NBN

Summary

NBN (nibrin, HGNC:7652) is a protein-coding gene on chromosome 8q21.3, encoding Nibrin (O60934). Component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis.

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.

Source: NCBI Gene 4683 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Nijmegen breakage syndrome (Definitive, ClinGen) — +4 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 3,684 total — 233 pathogenic, 188 likely-pathogenic
• Phenotypes (HPO): 94
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_002485

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7652
Approved symbol	NBN
Name	nibrin
Location	8q21.3
Locus type	gene with protein product
Status	Approved
Aliases	ATV, AT-V2, AT-V1
Ensembl gene	ENSG00000104320
Ensembl biotype	protein_coding
OMIM	602667
Entrez	4683

Gene structure

Transcript identifiers

Ensembl transcripts: 44 — 22 protein_coding, 12 nonsense_mediated_decay, 10 retained_intron

ENST00000265433, ENST00000396252, ENST00000409330, ENST00000474821, ENST00000494804, ENST00000517337, ENST00000517772, ENST00000519426, ENST00000520325, ENST00000523444, ENST00000613033, ENST00000697292, ENST00000697293, ENST00000697294, ENST00000697295, ENST00000697296, ENST00000697297, ENST00000697298, ENST00000697299, ENST00000697300, ENST00000697301, ENST00000697302, ENST00000697303, ENST00000697304, ENST00000697305, ENST00000697306, ENST00000697307, ENST00000697308, ENST00000697309, ENST00000697310, ENST00000697311, ENST00000697312, ENST00000697313, ENST00000697314, ENST00000697315, ENST00000697316, ENST00000697317, ENST00000697318, ENST00000883933, ENST00000883934, ENST00000915948, ENST00000969898, ENST00000969899, ENST00000969900

RefSeq mRNA: 2 — MANE Select: NM_002485 NM_001024688, NM_002485

CCDS: CCDS43753, CCDS6249

Canonical transcript exons

ENST00000265433 — 16 exons

Exon	Start	End
ENSE00003472599	89964410	89964507
ENSE00003499953	89958725	89958854
ENSE00003516469	89971173	89971290
ENSE00003518702	89978220	89978323
ENSE00003530226	89943253	89943366
ENSE00003558782	89937026	89937075
ENSE00003568222	89946140	89946295
ENSE00003616198	89955283	89955555
ENSE00003620322	89980734	89980893
ENSE00003636732	89947824	89947892
ENSE00003646460	89970364	89970557
ENSE00003652625	89982722	89982855
ENSE00003672812	89981375	89981523
ENSE00003678671	89953244	89953691
ENSE00003970213	89984525	89984667
ENSE00003970238	89933331	89935612

Expression profiles

Bgee: expression breadth ubiquitous, 299 present calls, max score 97.36.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 40.3968 / max 1630.0378, expressed in 1821 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
93880	28.6128	1819
93871	7.8065	313
93879	2.1061	1226
93878	1.1075	725
93874	0.4088	83
93876	0.1564	45
93875	0.1108	36
93877	0.0478	9
93873	0.0401	24

Top tissues by expression

299 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
endometrium epithelium	UBERON:0004811	97.36	gold quality
mammary duct	UBERON:0001765	95.45	gold quality
cauda epididymis	UBERON:0004360	95.06	gold quality
epithelium of mammary gland	UBERON:0003244	94.99	gold quality
trigeminal ganglion	UBERON:0001675	94.57	gold quality
germinal epithelium of ovary	UBERON:0001304	94.33	gold quality
parietal pleura	UBERON:0002400	94.01	gold quality
decidua	UBERON:0002450	93.87	gold quality
superior surface of tongue	UBERON:0007371	93.71	gold quality
calcaneal tendon	UBERON:0003701	93.43	gold quality
palpebral conjunctiva	UBERON:0001812	93.41	gold quality
pleura	UBERON:0000977	93.37	gold quality
bone marrow	UBERON:0002371	93.34	gold quality
myometrium	UBERON:0001296	92.87	gold quality
monocyte	CL:0000576	92.86	gold quality
mononuclear cell	CL:0000842	92.81	gold quality
endometrium	UBERON:0001295	92.67	gold quality
mucosa of paranasal sinus	UBERON:0005030	92.61	gold quality
visceral pleura	UBERON:0002401	92.54	gold quality
mammary gland	UBERON:0001911	92.53	gold quality
thoracic mammary gland	UBERON:0005200	92.53	gold quality
leukocyte	CL:0000738	92.46	gold quality
pericardium	UBERON:0002407	92.37	gold quality
esophagus squamous epithelium	UBERON:0006920	92.34	gold quality
adrenal tissue	UBERON:0018303	92.33	gold quality
caecum	UBERON:0001153	92.22	gold quality
lower esophagus muscularis layer	UBERON:0035833	92.22	gold quality
lower esophagus	UBERON:0013473	92.17	gold quality
cranial nerve II	UBERON:0000941	92.12	gold quality
saphenous vein	UBERON:0007318	92.04	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.65

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTCF, FOXM1, HIF1A, MYC, MYCN, NKX3-1, SIRT1, SOX17

miRNA regulators (miRDB)

82 targeting NBN, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-34B-5P	99.78	67.56	1175
HSA-MIR-449C-5P	99.78	67.63	1168
HSA-MIR-3617-5P	99.75	69.41	1968
HSA-MIR-641	99.75	69.35	1975
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-2682-5P	99.73	67.38	1055
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-1284	99.67	73.56	1353
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-5003-5P	99.61	69.13	1624
HSA-MIR-2113	99.58	71.22	1521
HSA-MIR-6758-3P	99.57	67.55	1078
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-7159-3P	99.51	70.17	1920

