudogene No SETD2 pseudogene has been reported.

Protein

 
  Graphic representation of SETD2 protein. SETD2 (isoform 1) is a 2564 aa protein. AWS, associated with SET; SET, Su(var)3-9, enhancer-of-zeste, trithorax; PS, post-SET; WW, rsp5-domain; CC, coiled-coil; LCR, low-charged region; SRI, Set2 Rpb1 Interacting.
Description Human SETD2 is a methyltransferase with 2 main isoforms. Isoform 1 is 2,564 amino acids with a molecular weight of 287.5 kDa. Isoform 2 is 44 residues shorter than isoform 1 at the N-terminus, and is 2520 amino acids with a molecular weight of 282.6 kDa. Three conserved functional domains have been identified in the SETD2: the triplicate AWS-SET-PostSET domains, a WW domain, and a Set2 Rpb1 Interacting (SRI) domain (Li et al., 2016).
The triplicate AWS-SET-PostSET domain mediates methyltransferase activity specific for histone H3 lysine 36 (H3K36) (Edmunds et al., 2008), and a few other non-histone targets (Park et al., 2016). The SET (Suppressor of Variegation, Enhancer of zeste and Trithorax) domain is an evolutionarily conserved motif of 130 amino acids (Rea et al., 2000; Tschiersch et al., 1994), usually present as part of a multi-domain where it is flanked by an AWS (Associated with SET domain) and a PostSET domain. It includes a beta-sheet structure that facilitates multiple rounds of methylation without substrate disassociation (Zhang et al., 2003).
The WW domain, located in the C-terminal region of SETD2, contains two conserved tryptophan (W) residues (Sudol et al., 1995). The WW domain preferentially binds proline-rich segments of other proteins, mediating protein-protein interactions, such as the proline-rich motifs in the Huntingtin protein in Huntington's disease (Gao et al., 2014).
The SRI domain encompasses a 79 amino acid region towards the C-terminal end of SETD2 and is the primary docking site of RNA Pol II (Li et al., 2005; Kizer et al., 2005). It is composed of a low charged region rich in glutamine and proline. Human SETD2 associates with hyperphosphorylated C-terminal domain (CTD) of RNA polymerase II (RNAPII), linking SETD2 to the transcription elongation process (Li et al., 2002). In yeast, deletion of the CTD region on RNA polymerase II defects trimethylation of H3K36, suggesting that H3K36 trimethylation and transcription elongation are coupled processes (Krogan et al., 2003).
Expression SETD2 is ubiquitously expressed in all human tissues and cell lines tested, including many cancer-derived cell lines. Expression is relatively high in bone marrow, lymph node, testis and thyroid tissue, and it is relatively low in pancreas, heart and salivary gland tissue (Fagerberg et al., 2014).
Localisation SETD2 localizes as nuclear speckles and additionally in cytosol.
Function SETD2 is a lysine methyltransferase and transcriptional regulator involved in histone modification, DNA repair, mRNA regulation, genomic stability, alternative splicing, and interferon-α signaling (Aymard et al., 2014; Skucha, et al., 2019; Luco et al., 2010; de Almeida et al., 2011). The C-terminal end of SETD2 complexes with Heterogeneous Nuclear Ribonucleoprotein L ( HNRNPL) and mediates a non-redundant, co-transcriptional trimethylation to histone H3 at lysine 36 (H3K36me). (Yuan et al., 2009) It was demonstrated that Setd2, the mouse homologue of human Huntingtin-interacting protein HYPB, can modulate all detectable K36me3, but not K36me2 or K36me1, throughout the nucleus using siRNA experiments (Edmunds et al., 2008). Similarly, in yeast, knockdown of Setd2 results in complete absence of H3Kme3 without affecting H3Kme1 or H3Kme2. Loss of SETD2 is associated with greater chromatin accessibility (Carvalho et al., 2014; Simon et al., 2014).
In addition to H3K36, SETD2 methylates two other non-histone targets: the α-tubulin on lysine 40 of mitotic microtubules (Park et al., 2016) and the signal transducer and transcription activator ( STAT1) on lysine 525 (Chen et al., 2017).
SETD2 is also a critical amplifier of interferon-α signaling as STAT1 methylation on lysine 525 catalyzed by SETD2 is an essential signaling event on the induction of interferon stimulating genes, such as ISG15 and MX2 (Chen et al., 2017).
The C-terminal domain of SETD2 has been shown to interact with the tumor suppressor TP53, and modulate the expression of its downstream target genes (Xie et al., 2008; Carvalho et al., 2019).
Homology The AWS-SET-postSET domains in human SETD2 share sequence homology and functional similarity with those in yeast Setd2. The SET domain that mediates methyltransferase activity is a ~130 amino acid sequence motif that is evolutionarily conserved from mammals to yeast and even in some bacteria and viruses (Rea et al., 2000; Tschiersch et al., 1994).

