======= NBN =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: NBN
  * **<color #00a2e8>Official Name</color>**: nibrin
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=4683|4683]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/O60934|O60934]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=NBN&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20NBN|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/602667|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  Mutations in this gene are associated with Nijmegen breakage syndrome, an autosomal recessive chromosomal instability syndrome characterized by microcephaly, growth retardation, immunodeficiency, and cancer predisposition. The encoded protein is a member of the MRE11/RAD50 double-strand break repair complex which consists of 5 proteins. This gene product is thought to be involved in DNA double-strand break repair and DNA damage-induced checkpoint activation. [provided by RefSeq, Jul 2008]. 
  * **<color #00a2e8>UniProt Summary</color>**:  Component of the MRE11-RAD50-NBN (MRN complex) which plays a critical role in the cellular response to DNA damage and the maintenance of chromosome integrity. The complex is involved in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity, cell cycle checkpoint control and meiosis. The complex possesses single-strand endonuclease activity and double-strand-specific 3'-5' exonuclease activity, which are provided by MRE11. RAD50 may be required to bind DNA ends and hold them in close proximity. NBN modulate the DNA damage signal sensing by recruiting PI3/PI4-kinase family members ATM, ATR, and probably DNA-PKcs to the DNA damage sites and activating their functions. It can also recruit MRE11 and RAD50 to the proximity of DSBs by an interaction with the histone H2AX. NBN also functions in telomere length maintenance by generating the 3' overhang which serves as a primer for telomerase dependent telomere elongation. NBN is a major player in the control of intra-S-phase checkpoint and there is some evidence that NBN is involved in G1 and G2 checkpoints. The roles of NBS1/MRN encompass DNA damage sensor, signal transducer, and effector, which enable cells to maintain DNA integrity and genomic stability. Forms a complex with RBBP8 to link DNA double-strand break sensing to resection. Enhances AKT1 phosphorylation possibly by association with the mTORC2 complex. {ECO:0000269|PubMed:10888888, ECO:0000269|PubMed:15616588, ECO:0000269|PubMed:19759395, ECO:0000269|PubMed:23762398, ECO:0000269|PubMed:9705271}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|FHA|
|Nbs1 C|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|telomeric 3 overhang formation|
|regulation of DNA-dependent DNA replication initiation|
|Mre11 complex|
|negative regulation of telomere capping|
|t-circle formation|
|formation of extrachromosomal circular DNA|
|telomere maintenance via telomere trimming|
|nuclear inclusion body|
|blastocyst growth|
|mitotic G2 DNA damage checkpoint|
|telomere capping|
|somatic diversification of immunoglobulins involved in immune response|
|isotype switching|
|somatic recombination of immunoglobulin genes involved in immune response|
|DNA double-strand break processing|
|DNA strand elongation|
|somatic recombination of immunoglobulin gene segments|
|replication fork|
|immunoglobulin production involved in immunoglobulin mediated immune response|
|positive regulation of protein autophosphorylation|
|regulation of telomere capping|
|mitotic G2/M transition checkpoint|
|G2 DNA damage checkpoint|
|somatic diversification of immunoglobulins|
|somatic cell DNA recombination|
|somatic diversification of immune receptors via germline recombination within a single locus|
|negative regulation of telomere maintenance|
|B cell activation involved in immune response|
|regulation of protein autophosphorylation|