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• reconstitution of the mammalian DNA double-strand break end-joining reaction reveals a requirement for an Mre11/Rad50/NBS1-containing fraction (PMID:11809878)
• Nbs1 promotes ATM dependent phosphorylation events including those required for G1/S arrest. (PMID:12082606)
• Adenovirus oncoproteins inactivate the Mre11-Rad50-NBS1 DNA repair complex (PMID:12124628)
• Six common polymorphisms spanning the NBS1 gene have been genotyped and provide no evidence for loss of heterozygosity in the NHL population overall, suggesting that mutations in NBS1 are not involved in NHL development in the United States. (PMID:12353271)
• Functional analysis of protein domains of NBS1 involved in chromatin association and DNA damage responses. (PMID:12433983)
• NBS1 and FANCD2 cooperate in two distinct cellular functions, one involved in the DNA crosslink response and one involved in the S-phase checkpoint response (PMID:12447395)
• Alterations in this gene and changes in nibrin expression were found in ovarian carcinomas. (PMID:12485469)
• Frequency of 657del(5) mutation of the NBS1 gene in the Czech population by polymerase chain reaction with sequence specific primers. (PMID:12505263)
• Novel NBS1 mutations and protein variants identified in 20 cancer cell lines suggest the possible involvement of NBS1 in tumor developmental mechanisms. (PMID:12508248)
• NBS1 is required for phosphorylation of Chk1, indicating that NBS1 might facilitate the access of Chk1 to ATM at the sites of DNA damage. (PMID:12588868)
• results indicate that Nijmegen breakage syndrome 1 gene (NBS1) is a direct transcriptional target of c-Myc and links the function of c-Myc to the regulation of DNA double-strand break repair pathway (PMID:12637527)
• activation in response to replication-dependent DNA double-strand breaks induced by mammalian DNA topoisomerase I cleavage complexes (PMID:12660252)
• Nibrin forkhead-associated domain and breast cancer C-terminal domain are both required for nuclear focus formation and phosphorylation (PMID:12679336)
• Assembly of functional ALT-associated promyelocytic leukemia bodies requires Nijmegen Breakage Syndrome 1. (PMID:12750284)
• nibrin1 is involved in a signaling pathway that induces ATF3 after ionizing radiation (PMID:12833146)
• Preliminary data suggest that NBS1 mutation carriers can be predisposed to malignant disorders. (PMID:12833396)
• Germline 657del5 mutation in the NBS1 gene is associated with breast cancer (PMID:12845677)
• multiple functional domains of NBS1 are required for ATM-dependent activation of CHK2, nuclear focus formation, S phase checkpoint control, and cell survival after exposure to ionizing radiation (PMID:12861053)
• The 657del5 mutation of exon 6 of NBS1 gene may be responsible for the occurrence of a small proportion of malignant melanoma patients, characterized by the occurrence of breast cancer among their relatives. (PMID:12883362)
• The NBS1-185Gln variant is related with p53 gene mutations in lung cancer patients (PMID:12917199)
• ATM-dependent phosphorylation of NBS1 is required for the suppression of TLK activity, indicating a role for NBS1 as an adaptor or scaffold in the ATM/TLK pathway. (PMID:12955071)
• We have developed a novel molecular therapy that inhibits the MRN(95) complex in tumor cells. Disruption the MRN(95) complex and thus DNA repair should result in enhanced tumor killing after classic external-beam radiation therapy. (PMID:12972939)
• ATM and NBS regulate several genes in common, both of these proteins also have distinct patterns of gene regulation. (PMID:14745549)
• The transient slow-down of DNA synthesis was abolished in cells lacking ATR, whereas CHK1-siRNA-treated cells, NBS1 or Fanconi anemia cells showed partial S-phase arrest. (PMID:14988723)
• Results suggest that E2F1 plays a central role in signaling disturbances in the retinoblastoma growth control pathway and, by upregulation of Chk2 by Atm and Nbs1, may sensitize cells to undergo apoptosis. (PMID:15024084)
• WRN associates with the Mre11 complex via binding to Nbs1 in vitro and in vivo (PMID:15026416)
• Mre11-Rad50-Nbs1 complex serves also as a modulator/amplifier of ATM activity. (PMID:15048089)
• demonstrated that MRN (Mre11, Rad50, and Nbs1 proteins) stimulates the kinase activity of ATM in vitro toward its substrates p53, Chk2, and histone H2AX (PMID:15064416)
• Replication protein A, Mre11, Rad50 and Nbs1 bind and have roles in DNA repair (PMID:15180989)
• MDC1 couples DNA ds-break recognition by NBS1 with its H2AFX-dependent chromatin retention. (PMID:15201865)
• Nibrin, Mre11 and Rad50 also act as adaptors for some downstream Atm phosphorylation events (PMID:15234984)
• NBS1 has a role in the functional role in the DNA damage response [review] (PMID:15279770)
• NBS1 has a role in development of the clinical manifestation of Nijmegen breakage syndrome [review] (PMID:15279809)
• NBS1 has at least two important roles in genome maintenance, as a DNA repair protein in HR pathway and as a signal modifier in intra-S phase checkpoints [review] (PMID:15493328)
• the NBS1 657del5 allele is not responsible for most breast cancer in Russia (PMID:15578693)
• Data suggest that Nijmegen breakage syndrome 1 (Nbs1) functions in both ATR- (ataxia-telangiectasia and Rad3-related protein) and ataxia telangiectasia mutated protein-dependent signalling. (PMID:15616588)
• the Mre11/Rad50/Nbs1 (MRN) complex may play a more universal role in the recognition and response to DNA lesions of all types, whereas the role of RPA may be limited to certain subsets of lesions (PMID:15653682)
• a novel pathway in which Nbs1 may recruit Werner syndrome protein to the site of DNA double strand breaks in an ATM-dependent manner (PMID:15733840)
• Nbs1 is a novel p53-independent Mdm2 binding protein and links Mdm2 to the Mre11-Nbs1-Rad50-regulated DNA repair response (PMID:15734743)
• identification of related, conserved carboxy-terminal motifs in human Nbs1, ATRIP and Ku80 proteins that are required for their interaction with ATM, ATR and DNA-PKcs, respectively (PMID:15758953)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	nbn	ENSDARG00000040303
mus_musculus	Nbn	ENSMUSG00000028224
rattus_norvegicus	Nbn	ENSRNOG00000008580
drosophila_melanogaster	nbs	FBGN0261530

