NBN (Nijmegen breakage syndrome 1)

2002-10-01 Nancy Uhrhammer , Jacques-Olivier Bay , Richard A Gatti Affiliation

Centre Jean-Perrin, BP 392, 63000 Clermont-Ferrand, France

Identity

HGNC

NBN

LOCATION

8q21.3

LOCUSID

4683

ALIAS

AT-V1,AT-V2,ATV,NBS,NBS1,P95

DNA/RNA

Description

spans over 51 kb; 16 exons

Transcription

4.4 and 2.6 kb (alternative polyadenylation); open reading frame of 2265 nucleotides

Proteins

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

Entity name

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)

Article Bibliography

Pubmed ID	Last Year	Title	Authors
11438675	2001	Chk2 activation dependence on Nbs1 after DNA damage.	Buscemi G et al
9590181	1998	The hMre11/hRad50 protein complex and Nijmegen breakage syndrome: linkage of double-strand break repair to the cellular DNA damage response.	Carney JP et al
10391882	1999	The Nijmegen breakage syndrome protein is essential for Mre11 phosphorylation upon DNA damage.	Dong Z et al
9271379	1997	Nijmegen breakage syndrome cells fail to induce the p53-mediated DNA damage response following exposure to ionizing radiation.	Jongmans W et al
9315668	1997	hMre11 and hRad50 nuclear foci are induced during the normal cellular response to DNA double-strand breaks.	Maser RS et al
11279524	2001	An alternative mode of translation permits production of a variant NBS1 protein from the common Nijmegen breakage syndrome allele.	Maser RS et al
9620777	1998	Positional cloning of the gene for Nijmegen breakage syndrome.	Matsuura S et al
11325820	2001	Mutations in the Nijmegen Breakage Syndrome gene (NBS1) in childhood acute lymphoblastic leukemia (ALL).	Varon R et al
9590180	1998	Nibrin, a novel DNA double-strand break repair protein, is mutated in Nijmegen breakage syndrome.	Varon R et al
11967151	2002	A murine model of Nijmegen breakage syndrome.	Williams BR et al
10426999	1999	Association of BRCA1 with the hRad50-hMre11-p95 complex and the DNA damage response.	Zhong Q et al
11756000	2001	Decreased immunoglobulin class switching in Nijmegen Breakage syndrome due to the DNA repair defect.	van Engelen BG et al

Other Information

Locus ID:

NCBI: 4683
MIM: 602667
HGNC: 7652
Ensembl: ENSG00000104320

Variants:

dbSNP: 4683
ClinVar: 4683
TCGA: ENSG00000104320
COSMIC: NBN

RNA/Proteins

Gene ID	Transcript ID	Uniprot
ENSG00000104320	ENST00000265433	O60934
ENSG00000104320	ENST00000396252	E2QRP0
ENSG00000104320	ENST00000409330	A0A0C4DG07
ENSG00000104320	ENST00000517337	E5RGN7
ENSG00000104320	ENST00000517772	E5RGR7
ENSG00000104320	ENST00000519426	E5RGU1
ENSG00000104320	ENST00000523444	E2QRP0
ENSG00000104320	ENST00000613033	A0A087X1V5

Expression (GTEx)