|somatic diversification of immune receptors|
|positive regulation of telomere maintenance|
|neuromuscular process controlling balance|
|regulation of DNA-dependent DNA replication|
|damaged DNA binding|
|site of double-strand break|
|double-strand break repair via nonhomologous end joining|
|DNA helicase activity|
|non-recombinational repair|
|DNA damage response, signal transduction by p53 class mediator|
|regulation of telomere maintenance|
|negative regulation of G2/M transition of mitotic cell cycle|
|mitotic DNA damage checkpoint|
|double-strand break repair via homologous recombination|
|blastocyst development|
|recombinational repair|
|telomere maintenance|
|PML body|
|negative regulation of cell cycle G2/M phase transition|
|telomere organization|
|mitotic DNA integrity checkpoint|
|signal transduction in response to DNA damage|
|protein N-terminus binding|
|neuromuscular process|
|regulation of DNA replication|
|nuclear chromosome, telomeric region|
|DNA duplex unwinding|
|lymphocyte activation involved in immune response|
|DNA geometric change|
|signal transduction by p53 class mediator|
|negative regulation of DNA metabolic process|
|DNA damage checkpoint|
|negative regulation of chromosome organization|
|DNA integrity checkpoint|
|cell cycle arrest|
|intrinsic apoptotic signaling pathway|
|mitotic cell cycle checkpoint|
|B cell activation|
|immunoglobulin production|
|positive regulation of chromosome organization|
|production of molecular mediator of immune response|
|double-strand break repair|
|regulation of signal transduction by p53 class mediator|
|cell cycle checkpoint|
|positive regulation of DNA metabolic process|
|regulation of G2/M transition of mitotic cell cycle|
|immunoglobulin mediated immune response|
|B cell mediated immunity|
|regulation of cell cycle G2/M phase transition|
|negative regulation of mitotic cell cycle phase transition|
|DNA replication|
|DNA recombination|
|meiotic cell cycle|
|negative regulation of cell cycle phase transition|
|lymphocyte mediated immunity|
|adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains|
|apoptotic signaling pathway|
|DNA conformation change|
|negative regulation of mitotic cell cycle|
|negative regulation of cell cycle process|
|transcription factor binding|
|anatomical structure homeostasis|
|regulation of chromosome organization|
|regulation of DNA metabolic process|
|negative regulation of organelle organization|
|in utero embryonic development|
|lymphocyte activation|
|developmental growth|
|growth|
|regulation of mitotic cell cycle phase transition|
|regulation of cell cycle phase transition|
|DNA repair|
|cell population proliferation|
|negative regulation of cell cycle|
|positive regulation of kinase activity|
|mitotic cell cycle process|
|adaptive immune response|
|positive regulation of organelle organization|
|leukocyte activation involved in immune response|
|cell activation involved in immune response|
|regulation of mitotic cell cycle|
|chordate embryonic development|
|immune system development|
|embryo development ending in birth or egg hatching|
|positive regulation of transferase activity|
|mitotic cell cycle|
|negative regulation of cellular component organization|
|DNA metabolic process|
|regulation of cell cycle process|
|leukocyte mediated immunity|
|cellular response to DNA damage stimulus|
|nucleolus|
|regulation of kinase activity|
|apoptotic process|
|leukocyte activation|
|regulation of transferase activity|
|embryo development|
|cell cycle process|
|positive regulation of protein phosphorylation|
|programmed cell death|
|positive regulation of phosphorylation|
|chromosome organization|
|cell activation|
|immune effector process|
|cell death|
|positive regulation of phosphate metabolic process|
|positive regulation of phosphorus metabolic process|
|regulation of cell cycle|
