NBN

Chr 8

nibrin

Also known as: AT-V1, AT-V2, ATV, NBS, NBS1, P95, hNbs1

NCBI Gene: 4683ENSG00000104320UniProt: O60934

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]

Primary Disease Associations & Inheritance

UniProtNijmegen breakage syndrome
UniProtBreast cancer
UniProtAplastic anemia
484
ClinVar variants
68
Pathogenic / LP
0.00
pLI score
12
Active trials
Clinical Summary— NBN
🧬
Gene-Disease Validity (ClinGen)
hereditary breast carcinoma · ADRefuted

Refuted — evidence has disproved this relationship

2 total gene-disease associations curated

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
68 Pathogenic / Likely Pathogenic· 289 VUS of 484 total submissions
💊
Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available
Some data sources returned errors (2)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.01LOEUF
pLI 0.000
Z-score 1.50
OE 0.74 (0.56–1.01)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.61Z-score
OE missense 0.91 (0.83–1.00)
344 obs / 377.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.74 (0.56–1.01)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.91 (0.83–1.00)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.07
0≤1.21.6
LoF obs/exp: 30 / 40.3Missense obs/exp: 344 / 377.3Syn Z: -0.68

ClinVar Variant Classifications

484 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic49
Likely Pathogenic19
VUS289
Likely Benign125
Conflicting2
49
Pathogenic
19
Likely Pathogenic
289
VUS
125
Likely Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
22
0
27
0
49
Likely Pathogenic
9
2
8
0
19
VUS
4
255
26
4
289
Likely Benign
0
8
49
68
125
Benign
0
0
0
0
0
Conflicting
—2
Total3526511072484

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

NBN · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

NBN-related Nijmegen breakage syndrome

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

📖
GeneReview available — NBN
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Antipsychotic Drugs: A Concise Review of History, Classification, Indications, Mechanism, Efficacy, Side Effects, Dosing, and Clinical Application.
Leucht S et al.·Am J Psychiatry
2024Review
Homologous Recombination Deficiencies and Hereditary Tumors.
Yamamoto H et al.·Int J Mol Sci
2021Review
Treatment-resistant OCD: Pharmacotherapies in adults.
van Roessel PJ et al.·Compr Psychiatry
2023Review
A Population-Based Study of Genes Previously Implicated in Breast Cancer.
Hu C et al.·N Engl J Med
2021
Hereditary Ovarian Carcinoma: Cancer Pathogenesis Looking beyond BRCA1 and BRCA2.
Samuel D et al.·Cells
2022Review
Germline Mutations in the BRIP1, BARD1, PALB2, and NBN Genes in Women With Ovarian Cancer.
Ramus SJ et al.·J Natl Cancer Inst
2015
Frequency of Germline Mutations in 25 Cancer Susceptibility Genes in a Sequential Series of Patients With Breast Cancer.
Tung N et al.·J Clin Oncol
2016Cohort
Germline pathogenic variants in the MRE11, RAD50, and NBN (MRN) genes in cancer predisposition: A systematic review and meta-analysis.
Stastna B et al.·Int J Cancer
2024Meta-analysis
NBN Pathogenic Germline Variants are Associated with Pan-Cancer Susceptibility and In Vitro DNA Damage Response Defects.
Belhadj S et al.·Clin Cancer Res
2023
Pathogenic and likely pathogenic variants in PALB2, CHEK2, and other known breast cancer susceptibility genes among 1054 BRCA-negative Hispanics with breast cancer.
Weitzel JN et al.·Cancer
2019
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Investigating the association of NBN gene polymorphisms with multiple cancers through statistical meta-analysis and bioinformatics insights.
Harun-Or-Roshid M et al.·Biol Methods Protoc
2026🔓 Open Access
Risk of ovarian cancer in women with a pathogenic or likely pathogenic variant in NBN: a systematic review and meta-analysis.
Ganesan S et al.·Am J Obstet Gynecol
2026Review
Controlling Aggregation-Induced Emission by Sterics in Nitrogen-Boron-Nitrogen (NBN)-Doped Tetraphenylethylene-Like Molecular Propellers.
Groß N et al.·Chemistry
2026
Protective Effects of Olea europaea L. Leaves and Equisetum arvense L. Extracts Against Testicular Toxicity Induced by Metronidazole Through Reducing Oxidative Stress and Regulating NBN, INSL-3, STAR, HSD-3β, and CYP11A1 Signaling Pathways.
Azouz AA et al.·Toxics
2025🔓 Open Access
Acoustic phonon-restricted four-phonon interactions: impact on thermal and thermoelectric transport in monolayer h-NbN.
Murari H et al.·Nanoscale
2025
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Hypertension

