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BAK1 (BCL2-antagonist/killer 1)

Written2010-02Grant Dewson, Ruth Kluck
The Walter, Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville 3050, Melbourne, Australia

(Note : for Links provided by Atlas : click)

Identity

Alias_namesCDN1
BCL2-antagonist/killer 1
Alias_symbol (synonym)BCL2L7
BAK
Other aliasBAK-LIKE
Bcl2-L-7
MGC117255
MGC3887
HGNC (Hugo) BAK1
LocusID (NCBI) 578
Atlas_Id 752
Location 6p21.31  [Link to chromosome band 6p21]
Location_base_pair Starts at 33572546 and ends at 33580293 bp from pter ( according to hg19-Feb_2009)  [Mapping BAK1.png]
Local_order Orientation: minus strand.
Located approximately 380 kb centromeric to the human major histocompatibility complex (MHC) class II region.
Note The BAK1 gene produces the Bak protein, a pro-apoptotic protein from the Bcl-2 protein family. Either Bak or Bax is required to permeabilize the mitochondrial outer membrane during the mitochondrial (intrinsic) pathway of apoptotic cell death. Bak is a single-pass membrane protein that localises to the mitochondrial outer membrane in healthy cells, while Bax moves to mitochondria during apoptosis. Both Bak and Bax convert to the activated, pro-apoptotic form by undergoing a large conformational change before oligomerising to form apoptotic pores in the mitochondrial outer membrane. Pore formation allows the release of cytochrome c, Smac and other proteins that promote protease (caspase) activity to kill the cell. Thus, Bak/Bax pore formation is a major point of no return in cell death. The activation of Bak (and Bax) is initiated when the cell up-regulates the pro-apoptotic BH3-only members of the Bcl-2 family. Bak activation is blocked if sufficient prosurvival (anti-apoptotic) Bcl-2 family members (e.g. Bcl-xL, Mcl-1, Bcl-2 and A1) are present to sequester the BH3-only proteins and also perhaps the activated Bak and Bax proteins. As cancer cells often express high levels of these prosurvival proteins, several agents that target the prosurvival proteins are being developed as novel cancer therapeutics.

DNA/RNA

Description The BAK1 gene, with 7748 bases in length, and contains 6 exons. The first exon is non-coding, and most of the largest, final exon is untranslated.
Transcription The BAK1 gene transcribes a 211 aa protein Bak. A possible 101 aa splice variant, called BAK-like, contains BH1, BH2 and TM domains, but no BH3 domain, with a 2.4 kb transcript of BAK-like detected in most human tissues and exhibiting pro-apoptotic activity. Two other human BAK1 mRNA variants are present in GenBak but may not be expressed: the BakM variant would be 190 aa and lack 21 amino acids in the linker region between alpha-helices 1 and 2; another would be 153 aa with the stop codon upstream of a splice junction and therefore predicted to be subject to nonsense-mediated mRNA decay. However in mice, a similar 151 aa N-Bak that contains only the BH3 domain is reportedly expressed in neurons.
Pseudogene There are two pseudogenes: Bak2 (chromosome 20) and Bak3 (chromosome 11).

Protein

Note The BAK1 gene encodes for a 23409 Da protein, named Bak. The Bak cDNA was isolated by three groups by virtue of its protein product interacting with the adenovirus E1B 19K protein, or its homology to the BH1 and BH2 domains of Bcl-2. The BH3 domain of Bak is essential for its binding to a hydrophobic surface groove on the prosurvival proteins Bcl-xL and Mcl-1. The Bak BH3 domain is also important for binding to a similar hydrophobic groove in another activated Bak molecule to form Bak oligomers and the formation of pores.
 
