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

NBN (Nijmegen breakage syndrome 1)

Written2002-10Nancy Uhrhammer, Jacques-Olivier Bay, Richard A Gatti
Centre Jean-Perrin, BP 392, 63000 Clermont-Ferrand, France
This article is an update of :
1999-10Nancy Uhrhammer, Jacques-Olivier Bay, Richard A Gatti
Centre Jean-Perrin, BP 392, 63000 Clermont-Ferrand, France
1998-11Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

(Note : for Links provided by Atlas : click)

Identity

Alias (NCBI)NBS1 (Nijmegen breakage syndrome 1)
HGNC (Hugo) NBN
HGNC Alias symbATV
AT-V2
AT-V1
HGNC Previous nameNBS
 NBS1
HGNC Previous nameNijmegen breakage syndrome 1 (nibrin)
LocusID (NCBI) 4683
Atlas_Id 160
Location 8q21.3  [Link to chromosome band 8q21]
Location_base_pair Starts at 89933331 and ends at 89984667 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping NBN.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 see also, in Deep Insight section: Ataxia-Telangiectasia and variants

DNA/RNA

Description spans over 51 kb; 16 exons
Transcription 4.4 and 2.6 kb (alternative polyadenylation); open reading frame of 2265 nucleotides

Protein

Description the 754 amino acid protein is called nibrin; predicted MW 85 kDa, 95 kDa by SDS-PAGE; contains in N-term a forkhead associated domain (amino acids 24-100) and a breast cancer domain (BRCT; amino acids 105-190), both domains being found in the various DNA damage responsive cell cycle checkpoint proteins; 4 possible nuclear localization domains in the C-term half. Identified as the p95 subunit of the Rad50/Mre11/p95 double-strand DNA break repair complex. Nibrin is an essential component of this complex, and is responsible for its nuclear localization.
Expression wide; shorter transcript expressed at higher level in the testis (plays a role in DNA damage repair, though not in meiotic recombination, as ATM does)
Function member of the MRE/RAD50/nibrin double-strand break repair complex of 1600 kDa; necessary for localization of Rad50/Mre11 at DSB sites, and for the nucleolytic activities of this complex. Mice homozygous for null alleles of Nbs1 are inviable, while those with mutations corresponding to the common human mutation recapitulate the NBS phenotype. A 70 kDa protein containing the C-terminal portion of NBS1 produced from an alternative initiation site is associates with Rad50 and Mre11 and is apparently partially functional.
Homology no known homology

Mutations

Germinal missense mutations in the BRCT domain or truncating mutations downstream the BRCT are found in Nijmegen breakage syndrome (see below); most mutations are a 5 base deletion at codon 218, called 657del5, and are due to a founder effect
Somatic Missense mutations in NBS1 have been associated with childhood acute lymphoblastic leukemia.

Implicated in

Note
  
Entity Nijmegen breakage syndrome
Disease Nijmegen breakage syndrome is a chromosome instability syndrome/cancer prone disease at risk of non Hodgkin lymphomas
Cytogenetics chromosome rearrangements involving immunoglobulin superfamilly genes, in particular inv(7)(p13q35)
  

Bibliography

Chk2 activation dependence on Nbs1 after DNA damage.
Buscemi G, Savio C, Zannini L, Miccichè F, Masnada D, Nakanishi M, Tauchi H, Komatsu K, Mizutani S, Khanna K, Chen P, Concannon P, Chessa L, Delia D
Molecular and cellular biology. 2001 ; 21 (15) : 5214-5222.
PMID 11438675
 
The hMre11/hRad50 protein complex and Nijmegen breakage syndrome: linkage of double-strand break repair to the cellular DNA damage response.
Carney JP, Maser RS, Olivares H, Davis EM, Le Beau M, Yates JR 3rd, Hays L, Morgan WF, Petrini JH
Cell. 1998 ; 93 (3) : 477-486.
PMID 9590181
 
The Nijmegen breakage syndrome protein is essential for Mre11 phosphorylation upon DNA damage.
Dong Z, Zhong Q, Chen PL
The Journal of biological chemistry. 1999 ; 274 (28) : 19513-19516.
PMID 10391882
 
