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BEX1 (brain expressed, X-linked 1)

Written2012-01Biaoyang Lin, Jing Zhang, Greg Foltz
Swedish Medical Center, Seattle, WA, USA (BL, GF); Zhejiang-California International NanoSystems Institute, Zhejiang Univ Hangzhou, China (BL, JZ)

(Note : for Links provided by Atlas : click)


Other aliasBEX2
HGNC (Hugo) BEX1
LocusID (NCBI) 55859
Atlas_Id 44161
Location Xq22.1  [Link to chromosome band Xq22]
Location_base_pair Starts at 103062653 and ends at 103064240 bp from pter ( according to hg19-Feb_2009)  [Mapping BEX1.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)


Note There was some confusion in the nomenclature of the human BEX genes. The BEX1 referred in the publications (Quentmeier et al., 2005; Yang et al., 2002) is actually BEX2. BEX2, represented by the Genbank accession number AF220189, was called BEX1 by Yang et al. and others (Quentmeier et al., 2005; Yang et al., 2002). Later on, Alvarez et al. found that AF220189 is more similar to mouse Bex2 than to mouse Bex1 (74% and 68% identical, respectively) and that its chromosomal localization matches that of mouse Bex2 (Alvarez et al., 2005). Therefore, AF220189 is considered the human homologue of mouse Bex2, and is human BEX2.
  A diagram using the UCSC genome browser showing the locations of the five BEX members in the order of BEX5-BEX1-BEX4-BEX2-NGFRAP1 (nerve growth factor receptor (TNFRSF16) associated protein 1, BEX3) on the X chromosome at Xq22.1-2, along with other genes in the region.
Description BEX1 encodes a gene belonging to the brain expressed X-linked gene family. It is a putative tumor suppressor as it is silenced in human glioma (Foltz et al., 2006). The BEX1 gene contains three exons, but the coding region is contained in one single exon.


Note Interacts with neurotrophin receptor p75NTR/NGFR (Naderi et al., 2007). Interacts with olfactory marker protein (OMP) (Koo et al., 2004).
Description The BEX1 protein (NP_060946.3) has 125 amino acid residues.
Expression Koo et al. assessed the expression pattern of Bex proteins in several different mouse tissues by western blot analysis (Koo et al., 2004). They used a polyclonal chicken antibody directed against a peptide common to the C-terminal region of mouse Bex1 and -2, which are 87% identical and 90% similar in amino acid sequences. They found that Bex1 and -2 proteins are expressed in mouse whole brain without olfactory bulb, olfactory bulb, olfactory epithelium and at a lower level in the heart, kidney, and liver but, not in the lung (Koo et al., 2004).
Localisation Nucleus and cytoplasm (Koo et al., 2004).
Function BEX1 plays a role in cell cycle progression as Bex1 levels oscillated during the cell cycle (Vilar et al., 2006). BEX1 also participates in neuronal differentiation (Vilar et al., 2006). Nerve growth factor (NGF) is a member of the neurotrophin family proteins that mediate survival, growth and differentiation of neuronal and glial cells by binding to two different types of cell surface receptors, the Trk tyrosine kinases - TrkA, TrkB and TrkC - and the p75 neurotrophin receptor (p75NTR). Vilar et al. showed that Bex1 competed with RIP2 (receptor-interacting serine-threonine kinase 2) for binding to the p75NTR intracellular domain, and elevating RIP2 levels restored the ability of cells overexpressing Bex1 to differentiate in response to NGF (Vilar et al., 2006). They further demonstrated that, in PC12 cells, Bex1 overexpression inhibited the induction of NF-kappaB activity by NGF without affecting activation of Erk1/Erk2 and AKT, while Bex1 knockdown accelerated neuronal differentiation and potentiated NF-kappaB activity in response to NGF (Vilar et al., 2006).
Homology Five BEX members have been identified in human. They are BEX1, BEX2, NGFRAP1 (nerve growth factor receptor (TNFRSF16) associated protein 1, BEX3), BEX4, and BEX5. They are all clustered on the X chromosome at Xq22.1-2 (Alvarez et al., 2005).


Note None identified.