  The human Bak protein is 211 aa in length. Bcl-2 homology (BH) domains indicate regions of sequence homology with other Bcl-2 family members, with the BH3 domain being present in all members. The structure of non-activated Bak is similar to that of the prosurvival Bcl-2 family members, with alpha helices 1-9 indicated. The oligomerization domain is important for homo-oligomerization and pore formation, while the transmembrane domain anchors Bak in the mitochondrial outer membrane.
Expression BAK1 mRNA is expressed widely in different tissues as an approximately 2.4 kb transcript. Highest mRNA levels are in the heart and skeletal muscle.
Localisation The Bak protein is inserted in the mitochondrial outer membrane in healthy cells, while its close homologue Bax translocates to mitochondria after an apoptotic stimulus. A small proportion of Bak has also been detected at the endoplasmic reticulum membrane.
Function Bak (or Bax) is required to form pores in the mitochondrial outer membrane during apoptotic cell death. The killing activity of Bak is regulated by other members of the Bcl-2 family. For example, certain BH3-only proteins (Bim and Bid) are reported to directly bind Bak to convert it into the activated conformation, while the prosurvival proteins (e.g. Bcl-xL and Mcl-1) can sequester activated Bak and so prevent Bak homo-oligomerization and pore formation. The role of Bak at the ER membrane is unclear.
Homology Human Bak shares 99.5% amino acid identity with Pan troglodytes, 91.9% identity with Canis lupus familiaris, 86.2% with Bos taurus, 77.2% with Rattus norvegicus. BAK1 is not found in the Danio rerio genome. Human Bak has 53% amino-acid sequence identity with the BH1 and BH2 domains of Bcl-2. Over the full sequence, Bak is 25, 33 and 19% identical to Bcl-2, Bcl-xL and Bax, respectively.

Mutations

Note Several Bak single point mutations have been associated with autoimmune diseases, aortic aneurysms, and cervical, colorectal and gastric cancers, although the causal relationship is not clear. In addition, around 200 SNPs, with unknown clinical association have been reported in Entrez SNP database.
Somatic Somatic mutations were increased in uterine cervical carcinoma (6 from 42) compared with non-neoplastic tissue (0 from 32). While an early study reported somatic mutations in 17% of samples of colorectal and gastric cancers in Korean patients, a later study reported no somatic mutations in 192 colorectal and gastric cancers.

Implicated in

Note
  
Entity Lymphoma and leukemia
Note Lymphomas and leukemias have high levels of Bcl-2 prosurvival proteins that prevent Bak (and Bax) from inducing apoptosis. New anti-cancer therapies that target prosurvival proteins can activate Bak (or Bax) to re-instate apoptotic cell death. In one example, a new drug, GX15-070, was found to induce apoptosis in mantle cell lymphoma cell lines by binding to Mcl-1 and assist in Bak activation (Pérez-Galán et al., 2007). This drug is in clinical trials for refractory chronic lymphocytic leukemia (Storey, 2008), and is presumably acting by indirectly activating Bak (or Bax).
  
  
Entity Gastric and colorectal cancer
Note The first report of Bak mutations being associated with gastrointestinal cancers was of missense BAK1 mutations in 3 of 24 gastric cancers and 2 of 20 colorectal cancers, with mutations observed only in advanced-stage cancers (Kondo et al., 2000). In another study, BAK1 mutations were also rare (3/107) in patients with gastric adenocarcinomas, and were each associated with late stage disease (Kim et al., 2003). However, no somatic mutations were found in 192 patients with colorectal and gastric cancers, and the rare single-nucleotide substitutions (4/129) were also found in the corresponding normal tissue samples (Sakamoto et al., 2004).
  
  
Entity Uterine cervical carcinoma
Note Possible role for Bak mutation in uterine cervical carcinoma was reported (Wani et al., 2003). In a study of 42 patients, 6 missense (M60V, D30N, D57N, V74M, I80T and V191A) and one silent mutations in the coding region of BAK1 were found, with no mutations detected in 32 non-neoplastic cervix tissue samples. Mutations were associated with late-stage disease and with resistance to chemotherapy, but were not statistically significant due to sample size.
  
  
Entity Melanoma
Note In patients with superficial-spreading melanoma high Bak levels corresponded to improved survival (10-year survival of 62%), while low Bak correlated with low survival (10-year survival of 10%) (Fecker et al., 2006). Bax levels correlated in a similar way.
  
  
Entity Autoimmune diseases
Note Severe autoimmune disease occurs in adult mice following deletion of both Bak and its close relative Bax (Takeuchi et al., 2005). The mice accumulate excess memory B- and T-cells in lymphoid and mesenchymal organs, leading to hepato-splenomegaly, lymphadenopathy, and thymic selection impairment. In humans, similar deletion of two copies of BAK1 (and BAX) does not occur, however less marked changes in Bak protein levels, as well as BAK1 mutations, have been associated with autoimmune disease in rare cases (see below).
  