Nijmegen breakage syndrome cells fail to induce the p53-mediated DNA damage response following exposure to ionizing radiation.
Jongmans W, Vuillaume M, Chrzanowska K, Smeets D, Sperling K, Hall J
Molecular and cellular biology. 1997 ; 17 (9) : 5016-5022.
PMID 9271379
 
hMre11 and hRad50 nuclear foci are induced during the normal cellular response to DNA double-strand breaks.
Maser RS, Monsen KJ, Nelms BE, Petrini JH
Molecular and cellular biology. 1997 ; 17 (10) : 6087-6096.
PMID 9315668
 
An alternative mode of translation permits production of a variant NBS1 protein from the common Nijmegen breakage syndrome allele.
Maser RS, Zinkel R, Petrini JH
Nature genetics. 2001 ; 27 (4) : 417-421.
PMID 11279524
 
Positional cloning of the gene for Nijmegen breakage syndrome.
Matsuura S, Tauchi H, Nakamura A, Kondo N, Sakamoto S, Endo S, Smeets D, Solder B, Belohradsky BH, Der Kaloustian VM, Oshimura M, Isomura M, Nakamura Y, Komatsu K
Nature genetics. 1998 ; 19 (2) : 179-181.
PMID 9620777
 
Mutations in the Nijmegen Breakage Syndrome gene (NBS1) in childhood acute lymphoblastic leukemia (ALL).
Varon R, Reis A, Henze G, von Einsiedel HG, Sperling K, Seeger K
Cancer research. 2001 ; 61 (9) : 3570-3572.
PMID 11325820
 
Nibrin, a novel DNA double-strand break repair protein, is mutated in Nijmegen breakage syndrome.
Varon R, Vissinga C, Platzer M, Cerosaletti KM, Chrzanowska KH, Saar K, Beckmann G, Seemanov´ E, Cooper PR, Nowak NJ, Stumm M, Weemaes CM, Gatti RA, Wilson RK, Digweed M, Rosenthal A, Sperling K, Concannon P, Reis A
Cell. 1998 ; 93 (3) : 467-476.
PMID 9590180
 
A murine model of Nijmegen breakage syndrome.
Williams BR, Mirzoeva OK, Morgan WF, Lin J, Dunnick W, Petrini JH
Current biology : CB. 2002 ; 12 (8) : 648-653.
PMID 11967151
 
Association of BRCA1 with the hRad50-hMre11-p95 complex and the DNA damage response.
Zhong Q, Chen CF, Li S, Chen Y, Wang CC, Xiao J, Chen PL, Sharp ZD, Lee WH
Science (New York, N.Y.). 1999 ; 285 (5428) : 747-750.
PMID 10426999
 
Decreased immunoglobulin class switching in Nijmegen Breakage syndrome due to the DNA repair defect.
van Engelen BG, Hiel JA, Gabreëls FJ, van den Heuvel LP, van Gent DC, Weemaes CM
Human immunology. 2001 ; 62 (12) : 1324-1327.
PMID 11756000
 

Citation

This paper should be referenced as such :
Uhrhammer, N ; Bay, JO ; Gatti, RA
NBS1 (Nijmegen breakage syndrome 1)
Atlas Genet Cytogenet Oncol Haematol. 2003;7(1):10-11.
Free journal version : [ pdf ]   [ DOI ]
History of this paper:
Huret, JL. NBS1 (Nijmegen breakage syndrome 1). Atlas Genet Cytogenet Oncol Haematol. 1999;3(1):13-14.
http://documents.irevues.inist.fr/bitstream/handle/2042/37477/11-1998-NBS1ID160.pdf
Uhrhammer, N ; Bay, JO ; Gatti, RA. NBS1 (Nijmegen breakage syndrome 1). Atlas Genet Cytogenet Oncol Haematol. 1999;3(4):175-176.
http://documents.irevues.inist.fr/bitstream/handle/2042/37551/10-1999-NBS1ID160.pdf


Other Cancer prone implicated (Data extracted from papers in the Atlas) [ 1 ]
  Nijmegen breakage syndrome


External links

 