Mutations

Note Inactivating SETD2 mutations are common in clear cell renal cell cancer but have been identified also in other cancers including lung cancer, acute lymphoblastic leukemia, and glioma (Fahey and Davis, 2017). The majority of somatic SETD2 mutations are missense mutations (Li et al., 2016). SETD2-deficient cancers exhibit a wide range of mutations, including insertions, deletions, and chromosomal aberrations, suggesting an additional role for SETD2 in genome stability (Li et al., 2016). Homozygous deletion of Setd2 in mice has been shown to result in embryonic lethality (Hu et al., 2010).

Implicated in

  
Entity Clear cell renal cell carcinoma (ccRCC)
Note The overall frequency of SETD2 mutations in ccRCC is approximately 15.6% (Cancer Genome Atlas Research Network, 2013). SETD2 mutations were found to be associated with shorter cancer-specific survival (P = 0.036; HR 1.68; 95% CI 1.04-2.73) (Hakimi et al., 2013). The presence of SETD2 mutations was a predictor of ccRCC recurrence. The fraction of truncating SETD2 mutations in ccRCC (57%) was significantly higher than the fraction of truncating SETD2 mutations in non-ccRCC tumors (32%).
  
  
Entity Pancreatic adenocarcinoma
Note Low SETD2 expression was correlated with poor prognosis in patients with pancreatic adenocarcinoma. In vivo, Setd2 loss in murine pancreatic acinar cells facilitated Kras-induced acinar-to-ductal reprogramming, mainly through epigenetic dysregulation of Fbxw7. This suggests that Setd2 may act as a putative tumor suppressor in Kras-driven pancreatic carcinogenesis. A Setd2 ablation in murine pancreatic cancer cells enhanced epithelial-mesenchymal transition (EMT) through impaired epigenetic regulation of a-catenin (Ctnna1). Setd2 deficiency in murine pancreatic cancer cell lines also led to sustained Akt activation (Niu et al., 2020).
  
  
Entity Malignant Mesothelioma (MM):
Note SETD2 is located in a region frequently lost in malignant pleural mesothelioma (MPM). In 2016, a comprehensive genomic analysis of 212 MPM patients identified SETD2 to be frequently mutated in this disease. In addition, gene fusions and splice-site alterations were also frequent mechanisms for inactivation of SETD2 in MPM (Bueno et al., 2016). In a cohort of 33 malignant mesotheliomas, 27% showed minute biallelic deletions or loss of heterozygosity combined with point mutations in SETD2 by using combined high-density comparative genomic hybridization array and whole exome sequencing analyses (Yoshikawa et al., 2015).
  
  
Entity Acute Leukemia
Note SETD2 mutations have been found to be frequent (22%) in acute lymphoid and myeloid leukemias (ALL and AML) carrying a mixed lineage leukemia (MLL)-rearrangement. Knockdown of SETD2 in pre-leukemic cells carrying a KMT2A (MLL) fusion-gene increased both clonogenicity and proliferation of these cells, suggesting that loss of function of SETD2 may promote progression of the disease. In acute leukemia, SETD2 was found mutated in 6% of cases (Zhu et al., 2014). These mutations were commonly nonsense or frameshift, mostly affecting the SRI domain, and approximately a quarter of samples carried bi-allelic SETD2 mutations. A comparison of matched primary and relapsed ALL samples suggested that mutations in epigenetic regulators as a class, including SETD2 mutations, were more common at relapse (Mar et al., 2014).
  