  
Entity Sjogren's syndrome
Note The Bak protein and its gene mutation may participate in the pathology and susceptibility of Sjogren's syndrome, as Bak was over-expressed in patient autoimmune lesions (Anaya et al., 2005). In a later study three polymorphisms in BAK1 were associated with Sjogren's syndrome (Delgado-Vega et al., 2009).
  
  
Entity Coeliac disease
Note A significant increase in Bak mRNA and protein levels was found in the intestinal lesions of patients with untreated coeliac disease (Chernavsky et al., 2002). The increase in Bak and in apoptosis of enterocytes may be due to increased IFN-gamma signalling.
  
  
Entity Graves' disease
Note Differential expression of Bak (and Bcl-2 and Bax) was associated with apoptosis in thyrocytes and lymphoid follicles, implicating Bak in the pathology of Grave's disease (Hiromatsu et al., 2004).
  
  
Entity Multiple sclerosis
Note Bak mRNA levels were increased in the autoimmune lesions of patients with multiple sclerosis (Banisor and Kalman, 2004).
  
  
Entity Ataxia telangiectasia
Note BAK1 mutations were observed in 8 of 50 patients with ataxia telangiectasia, and were each a silent mutation in exon 2 in codon 14 (TGC>TGT), while none of the healthy controls had such an alteration (Isaian et al., 2009).
  
  
Entity Transient platelet loss
Note Bak can be activated to kill platelets as a side effect of new anti-cancer treatments (Mason et al., 2007; Oltersdorf et al., 2005). The small molecule ABT-737 is a BH3-mimetic that binds specifically to prosurvival proteins (Bcl-2, Bcl-xL, Bcl-w) that are commonly over-expressed in cancers. As platelets contain Bcl-xL as the predominant prosurvival protein guarding Bak, ABT-737 causes Bak activation and transient loss of platelets.
  
  
Entity Age-related hearing loss
Note In mice, Bak-mediated apoptosis exacerbated age-related hearing loss (Someya et al., 2009; Someya et al., 2007). Moreover, hearing loss was decreased if Bak was deleted, if mice were kept on a calorie restriction diet, or given oral supplementation with antioxidants. In keeping with oxidative stress was proposed to induce Bak expression in primary cells from cochlear cells.
  
  
Entity Aortic aneurysms
Note A possible role for Bak mutation in aortic aneurysms was evident in a study of 31 patients with abdominal aortic aneurysms (Gottlieb et al., 2009). Two single nucleotide polymorphisms (R42H and V52A) in the BAK1 gene were present in both diseased (31 cases) and healthy aortic tissue (5 cases), but not in matching blood samples. The authors propose that multiple variants of a gene such as BAK1 might pre-exist within disease-susceptible tissues, and can be selected for during disease progression.
  

To be noted

The Bak protein plays a role in many diseases due to its central role in apoptotic cell death. However, most Bak dysregulation is not due to mutations in Bak, but rather to altered expression or mutation of Bak regulators (e.g. Bcl-xL and Mcl-1). If Bak (and its homologue Bax) fail to activate and form a pore in mitochondria, the cell may survive when it was meant to die, and so contribute to cancer. In the opposite scenario, if Bak (or Bax) is activated inappropriately and mitochondria are permeabilized, excessive cell death can occur, for example, in neurodegenerative disease, autoimmune disease, and platelet loss following anti-cancer treatments. Agents that can trigger Bak-mediated apoptosis in a non-targeted way include most anti-cancer agents, while agents that may trigger Bak (and Bax) indirectly by targeting Bcl-2, Bcl-xL, Bcl-w, Mcl-1 and A1, include antisense, antibody and small molecule approaches (Storey, 2008).