Nomenclature
HGNC (Hugo)NBN   7652
LRG (Locus Reference Genomic)LRG_158
Cards
AtlasNBS1ID160
Atlas Explorer : (Salamanque)NBN
Entrez_Gene (NCBI)NBN    nibrin
AliasesAT-V1; AT-V2; ATV; NBS; 
NBS1; P95
GeneCards (Weizmann)NBN
Ensembl hg19 (Hinxton)ENSG00000104320 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000104320 [Gene_View]  ENSG00000104320 [Sequence]  chr8:89933331-89984667 [Contig_View]  NBN [Vega]
ICGC DataPortalENSG00000104320
TCGA cBioPortalNBN
AceView (NCBI)NBN
Genatlas (Paris)NBN
SOURCE (Princeton)NBN
Genetics Home Reference (NIH)NBN
Genomic and cartography
GoldenPath hg38 (UCSC)NBN  -     chr8:89933331-89984667 -  8q21.3   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)NBN  -     8q21.3   [Description]    (hg19-Feb_2009)
GoldenPathNBN - 8q21.3 [CytoView hg19]  NBN - 8q21.3 [CytoView hg38]
ImmunoBaseENSG00000104320
Genome Data Viewer NCBINBN [Mapview hg19]  
OMIM251260   602667   609135   613065   
Gene and transcription
Genbank (Entrez)AF051334 AF058696 AK001017 AK223256 AK289848
RefSeq transcript (Entrez)NM_001024688 NM_002485
Consensus coding sequences : CCDS (NCBI)NBN
Gene ExpressionNBN [ NCBI-GEO ]   NBN [ EBI - ARRAY_EXPRESS ]   NBN [ SEEK ]   NBN [ MEM ]
Gene Expression Viewer (FireBrowse)NBN [ Firebrowse - Broad ]
GenevisibleExpression of NBN in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)4683
GTEX Portal (Tissue expression)NBN
Human Protein AtlasENSG00000104320-NBN [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtO60934   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtO60934  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProO60934
PhosPhoSitePlusO60934
Domaine pattern : Prosite (Expaxy)FHA_DOMAIN (PS50006)   
Domains : Interpro (EBI)BRCT_dom_sf    DNA-repair_Nbs1_C    FHA_dom    Nibrin-rel    Nibrin_BRCT2    Nibrin_BRCT2_sf    Nibrin_met    SMAD_FHA_dom_sf   
Domain families : Pfam (Sanger)FHA (PF00498)    Nbs1_C (PF08599)    NIBRIN_BRCT_II (PF16508)   
Domain families : Pfam (NCBI)pfam00498    pfam08599    pfam16508   
Domain families : Smart (EMBL)FHA (SM00240)  Nbs1_C (SM01348)  
Conserved Domain (NCBI)NBN
PDB (RSDB)5WQD   
PDB Europe5WQD   
PDB (PDBSum)5WQD   
PDB (IMB)5WQD   
Structural Biology KnowledgeBase5WQD   
SCOP (Structural Classification of Proteins)5WQD   
CATH (Classification of proteins structures)5WQD   
SuperfamilyO60934
AlphaFold pdb e-kbO60934   
Human Protein Atlas [tissue]ENSG00000104320-NBN [tissue]
HPRD04050
Protein Interaction databases
DIP (DOE-UCLA)O60934
IntAct (EBI)O60934
BioGRIDNBN
STRING (EMBL)NBN
ZODIACNBN
Ontologies - Pathways
QuickGOO60934
Ontology : AmiGODNA damage checkpoint signaling  telomere maintenance  double-strand break repair via homologous recombination  chromosome, telomeric region  chromosome, telomeric region  chromosome, telomeric region  blastocyst growth  damaged DNA binding  damaged DNA binding  protein binding  nucleus  nucleoplasm  replication fork  nucleolus  cytosol  double-strand break repair  mitotic G2 DNA damage checkpoint signaling  mitotic G2 DNA damage checkpoint signaling  cell population proliferation  PML body  regulation of DNA-dependent DNA replication initiation  DNA damage response, signal transduction by p53 class mediator  Mre11 complex  Mre11 complex  Mre11 complex  Mre11 complex  telomeric 3' overhang formation  positive regulation of protein autophosphorylation  positive regulation of telomere maintenance  DNA duplex unwinding  DNA duplex unwinding  positive regulation of kinase activity  site of double-strand break  nuclear inclusion body  isotype switching  protein N-terminus binding  neuromuscular process controlling balance  meiotic cell cycle  regulation of cell cycle  BRCA1-C complex  t-circle formation  telomere maintenance via telomere trimming  intrinsic apoptotic signaling pathway  DNA-binding transcription factor binding  negative regulation of telomere capping  