  
Entity Gastrointestinal Stromal Tumors
Note SETD2 loss has been associated with more aggressive gastrointestinal stromal tumors (Huang et al., 2016).
  
  
Entity Lung Adenocarcinoma
Note SETD2 mutations were found to occur in 9% of lung adenocarcinomas (Cancer Genome Atlas Research Network, 2015). SETD2 fusion mutations are more common than point mutations in lung adenocarcinoma (Lee et al., 2019; Rosell et al., 2020). It has been also shown that suppression of SETD2 or CREB1 confers resistance to cisplatin through inhibition of H3K36me3 and ERK activation in non-small cell lung cancer cell lines (Kim et al., 2019).
  
  
Entity Lung Neuroendocrine Tumors
Note Genome wide SNP array analysis of 11 well-differentiated pulmonary carcinoid tumors has revealed loss of heterozygosity of SETD2 in these tumors (Cros et al., 2020).
  
  
Entity Primary Central Nervous System Tumors
Note A study published in 2013 showed that 15-28% of pediatric high-grade gliomas (HGGs) and 8% of adult HGGs displayed SETD2 mutations (Fontebasso et al., 2013).
  
  
Entity Bladder Carcinoma
Note SETD2 mutations have been observed in 6-10% of bladder urothelial carcinomas (Van Allen et al., 2014).
  
  
Entity Huntington's Disease
Note SETD2 was first identified as a huntingtin-interacting protein, implicated in the pathogenesis of Huntington's disease (Faber et al., 1998). The WW domain of SETD2 was found to interact with the N-terminal PRR region of huntingtin protein. (Passani et al., 2000). A stretch of polyproline residues preceding the WW domain was found to modulate the interaction between the SETD2 and huntingtin proteins (Gao et al., 2014).
  

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Citation

This paper should be referenced as such :
Wang V, De Rienzo A
SETD2 (SET domain containing 2, histone lysine methyltransferase);
Atlas Genet Cytogenet Oncol Haematol. in press


Other Leukemias implicated (Data extracted from papers in the Atlas) [ 2 ]
  Early T-cell precursor acute lymphoblastic leukemia
t(3;3)(p21;p21) SETD2/CCDC12


Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 11 ]
  Malignant Mesothelioma
Nervous system: Astrocytoma with t(1;17)(p36;q21) SPOP/PRDM16
t(3;3)(p14;p21) SETD2/SPATA12
MANF/SETD2 (3p21)
NBEAL2/SETD2 (3p21)
NEK4/SETD2 (3p21)
SETD2/KIF9 (3p21)
SETD2/NBEAL2 (3p21)
SETD2/QRICH1 (3p21)
t(3;3)(p21;p22) SETD2/ULK4
t(3;3)(p21;q13) SETD2/POGLUT1