Bibliography

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PMID 17035996
 
Modulation of apoptosis by the widely distributed Bcl-2 homologue Bak.
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PMID 7715731
 
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PMID 15003505
 
Mutations of the BAK gene are infrequent in advanced gastric adenocarcinomas in Koreans.
Kim SP, Hwang MS, Cho YR, Kwon SY, Kang YN, Kim IH, Sohn SS, Mun KC, Kwon TK, Lee SR, Suh SI.
Cancer Lett. 2003 May 30;195(1):87-91.
PMID 12767516
 
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Citation

This paper should be referenced as such :
Dewson, G ; Kluck, R
BAK1 (BCL2-antagonist/killer 1)
Atlas Genet Cytogenet Oncol Haematol. 2010;14(11):1070-1074.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/BAK1ID752ch6p21.html

Other Leukemias implicated (Data extracted from papers in the Atlas) [ 1 ]
  Double Hit Lymphoma (DHL)::Triple Hit Lymphoma (THL)

External links

Nomenclature
HGNC (Hugo)BAK1   949
Cards
AtlasBAK1ID752ch6p21
Entrez_Gene (NCBI)BAK1  578  BCL2 antagonist/killer 1
AliasesBAK; BAK-LIKE; BCL2L7; CDN1
GeneCards (Weizmann)BAK1
Ensembl hg19 (Hinxton)ENSG00000030110 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000030110 [Gene_View]  chr6:33572546-33580293 [Contig_View]  BAK1 [Vega]
ICGC DataPortalENSG00000030110
TCGA cBioPortalBAK1
AceView (NCBI)BAK1
Genatlas (Paris)BAK1
WikiGenes578
SOURCE (Princeton)BAK1
Genetics Home Reference (NIH)BAK1
Genomic and cartography
GoldenPath hg38 (UCSC)BAK1  -     chr6:33572546-33580293 -  6p21.31   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)BAK1  -     6p21.31   [Description]    (hg19-Feb_2009)
EnsemblBAK1 - 6p21.31 [CytoView hg19]  BAK1 - 6p21.31 [CytoView hg38]
Mapping of homologs : NCBIBAK1 [Mapview hg19]  BAK1 [Mapview hg38]
OMIM600516   
Gene and transcription
Genbank (Entrez)AF520590 AK091807 AK292093 AK293547 AK303422
RefSeq transcript (Entrez)NM_001188
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)BAK1
Cluster EST : UnigeneHs.485139 [ NCBI ]
CGAP (NCI)Hs.485139
Alternative Splicing GalleryENSG00000030110
Gene ExpressionBAK1 [ NCBI-GEO ]   BAK1 [ EBI - ARRAY_EXPRESS ]   BAK1 [ SEEK ]   BAK1 [ MEM ]
Gene Expression Viewer (FireBrowse)BAK1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)578
GTEX Portal (Tissue expression)BAK1
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ16611   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ16611  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ16611
Splice isoforms : SwissVarQ16611
PhosPhoSitePlusQ16611
Domaine pattern : Prosite (Expaxy)BCL2_FAMILY (PS50062)    BH1 (PS01080)    BH2 (PS01258)    BH3 (PS01259)   
Domains : Interpro (EBI)BAK    Bcl2-like    Bcl2_BH1_motif_CS    Bcl2_BH2_motif_CS    Bcl2_BH3_motif_CS    Blc2_fam   
Domain families : Pfam (Sanger)Bcl-2 (PF00452)   
Domain families : Pfam (NCBI)pfam00452   
Conserved Domain (NCBI)BAK1
DMDM Disease mutations578
Blocks (Seattle)BAK1
PDB (SRS)1BXL    2IMS    2IMT    2JBY    2JCN    2LP8    2M5B    2XPX    2YV6    3I1H    3QBR    4D2L    4U2U    4U2V    4UF1    5AJK    5FMI    5FMK   
PDB (PDBSum)1BXL    2IMS    2IMT    2JBY    2JCN    2LP8    2M5B    2XPX    2YV6    3I1H    3QBR    4D2L    4U2U    4U2V    4UF1    5AJK    5FMI    5FMK   
PDB (IMB)1BXL    2IMS    2IMT    2JBY    2JCN    2LP8    2M5B    2XPX    2YV6    3I1H    3QBR    4D2L    4U2U    4U2V    4UF1    5AJK    5FMI    5FMK   
PDB (RSDB)1BXL    2IMS    2IMT    2JBY    2JCN    2LP8    2M5B    2XPX    2YV6    3I1H    3QBR    4D2L    4U2U    4U2V    4UF1    5AJK    5FMI    5FMK   
Structural Biology KnowledgeBase1BXL    2IMS    2IMT    2JBY    2JCN    2LP8    2M5B    2XPX    2YV6    3I1H    3QBR    4D2L    4U2U    4U2V    4UF1    5AJK    5FMI    5FMK   
SCOP (Structural Classification of Proteins)1BXL    2IMS    2IMT    2JBY    2JCN    2LP8    2M5B    2XPX    2YV6    3I1H    3QBR    4D2L    4U2U    4U2V    4UF1    5AJK    5FMI    5FMK   