Protein

Protein identifiers

Nibrin — O60934 (reviewed: O60934)

Alternative names: Cell cycle regulatory protein p95, Nijmegen breakage syndrome protein 1

All UniProt accessions (21): A0A087X1V5, A0A0C4DG07, A0A8V8TKV9, A0A8V8TKW6, A0A8V8TKY0, A0A8V8TKY5, A0A8V8TL91, A0A8V8TL95, A0A8V8TL98, A0A8V8TLA3, A0A8V8TM80, A0A8V8TM88, A0A8V8TM94, A0A8V8TMG0, A0A8V8TMG6, O60934, A0A8V8TMH1, A0A8V8TMH6, E2QRP0, E5RGR7, E5RGU1

UniProt curated annotations — full annotation on UniProt →

Function. Component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis. The MRN complex is involved in the repair of DNA double-strand breaks (DSBs) via homologous recombination (HR), an error-free mechanism which primarily occurs during S and G2 phases. The complex (1) mediates the end resection of damaged DNA, which generates proper single-stranded DNA, a key initial steps in HR, and is (2) required for the recruitment of other repair factors and efficient activation of ATM and ATR upon DNA damage. The MRN complex possesses single-strand endonuclease activity and double-strand-specific 3’-5’ exonuclease activity, which are provided by MRE11, to initiate end resection, which is required for single-strand invasion and recombination. Within the MRN complex, NBN acts as a protein-protein adapter, which specifically recognizes and binds phosphorylated proteins, promoting their recruitment to DNA damage sites. Recruits MRE11 and RAD50 components of the MRN complex to DSBs in response to DNA damage. Promotes the recruitment of PI3/PI4-kinase family members ATM, ATR, and probably DNA-PKcs to the DNA damage sites, activating their functions. Mediates the recruitment of phosphorylated RBBP8/CtIP to DSBs, leading to cooperation between the MRN complex and RBBP8/CtIP to initiate end resection. RBBP8/CtIP specifically promotes the endonuclease activity of the MRN complex to clear DNA ends containing protein adducts. The MRN complex is also required for the processing of R-loops. NBN also functions in telomere length maintenance via its interaction with TERF2: interaction with TERF2 during G1 phase preventing recruitment of DCLRE1B/Apollo to telomeres. NBN also promotes DNA repair choice at dysfunctional telomeres: NBN phosphorylation by CDK2 promotes non-homologous end joining repair at telomeres, while unphosphorylated NBN promotes microhomology-mediated end-joining (MMEJ) repair. Enhances AKT1 phosphorylation possibly by association with the mTORC2 complex.

Subunit / interactions. Component of the MRN complex composed of two heterodimers RAD50 and MRE11 associated with a single NBN. The MRN complexes dimerize on DNA to form joined MRN-MRN oligomers required for DNA double-strand break repair. As part of the MRN complex, interacts with MCM9; the interaction recruits the complex to DNA repair sites. Component of the BASC complex, at least composed of BRCA1, MSH2, MSH6, MLH1, ATM, BLM, RAD50, MRE11 and NBN. Interacts with histone H2AX; this requires phosphorylation of H2AX on ‘Ser-139’ and promotes NBN recruitment to DNA damage sites. Interacts with (phosphorylated) MDC1; promoting NBN recruitment to DNA damage sites. Interacts with (phosphorylated) RAD17; promoting NBN recruitment to DNA damage sites. Interacts (via FxF/Y motif) with ATM. Interacts with HJURP. Interacts with INTS3. Interacts with KPNA2. Interacts with TERF2; interaction is disrupted upon NBN phosphorylation by CDK2. Interacts with (phosphorylated) RBBP8/CtIP; the interaction links the role of the MRN complex in DNA double-strand break sensing to resection. Interacts with SP100; recruits NBN to PML bodies. Interacts with ATF2. Interacts with MTOR, MAPKAP1 isoform 2 and RICTOR; indicative for an association with the mTORC2 complex. Interacts with MRNIP. Interacts with UFL1; promoting UFL1 recruitment to double-strand breaks following DNA damage. Interacts with CYREN (via XLF motif). (Microbial infection) Interacts with herpes simplex virus 1 protein UL12.

Subcellular location. Nucleus. Chromosome. PML body. Telomere.

Tissue specificity. Ubiquitous. Expressed at high levels in testis.

Post-translational modifications. Phosphorylated by ATM in response of ionizing radiation, and such phosphorylation is responsible intra-S phase checkpoint control and telomere maintenance. Phosphorylated at Ser-432 by CDK2 in S/G2 phases abolishes interaction with TERF2, enabling DCLRE1B/Apollo recruitment to telomeres. Phosphorylation at Ser-432 in response to dysfunctional telomeres promotes non-homologous end joining repair at telomeres, while dephosphorylation by PPP1CA promotes microhomology-mediated end-joining (MMEJ) repair. Ubiquitinated at Lys-435 via ‘Lys-6’-linked ubiquitin chains by RNF8, promoting NBN recruitment to DNA double-strand breaks (DSBs). Ubiquitinated at Lys-686 and Lys-689 via ‘Lys-63’-linked ubiquitin chains by PELI1: ubiquitination takes place following PELI1 phosphorylation and promotes ATM activation and DNA repair. Ubiquitinated at Lys-735 via ‘Lys-63’-linked ubiquitin chains by the SCF(SKP2) complex: ubiquitination takes place following SKP2 phosphorylation and promotes ATM activation and DNA repair. Lactylation at Lys-388 by KAT5 in response to DNA damage promotes recruitment of the MRN complex to DNA damage sites. Delactylated by HDAC3.