External links

Nomenclature
HGNC (Hugo)SETD2   18420
LRG (Locus Reference Genomic)LRG_775
Cards
AtlasSETD2ID51302ch3p21
Entrez_Gene (NCBI)SETD2  29072  SET domain containing 2, histone lysine methyltransferase
AliasesHBP231; HIF-1; HIP-1; HSPC069; 
HYPB; KMT3A; LLS; SET2; p231HBP
GeneCards (Weizmann)SETD2
Ensembl hg19 (Hinxton)ENSG00000181555 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000181555 [Gene_View]  ENSG00000181555 [Sequence]  chr3:47016408-47163977 [Contig_View]  SETD2 [Vega]
ICGC DataPortalENSG00000181555
TCGA cBioPortalSETD2
AceView (NCBI)SETD2
Genatlas (Paris)SETD2
WikiGenes29072
SOURCE (Princeton)SETD2
Genetics Home Reference (NIH)SETD2
Genomic and cartography
GoldenPath hg38 (UCSC)SETD2  -     chr3:47016408-47163977 -  3p21.31   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)SETD2  -     3p21.31   [Description]    (hg19-Feb_2009)
GoldenPathSETD2 - 3p21.31 [CytoView hg19]  SETD2 - 3p21.31 [CytoView hg38]
ImmunoBaseENSG00000181555
genome Data Viewer NCBISETD2 [Mapview hg19]  
OMIM612778   616831   
Gene and transcription
Genbank (Entrez)AB051519 AF049103 AF049610 AF161554 AI671342
RefSeq transcript (Entrez)NM_001349370 NM_012271 NM_014159
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)SETD2
Alternative Splicing GalleryENSG00000181555
Gene ExpressionSETD2 [ NCBI-GEO ]   SETD2 [ EBI - ARRAY_EXPRESS ]   SETD2 [ SEEK ]   SETD2 [ MEM ]
Gene Expression Viewer (FireBrowse)SETD2 [ Firebrowse - Broad ]
GenevisibleExpression of SETD2 in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)29072
GTEX Portal (Tissue expression)SETD2
Human Protein AtlasENSG00000181555-SETD2 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9BYW2   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ9BYW2  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ9BYW2
Splice isoforms : SwissVarQ9BYW2
PhosPhoSitePlusQ9BYW2
Domaine pattern : Prosite (Expaxy)AWS (PS51215)    POST_SET (PS50868)    SET (PS50280)    WW_DOMAIN_1 (PS01159)    WW_DOMAIN_2 (PS50020)   
Domains : Interpro (EBI)AWS_dom    Post-SET_dom    SET_dom    SETD2    SRI    SRI_sf    TFIIS/LEDGF_dom_sf    WW_dom    WW_dom_sf   
Domain families : Pfam (Sanger)AWS (PF17907)    SET (PF00856)    SRI (PF08236)    WW (PF00397)   
Domain families : Pfam (NCBI)pfam17907    pfam00856    pfam08236    pfam00397   
Domain families : Smart (EMBL)AWS (SM00570)  PostSET (SM00508)  SET (SM00317)  WW (SM00456)  
Conserved Domain (NCBI)SETD2
DMDM Disease mutations29072
Blocks (Seattle)SETD2
PDB (RSDB)2A7O    2MDC    2MDI    2MDJ    4FMU    4H12    5JJY    5JLB    5JLE    5LSS    5LSX    5LSY    5LSZ    5LT6    5LT7    5LT8    5V21    5V22   
PDB Europe2A7O    2MDC    2MDI    2MDJ    4FMU    4H12    5JJY    5JLB    5JLE    5LSS    5LSX    5LSY    5LSZ    5LT6    5LT7    5LT8    5V21    5V22   
PDB (PDBSum)2A7O    2MDC    2MDI    2MDJ    4FMU    4H12    5JJY    5JLB    5JLE    5LSS    5LSX    5LSY    5LSZ    5LT6    5LT7    5LT8    5V21    5V22   
PDB (IMB)2A7O    2MDC    2MDI    2MDJ    4FMU    4H12    5JJY    5JLB    5JLE    5LSS    5LSX    5LSY    5LSZ    5LT6    5LT7    5LT8    5V21    5V22   
Structural Biology KnowledgeBase2A7O    2MDC    2MDI    2MDJ    4FMU    4H12    5JJY    5JLB    5JLE    5LSS    5LSX    5LSY    5LSZ    5LT6    5LT7    5LT8    5V21    5V22   
SCOP (Structural Classification of Proteins)2A7O    2MDC    2MDI    2MDJ    4FMU    4H12    5JJY    5JLB    5JLE    5LSS    5LSX    5LSY    5LSZ    5LT6    5LT7    5LT8    5V21    5V22   
