NBN Gene (Nibrin)
Key player in DNA double-strand break repair and genomic stability
Gene Information Card
| Symbol | NBN |
|---|---|
| Full Name | Nibrin |
| Gene Type | Protein coding |
| Chromosomal Location | 8q21.3 |
| NCBI Gene ID | 4683 ncbi.nlm.nih.gov/gene/4683 |
| Ensembl ID | ENSG00000104320 |
| UniProt ID | O60934 |
| OMIM ID | 602667 |
| HGNC ID | 7652 |
| Aliases | NBS1, p95, AT-V1, AT-V2, NBS |
Description
The NBN gene encodes nibrin, a component of the MRE11/RAD50/NBN (MRN) complex essential for DNA double-strand break repair, telomere maintenance, and cell cycle checkpoint activation. Nibrin recruits the ATM kinase to sites of DNA damage, facilitating repair and signaling. Loss-of-function mutations cause Nijmegen breakage syndrome (NBS), characterized by microcephaly, immunodeficiency, and cancer predisposition. NBN variants are also associated with increased risk of various cancers, including breast, ovarian, and lymphoid malignancies.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Nijmegen breakage syndrome (NBS) | Loss-of-function mutations in NBN disrupt MRN complex assembly, impairing DNA repair and leading to chromosomal instability, radiosensitivity, and immune defects. | ClinVar, OMIM |
| Breast cancer | Hypomorphic NBN variants (e.g., c.657del5) increase susceptibility to breast cancer through defective DNA repair and genomic instability. | ClinVar, COSMIC |
| Acute lymphoblastic leukemia (ALL) | NBN mutations contribute to leukemogenesis via impaired DNA damage response and accumulation of chromosomal aberrations. | COSMIC, NCBI |
| Ovarian cancer | NBN germline variants are associated with increased ovarian cancer risk, likely due to compromised homologous recombination repair. | ClinVar |
| Colorectal cancer | Somatic NBN alterations are observed in colorectal tumors, potentially driving genomic instability. | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 12.5 | Medium |
| Spleen | 10.8 | Medium |
| Bone marrow | 9.2 | Medium |
| Testis | 8.7 | Medium |
| Small intestine | 7.1 | Low |
| Brain | 4.3 | Low |
| Liver | 3.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K562 (leukemia) | 14.2 | High expression |
| HeLa (cervical) | 11.5 | Medium expression |
| A549 (lung) | 9.8 | Medium expression |
| MCF7 (breast) | 8.1 | Low expression |
| HepG2 (liver) | 6.4 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.657del5 (p.Lys219Asnfs*16) | Deletion | ~1% in Slavic populations | Loss-of-function; founder mutation in NBS |
| c.511A>G (p.Ile171Val) | Missense | Rare | Hypomorphic; associated with cancer risk |
| c.643C>T (p.Arg215Trp) | Missense | Rare | Impaired MRN complex formation |
| c.1089C>A (p.Tyr363*) | Nonsense | Rare | Truncation; loss of function |
| c.1390G>A (p.Glu464Lys) | Missense | Rare | Reduced ATM activation |
Mutation functional classification
Loss of Function (LOF)
Most NBN mutations (e.g., c.657del5, nonsense) lead to truncated or unstable nibrin, disrupting MRN complex and DNA repair, causing NBS.
Gain of Function (GOF)
No well-established gain-of-function mutations reported; NBN primarily acts as a tumor suppressor.
Dominant Negative (DN)
Some missense variants (e.g., p.Ile171Val) may exert dominant-negative effects by interfering with wild-type nibrin function, though evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • DNA double-strand break repair (GO:0006302) | • Telomere maintenance (GO:0000723) |
| • Cell cycle checkpoint (GO:0000075) | • DNA damage response (GO:0006974) |
| • Protein binding (GO:0005515) | • Nuclease activity (GO:0004518) |
Pathways
• Homologous recombination (Reactome R-HSA-5693568)
• Non-homologous end joining (Reactome R-HSA-5693571)
• ATM signaling (Reactome R-HSA-5693565)
• Telomere maintenance (Reactome R-HSA-157579)
Protein Summary
Nibrin (p95/NBS1) is a 754-amino acid protein with a forkhead-associated (FHA) domain and two BRCA1 C-terminal (BRCT) domains at the N-terminus, mediating protein-protein interactions. It forms the MRN complex with MRE11 and RAD50, localizing to DNA double-strand breaks. Nibrin is phosphorylated by ATM in response to damage, activating cell cycle checkpoints and repair. Its C-terminus contains a MRE11-binding region and a nuclear localization signal. Defects in nibrin lead to radiosensitivity, chromosomal instability, and NBS.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NBN Knockout HEK293 Cell Line | EDJ-KQ3180 | Human | 4683 | Details Get a Quote |
| NBN Knockout A-549 Cell Line | EDJ-KQ24607 | Human | 4683 | Details Get a Quote |
| NBN Knockout HCT 116 Cell Line | EDJ-KQ24608 | Human | 4683 | Details Get a Quote |
| NBN Knockout HeLa Cell Line | EDJ-KQ24609 | Human | 4683 | Details Get a Quote |
| NBN (p.A127=) Point Mutation in HAP1 Cell Line | EDC03560 | Human | 4683 | Details Get a Quote |
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