Disease relevance. Nijmegen breakage syndrome (NBS) [MIM:251260] A disorder characterized by chromosomal instability, radiation sensitivity, microcephaly, growth retardation, immunodeficiency and predisposition to cancer, particularly to lymphoid malignancies. The disease is caused by variants affecting the gene represented in this entry. Breast cancer (BC) [MIM:114480] A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case. Disease susceptibility is associated with variants affecting the gene represented in this entry. Aplastic anemia (AA) [MIM:609135] A form of anemia in which the bone marrow fails to produce adequate numbers of peripheral blood elements. It is characterized by peripheral pancytopenia and marrow hypoplasia. Disease susceptibility may be associated with variants affecting the gene represented in this entry. Defects in NBN might play a role in the pathogenesis of childhood acute lymphoblastic leukemia (ALL).

Domain organisation. The FHA and BRCT domains specifically recognize and bind phosphorylated proteins. The C-terminal domain contains a MRE11-binding site, and this interaction is required for the nuclear localization of the MRN complex. The FxF/Y motif (also named EEXXXDDL motif) is required for the interaction with ATM and its recruitment to sites of DNA damage and promote the phosphorylation of ATM substrates, leading to the events of DNA damage response.

Induction. Up-regulated by ionizing radiation (IR).

Similarity. Belongs to the Nibrin family.

RefSeq proteins (2): NP_001019859, NP_002476* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000253	FHA_dom	Domain
IPR001357	BRCT_dom	Domain
IPR008984	SMAD_FHA_dom_sf	Homologous_superfamily
IPR013908	Nibrin_C	Domain
IPR016592	Nibrin_met	Family
IPR032429	Nibrin_BRCT2	Domain
IPR036420	BRCT_dom_sf	Homologous_superfamily
IPR040227	Nibrin-rel	Family
IPR043014	Nibrin_BRCT2_sf	Homologous_superfamily

Pfam: PF00498, PF00533, PF08599, PF16508

UniProt features (82 total): mutagenesis site 32, sequence variant 15, modified residue 12, cross-link 7, region of interest 5, domain 3, compositionally biased region 3, short sequence motif 2, turn 2, chain 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
7SID	ELECTRON MICROSCOPY	2.53
9Q9J	ELECTRON MICROSCOPY	2.71
9Q9I	ELECTRON MICROSCOPY	2.79
9Q9M	ELECTRON MICROSCOPY	2.81
5WQD	X-RAY DIFFRACTION	3
9ULO	ELECTRON MICROSCOPY	3.91
8BAH	ELECTRON MICROSCOPY	4.13

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60934-F1	63.08	0.29

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (19): 278, 337, 343, 347, 388, 397, 402, 432, 509, 518, 615, 673, 435, 529, 571, 582, 686, 690, 735

Mutagenesis-validated functional residues (32):

Position	Phenotype
28	disrupts nuclear foci formation and block phosphorylation in response to ionizing radiation. decreased ability to recogn
42	decreased ability to recognize and bind phosphorylated proteins.
43	in rrhk mutant; abolished ability to recognize and bind phosphorylated proteins, such as rbbp8; when associated with a-2
45	disrupts nuclear foci formation and block phosphorylation in response to ionizing radiation. decreased ability to recogn
136–137	disrupts nuclear foci formation and block phosphorylation in response to ionizing radiation.
160	decreased ability to recognize and bind phosphorylated proteins, such as mdc1. in rrhk mutant; abolished ability to reco
176	disrupts nuclear foci formation and block phosphorylation in response to ionizing radiation.
233	abolished recruitment to dna damage sites.
233	does not affect recruitment to dna damage sites.
247	abolished recruitment to dna damage sites.
270	abolished recruitment to dna damage sites.
271	abolished recruitment to dna damage sites.
343	abrogates atm-dependent phosphorylation.
388	abolished lactylation, leading to decreased recruitment of the mrn complex to dna damage sites.
397	abrogates atm-dependent phosphorylation. no loss of interaction with kpna2.
432	does not affect interaction with terf2.
432	mimics phosphorylation; impaired interaction with terf2.
465–466	blocks the association with kpna2, and reduces nuclear foci formation in response to ionizing radiation.
583	no loss of interaction with kpna2.
615	abrogates atm-dependent phosphorylation.
665	does not affect ubiquitination by peli1; when associated with r-683.
683	does not affect ubiquitination by peli1; when associated with r-665.
686–690	abolished ubiquitination by peli1.
735	abolished ubiquitination by the scf(skp2) complex.
736–737	decreases atm-binding.

Function

Pathways and Gene Ontology

Reactome pathways

44 pathways

ID	Pathway
R-HSA-2559586	DNA Damage/Telomere Stress Induced Senescence
R-HSA-5685938	HDR through Single Strand Annealing (SSA)
R-HSA-5685939	HDR through MMEJ (alt-NHEJ)
R-HSA-5685942	HDR through Homologous Recombination (HRR)
R-HSA-5693548	Sensing of DNA Double Strand Breaks
R-HSA-5693554	Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)
R-HSA-5693565	Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks
R-HSA-5693568	Resolution of D-loop Structures through Holliday Junction Intermediates
R-HSA-5693571	Nonhomologous End-Joining (NHEJ)
R-HSA-5693579	Homologous DNA Pairing and Strand Exchange
R-HSA-5693607	Processing of DNA double-strand break ends
R-HSA-5693616	Presynaptic phase of homologous DNA pairing and strand exchange
R-HSA-6804756	Regulation of TP53 Activity through Phosphorylation
R-HSA-69473	G2/M DNA damage checkpoint
R-HSA-912446	Meiotic recombination
R-HSA-9701192	Defective homologous recombination repair (HRR) due to BRCA1 loss of function
R-HSA-9704331	Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function
R-HSA-9704646	Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function
R-HSA-9709570	Impaired BRCA2 binding to RAD51
R-HSA-9709603	Impaired BRCA2 binding to PALB2
R-HSA-1474165	Reproduction
R-HSA-1500620	Meiosis
R-HSA-1640170	Cell Cycle
R-HSA-1643685	Disease
R-HSA-212436	Generic Transcription Pathway
R-HSA-2262752	Cellular responses to stress
R-HSA-2559583	Cellular Senescence
R-HSA-3700989	Transcriptional Regulation by TP53
R-HSA-5633007	Regulation of TP53 Activity
R-HSA-5693532	DNA Double-Strand Break Repair