CATH (Classification of proteins structures)2A7O    2MDC    2MDI    2MDJ    4FMU    4H12    5JJY    5JLB    5JLE    5LSS    5LSX    5LSY    5LSZ    5LT6    5LT7    5LT8    5V21    5V22   
SuperfamilyQ9BYW2
Human Protein Atlas [tissue]ENSG00000181555-SETD2 [tissue]
Peptide AtlasQ9BYW2
HPRD11043
IPIIPI00307733   IPI00796144   IPI00442150   IPI01009244   IPI00916993   IPI00917578   
Protein Interaction databases
DIP (DOE-UCLA)Q9BYW2
IntAct (EBI)Q9BYW2
BioGRIDSETD2
STRING (EMBL)SETD2
ZODIACSETD2
Ontologies - Pathways
QuickGOQ9BYW2
Ontology : AmiGOangiogenesis  morphogenesis of a branching structure  neural tube closure  protein binding  nucleus  nucleoplasm  chromosome  mismatch repair  regulation of transcription, DNA-templated  transcription elongation from RNA polymerase II promoter  regulation of double-strand break repair via homologous recombination  regulation of mRNA export from nucleus  viral process  protein-lysine N-methyltransferase activity  peptidyl-lysine trimethylation  histone-lysine N-methyltransferase activity  histone-lysine N-methyltransferase activity  histone-lysine N-methyltransferase activity  peptidyl-lysine monomethylation  forebrain development  regulation of cytokinesis  positive regulation of interferon-alpha production  response to type I interferon  nucleosome organization  cell migration involved in vasculogenesis  endodermal cell differentiation  alpha-tubulin binding  metal ion binding  histone methyltransferase activity (H3-K36 specific)  mesoderm morphogenesis  embryonic cranial skeleton morphogenesis  stem cell differentiation  stem cell development  defense response to virus  pericardium development  embryonic placenta morphogenesis  coronary vasculature morphogenesis  histone H3-K36 trimethylation  histone H3-K36 trimethylation  histone H3-K36 dimethylation  microtubule cytoskeleton organization involved in mitosis  regulation of protein localization to chromatin  
Ontology : EGO-EBIangiogenesis  morphogenesis of a branching structure  neural tube closure  protein binding  nucleus  nucleoplasm  chromosome  mismatch repair  regulation of transcription, DNA-templated  transcription elongation from RNA polymerase II promoter  regulation of double-strand break repair via homologous recombination  regulation of mRNA export from nucleus  viral process  protein-lysine N-methyltransferase activity  peptidyl-lysine trimethylation  histone-lysine N-methyltransferase activity  histone-lysine N-methyltransferase activity  histone-lysine N-methyltransferase activity  peptidyl-lysine monomethylation  forebrain development  regulation of cytokinesis  positive regulation of interferon-alpha production  response to type I interferon  nucleosome organization  cell migration involved in vasculogenesis  endodermal cell differentiation  alpha-tubulin binding  metal ion binding  histone methyltransferase activity (H3-K36 specific)  mesoderm morphogenesis  embryonic cranial skeleton morphogenesis  stem cell differentiation  stem cell development  defense response to virus  pericardium development  embryonic placenta morphogenesis  coronary vasculature morphogenesis  histone H3-K36 trimethylation  histone H3-K36 trimethylation  histone H3-K36 dimethylation  microtubule cytoskeleton organization involved in mitosis  regulation of protein localization to chromatin  
Pathways : KEGGLysine degradation   
NDEx NetworkSETD2
Atlas of Cancer Signalling NetworkSETD2
Wikipedia pathwaysSETD2
Orthology - Evolution
OrthoDB29072
GeneTree (enSembl)ENSG00000181555
Phylogenetic Trees/Animal Genes : TreeFamSETD2