Implicated in

Entity Glioma
Note We showed that BEX1 and BEX2 are candidate tumor suppressor genes in malignant glioma in a genome-wide analysis of epigenetic silencing in gliomas (Foltz et al., 2006). We found that BEX1 and BEX2 were reactivated by trichostatin A (TSA), a histone deacetylase inhibitor, or 5-aza-2'-deoxycytidine (5-AzaC), a DNA methyltransferase inhibitor in glioma cell line T98 and U87, and 10 patient-derived primary glioma cell lines (Foltz et al., 2006). We demonstrated that BEX1 and BEX2's expression were silenced in GBM specimens because of extensive promoter hypermethylation at their promoters. Re-expression of either BEX1 or BEX2 led to increased sensitivity to chemotherapy-induced apoptosis and potent tumor suppressor effects in vitro and in a xenograft mouse model (Foltz et al., 2006). We further showed that BEX1 and BEX2 in GBM cells were down regulated by SOX2, a key gene implicated in maintaining the stemness of embryonic and adult stem cells (Fang et al., 2011).
Disease Gliomas are the primary cancers derived from glial cells in the brain. It is the most frequent cerebral neoplasias. Astrocytomas are the most common type of gliomas. They are slow-growing, and can be found anywhere in the brain, but most often found in the cerebrum. They can be clinically divided into four grades, with glioblastoma (World Health Organization grade IV) being the most common and aggressive.


Characterization of the Bex gene family in humans, mice, and rats.
Alvarez E, Zhou W, Witta SE, Freed CR.
Gene. 2005 Aug 29;357(1):18-28.
PMID 15958283
The SOX2 response program in glioblastoma multiforme: an integrated ChIP-seq, expression microarray, and microRNA analysis.
Fang X, Yoon JG, Li L, Yu W, Shao J, Hua D, Zheng S, Hood L, Goodlett DR, Foltz G, Lin B.
BMC Genomics. 2011 Jan 6;12:11.
PMID 21211035
Genome-wide analysis of epigenetic silencing identifies BEX1 and BEX2 as candidate tumor suppressor genes in malignant glioma.
Foltz G, Ryu GY, Yoon JG, Nelson T, Fahey J, Frakes A, Lee H, Field L, Zander K, Sibenaller Z, Ryken TC, Vibhakar R, Hood L, Madan A.
Cancer Res. 2006 Jul 1;66(13):6665-74.
PMID 16818640
The interaction of Bex and OMP reveals a dimer of OMP with a short half-life.
Koo JH, Gill S, Pannell LK, Menco BP, Margolis JW, Margolis FL.
J Neurochem. 2004 Jul;90(1):102-16.
PMID 15198671
BEX2 is overexpressed in a subset of primary breast cancers and mediates nerve growth factor/nuclear factor-kappaB inhibition of apoptosis in breast cancer cell lines.
Naderi A, Teschendorff AE, Beigel J, Cariati M, Ellis IO, Brenton JD, Caldas C.
Cancer Res. 2007 Jul 15;67(14):6725-36.
PMID 17638883
Expression of BEX1 in acute myeloid leukemia with MLL rearrangements.
Quentmeier H, Tonelli R, Geffers R, Pession A, Uphoff CC, Drexler HG.
Leukemia. 2005 Aug;19(8):1488-9.
PMID 15920485
Bex1, a novel interactor of the p75 neurotrophin receptor, links neurotrophin signaling to the cell cycle.
Vilar M, Murillo-Carretero M, Mira H, Magnusson K, Besset V, Ibanez CF.
EMBO J. 2006 Mar 22;25(6):1219-30. Epub 2006 Feb 23.
PMID 16498402
Cloning and expression pattern of a spermatogenesis-related gene, BEX1, mapped to chromosome Xq22.
Yang QS, Xia F, Gu SH, Yuan HL, Chen JZ, Yang QS, Ying K, Xie Y, Mao YM.
Biochem Genet. 2002 Feb;40(1-2):1-12.
PMID 11989783


This paper should be referenced as such :
Lin, B ; Zhang, J ; Foltz, G
BEX1 (brain expressed, X-linked 1)
Atlas Genet Cytogenet Oncol Haematol. 2012;16(6):385-387.
Free journal version : [ pdf ]   [ DOI ]
On line version :