MSigDB gene sets: 675 (showing top): PID_FANCONI_PATHWAY, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, GOBP_DNA_TEMPLATED_DNA_REPLICATION_MAINTENANCE_OF_FIDELITY, GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, REACTOME_MEIOTIC_RECOMBINATION, GOBP_CHROMOSOME_ORGANIZATION, GOBP_REGULATION_OF_DNA_RECOMBINATION, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, PID_TELOMERASE_PATHWAY, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, MORF_RAB5A, GOBP_REGULATION_OF_DNA_TEMPLATED_DNA_REPLICATION, GOBP_TELOMERE_CAPPING

GO Biological Process (35): DNA damage checkpoint signaling (GO:0000077), telomere maintenance (GO:0000723), double-strand break repair via homologous recombination (GO:0000724), DNA double-strand break processing (GO:0000729), blastocyst growth (GO:0001832), double-strand break repair (GO:0006302), mitotic G2 DNA damage checkpoint signaling (GO:0007095), neuroblast proliferation (GO:0007405), regulation of DNA-templated DNA replication initiation (GO:0030174), DNA damage response, signal transduction by p53 class mediator (GO:0030330), protection from non-homologous end joining at telomere (GO:0031848), telomeric 3’ overhang formation (GO:0031860), positive regulation of telomere maintenance (GO:0032206), homologous recombination (GO:0035825), telomere maintenance in response to DNA damage (GO:0043247), mitotic G2/M transition checkpoint (GO:0044818), isotype switching (GO:0045190), neuromuscular process controlling balance (GO:0050885), meiotic cell cycle (GO:0051321), regulation of cell cycle (GO:0051726), R-loop processing (GO:0062176), protein K63-linked ubiquitination (GO:0070534), t-circle formation (GO:0090656), telomere maintenance via telomere trimming (GO:0090737), intrinsic apoptotic signaling pathway (GO:0097193), double-strand break repair via alternative nonhomologous end joining (GO:0097681), DNA strand resection involved in replication fork processing (GO:0110025), negative regulation of telomere capping (GO:1904354), positive regulation of double-strand break repair via homologous recombination (GO:1905168), protein localization to site of double-strand break (GO:1990166), positive regulation of double-strand break repair (GO:2000781), in utero embryonic development (GO:0001701), DNA repair (GO:0006281), DNA damage response (GO:0006974), mitotic cell cycle checkpoint signaling (GO:0007093)

GO Molecular Function (7): damaged DNA binding (GO:0003684), histone binding (GO:0042393), protein serine/threonine kinase activator activity (GO:0043539), phosphorylation-dependent protein binding (GO:0140031), DNA-binding transcription factor binding (GO:0140297), chromatin-protein adaptor activity (GO:0140463), protein binding (GO:0005515)

GO Cellular Component (14): chromosome, telomeric region (GO:0000781), nucleus (GO:0005634), nucleoplasm (GO:0005654), replication fork (GO:0005657), nucleolus (GO:0005730), Golgi apparatus (GO:0005794), cytosol (GO:0005829), PML body (GO:0016605), Mre11 complex (GO:0030870), site of double-strand break (GO:0035861), nuclear inclusion body (GO:0042405), BRCA1-C complex (GO:0070533), chromosomal region (GO:0098687), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	3
DNA Double Strand Break Response	2
Resolution of D-Loop Structures	2
Defective homologous recombination repair (HRR) due to PALB2 loss of function	2
Defective homologous recombination repair (HRR) due to BRCA2 loss of function	2
Cellular Senescence	1
Homology Directed Repair	1
DNA Double-Strand Break Repair	1
HDR through Homologous Recombination (HRR)	1
Homologous DNA Pairing and Strand Exchange	1
Regulation of TP53 Activity	1
G2/M Checkpoints	1
Meiosis	1
Diseases of DNA Double-Strand Break Repair	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
signal transduction in response to DNA damage	2
DNA metabolic process	2
double-strand break repair	2
telomere capping	2
telomere maintenance	2
cell cycle	2
intracellular membrane-bounded organelle	2
nuclear lumen	2
chromosome	2
intracellular membraneless organelle	2
cytoplasm	2
nuclear protein-containing complex	2
DNA integrity checkpoint signaling	1
telomere organization	1
recombinational repair	1
5’-3’ DNA exonuclease activity	1
blastocyst development	1
developmental growth	1
DNA repair	1
mitotic G2 phase	1
mitotic DNA damage checkpoint signaling	1
mitotic G2/M transition checkpoint	1
generation of neurons	1
neural precursor cell proliferation	1
DNA replication initiation	1
regulation of DNA-templated DNA replication	1
signal transduction by p53 class mediator	1
telomere maintenance in response to DNA damage	1
DNA strand elongation	1
regulation of telomere maintenance	1
positive regulation of DNA metabolic process	1
positive regulation of chromosome organization	1
DNA recombination	1
DNA damage response	1
mitotic cell cycle checkpoint signaling	1
negative regulation of G2/M transition of mitotic cell cycle	1
somatic recombination of immunoglobulin genes involved in immune response	1
B cell activation involved in immune response	1
musculoskeletal movement	1

Protein interactions and networks

STRING

1320 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NBN	MRE11	P49959	997
NBN	RAD50	Q92878	995
NBN	RBBP8	Q99708	979
NBN	ATM	Q13315	936
NBN	BRCA1	P38398	903
NBN	MSH6	P52701	862
NBN	MDC1	Q14676	846
NBN	CHEK2	O96017	822
NBN	RFC4	P35249	815
NBN	LIG4	P49917	814
NBN	RAD51	Q06609	812
NBN	XRCC6	P12956	799
NBN	BRCA2	P51587	796
NBN	MLH1	P40692	775
NBN	PRKDC	P78527	773