HOGENOMQ9BYW2
Homologs : HomoloGeneSETD2
Homology/Alignments : Family Browser (UCSC)SETD2
Gene fusions - Rearrangements
Fusion : MitelmanMANF/SETD2 [3p21.2/3p21.31]  
Fusion : MitelmanNEK4/SETD2 [3p21.1/3p21.31]  
Fusion : MitelmanSETD2/KIF9 [3p21.31/3p21.31]  
Fusion : MitelmanSETD2/POGLUT1 [3p21.31/3q13.33]  
Fusion : MitelmanSETD2/QRICH1 [3p21.31/3p21.31]  
Fusion : MitelmanSETD2/ULK4 [3p21.31/3p22.1]  
Fusion PortalMANF 3p21.2 SETD2 3p21.31 BRCA
Fusion PortalNEK4 3p21.1 SETD2 3p21.31 BLCA
Fusion PortalSETD2 3p21.31 KIF9 3p21.31 LUAD
Fusion PortalSETD2 3p21.31 POGLUT1 3q13.33 LUAD
Fusion PortalSETD2 3p21.31 ULK4 3p22.1 BRCA
Fusion : Fusion_HubADPRH--SETD2    APPBP2--SETD2    CCDC12--SETD2    EIF4A2--SETD2    GP2--SETD2    HN1--SETD2    KCNMA1--SETD2    KIAA0196--SETD2    KLHL2--SETD2    LIN7C--SETD2    LRRFIP2--SETD2    MACF1--SETD2    MAGI1--SETD2    MANF--SETD2    NAT6--SETD2   
NBEAL2--SETD2    NEK4--SETD2    NF1--SETD2    POLR1A--SETD2    PRDM2--SETD2    PRR11--SETD2    SETD2--AGFG1    SETD2--AHNAK    SETD2--ATF2    SETD2--ATP11B    SETD2--C10ORF76    SETD2--C6ORF89    SETD2--CCDC12    SETD2--CCRL2    SETD2--CLASP2   
SETD2--DOCK3    SETD2--DTD1    SETD2--F3    SETD2--FANCL    SETD2--GLRX3    SETD2--GNL1    SETD2--GOLGA4    SETD2--HMGCR    SETD2--KIF9    SETD2--KLHL18    SETD2--MACROD2    SETD2--MAP4    SETD2--MERTK    SETD2--NASP    SETD2--NISCH   
SETD2--PALMD    SETD2--PART1    SETD2--PIK3CA    SETD2--PIPOX    SETD2--POGLUT1    SETD2--PSMB1    SETD2--QRICH1    SETD2--RBM6    SETD2--SCAP    SETD2--SETD2    SETD2--SKIL    SETD2--SMARCC1    SETD2--SMG6    SETD2--SORBS1    SETD2--SPATA12   
SETD2--TANC1    SETD2--TLK1    SETD2--TTLL1    SETD2--ULK4    SETD2--ZC3H11A    SPIDR--SETD2    UMPS--SETD2   
Fusion : QuiverSETD2
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerSETD2 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)SETD2
dbVarSETD2
ClinVarSETD2
MonarchSETD2
1000_GenomesSETD2 
Exome Variant ServerSETD2
GNOMAD BrowserENSG00000181555
Varsome BrowserSETD2
Genetic variants : HAPMAP29072
Genomic Variants (DGV)SETD2 [DGVbeta]
DECIPHERSETD2 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisSETD2 
Mutations
ICGC Data PortalSETD2 
TCGA Data PortalSETD2 
Broad Tumor PortalSETD2
OASIS PortalSETD2 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICSETD2  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DSETD2
Mutations and Diseases : HGMDSETD2
intOGen PortalSETD2
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 SETD2
DgiDB (Drug Gene Interaction Database)SETD2
DoCM (Curated mutations)SETD2 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)SETD2 (select a term)
intoGenSETD2
OncoKBSETD2
NCG6 (London) select SETD2
Cancer3DSETD2(select the gene name)
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM612778    616831   
Orphanet588   
DisGeNETSETD2
MedgenSETD2
Genetic Testing Registry SETD2
NextProtQ9BYW2 [Medical]
TSGene29072
GENETestsSETD2
Target ValidationSETD2
Huge Navigator SETD2 [HugePedia]
snp3D : Map Gene to Disease29072
BioCentury BCIQSETD2
ClinGenSETD2
Clinical trials, drugs, therapy
Protein Interactions : CTD29072
Pharm GKB GenePA143485612
Drug Sensitivity SETD2
Clinical trialSETD2
Miscellaneous
canSAR (ICR)SETD2 (select the gene name)
HarmonizomeSETD2
DataMed IndexSETD2
Probes
Litterature
PubMed118 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineSETD2
EVEXSETD2
GoPubMedSETD2
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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