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Pathways

Pathway	Source	External ID
Homologous recombination	KEGG	ko03440
Homologous recombination	KEGG	hsa03440
MRN complex	KEGG	hsa_M00291
BRCA1-associated genome surveillance complex (BASC)	KEGG	hsa_M00295
MRN complex	KEGG	M00291
BRCA1-associated genome surveillance complex (BASC)	KEGG	M00295
Gene Expression	REACTOME	R-HSA-74160
Generic Transcription Pathway	REACTOME	R-HSA-212436
Transcriptional Regulation by TP53	REACTOME	R-HSA-3700989
Cell Cycle	REACTOME	R-HSA-1640170
Cell Cycle Checkpoints	REACTOME	R-HSA-69620
G2/M Checkpoints	REACTOME	R-HSA-69481
G2/M DNA damage checkpoint	REACTOME	R-HSA-69473
Meiosis	REACTOME	R-HSA-1500620
Meiotic recombination	REACTOME	R-HSA-912446
DNA Repair	REACTOME	R-HSA-73894
Cellular responses to stress	REACTOME	R-HSA-2262752
Cellular Senescence	REACTOME	R-HSA-2559583
DNA Damage/Telomere Stress Induced Senescence	REACTOME	R-HSA-2559586
DNA Double-Strand Break Repair	REACTOME	R-HSA-5693532
DNA Double Strand Break Response	REACTOME	R-HSA-5693606
Sensing of DNA Double Strand Breaks	REACTOME	R-HSA-5693548
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks	REACTOME	R-HSA-5693565
Homology Directed Repair	REACTOME	R-HSA-5693538
HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA)	REACTOME	R-HSA-5693567
Processing of DNA double-strand break ends	REACTOME	R-HSA-5693607
HDR through Homologous Recombination (HRR)	REACTOME	R-HSA-5685942
Homologous DNA Pairing and Strand Exchange	REACTOME	R-HSA-5693579
Presynaptic phase of homologous DNA pairing and strand exchange	REACTOME	R-HSA-5693616
Resolution of D-Loop Structures	REACTOME	R-HSA-5693537
Resolution of D-loop Structures through Holliday Junction Intermediates	REACTOME	R-HSA-5693568
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	REACTOME	R-HSA-5693554
HDR through Single Strand Annealing (SSA)	REACTOME	R-HSA-5685938
HDR through MMEJ (alt-NHEJ)	REACTOME	R-HSA-5685939
Nonhomologous End-Joining (NHEJ)	REACTOME	R-HSA-5693571
Regulation of TP53 Activity	REACTOME	R-HSA-5633007
Regulation of TP53 Activity through Phosphorylation	REACTOME	R-HSA-6804756

Protein levels (Protein atlas)

Not detected

Low

Medium

High

References

Pubmed ID	Year	Title	Citations
38192153	2024	Suppression of NBS1 Upregulates CyclinB to Induce Olaparib Sensitivity in Ovarian Cancer.	0
38192153	2024	Suppression of NBS1 Upregulates CyclinB to Induce Olaparib Sensitivity in Ovarian Cancer.	0
36346689	2023	NBN Pathogenic Germline Variants are Associated with Pan-Cancer Susceptibility and In Vitro DNA Damage Response Defects.	3
36806726	2023	The NBN founder mutation-Evidence for a country specific difference in age at cancer manifestation.	0
37006067	2023	XRCC3 and NBS1 gene polymorphisms modulate the risk of pre-oral cancer and oral cancer in the North Indian population.	1
37296499	2023	Simultaneous Nbs1 and p53 inactivation in neural progenitors triggers high-grade gliomas.	1
36346689	2023	NBN Pathogenic Germline Variants are Associated with Pan-Cancer Susceptibility and In Vitro DNA Damage Response Defects.	3
36806726	2023	The NBN founder mutation-Evidence for a country specific difference in age at cancer manifestation.	0
37006067	2023	XRCC3 and NBS1 gene polymorphisms modulate the risk of pre-oral cancer and oral cancer in the North Indian population.	1
37296499	2023	Simultaneous Nbs1 and p53 inactivation in neural progenitors triggers high-grade gliomas.	1
34674288	2022	Association of germline rare pathogenic mutations in guideline-recommended genes with prostate cancer progression: A meta-analysis.	4
35019694	2022	Disruption of NBS1/MRN Complex Formation by E4orf3 Supports NF-κB That Licenses E1B55K-Deleted Adenovirus-Infected Cells to Accumulate DNA>4n.	4
35076389	2022	Structure of the human ATM kinase and mechanism of Nbs1 binding.	16
35164849	2022	Association of DNA repair genes polymorphisms with childhood acute lymphoblastic leukemia: a high-resolution melting analysis.	0
34674288	2022	Association of germline rare pathogenic mutations in guideline-recommended genes with prostate cancer progression: A meta-analysis.	4

Citation

Nancy Uhrhammer ; Jacques-Olivier Bay ; Richard A Gatti

NBN (Nijmegen breakage syndrome 1)

Atlas Genet Cytogenet Oncol Haematol. 2002-10-01

Online version: http://atlasgeneticsoncology.org/gene/160/nbn-(nijmegen-breakage-syndrome-1)

Historical Card

1999-10-01 NBN (Nijmegen breakage syndrome 1) by Nancy Uhrhammer,Jacques-Olivier Bay,Richard A Gatti Affiliation

Centre Jean-Perrin, BP 392, 63000 Clermont-Ferrand, France

1998-11-01 NBN (Nijmegen breakage syndrome 1) by Jean-Loup Huret Affiliation

Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France