IntAct

177 interactions, top by confidence:

A	B	Type	Score
NBN	MDC1	psi-mi:“MI:0915”(physical association)	0.970
NBN	MDC1	psi-mi:“MI:0403”(colocalization)	0.970
MDC1	NBN	psi-mi:“MI:0915”(physical association)	0.970
NBN	MDC1	psi-mi:“MI:0407”(direct interaction)	0.970
MDC1	NBN	psi-mi:“MI:0407”(direct interaction)	0.970
MDC1	NBN	psi-mi:“MI:0914”(association)	0.970

BioGRID (492): MTOR (Affinity Capture-Western), NBN (Affinity Capture-Western), RICTOR (Affinity Capture-Western), MAPKAP1 (Affinity Capture-Western), NBN (Affinity Capture-Western), NBN (Affinity Capture-Western), NBN (Affinity Capture-MS), NBN (Reconstituted Complex), NBN (Affinity Capture-MS), NBN (Affinity Capture-MS), NBN (Affinity Capture-Western), PHRF1 (Affinity Capture-Western), NBN (Affinity Capture-Western), RAD50 (Co-fractionation), BAP1 (Two-hybrid)

ESM2 similar proteins: A0A3Q2TTB3, A0JMR6, A4IIA7, F4JNY0, F6RRD7, I3XHK1, O60934, O88622, P14629, P28715, P79457, Q08DZ8, Q12789, Q17RS7, Q1LWH4, Q28I29, Q32PL8, Q3B7T1, Q4R7Q1, Q5FWP4, Q5M954, Q5QJC2, Q5RA37, Q5RCV3, Q5ZIN2, Q66J91, Q6GQV7, Q6NVF4, Q6P1E7, Q6P1H6, Q6P256, Q6P7W5, Q76CY8, Q7TP65, Q86W56, Q8BMI4, Q8C0W1, Q8C5W4, Q8GT06, Q8IXW5

Diamond homologs: O60934, Q5I2W8, Q5RCV3, Q6XV80, Q9DE07, Q9JIL9, Q9R207, B8BHK8, Q7XD82, Q0H8D7, Q5RF77

SIGNOR signaling

15 interactions.

A	Effect	B	Mechanism
H2AX	up-regulates	NBN	binding
NBN	up-regulates	ATM	binding
ATR	up-regulates	NBN	phosphorylation
MRE11	up-regulates	NBN	binding
MDC1	up-regulates	NBN	binding
RPA2	up-regulates	NBN	binding
TCOF1	“up-regulates activity”	NBN	relocalization
CDK2	“up-regulates activity”	NBN	phosphorylation
ATM	up-regulates	NBN	phosphorylation
NBN	“form complex”	MRE11/RAD50/NBS1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 105 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
DNA Double Strand Break Response	7	40.6×	4e-08
Impaired BRCA2 binding to PALB2	5	27.9×	4e-05
Defective homologous recombination repair (HRR) due to BRCA1 loss of function	5	25.8×	5e-05
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function	5	25.8×	5e-05
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function	5	25.8×	5e-05
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks	14	25.0×	1e-13
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	5	24.0×	6e-05
Homologous DNA Pairing and Strand Exchange	5	23.2×	6e-05

GO biological processes:

GO term	Partners	Fold	FDR
mitotic intra-S DNA damage checkpoint signaling	5	47.8×	1e-05
mitotic G2/M transition checkpoint	5	40.9×	1e-05
double-strand break repair via nonhomologous end joining	6	25.8×	1e-05
positive regulation of DNA repair	7	25.6×	2e-06
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	5	25.3×	1e-04
DNA damage checkpoint signaling	6	24.0×	2e-05
double-strand break repair	11	22.8×	9e-10
response to ionizing radiation	5	21.0×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

3684 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	233
Likely pathogenic	188
Uncertain significance	1779
Likely benign	975
Benign	79

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1068989	NM_002485.5(NBN):c.2172_2173delinsTT (p.Arg724_Gln725delinsSerTer)	Pathogenic
1069236	NM_002485.5(NBN):c.1986_2001del (p.Val663fs)	Pathogenic
1070578	NM_002485.5(NBN):c.113_114insGGCCGGGCGCGGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCCGAGGCGGGTGGATCATGAGGTCAGGAGATCGAGACCATCCTGGCTAACAAGGTGAAANNNNNNNNNNAAAAAAAAAAAAAAAAAAAAGAAAATGA (p.Asp38delinsGluAlaGlyArgGlyGlySerArgLeuTer)	Pathogenic
1070710	NM_002485.5(NBN):c.520_521insT (p.Pro174fs)	Pathogenic
1071046	NM_002485.5(NBN):c.1554del (p.Asp519fs)	Pathogenic
1071444	NM_002485.5(NBN):c.157del (p.Ser53fs)	Pathogenic
1072536	NC_000008.10:g.(?90990438)(90990561_?)del	Pathogenic
1072538	NC_000008.10:g.(?90958358)(90960130_?)del	Pathogenic
1072539	NC_000008.10:g.(?90955471)(90976745_?)del	Pathogenic
1072749	NM_002485.5(NBN):c.765_801del (p.Asn256fs)	Pathogenic
1073031	NM_002485.5(NBN):c.1417C>T (p.Gln473Ter)	Pathogenic
1073255	NM_002485.5(NBN):c.1939del (p.Ser647fs)	Pathogenic
1073911	NM_002485.5(NBN):c.1496C>A (p.Ser499Ter)	Pathogenic
1074632	NM_002485.5(NBN):c.2089G>T (p.Gly697Ter)	Pathogenic
1075300	NM_002485.5(NBN):c.1993A>T (p.Lys665Ter)	Pathogenic
1075344	NM_002485.5(NBN):c.1695_1698dup (p.Phe567fs)	Pathogenic
1075360	NM_002485.5(NBN):c.1190C>G (p.Ser397Ter)	Pathogenic
1075578	NM_002485.5(NBN):c.1362dup (p.Ile455fs)	Pathogenic
1075823	NM_002485.5(NBN):c.228_231dup (p.Val78fs)	Pathogenic
1076528	NM_002485.5(NBN):c.1778_1779insGGCCGGGCGCGGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCCGAGGCGGGTGGATCATGAGGTCAGGAGATCGAGACCATCCTGGCTAACAAGGTGAAACCCCNNNNNNNNNNAAAAAAAAAAAAAAAAAAAAGAAAAAGGCC (p.Pro593_Arg594insAlaGlyArgGlyGlySerArgLeuTer)	Pathogenic
1076558	NM_002485.5(NBN):c.1192C>T (p.Gln398Ter)	Pathogenic
127878	NM_002485.5(NBN):c.698_701del (p.Lys233fs)	Pathogenic
1319192	NM_002485.5(NBN):c.1342C>T (p.Gln448Ter)	Pathogenic
1355027	NM_002485.5(NBN):c.1405del (p.Asp469fs)	Pathogenic
1360506	NM_002485.5(NBN):c.298G>T (p.Gly100Ter)	Pathogenic
1369636	NM_002485.5(NBN):c.393_400del (p.Ile132fs)	Pathogenic
1382638	NM_002485.5(NBN):c.1644dup (p.Lys549Ter)	Pathogenic
1384633	NM_002485.5(NBN):c.1982C>G (p.Ser661Ter)	Pathogenic
1388193	NM_002485.5(NBN):c.1583T>G (p.Leu528Ter)	Pathogenic
1393646	NM_002485.5(NBN):c.205_212del (p.Lys69fs)	Pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