External links

HGNC (Hugo)BEX1   1036
Entrez_Gene (NCBI)BEX1  55859  brain expressed X-linked 1
AliasesBEX2; HBEX2; HGR74-h
GeneCards (Weizmann)BEX1
Ensembl hg19 (Hinxton)ENSG00000133169 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000133169 [Gene_View]  ENSG00000133169 [Sequence]  chrX:103062653-103064240 [Contig_View]  BEX1 [Vega]
ICGC DataPortalENSG00000133169
TCGA cBioPortalBEX1
AceView (NCBI)BEX1
Genatlas (Paris)BEX1
SOURCE (Princeton)BEX1
Genetics Home Reference (NIH)BEX1
Genomic and cartography
GoldenPath hg38 (UCSC)BEX1  -     chrX:103062653-103064240 -  Xq22.1|Xq22   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)BEX1  -     Xq22.1|Xq22   [Description]    (hg19-Feb_2009)
GoldenPathBEX1 - Xq22.1|Xq22 [CytoView hg19]  BEX1 - Xq22.1|Xq22 [CytoView hg38]
Mapping of homologs : NCBIBEX1 [Mapview hg19]  BEX1 [Mapview hg38]
Gene and transcription
Genbank (Entrez)AF183416 AF220189 AF237783 AK290958 AY833561
RefSeq transcript (Entrez)NM_018476
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)BEX1
Cluster EST : UnigeneHs.334370 [ NCBI ]
CGAP (NCI)Hs.334370
Alternative Splicing GalleryENSG00000133169
Gene ExpressionBEX1 [ NCBI-GEO ]   BEX1 [ EBI - ARRAY_EXPRESS ]   BEX1 [ SEEK ]   BEX1 [ MEM ]
Gene Expression Viewer (FireBrowse)BEX1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevestigatorExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)55859
GTEX Portal (Tissue expression)BEX1
Human Protein AtlasENSG00000133169-BEX1 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9HBH7   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ9HBH7  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ9HBH7
Splice isoforms : SwissVarQ9HBH7
Domains : Interpro (EBI)BEX    TF_A-like/BEX   
Domain families : Pfam (Sanger)BEX (PF04538)   
Domain families : Pfam (NCBI)pfam04538   
Conserved Domain (NCBI)BEX1
DMDM Disease mutations55859
Blocks (Seattle)BEX1
Human Protein Atlas [tissue]ENSG00000133169-BEX1 [tissue]
Peptide AtlasQ9HBH7
Protein Interaction databases
IntAct (EBI)Q9HBH7
Ontologies - Pathways
Ontology : AmiGORNA polymerase II activating transcription factor binding  protein binding  nucleus  transcription factor complex  cytoplasm  nervous system development  cell differentiation  positive regulation of transcription by RNA polymerase II  positive regulation of DNA-binding transcription factor activity  
Ontology : EGO-EBIRNA polymerase II activating transcription factor binding  protein binding  nucleus  transcription factor complex  cytoplasm  nervous system development  cell differentiation  positive regulation of transcription by RNA polymerase II  positive regulation of DNA-binding transcription factor activity  
NDEx NetworkBEX1
Atlas of Cancer Signalling NetworkBEX1
Wikipedia pathwaysBEX1
Orthology - Evolution
GeneTree (enSembl)ENSG00000133169
Phylogenetic Trees/Animal Genes : TreeFamBEX1
Homologs : HomoloGeneBEX1
Homology/Alignments : Family Browser (UCSC)BEX1
Gene fusions - Rearrangements
Fusion : Fusion_HubBEX1--BCL2    BEX1--BEX2   
Fusion : QuiverBEX1
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerBEX1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)BEX1
Exome Variant ServerBEX1
ExAC (Exome Aggregation Consortium)ENSG00000133169
GNOMAD BrowserENSG00000133169
Varsome BrowserBEX1
Genetic variants : HAPMAP55859
Genomic Variants (DGV)BEX1 [DGVbeta]
DECIPHERBEX1 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisBEX1 
ICGC Data PortalBEX1 
TCGA Data PortalBEX1 
Broad Tumor PortalBEX1
OASIS PortalBEX1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICBEX1  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DBEX1
Mutations and Diseases : HGMDBEX1
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch BEX1
DgiDB (Drug Gene Interaction Database)BEX1
DoCM (Curated mutations)BEX1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)BEX1 (select a term)
NCG5 (London)BEX1
Cancer3DBEX1(select the gene name)
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry BEX1
NextProtQ9HBH7 [Medical]
Target ValidationBEX1
Huge Navigator BEX1 [HugePedia]
snp3D : Map Gene to Disease55859
BioCentury BCIQBEX1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD55859
Chemical/Pharm GKB GenePA25340
Clinical trialBEX1
canSAR (ICR)BEX1 (select the gene name)
DataMed IndexBEX1
PubMed24 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 : Wed Nov 13 21:04:35 CET 2019

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