|positive regulation of cellular component organization|
|positive regulation of protein modification process|
|regulation of organelle organization|
|cell cycle|
|nervous system process|
|reproductive process|
|reproduction|
|positive regulation of catalytic activity|
|negative regulation of nucleobase-containing compound metabolic process|
|regulation of protein phosphorylation|
|regulation of phosphorylation|
|positive regulation of cellular protein metabolic process|
|homeostatic process|
|intracellular signal transduction|
|cellular response to stress|
|positive regulation of protein metabolic process|
|cellular macromolecule biosynthetic process|
|macromolecule biosynthetic process|
|positive regulation of molecular function|
|regulation of phosphate metabolic process|
|regulation of phosphorus metabolic process|
|regulation of intracellular signal transduction|
|regulation of protein modification process|
|immune response|
|positive regulation of nucleobase-containing compound metabolic process|
|system process|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='primary' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
^Screen^Score^
|[[:results:exp270|Campthothecin 0.001μM R06 exp270]]|-2.65|
|[[:results:exp350|Deferoxamine 11μM R07 exp350]]|1.74|
|[[:results:exp8|Brefeldin A 0.02μM R00 exp8]]|1.78|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:g:gemin6|GEMIN6]]|0.545|
|[[:human genes:u:uhrf1|UHRF1]]|0.508|
|[[:human genes:p:ppcs|PPCS]]|0.499|
|[[:human genes:t:thg1l|THG1L]]|0.499|
|[[:human genes:r:rad50|RAD50]]|0.493|
|[[:human genes:h:hars|HARS]]|0.474|
|[[:human genes:a:atxn10|ATXN10]]|0.471|
|[[:human genes:t:ten1|TEN1]]|0.469|
|[[:human genes:g:gtf3c6|GTF3C6]]|0.463|
|[[:human genes:s:srp14|SRP14]]|0.459|
|[[:human genes:x:xrcc2|XRCC2]]|0.459|
|[[:human genes:u:uba3|UBA3]]|0.457|
|[[:human genes:a:alg1|ALG1]]|0.455|
|[[:human genes:n:nae1|NAE1]]|0.453|
|[[:human genes:g:gemin7|GEMIN7]]|0.452|
|[[:human genes:c:chchd4|CHCHD4]]|0.449|
|[[:human genes:p:ppa2|PPA2]]|0.448|
|[[:human genes:c:cep57|CEP57]]|0.447|
|[[:human genes:g:gemin8|GEMIN8]]|0.447|
|[[:human genes:p:ppcdc|PPCDC]]|0.442|
|[[:human genes:t:trmt5|TRMT5]]|0.439|
|[[:human genes:s:slc25a26|SLC25A26]]|0.438|
|[[:human genes:d:dhrsx|DHRSX]]|0.437|
|[[:human genes:r:rtcb|RTCB]]|0.432|
|[[:human genes:t:triap1|TRIAP1]]|0.428|
|[[:human genes:p:pgm3|PGM3]]|0.427|
|[[:human genes:v:vezt|VEZT]]|0.426|
|[[:human genes:p:pik3r4|PIK3R4]]|0.423|
|[[:human genes:a:aasdhppt|AASDHPPT]]|0.423|
|[[:human genes:l:lsm10|LSM10]]|0.423|
|[[:human genes:u:uap1|UAP1]]|0.421|
|[[:human genes:r:rfk|RFK]]|0.418|
|[[:human genes:g:gmppb|GMPPB]]|0.417|
|[[:human genes:z:zrsr2|ZRSR2]]|0.414|
|[[:human genes:c:ctc1|CTC1]]|0.414|
|[[:human genes:a:alg13|ALG13]]|0.413|
|[[:human genes:r:rabggtb|RABGGTB]]|0.412|
|[[:human genes:h:hspa9|HSPA9]]|0.411|
|[[:human genes:a:adsl|ADSL]]|0.41|
|[[:human genes:d:dolk|DOLK]]|0.409|
|[[:human genes:a:atm|ATM]]|0.407|
|[[:human genes:e:elac2|ELAC2]]|0.405|
|[[:human genes:r:rpp21|RPP21]]|0.405|
|[[:human genes:p:pmm2|PMM2]]|0.405|
|[[:human genes:t:tprkb|TPRKB]]|0.404|
|[[:human genes:g:gtf3c4|GTF3C4]]|0.404|
|[[:human genes:c:c15orf41|C15orf41]]|0.403|
|[[:human genes:d:dpagt1|DPAGT1]]|0.403|
|[[:human genes:t:ttc4|TTC4]]|0.402|
|[[:human genes:r:rft1|RFT1]]|0.401|
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 0/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/26|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/16|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/16|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/9|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 4278
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 6.52 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='NBN Expression in NALM6 Cells: 6.52'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>