4997 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:89982757:C:G	A46P	0.998
8:89982816:A:T	V26D	0.998
8:89980787:A:G	W143R	0.997
8:89980787:A:T	W143R	0.997
8:89982756:G:T	A46D	0.997
8:89982809:C:A	R28S	0.997
8:89982809:C:G	R28S	0.997
8:89982810:C:G	R28T	0.997
8:89982813:C:T	G27E	0.997
8:89984558:A:G	W2R	0.997
8:89984558:A:T	W2R	0.997
8:89943314:A:G	L708P	0.996
8:89980765:A:G	L150P	0.996
8:89981396:C:T	G100E	0.996
8:89982765:C:G	R43P	0.996
8:89982767:G:C	S42R	0.996
8:89982767:G:T	S42R	0.996
8:89982769:T:G	S42R	0.996
8:89982810:C:A	R28M	0.996
8:89982814:C:G	G27R	0.996
8:89982814:C:T	G27R	0.996
8:89971210:A:G	F222S	0.995
8:89971221:T:A	R218S	0.995
8:89971221:T:G	R218S	0.995
8:89981487:C:G	D70H	0.995
8:89946152:C:A	K686N	0.994
8:89946152:C:G	K686N	0.994
8:89980735:T:A	K160I	0.994
8:89981399:A:G	F99S	0.994
8:89982813:C:A	G27V	0.994

dbSNP variants (sampled 300 via entrez): RS1000023054 (8:89974351 ATACTAGTC>A), RS1000029329 (8:89934863 C>A), RS1000105939 (8:89948075 A>T), RS1000123382 (8:89952366 G>A), RS1000181272 (8:89982818 A>C), RS1000198810 (8:89938753 T>C), RS1000224889 (8:89985914 T>C), RS1000396368 (8:89979738 C>T), RS1000479545 (8:89974579 T>C), RS1000547137 (8:89976886 A>G), RS1000677568 (8:89963822 A>T), RS1000682067 (8:89969421 G>A), RS1000707009 (8:89983146 A>G,T), RS1000713564 (8:89933043 C>T), RS1000731792 (8:89940108 T>C)

Disease associations

OMIM: gene MIM:602667 | disease phenotypes: MIM:251260, MIM:609135, MIM:604370, MIM:114480, MIM:613659, MIM:167000, MIM:613065, MIM:114550, MIM:607432, MIM:176807, MIM:612555

GenCC curated gene-disease

Disease	Classification	Inheritance
Nijmegen breakage syndrome	Definitive	Autosomal recessive
rhabdomyosarcoma	Moderate	Autosomal recessive
prostate cancer	Limited	Autosomal dominant
idiopathic aplastic anemia	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Nijmegen breakage syndrome	Definitive	AR
hereditary breast carcinoma	Refuted	AD

Mondo (28): Nijmegen breakage syndrome (MONDO:0009623), hereditary neoplastic syndrome (MONDO:0015356), aplastic anemia (MONDO:0015909), breast-ovarian cancer, familial, susceptibility to, 1 (MONDO:0011450), breast cancer (MONDO:0007254), acute lymphoblastic leukemia (MONDO:0004967), hereditary breast ovarian cancer syndrome (MONDO:0003582), ovarian carcinoma (MONDO:0005140), hereditary breast carcinoma (MONDO:0016419), prostate cancer (MONDO:0008315), gastric cancer (MONDO:0001056), diffuse midline glioma, H3 K27-altered (MONDO:1060171), ovarian cancer (MONDO:0008170), lymphoma (MONDO:0005062), leukemia, acute lymphocytic, susceptibility to, 1 (MONDO:0013108)

Orphanet (15): Inherited cancer-predisposing syndrome (Orphanet:140162), Nijmegen breakage syndrome (Orphanet:647), Rare aplastic anemia (Orphanet:182040), Idiopathic aplastic anemia (Orphanet:88), Hereditary breast and/or ovarian cancer syndrome (Orphanet:145), Acute lymphoblastic leukemia (Orphanet:513), Hereditary breast cancer (Orphanet:227535), Familial prostate cancer (Orphanet:1331), Rare ovarian cancer (Orphanet:213500), Lymphoma (Orphanet:223735), Diffuse large B-cell lymphoma (Orphanet:544), Familial pancreatic carcinoma (Orphanet:1333), Rare carcinoma of pancreas (Orphanet:217074), Lissencephaly (Orphanet:48471), Hepatocellular carcinoma (Orphanet:88673)