Ontology : EGO-EBIDNA damage checkpoint signaling  telomere maintenance  double-strand break repair via homologous recombination  chromosome, telomeric region  chromosome, telomeric region  chromosome, telomeric region  blastocyst growth  damaged DNA binding  damaged DNA binding  protein binding  nucleus  nucleoplasm  replication fork  nucleolus  cytosol  double-strand break repair  mitotic G2 DNA damage checkpoint signaling  mitotic G2 DNA damage checkpoint signaling  cell population proliferation  PML body  regulation of DNA-dependent DNA replication initiation  DNA damage response, signal transduction by p53 class mediator  Mre11 complex  Mre11 complex  Mre11 complex  Mre11 complex  telomeric 3' overhang formation  positive regulation of protein autophosphorylation  positive regulation of telomere maintenance  DNA duplex unwinding  DNA duplex unwinding  positive regulation of kinase activity  site of double-strand break  nuclear inclusion body  isotype switching  protein N-terminus binding  neuromuscular process controlling balance  meiotic cell cycle  regulation of cell cycle  BRCA1-C complex  t-circle formation  telomere maintenance via telomere trimming  intrinsic apoptotic signaling pathway  DNA-binding transcription factor binding  negative regulation of telomere capping  
Pathways : BIOCARTABIOCARTA_ATMPATHWAY    BIOCARTA_ATRBRCAPATHWAY   
Pathways : KEGGKEGG_HOMOLOGOUS_RECOMBINATION   
REACTOMEO60934 [protein]
REACTOME PathwaysR-HSA-912446 [pathway]   
NDEx NetworkNBN
Atlas of Cancer Signalling NetworkNBN
Wikipedia pathwaysNBN
Orthology - Evolution
OrthoDB4683
GeneTree (enSembl)ENSG00000104320
Phylogenetic Trees/Animal Genes : TreeFamNBN
Homologs : HomoloGeneNBN
Homology/Alignments : Family Browser (UCSC)NBN
Gene fusions - Rearrangements
Fusion : FusionHubDDX60L--NBN    NBN--ACTR6    NBN--ATP6V0E2    NBN--DECR1    NBN--MFNG    NBN--RHOA    NBN--RIPK2    NBN--SLC26A7    NBN--STK3    NBN--UBXN4   
SLC26A7--NBN   
Fusion : QuiverNBN
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerNBN [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)NBN
dbVarNBN
ClinVarNBN
MonarchNBN
1000_GenomesNBN 
Exome Variant ServerNBN
GNOMAD BrowserENSG00000104320
Varsome BrowserNBN
ACMGNBN variants
VarityO60934
Genomic Variants (DGV)NBN [DGVbeta]
DECIPHERNBN [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisNBN 
Mutations
ICGC Data PortalNBN 
TCGA Data PortalNBN 
Broad Tumor PortalNBN
OASIS PortalNBN [ Somatic mutations - Copy number]
Cancer Gene: CensusNBN 
Somatic Mutations in Cancer : COSMICNBN  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DNBN
Mutations and Diseases : HGMDNBN
LOVD (Leiden Open Variation Database)[gene] [transcripts] [variants]
BioMutaNBN
DgiDB (Drug Gene Interaction Database)NBN
DoCM (Curated mutations)NBN
CIViC (Clinical Interpretations of Variants in Cancer)NBN
OncoKBNBN
NCG (London)NBN
Cancer3DNBN
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM251260    602667    609135    613065   
Orphanet903    2823    3384   
DisGeNETNBN
MedgenNBN
Genetic Testing Registry NBN
NextProtO60934 [Medical]
GENETestsNBN
Target ValidationNBN
Huge Navigator NBN [HugePedia]
ClinGenNBN
Clinical trials, drugs, therapy
MyCancerGenomeNBN
Protein Interactions : CTDNBN
Pharm GKB GenePA31457
PharosO60934
Clinical trialNBN
Miscellaneous
canSAR (ICR)NBN
HarmonizomeNBN
ARCHS4NBN
DataMed IndexNBN
Probes
Litterature
PubMed499 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
EVEXNBN
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 : Thu Jan 20 14:12:49 CET 2022

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

For comments and suggestions or contributions, please contact us

jlhuret@AtlasGeneticsOncology.org.