CATH (Classification of proteins structures)1BXL    2IMS    2IMT    2JBY    2JCN    2LP8    2M5B    2XPX    2YV6    3I1H    3QBR    4D2L    4U2U    4U2V    4UF1    5AJK    5FMI    5FMK   
SuperfamilyQ16611
Human Protein AtlasENSG00000030110
Peptide AtlasQ16611
HPRD02744
IPIIPI00910780   IPI00953562   IPI00386229   IPI00924856   
Protein Interaction databases
DIP (DOE-UCLA)Q16611
IntAct (EBI)Q16611
FunCoupENSG00000030110
BioGRIDBAK1
STRING (EMBL)BAK1
ZODIACBAK1
Ontologies - Pathways
QuickGOQ16611
Ontology : AmiGOB cell homeostasis  B cell apoptotic process  release of cytochrome c from mitochondria  release of cytochrome c from mitochondria  blood vessel remodeling  myeloid cell homeostasis  B cell negative selection  molecular_function  protein binding  mitochondrion  mitochondrial outer membrane  endoplasmic reticulum  cytosol  apoptotic process  activation of signaling protein activity involved in unfolded protein response  brain development  aging  mitochondrial fusion  cell proliferation  negative regulation of cell proliferation  intrinsic apoptotic signaling pathway in response to DNA damage  activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c  response to fungus  response to mycotoxin  response to UV-C  establishment or maintenance of transmembrane electrochemical gradient  response to gamma radiation  positive regulation of calcium ion transport into cytosol  negative regulation of gene expression  response to organic cyclic compound  cytolysis  endocrine pancreas development  heat shock protein binding  animal organ regeneration  integral component of mitochondrial outer membrane  endoplasmic reticulum calcium ion homeostasis  negative regulation of endoplasmic reticulum calcium ion concentration  negative regulation of peptidyl-serine phosphorylation  cellular response to UV  cellular response to UV  limb morphogenesis  response to drug  response to hydrogen peroxide  identical protein binding  protein homodimerization activity  positive regulation of apoptotic process  positive regulation of apoptotic process  regulation of protein homodimerization activity  regulation of protein heterodimerization activity  ion channel binding  fibroblast apoptotic process  response to ethanol  positive regulation of proteolysis  metal ion binding  regulation of mitochondrial membrane permeability  pore complex  protein heterodimerization activity  post-embryonic camera-type eye morphogenesis  chaperone binding  BH domain binding  regulation of cell cycle  regulation of mitochondrial membrane potential  vagina development  intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress  thymocyte apoptotic process  cellular response to mechanical stimulus  positive regulation of release of cytochrome c from mitochondria  apoptotic signaling pathway  extrinsic apoptotic signaling pathway in absence of ligand  activation of cysteine-type endopeptidase activity  positive regulation of endoplasmic reticulum unfolded protein response  positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway  apoptotic process involved in blood vessel morphogenesis  positive regulation of IRE1-mediated unfolded protein response  
Ontology : EGO-EBIB cell homeostasis  B cell apoptotic process  release of cytochrome c from mitochondria  release of cytochrome c from mitochondria  blood vessel remodeling  myeloid cell homeostasis  B cell negative selection  molecular_function  protein binding  mitochondrion  mitochondrial outer membrane  endoplasmic reticulum  cytosol  apoptotic process  activation of signaling protein activity involved in unfolded protein response  brain development  aging  mitochondrial fusion  cell proliferation  negative regulation of cell proliferation  intrinsic apoptotic signaling pathway in response to DNA damage  activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c  response to fungus  response to mycotoxin  response to UV-C  establishment or maintenance of transmembrane electrochemical gradient  response to gamma radiation  positive regulation of calcium ion transport into