NBN

Chr 8AR

nibrin

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

NCBI Gene: 4683 ENSG00000104320 UniProt: O60934 OMIM: 602667

NBN encodes a protein that acts as an adapter within the MRN complex, specifically recognizing and binding phosphorylated proteins to recruit DNA repair factors to sites of double-strand breaks. Mutations cause Nijmegen breakage syndrome, an autosomal recessive disorder characterized by microcephaly, growth retardation, immunodeficiency, and cancer predisposition including acute lymphoblastic leukemia and aplastic anemia. The gene is extremely intolerant to loss-of-function variants (pLI near 0), reflecting the critical importance of DNA repair pathways in human development.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

LOFmechanismARLOEUF 1.013 OMIM phenotypes

Clinical Summary— NBN

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Gene-Disease Validity (ClinGen)

hereditary breast carcinoma · ADRefuted

Refuted — evidence has disproved this relationship

2 total gene-disease associations curated

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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Clinical Trials

12 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint

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

0.61Z-score

OE missense 0.91 (0.83–1.00)

344 obs / 377.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios

LoF OE0.74 (0.56–1.01)

0≤0.351.4

Missense OE0.91 (0.83–1.00)

0≤0.61.4

Synonymous OE1.07

0≤1.21.6

LoF obs/exp: 30 / 40.3Missense obs/exp: 344 / 377.3Syn Z: -0.68

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveNBN-related Nijmegen breakage syndromeLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.5477th %ile

GOF

0.3094th %ile

LOF

0.50top 25%

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Literature Evidence

LOFBogdanova N, et al. the 657del5 variant was identified in 15/1,588 breast cancer cases (0.9%) from Belarus and in 1/1,076 cases (0.1%) from Germany but in only 1/1,014 population controls from Belarus and 0/1017 German controls (p < 0.01). Also reviewed four other publications and combined with theiPMID:17957789

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

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.

3D Protein StructureAlphaFold

External Resources

Links to major genomics databases and tools

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Advanced Solid TumorsEwing SarcomaHepatocellular Carcinoma (HCC)

A Phase 1/1B Study of ST-01156, a Small Molecule RBM39 Degrader, in Patients With Advanced Solid Malignancies

RECRUITING

NCT07197554Phase PHASE1SEED Therapeutics, Inc.Started 2025-12-01

ST-01156

Parkinson Disease

To Evaluate the Dose-response Effects of a Defined Volume of Physical Exercise on the Change of Peripheral Biomarkers, Clinical Response and Brain Connectivity in Parkinson's Disease: a Prospective, Observational, Cohort Pilot Study

RECRUITING

NCT06339398Casa di Cura San Raffaele CassinoStarted 2025-02-11

Aerobic exercise

Polycythemia VeraEssential ThrombocythaemiaMyelofibrosis

Prevalence Of Germline Gene Mutations In Patients With Myeloproliferative Neoplasms With Family History

NOT YET RECRUITING

NCT06923670Phase NAFondazione Policlinico Universitario Agostino Gemelli IRCCSStarted 2025-05-21

NGS testingNGS analysis for mutations in genes involved in familial predisposition to hematological malignancies

Preterm BirthMother-Infant InteractionInfant Development

Continuous Delivery Room Skin-to-skin-study for Moderate and Late Preterm Infants

RECRUITING

NCT05975203Phase NAUniversity of CologneStarted 2023-08-04