Exergaming Training Among Hypertensive Patients

RECRUITING
NCT06777927Phase NARiphah International UniversityStarted 2025-01-16
ExerciseExerciseNo intervention
Huntington Disease

Study of BDNF Pathway Biomarkers in the Cerebrospinal Fluid in Patients With Huntington's Disease

RECRUITING
NCT04012411Phase NAUniversity Hospital, MontpellierStarted 2020-03-03
Brain MRILumbar PunctionBlood sample
Prostate Cancer Metastatic Castration-ResistantAbnormal DNA RepairMetastatic Prostate Carcinoma

Abiraterone/Prednisone, Olaparib, or Abiraterone/Prednisone + Olaparib in Patients With Metastatic Castration-Resistant Prostate Cancer With DNA Repair Defects

ACTIVE NOT RECRUITING
NCT03012321Phase PHASE2Northwestern UniversityStarted 2017-01-12
OlaparibAbiraterone AcetatePrednisone
Ischemic Stroke, AcuteSleep Disorders, Circadian Rhythm

The Role of Circadian Factors in Regulation of Neuroplasticity in Ischemic Stroke (Interventional)

RECRUITING
NCT05247125Phase PHASE4Federal State Budgetary Institution, V. A. Almazov Federal North-West Medical Research Centre, of the Ministry of HealthStarted 2022-03-01
Blue light exposure + Melatonin treatmentMelatonin treatmentBlue light exposure
Chronic Widespread PainFibromyalgia (FM)

The Added Value of Transcranial Direct Current Stimulation (tDCS) During Exercise for People With Chronic Widespread Pain

NOT YET RECRUITING
NCT07212829Phase NAVrije Universiteit BrusselStarted 2026-02-01
Active tDCSAerobic exerciseSham tDCS
Physiological AdaptationsSport PerformanceAerobic Capacity

Molecular Hydrogen Inhalation: Effects on Health, Exercise Capacity and Inflammatory Response - in Vivo/in Vitro Studies

NOT YET RECRUITING
NCT07130942Phase NAGdansk University of Physical Education and SportStarted 2025-10-01
Inhalation using a molecular hydrogen generator
MigraineMigraine HeadacheMigraine Headache, With or Without Aura

The Impact of Acupuncture on Biomarkers of Brain Injury and Inflammatory Response in Migraine

ACTIVE NOT RECRUITING
NCT07292506Phase NAUniversity Medical Centre LjubljanaStarted 2025-11-03
Standard acupunctureElectroacupunctureLaser Acupuncture
Alzheimer DiseaseInactivityPreventive Therapy

The Link Between Physical Activity and Brain Health in Healthy Adults

RECRUITING
NCT07025070Technical University of MadridStarted 2024-11-25
Advanced or Metastatic Solid TumorsBreast CancerOvarian Cancer

A Study of PARG Inhibitor IDE161 in Participants With Advanced Solid Tumors

RECRUITING
NCT05787587Phase PHASE1IDEAYA BiosciencesStarted 2023-04-18
IDE-161Pembrolizumab
Gonad Regulating Hormone Adverse ReactionAnalgesic Adverse ReactionDevelopmental Disability

Neurobehavioral Development in Toddlers and Preschoolers in Relation to Prenatal Exposure of Mild Analgesics (NeuroToP - a COPANA Follow up)

ENROLLING BY INVITATION
NCT07316387Rigshospitalet, DenmarkStarted 2024-05-27
AgingCardiovascular Risk Factor

A Combined Multidomain Intervention to Prevent Cognitive Decline Associated With Cardiovascular Risk Factors.

RECRUITING
NCT04962061Phase NALouis BhererStarted 2021-09-01
Cognitive TrainingAerobic and resistance exercisesStretching and Toning
Treatment Resistant DepressionMajor Depressive EpisodeMajor Depression

University of Iowa Interventional Psychiatry Service Patient Registry

RECRUITING
NCT04480918Mark NiciuStarted 2020-11-02
Electroconvulsive Therapy (ECT)Transcranial Magnetic Stimulation (TMS)Ketamine

External Resources

Links to major genomics databases and tools