cytosol  negative regulation of gene expression  response to organic cyclic compound  cytolysis  endocrine pancreas development  heat shock protein binding  animal organ regeneration  integral component of mitochondrial outer membrane  endoplasmic reticulum calcium ion homeostasis  negative regulation of endoplasmic reticulum calcium ion concentration  negative regulation of peptidyl-serine phosphorylation  cellular response to UV  cellular response to UV  limb morphogenesis  response to drug  response to hydrogen peroxide  identical protein binding  protein homodimerization activity  positive regulation of apoptotic process  positive regulation of apoptotic process  regulation of protein homodimerization activity  regulation of protein heterodimerization activity  ion channel binding  fibroblast apoptotic process  response to ethanol  positive regulation of proteolysis  metal ion binding  regulation of mitochondrial membrane permeability  pore complex  protein heterodimerization activity  post-embryonic camera-type eye morphogenesis  chaperone binding  BH domain binding  regulation of cell cycle  regulation of mitochondrial membrane potential  vagina development  intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress  thymocyte apoptotic process  cellular response to mechanical stimulus  positive regulation of release of cytochrome c from mitochondria  apoptotic signaling pathway  extrinsic apoptotic signaling pathway in absence of ligand  activation of cysteine-type endopeptidase activity  positive regulation of endoplasmic reticulum unfolded protein response  positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway  apoptotic process involved in blood vessel morphogenesis  positive regulation of IRE1-mediated unfolded protein response  
Pathways : BIOCARTARole of Mitochondria in Apoptotic Signaling [Genes]   
Pathways : KEGGProtein processing in endoplasmic reticulum    Viral carcinogenesis    MicroRNAs in cancer   
REACTOMEQ16611 [protein]
REACTOME PathwaysR-HSA-111452 [pathway]   
NDEx NetworkBAK1
Atlas of Cancer Signalling NetworkBAK1
Wikipedia pathwaysBAK1
Orthology - Evolution
OrthoDB578
GeneTree (enSembl)ENSG00000030110
Phylogenetic Trees/Animal Genes : TreeFamBAK1
HOVERGENQ16611
HOGENOMQ16611
Homologs : HomoloGeneBAK1
Homology/Alignments : Family Browser (UCSC)BAK1
Gene fusions - Rearrangements
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerBAK1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)BAK1
dbVarBAK1
ClinVarBAK1
1000_GenomesBAK1 
Exome Variant ServerBAK1
ExAC (Exome Aggregation Consortium)BAK1 (select the gene name)
Genetic variants : HAPMAP578
Genomic Variants (DGV)BAK1 [DGVbeta]
DECIPHERBAK1 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisBAK1 
Mutations
ICGC Data PortalBAK1 
TCGA Data PortalBAK1 
Broad Tumor PortalBAK1
OASIS PortalBAK1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICBAK1  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDBAK1
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)MSeqDR-LSDB Mitochondrial Disease Locus Specific Database
BioMutasearch BAK1
DgiDB (Drug Gene Interaction Database)BAK1
DoCM (Curated mutations)BAK1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)BAK1 (select a term)
intoGenBAK1
NCG5 (London)BAK1
Cancer3DBAK1(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM600516   
Orphanet
MedgenBAK1
Genetic Testing Registry BAK1
NextProtQ16611 [Medical]
TSGene578
GENETestsBAK1
Target ValidationBAK1
Huge Navigator BAK1 [HugePedia]
snp3D : Map Gene to Disease578
BioCentury BCIQBAK1
ClinGenBAK1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD578
Chemical/Pharm GKB GenePA25253
Clinical trialBAK1
Miscellaneous
canSAR (ICR)BAK1 (select the gene name)
Other databaseBcl-2 Family Database
Other databaseDeathbase
Probes
Litterature
PubMed290 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineBAK1
EVEXBAK1
GoPubMedBAK1
iHOPBAK1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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