HPO phenotypes

94 total (30 of 94 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000010	Recurrent urinary tract infections
HP:0000126	Hydronephrosis
HP:0000175	Cleft palate
HP:0000204	Cleft upper lip
HP:0000246	Sinusitis
HP:0000252	Microcephaly
HP:0000265	Mastoiditis
HP:0000271	Abnormality of the face
HP:0000278	Retrognathia
HP:0000286	Epicanthus
HP:0000294	Low anterior hairline
HP:0000340	Sloping forehead
HP:0000347	Micrognathia
HP:0000364	Hearing abnormality
HP:0000400	Macrotia
HP:0000403	Recurrent otitis media
HP:0000426	Prominent nasal bridge
HP:0000444	Convex nasal ridge
HP:0000448	Prominent nose
HP:0000453	Choanal atresia
HP:0000470	Short neck
HP:0000492	Abnormal eyelid morphology
HP:0000524	Conjunctival telangiectasia
HP:0000582	Upslanted palpebral fissure
HP:0000750	Delayed speech and language development
HP:0000752	Hyperactivity
HP:0000957	Cafe-au-lait spot
HP:0000992	Cutaneous photosensitivity
HP:0001249	Intellectual disability

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST90002388_254	Lymphocyte count	3.000000e-18
GCST90002389_181	Lymphocyte percentage of white cells	7.000000e-10

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004587	lymphocyte count
EFO:0007993	lymphocyte percentage of leukocytes

MeSH disease descriptors (16)

Descriptor	Name	Tree numbers
D000741	Anemia, Aplastic	C15.378.050.085; C15.378.190.223.250
D006528	Carcinoma, Hepatocellular	C04.557.470.200.025.255; C04.588.274.623.160; C06.301.623.160; C06.552.697.160
D061325	Hereditary Breast and Ovarian Cancer Syndrome	C04.588.180.483; C04.588.322.455.431; C04.700.517; C12.050.351.500.056.630.705.431; C12.050.351.937.418.685.431; C12.100.250.056.630.705.431; C12.900.418.685.431; C16.320.700.517; C17.800.090.500.483; C19.344.410.431; C19.391.630.705.431
D054082	Lissencephaly	C10.500.507.450.499; C16.131.666.507.450.499
D008223	Lymphoma	C04.557.386; C15.604.515.569; C20.683.515.761
D016403	Lymphoma, Large B-Cell, Diffuse	C04.557.386.480.150.585; C15.604.515.569.480.150.585; C20.683.515.761.480.150.585
D008594	Menopause, Premature	C12.050.351.500.056.630.250; C12.100.250.056.630.250; G08.686.157.500.500; G08.686.841.249.500.500
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700
D049932	Nijmegen Breakage Syndrome	C18.452.284.600
D010051	Ovarian Neoplasms	C04.588.322.455; C12.050.351.500.056.630.705; C12.050.351.937.418.685; C12.100.250.056.630.705; C12.900.418.685; C19.344.410; C19.391.630.705
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750
D012208	Rhabdomyosarcoma	C04.557.450.590.550.660; C04.557.450.795.550.660
C538494	Aplastic anemia, idiopathic (supp.)
C562840	Breast Cancer, Familial (supp.)
C537243	Prostate cancer, familial (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5169101 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

66 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Doxorubicin	affects response to substance, affects phosphorylation, decreases reaction, increases phosphorylation, increases reaction (+2 more)	4
Valproic Acid	affects expression, decreases expression, decreases methylation	4
methylmercuric chloride	increases expression, affects cotreatment	3
Resveratrol	increases phosphorylation, affects cotreatment, increases expression, affects binding, decreases expression	3
sodium arsenite	decreases expression, increases abundance, increases expression	2
Air Pollutants	increases oxidation, affects expression, affects cotreatment, increases abundance	2
Cisplatin	decreases response to substance, increases expression	2
Mustard Gas	decreases expression	2
Ozone	affects cotreatment, increases oxidation, increases abundance, affects expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
TAK-243	increases sumoylation	1
myristicin	decreases expression	1
oxybenzone	increases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
Nonidet P-40	increases expression	1
trichostatin A	affects expression	1
riddelliine	decreases expression, increases metabolic processing	1
delphinidin	increases expression	1
butyraldehyde	decreases expression	1
fludarabine	affects cotreatment, decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
4-hydroxy-2-nonenal	decreases expression	1
methacrylaldehyde	increases abundance, affects cotreatment, increases oxidation	1
ptaquiloside	decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
celastrol	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
gedunin	decreases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5117745	Binding	Activation of NBS1 phosphorylation in human MDA-MB-231 cells at 5 to 20 uM measured after 6 to 48 hrs by Western blot analysis	Discovery of fused benzimidazole-imidazole autophagic flux inhibitors for treatment of triple-negative breast cancer. — Eur J Med Chem

Cellosaurus cell lines

44 cell lines: 30 transformed cell line, 6 cancer cell line, 5 finite cell line, 3 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_0Q04	GM08037	Transformed cell line	Female
CVCL_0Q30	GM15788	Transformed cell line	Female
CVCL_0Q31	GM15789	Finite cell line	Male
CVCL_0Q32	GM15790	Transformed cell line	Male
CVCL_0Q33	GM15810	Transformed cell line	Female
CVCL_0Q34	GM15811	Transformed cell line	Male
CVCL_0Q35	GM15813	Transformed cell line	Female
CVCL_0Q36	GM15815	Transformed cell line	Female
CVCL_0Q37	GM15816	Transformed cell line	Male
CVCL_0Q39	GM15820	Transformed cell line	Female

Clinical trials (associated diseases)

557 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer