RAD50

Summary

RAD50 (RAD50 double strand break repair protein, HGNC:9816) is a protein-coding gene on chromosome 5q31.1, encoding DNA repair protein RAD50 (Q92878). Component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis. In precision oncology, RAD50 L1237F confers sensitivity to Irinotecan + Checkpoint Kinase Inhibitor AZD7762 in Ureter Small Cell Carcinoma (CIViC Level C).

The protein encoded by this gene is highly similar to Saccharomyces cerevisiae Rad50, a protein involved in DNA double-strand break repair. This protein forms a complex with MRE11 and NBS1. The protein complex binds to DNA and displays numerous enzymatic activities that are required for nonhomologous joining of DNA ends. This protein, cooperating with its partners, is important for DNA double-strand break repair, cell cycle checkpoint activation, telomere maintenance, and meiotic recombination. Knockout studies of the mouse homolog suggest this gene is essential for cell growth and viability. Mutations in this gene are the cause of Nijmegen breakage syndrome-like disorder.

Source: NCBI Gene 10111 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Nijmegen breakage syndrome-like disorder (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 43
• Clinical variants (ClinVar): 4,437 total — 308 pathogenic, 100 likely-pathogenic
• Phenotypes (HPO): 18
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 1 curated variant–drug association
• Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types
• Dosage sensitivity (ClinGen): haploinsufficiency little evidence, triplosensitivity no evidence
• MANE Select transcript: NM_005732

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9816
Approved symbol	RAD50
Name	RAD50 double strand break repair protein
Location	5q31.1
Locus type	gene with protein product
Status	Approved
Aliases	hRad50, RAD50-2
Ensembl gene	ENSG00000113522
Ensembl biotype	protein_coding
OMIM	604040
Entrez	10111

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 9 protein_coding, 5 nonsense_mediated_decay, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000378823, ENST00000416135, ENST00000423956, ENST00000434288, ENST00000453394, ENST00000455677, ENST00000487596, ENST00000496204, ENST00000533482, ENST00000651160, ENST00000651249, ENST00000651541, ENST00000651658, ENST00000651723, ENST00000652016, ENST00000652485, ENST00000918903

RefSeq mRNA: 1 — MANE Select: NM_005732 NM_005732

CCDS: CCDS34233

Canonical transcript exons

ENST00000378823 — 25 exons

Exon	Start	End
ENSE00001084080	132642178	132646349
ENSE00003465013	132603300	132603489
ENSE00003466270	132591877	132592034
ENSE00003467955	132603920	132604046
ENSE00003484322	132594869	132595044
ENSE00003488133	132591224	132591406
ENSE00003490764	132559284	132559367
ENSE00003491836	132587562	132587690
ENSE00003494203	132595573	132595810
ENSE00003525453	132588687	132588880
ENSE00003537522	132618070	132618294
ENSE00003557477	132608615	132608725
ENSE00003566982	132579862	132580066
ENSE00003573329	132638081	132638223
ENSE00003573898	132589631	132589837
ENSE00003575441	132640672	132640805
ENSE00003595881	132609283	132609396
ENSE00003598521	132609117	132609209
ENSE00003628109	132637115	132637200
ENSE00003645556	132604806	132604999
ENSE00003652956	132616003	132616130
ENSE00003682925	132587924	132588089
ENSE00003714543	132575777	132575928
ENSE00003738386	132579317	132579502
ENSE00003842154	132556977	132557453

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 94.86.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.5018 / max 344.4867, expressed in 1793 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
58481	15.4328	1776
58483	1.9535	1067
58482	1.0174	660
58484	0.0980	16

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus callosum	UBERON:0002336	94.86	gold quality
calcaneal tendon	UBERON:0003701	93.97	gold quality
colonic epithelium	UBERON:0000397	92.57	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.04	gold quality
adrenal tissue	UBERON:0018303	91.91	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.64	gold quality
islet of Langerhans	UBERON:0000006	90.64	gold quality
stromal cell of endometrium	CL:0002255	90.63	gold quality
cortical plate	UBERON:0005343	90.16	gold quality
ventricular zone	UBERON:0003053	89.95	gold quality
endometrium	UBERON:0001295	89.89	gold quality
tonsil	UBERON:0002372	89.21	gold quality
sural nerve	UBERON:0015488	88.07	gold quality
ganglionic eminence	UBERON:0004023	87.66	gold quality
bone marrow cell	CL:0002092	86.76	gold quality
urinary bladder	UBERON:0001255	86.60	gold quality
muscle tissue	UBERON:0002385	86.59	gold quality
rectum	UBERON:0001052	86.32	gold quality
pancreas	UBERON:0001264	86.28	gold quality
skeletal muscle tissue	UBERON:0001134	85.90	gold quality
smooth muscle tissue	UBERON:0001135	85.90	gold quality
gall bladder	UBERON:0002110	85.53	gold quality
gastrocnemius	UBERON:0001388	85.10	gold quality
vermiform appendix	UBERON:0001154	85.01	gold quality
duodenum	UBERON:0002114	85.01	gold quality
mucosa of stomach	UBERON:0001199	84.64	gold quality
placenta	UBERON:0001987	84.64	gold quality
bone marrow	UBERON:0002371	84.49	gold quality
monocyte	CL:0000576	84.41	gold quality
muscle of leg	UBERON:0001383	84.41	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-29	yes	945.86
E-MTAB-8271	yes	6.44
E-ANND-3	yes	5.67
E-MTAB-7303	no	205.70

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HAND1, HAND2, MYC

miRNA regulators (miRDB)

88 targeting RAD50, 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-340-5P	100.00	72.50	4437
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690

Functional genomics

ClinGen dosage: haploinsufficiency 1 (little evidence), 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)
• Gastric carcinomas with high TRF1 and TRF2 expression may need a large quantity of the MRE11 complex. (PMID:12007281)
• Adenovirus oncoproteins inactivate the Mre11-Rad50-NBS1 DNA repair complex (PMID:12124628)
• DNA end-binding specificity of the human Rad50/Mre11 complex is influenced by ATP (PMID:12384589)
• activation in response to replication-dependent DNA double-strand breaks induced by mammalian DNA topoisomerase I cleavage complexes (PMID:12660252)
• the coiled-coil of the human Rad50 DNA repair protein contains specific segments of increased flexibility (PMID:12805565)
• NO-dependent cytoskeletal changes and inhibition of EC migration contribute to the suppression of angiogenesis by hRAD50 delivery in vivo (PMID:14550546)
• serine to arginine change in the Rad50 protein prevents ATP binding and disrupts the communication among the other ATP-binding loops (PMID:14698290)
• 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)
• Nibrin, Mre11 and Rad50 also act as adaptors for some downstream Atm phosphorylation events (PMID:15234984)
• 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)
• findings show that the Mre11-Rad50-Nbs1 (MRN) complex acts as a double-strand break sensor for ATM and recruits ATM to broken DNA molecules (PMID:15790808)
• The MRE11-RAD50-NBS1 complex accelerates somatic hypermutation and gene conversion of immunoglobulin variable regions. (PMID:15937485)
• Rad50 depletion impacts upon ATR-dependent DNA damage responses. (PMID:16087684)
• the dynamic architecture of human Rad50/Mre11/Nbs1 is markedly affected by DNA binding (PMID:16163361)
• Adenovirus 5 exploits the cellular aggresome response to accelerate inactivation of MRE11-RAD50-NBS1 (MRN) complexes that otherwise inhibit viral DNA replication and packaging. (PMID:16254336)
• Mutations in RAD50 is associated with breast cancer (PMID:16474176)
• the Mre11-Rad50-Nbs1 complex stayed in the nucleus and remained intact in response to hypertonicity (PMID:16788144)
• Mre11 stabilizes Nbs1 and Rad50 and MRN activates Chk2 downstream from ATM in response to replication-mediated DNA double strand breaks (PMID:16905549)
• MRE11, but not RAD50 or NBS1 variants, may play a role in non-Hodgkin’s lymphoma (PMID:17169801)
• Mre11/Rad50 complexes from three organisms catalyze the reversible adenylate kinase reaction in vitro. (PMID:17349953)
• mutation of conserved cysteines abrogates dimerization at the hook domain in Rad50; however, disrupting dimerization at this domain does not impair the interaction of Rad50 with itself and Mre11 or affect DNA-binding activity of the Mre11-Rad50 complex (PMID:17426050)
• Data reveal a role for the Rad50 complex in V(D)J recombination, and demonstrate that the protein product of the disease-causing allele responsible for Nijmegen breakage syndrome encodes a protein with residual DNA double-strand break repair activity. (PMID:17524422)
• the Mre11-Rad50-Nbs1 complex plays critical roles both upstream and downstream of ATR to regulate the S-phase checkpoint when replication forks are stalled (PMID:17526493)
• microsatelite instability and alterations in the MRE11 and RAD50 repeats that are associated with the reduced protein expression and functional impairment of the MRE11-RAD50-NBS1 complex in Lynch syndrome (PMID:17534377)
• the MRN (MRE11/RAD50/NBS1)complex, and especially NBS1, is required for alternative lengthening of telomeres (PMID:17693401)
• wild-type RAD50 downregulates telomeric association of TRF1 (PMID:17694070)
• These data support a role for RPA as an initial signal/sensor for DNA damage that facilitates recruitment of MRE11/RAD50/NBS1 and ATM/ATR to sites of damage, where they then work together to fully activate the DNA damage response. (PMID:17700070)
• Studies suggest new roles of Mre11/Rad50/Nbs1 complex in the maintenance of genome stability through preventing rereplication and rereplication-associated double-stranded breaks when licensing control is compromised. (PMID:17715134)
• Mre11/Rad50/Nbs1 complex (MRN) poses a barrier to adeno-associated virus and that the helper function provided by E1b55K/E4orf6 involves MRN degradation. (PMID:17898048)
• Hypothesis examined in a study of 559 breast cancer patients of single-nucleotide polymorphisms in Mre11, Rad50, and Nbs1 and by the in vivo detection of binding between Mre11 and BRCA1, encoded by the breast cancer susceptibility gene BRCA1. (PMID:17932350)
• hRAD50 may play different roles in the development of MSS and MSI coloreatal cancers. (PMID:18219098)
• Snm1B interacts with the Mre11-Rad50-Nbs1 (MRN) complex and with FancD2 further substantiating its role as a checkpoint/DNA repair protein. (PMID:18469862)
• These results suggest that Mre11-Rad50-Nbs1-dependent generation of ssDNA oligos, which constitute a unique signal of ongoing double-strand breaks repair not encountered in normal DNA metabolism, stimulates ATM activity. (PMID:18596698)
• Transcription-coupled DNA double-strand breaks are mediated via the nucleotide excision repair and the Mre11-Rad50-Nbs1 complex (PMID:18632984)
• ATM, Mre11, and Rad50 are required for survival after replication fork stalling. (PMID:18829552)
• RAD50/MRE11/NBS1 proteins interacted with each other, which had different clinicopathological significance in microsatellite-stable and -unstable colorectal cancer (PMID:18830935)
• Rad50 c.687delT does not contribute significantly to familial breast cancer in a French population. (PMID:19190165)
• The Mre11/Rad50/Nbs1 (MRN) complex is recruited to viral centres only during infection with adenoviruses lacking the early region E4 and ATR signaling is activated. (PMID:19197236)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rad50	ENSDARG00000038917
mus_musculus	Rad50	ENSMUSG00000020380
rattus_norvegicus	Rad50	ENSRNOG00000033065
drosophila_melanogaster	rad50	FBGN0034728
caenorhabditis_elegans		WBGENE00004296

Protein

Protein identifiers

DNA repair protein RAD50 — Q92878 (reviewed: Q92878)

All UniProt accessions (13): Q92878, A0A494BZW0, A0A494BZX5, A0A494BZX8, A0A494C0Y7, A0A494C122, A0A494C1B7, C9JNH8, E7EN38, E7ESD9, E9PM98, H7C0P8, H7C0V2

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 complex, RAD50 is both required to bind DNA ends and hold them in close proximity and regulate the activity of MRE11. RAD50 provides an ATP-dependent control of MRE11 by positioning DNA ends into the MRE11 active site: ATP-binding induces a large structural change from an open form with accessible MRE11 nuclease sites into a closed form. The MRN complex is also required for DNA damage signaling via activation of the ATM and ATR kinases: the nuclease activity of MRE11 is not required to activate ATM and ATR. The MRN complex is also required for the processing of R-loops. In telomeres the MRN complex may modulate t-loop formation.

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 MCM8 and 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. Found in a complex with TERF2. Interacts with RINT1. Interacts with BRCA1 via its N-terminal domain. Interacts with DCLRE1C/Artemis. Interacts with MRNIP. Interacts with CYREN (via XLF motif). Interacts with C1QBP and MRE11; interaction takes place in absence of DNA damage to form the MRC (MRE11-RAD50-C1QBP) complex that inhibits the activity of MRE11. (Microbial infection) Interacts with herpes simplex virus 1 protein UL12.

Subcellular location. Nucleus. Chromosome. Telomere.

Tissue specificity. Expressed at very low level in most tissues, except in testis where it is expressed at higher level. Expressed in fibroblasts.

Post-translational modifications. Phosphorylation at Ser-635 by ATM in response to DNA damage is required for double-strand break (DSB) repair.

Disease relevance. Nijmegen breakage syndrome-like disorder (NBSLD) [MIM:613078] A disorder similar to Nijmegen breakage syndrome and characterized by chromosomal instability, radiation sensitivity, microcephaly, growth retardation, short stature and bird-like face. Immunodeficiency is absent. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Binds 1 zinc ion per homodimer.

Domain organisation. The zinc-hook, which separates the large intramolecular coiled coil regions, contains 2 Cys residues that coordinate one molecule of zinc with the help of the 2 Cys residues of the zinc-hook of another RAD50 molecule, thereby forming a V-shaped homodimer. The two heads of the homodimer, which constitute the ATP-binding domain, interact with the MRE11 homodimer.

Similarity. Belongs to the SMC family. RAD50 subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q92878-1	1, RAD50-1, RAD50-2	yes
Q92878-2	2
Q92878-3	3, RAD50-3

RefSeq proteins (1): NP_005723* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004584	Rad50_eukaryotes	Family
IPR013134	Zn_hook_RAD50	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR038729	Rad50/SbcC_AAA	Domain

Pfam: PF04423, PF13476, PF13558

Catalyzed reactions (Rhea), 1 shown:

• ATP + H2O = ADP + phosphate + H(+) (RHEA:13065)

UniProt features (57 total): binding site 14, sequence variant 14, helix 6, coiled-coil region 5, mutagenesis site 5, modified residue 3, sequence conflict 3, splice variant 2, turn 2, chain 1, domain 1, strand 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
5GOX	X-RAY DIFFRACTION	2.4
9Q9K	ELECTRON MICROSCOPY	2.59
9Q9J	ELECTRON MICROSCOPY	2.71
9Q9I	ELECTRON MICROSCOPY	2.79
9Q9M	ELECTRON MICROSCOPY	2.81
9Q9H	ELECTRON MICROSCOPY	3.11

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92878-F1	82.83	0.14

Functional residue map

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

Ligand- & substrate-binding residues (14): 41; 42; 43; 43; 44; 67; 69; 159; 159; 681; 684; 13 …

Post-translational modifications (3): 635, 690, 959

Mutagenesis-validated functional residues (5):

Position	Phenotype
42	abolishes ability to degrade atp.
635	abolished phosphorylation by atm, leading to impaired ability to mediate dna repair.
675–679	decreased ability to mediate dna repair due to impaired mrn oligomers formation.
1202	abolished atpase activity and ability and activate atm.
1231	abolishes ability to degrade atp.

Function

Pathways and Gene Ontology

Reactome pathways

21 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-9976102	Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)

MSigDB gene sets: 396 (showing top): PID_FANCONI_PATHWAY, GOBP_DNA_TEMPLATED_DNA_REPLICATION_MAINTENANCE_OF_FIDELITY, GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, GOBP_RNA_TEMPLATED_DNA_BIOSYNTHETIC_PROCESS, REACTOME_MEIOTIC_RECOMBINATION, GOBP_CHROMOSOME_ORGANIZATION, GOBP_REGULATION_OF_DNA_RECOMBINATION, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, MULLIGHAN_NPM1_SIGNATURE_3_UP, GOMF_ENDONUCLEASE_ACTIVITY, PID_TELOMERASE_PATHWAY, GOBP_TELOMERE_CAPPING, BIOCARTA_ATM_PATHWAY, GOMF_NUCLEASE_ACTIVITY, REACTOME_G2_M_DNA_DAMAGE_CHECKPOINT

GO Biological Process (22): regulation of mitotic recombination (GO:0000019), telomere maintenance via recombination (GO:0000722), telomere maintenance (GO:0000723), double-strand break repair via homologous recombination (GO:0000724), DNA double-strand break processing (GO:0000729), DNA repair (GO:0006281), double-strand break repair (GO:0006302), DNA recombination (GO:0006310), DNA damage response (GO:0006974), telomere maintenance via telomerase (GO:0007004), reciprocal meiotic recombination (GO:0007131), telomeric 3’ overhang formation (GO:0031860), positive regulation of telomere maintenance (GO:0032206), homologous recombination (GO:0035825), mitotic G2/M transition checkpoint (GO:0044818), R-loop processing (GO:0062176), chromosome organization involved in meiotic cell cycle (GO:0070192), DNA strand resection involved in replication fork processing (GO:0110025), negative regulation of telomere capping (GO:1904354), positive regulation of double-strand break repair (GO:2000781), chromosome organization (GO:0051276), meiotic cell cycle (GO:0051321)

GO Molecular Function (16): DNA binding (GO:0003677), double-stranded telomeric DNA binding (GO:0003691), ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), protein-macromolecule adaptor activity (GO:0030674), identical protein binding (GO:0042802), single-stranded telomeric DNA binding (GO:0043047), protein serine/threonine kinase activator activity (GO:0043539), metal ion binding (GO:0046872), G-quadruplex DNA binding (GO:0051880), single-stranded DNA endonuclease activity (GO:0000014), nucleotide binding (GO:0000166), DNA helicase activity (GO:0003678), protein binding (GO:0005515), 3’-5’ exonuclease activity (GO:0008408), hydrolase activity (GO:0016787)

GO Cellular Component (10): chromosome, telomeric region (GO:0000781), condensed nuclear chromosome (GO:0000794), nucleus (GO:0005634), nucleoplasm (GO:0005654), membrane (GO:0016020), Mre11 complex (GO:0030870), site of double-strand break (GO:0035861), 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
DNA metabolic process	5
double-strand break repair	3
cellular anatomical structure	3
mitotic recombination	2
telomere maintenance	2
5’-3’ DNA exonuclease activity	2
meiotic cell cycle process	2
telomere capping	2
telomeric repeat DNA binding	2
protein binding	2
nuclear protein-containing complex	2
regulation of DNA recombination	1
telomere organization	1
recombinational repair	1
DNA damage response	1
DNA repair	1
cellular response to stress	1
telomerase activity	1
RNA-templated DNA biosynthetic process	1
telomere maintenance via telomere lengthening	1
telomere-telomerase complex assembly	1
meiosis I	1
reciprocal homologous recombination	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
mitotic cell cycle checkpoint signaling	1
negative regulation of G2/M transition of mitotic cell cycle	1
chromatin remodeling	1
chromosome organization	1
meiotic cell cycle	1
replication fork processing	1
negative regulation of telomere maintenance	1
regulation of telomere capping	1
positive regulation of DNA repair	1
regulation of double-strand break repair	1
nucleic acid binding	1
double-stranded DNA binding	1

Protein interactions and networks

STRING

1712 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RAD50	MRE11	P49959	997
RAD50	NBN	O60934	995
RAD50	BRCA1	P38398	762
RAD50	RINT1	Q6NUQ1	663
RAD50	ATM	Q13315	636
RAD50	MSH3	P20585	624
RAD50	ATR	Q13535	590
RAD50	LIG3	P49916	570
RAD50	XRCC5	P13010	564
RAD50	XRCC6	P12956	561
RAD50	RAD52	P43351	557
RAD50	XRCC1	P18887	528
RAD50	RAD51	Q06609	525
RAD50	REV3L	O60673	484
RAD50	RBBP8	Q99708	481

IntAct

222 interactions, top by confidence:

A	B	Type	Score
MRE11	XRS2	psi-mi:“MI:0915”(physical association)	0.970
MDC1	NBN	psi-mi:“MI:0914”(association)	0.970
H2AX	NBN	psi-mi:“MI:0914”(association)	0.860
MRE11	NBN	psi-mi:“MI:0914”(association)	0.820
NBN	MRE11	psi-mi:“MI:0914”(association)	0.820
RGS20	GLRX3	psi-mi:“MI:0914”(association)	0.810
RNF146	TNKS	psi-mi:“MI:0914”(association)	0.790
RFXANK	RFXAP	psi-mi:“MI:0914”(association)	0.780
RAD50	NBN	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
MDC1	MRE11	psi-mi:“MI:0914”(association)	0.670
RAD50	RAD50	psi-mi:“MI:0407”(direct interaction)	0.650
CSK	TNS3	psi-mi:“MI:0914”(association)	0.640
CHCHD4	SSNA1	psi-mi:“MI:0914”(association)	0.640
SIRT1	NBN	psi-mi:“MI:0914”(association)	0.630
FANCD2	NBN	psi-mi:“MI:0914”(association)	0.630

BioGRID (618): RAD50 (Affinity Capture-MS), RAD50 (Affinity Capture-MS), RAD50 (Affinity Capture-MS), RAD50 (Affinity Capture-MS), RAD50 (Affinity Capture-MS), RAD50 (Reconstituted Complex), RAD50 (Affinity Capture-MS), RAD50 (Affinity Capture-MS), RAD50 (Affinity Capture-Western), RAD50 (Affinity Capture-Western), RAD50 (Affinity Capture-Western), ILF2 (Affinity Capture-Western), MCM5 (Affinity Capture-Western), ILF3 (Affinity Capture-Western), RAD50 (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8GVF0, A0A1L8GXM0, A0A8M9PQ61, A2ZAC2, G0SHW7, G5EG17, O14777, O44199, O94383, O95347, P12753, P38989, P41003, P48996, P53692, P70388, Q09591, Q10173, Q12267, Q12749, Q196W6, Q336R3, Q4R630, Q503N2, Q54PK4, Q5U4X5, Q6DRJ7, Q6GQ71, Q6P9I7, Q6Q1P4, Q76I89, Q76I90, Q7ZW63, Q802R8, Q8AWF4, Q8AWF5, Q8CG48, Q90988, Q924W5, Q92878

Diamond homologs: A0A1L8GVF0, A0A1L8GXM0, C6KSQ6, P70388, Q8TXI4, Q92878, Q96YR5, Q97WH0, Q9JIL8, O31707, G0SHW7, O44199, P12753, Q54CS9, Q73L25, Q8SRK6, Q9SL02, Q9UTJ8, Q9W252, A3Q8S8, A6VR67, A8GYE5, B2FT82, B3PEM4, B4SR07, B8CH73, D4GUK1, O29230, O33600, O58687, O97594, P58301, P58302, P62134, Q21PV3, Q2P9L9, Q3BZS9, Q4V0S6, Q58718, Q5H713

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
ATM	unknown	RAD50	phosphorylation
RAD50	up-regulates	MRE11	binding
RAD50	up-regulates	ATM	binding
RBL2	“up-regulates activity”	RAD50	binding
RAD50	“up-regulates activity”	RINT1	binding
RAD50	up-regulates	BRCA1	binding
RAD50	“form complex”	MRE11/RAD50/NBS1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 250 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	5	14.7×	1e-03
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks	12	10.8×	8e-07
Nonhomologous End-Joining (NHEJ)	9	9.3×	2e-04
TAK1-dependent IKK and NF-kappa-B activation	5	9.3×	8e-03
Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes	6	8.0×	6e-03
TP53 Regulates Transcription of DNA Repair Genes	7	7.8×	2e-03
G2/M Checkpoints	9	7.5×	5e-04
G2/M DNA damage checkpoint	10	7.4×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
double-strand break repair via nonhomologous end joining	6	11.4×	5e-03
JNK cascade	7	8.6×	5e-03
double-strand break repair	9	8.2×	8e-04
DNA damage response	19	4.6×	3e-05

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 1 cancer types — GBM.

Clinical variants and AI predictions

ClinVar

4437 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	308
Likely pathogenic	100
Uncertain significance	2442
Likely benign	1270
Benign	71

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1064538	NM_005732.4(RAD50):c.2524G>A (p.Val842Ile)	Pathogenic
1068476	NM_005732.4(RAD50):c.1048C>T (p.Gln350Ter)	Pathogenic
1068560	NM_005732.4(RAD50):c.1934_1935dup (p.Lys646fs)	Pathogenic
1068568	NM_005732.4(RAD50):c.1579C>T (p.Gln527Ter)	Pathogenic
1068734	NM_005732.4(RAD50):c.1019_1022del (p.Asn340fs)	Pathogenic
1068959	NM_005732.4(RAD50):c.2296_2300dup (p.Asp767fs)	Pathogenic
1069071	NM_005732.4(RAD50):c.1507G>T (p.Glu503Ter)	Pathogenic
1069241	NM_005732.4(RAD50):c.2043C>A (p.Cys681Ter)	Pathogenic
1069393	NM_005732.4(RAD50):c.2371_2372del (p.Asp791fs)	Pathogenic
1069944	NM_005732.4(RAD50):c.1235del (p.Asn412fs)	Pathogenic
1070460	NM_005732.4(RAD50):c.1395_1396delinsTT (p.Gln465_Gln466delinsHisTer)	Pathogenic
1070572	NM_005732.4(RAD50):c.551+1dup	Pathogenic
1071594	NM_005732.4(RAD50):c.1576G>T (p.Glu526Ter)	Pathogenic
1072151	NM_005732.4(RAD50):c.877del (p.Met293fs)	Pathogenic
1072201	NM_005732.4(RAD50):c.2341del (p.Glu781fs)	Pathogenic
1072245	NC_000005.9:g.(?131891616)(131981313_?)del	Pathogenic
1072246	NC_000005.9:g.(?131893011)(131978062_?)del	Pathogenic
1072247	NC_000005.9:g.(?131893017)(131978056_?)del	Pathogenic
1072375	NM_005732.4(RAD50):c.1843del (p.Glu614_Leu615insTer)	Pathogenic
1072775	NM_005732.4(RAD50):c.2545_2546insGGCCGGGCGCGGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCCGAGGCGGGTGGATCATGAGGTCAAGAGATCGAGACCATCCTGGCTAACAAGGTGAAACCCCGTCTCTNNNNNNNNNNAAAAAAAAAAAAAAAAAAAAAAGATTGAATTGA (p.Asn849delinsArgProGlyAlaValAlaHisAlaCysAsnProSerThrLeuGlyGlyArgGlyGlyTrpIleMetArgSerArgAspArgAspHisProGlyTer)	Pathogenic
1073816	NM_005732.4(RAD50):c.2944_2945insTT (p.Lys982fs)	Pathogenic
1073908	NM_005732.4(RAD50):c.415G>T (p.Glu139Ter)	Pathogenic
1074938	NM_005732.4(RAD50):c.474_481del (p.His158fs)	Pathogenic
1075433	NM_005732.4(RAD50):c.1329_1330insAAGTT (p.Glu444fs)	Pathogenic
1075970	NM_005732.4(RAD50):c.2685dup (p.Thr896fs)	Pathogenic
1076008	NM_005732.4(RAD50):c.1412C>A (p.Ser471Ter)	Pathogenic
1076420	NM_005732.4(RAD50):c.1504del (p.Met502fs)	Pathogenic
127994	NM_005732.4(RAD50):c.1300_1306dup (p.Lys436delinsArgTer)	Pathogenic
127997	NM_005732.4(RAD50):c.1393C>T (p.Gln465Ter)	Pathogenic
128014	NM_005732.4(RAD50):c.2929_2932del (p.Glu977fs)	Pathogenic

SpliceAI

3966 predictions. Top by Δscore:

Variant	Effect	Δscore
5:132559282:A:AG	acceptor_gain	1.0000
5:132559283:G:GG	acceptor_gain	1.0000
5:132575773:A:AG	acceptor_gain	1.0000
5:132575773:AAAG:A	acceptor_gain	1.0000
5:132575774:A:G	acceptor_gain	1.0000
5:132575774:AAG:A	acceptor_gain	1.0000
5:132575775:A:AG	acceptor_gain	1.0000
5:132575775:A:T	acceptor_loss	1.0000
5:132575775:AG:A	acceptor_gain	1.0000
5:132575775:AGGTT:A	acceptor_gain	1.0000
5:132575776:G:GA	acceptor_gain	1.0000
5:132575776:GG:G	acceptor_gain	1.0000
5:132575776:GGTT:G	acceptor_gain	1.0000
5:132575776:GGTTG:G	acceptor_gain	1.0000
5:132575926:AAA:A	donor_gain	1.0000
5:132575927:AA:A	donor_gain	1.0000
5:132575929:G:GG	donor_gain	1.0000
5:132579316:GGC:G	acceptor_gain	1.0000
5:132587555:T:G	acceptor_gain	1.0000
5:132587556:TTTCA:T	acceptor_loss	1.0000
5:132587557:TTCAG:T	acceptor_loss	1.0000
5:132587558:TCA:T	acceptor_loss	1.0000
5:132587559:CAG:C	acceptor_loss	1.0000
5:132587560:A:AG	acceptor_gain	1.0000
5:132587560:AG:A	acceptor_loss	1.0000
5:132587561:G:GC	acceptor_gain	1.0000
5:132587561:GA:G	acceptor_gain	1.0000
5:132587561:GAAT:G	acceptor_gain	1.0000
5:132587561:GAATC:G	acceptor_gain	1.0000
5:132587673:G:GT	donor_gain	1.0000

AlphaMissense

8804 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:132557430:G:A	G36R	1.000
5:132557430:G:C	G36R	1.000
5:132557431:G:A	G36E	1.000
5:132557438:T:A	N38K	1.000
5:132557438:T:G	N38K	1.000
5:132557439:G:T	G39W	1.000
5:132557440:G:A	G39E	1.000
5:132557445:G:A	G41R	1.000
5:132557445:G:C	G41R	1.000
5:132557446:G:A	G41E	1.000
5:132559298:T:G	C48W	1.000
5:132575814:T:C	L84P	1.000
5:132579441:T:A	W164R	1.000
5:132579441:T:C	W164R	1.000
5:132579443:G:C	W164C	1.000
5:132579443:G:T	W164C	1.000
5:132579468:A:G	K173E	1.000
5:132579470:G:C	K173N	1.000
5:132579470:G:T	K173N	1.000
5:132579489:T:C	F180L	1.000
5:132579491:T:A	F180L	1.000
5:132579491:T:G	F180L	1.000
5:132595597:T:A	V665D	1.000
5:132595644:T:C	C681R	1.000
5:132595653:T:C	C684R	1.000
5:132637131:C:G	H1136D	1.000
5:132637176:T:A	W1151R	1.000
5:132637176:T:C	W1151R	1.000
5:132638099:T:A	I1165K	1.000
5:132638155:T:C	Y1184H	1.000

dbSNP variants (sampled 300 via entrez): RS1000052809 (5:132625481 C>T), RS1000083656 (5:132589967 G>T), RS1000117255 (5:132579646 T>C,G), RS1000136574 (5:132634120 G>T), RS1000160304 (5:132616241 A>C), RS1000199834 (5:132560823 A>G), RS1000330068 (5:132596169 A>G), RS1000363675 (5:132611869 TAC>T), RS1000377335 (5:132567342 T>C), RS1000388343 (5:132611567 C>A,G), RS1000533573 (5:132583885 C>T), RS1000569814 (5:132629134 C>G,T), RS1000583615 (5:132571630 A>G), RS1000593791 (5:132606016 A>G), RS1000597456 (5:132630227 A>G)

Disease associations

OMIM: gene MIM:604040 | disease phenotypes: MIM:613078, MIM:114480, MIM:167000, MIM:155255, MIM:604370, MIM:114550, MIM:613399, MIM:612555

GenCC curated gene-disease

Disease	Classification	Inheritance
Nijmegen breakage syndrome-like disorder	Strong	Autosomal recessive
familial ovarian cancer	Refuted Evidence	Autosomal dominant

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
hereditary breast carcinoma	Refuted	AD
familial ovarian cancer	Refuted	AD

Mondo (19): hereditary neoplastic syndrome (MONDO:0015356), Nijmegen breakage syndrome-like disorder (MONDO:0013118), hereditary breast carcinoma (MONDO:0016419), hereditary breast ovarian cancer syndrome (MONDO:0003582), ovarian cancer (MONDO:0008170), premature menopause (MONDO:0001119), skin neoplasm (MONDO:0002531), breast carcinoma (MONDO:0004989), medulloblastoma (MONDO:0007959), breast-ovarian cancer, familial, susceptibility to, 1 (MONDO:0011450), meningioma (MONDO:0016642), prostate cancer (MONDO:0008315), hepatocellular carcinoma (MONDO:0007256), lung sarcomatoid carcinoma (MONDO:0006279), myoepithelial tumor (MONDO:0002380)

Orphanet (9): Inherited cancer-predisposing syndrome (Orphanet:140162), Nijmegen breakage syndrome-like disorder (Orphanet:240760), Hereditary breast cancer (Orphanet:227535), Hereditary breast and/or ovarian cancer syndrome (Orphanet:145), Rare ovarian cancer (Orphanet:213500), Medulloblastoma (Orphanet:616), Meningioma (Orphanet:2495), Familial prostate cancer (Orphanet:1331), Hepatocellular carcinoma (Orphanet:88673)

HPO phenotypes

18 total (19 of 18 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000320	Bird-like facies
HP:0000540	Hypermetropia
HP:0001249	Intellectual disability
HP:0001251	Ataxia
HP:0001257	Spasticity
HP:0001510	Growth delay
HP:0002861	Melanoma
HP:0002894	Neoplasm of the pancreas
HP:0003002	Breast carcinoma
HP:0004313	Decreased circulating immunoglobulin concentration
HP:0004322	Short stature
HP:0010997	Chromosomal breakage induced by ionizing radiation
HP:0011027	Abnormal fallopian tube morphology
HP:0012125	Prostate cancer
HP:0030406	Primary peritoneal carcinoma
HP:0100615	Ovarian neoplasm
HP:0002858	Meningioma

GWAS associations

43 associations (top):

Study	Trait	p-value
GCST000222_2	IgE levels	4.000000e-08
GCST000576_1	Asthma	3.000000e-07
GCST002100_2	Atopic dermatitis	2.000000e-17
GCST002275_4	Asthma (childhood onset)	8.000000e-07
GCST002737_2	Atopic dermatitis	5.000000e-09
GCST002740_16	Inflammatory skin disease	2.000000e-18
GCST002844_3	Atopic dermatitis	4.000000e-07
GCST003144_5	Polycystic ovary syndrome	4.000000e-09
GCST003184_32	Atopic dermatitis	4.000000e-17
GCST003831_20	Asthma	2.000000e-07
GCST003987_9	Asthma	2.000000e-16
GCST004068_15	Venous thromboembolism adjusted for sickle cell variant rs77121243-T	9.000000e-06
GCST004600_161	Eosinophil percentage of white cells	2.000000e-65
GCST004606_127	Eosinophil count	4.000000e-70
GCST004617_106	Eosinophil percentage of granulocytes	3.000000e-63
GCST004624_90	Sum eosinophil basophil counts	1.000000e-63
GCST004633_55	Neutrophil percentage of white cells	2.000000e-09
GCST004861_69	Itch intensity from mosquito bite	2.000000e-10
GCST005038_125	Allergic disease (asthma, hay fever or eczema)	4.000000e-21
GCST005212_28	Asthma	5.000000e-16
GCST005213_2	Asthma (childhood onset)	2.000000e-09
GCST005790_50	Rosacea symptom severity	5.000000e-08
GCST005975_11	Eosinophil count	9.000000e-19
GCST006409_25	Allergic rhinitis	2.000000e-09
GCST006862_12	Asthma	1.000000e-14
GCST006911_19	Asthma (moderate or severe)	2.000000e-15
GCST007089_3	Polycystic ovary syndrome	1.000000e-10
GCST007564_14	Asthma or allergic disease (pleiotropy)	4.000000e-11
GCST007797_33	Asthma onset (childhood vs adult)	7.000000e-09
GCST007798_27	Asthma	7.000000e-32

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004842	eosinophil count
EFO:0007996	eosinophil percentage of granulocytes
EFO:0005090	basophil count
EFO:0007990	neutrophil percentage of leukocytes
EFO:0008377	mosquito bite reaction itch intensity measurement
EFO:0009180	rosacea severity measurement
EFO:0004847	age at onset

MeSH disease descriptors (12)

Descriptor	Name	Tree numbers
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
D008527	Medulloblastoma	C04.557.465.625.600.380.515; C04.557.465.625.600.590.500; C04.557.470.670.380.515; C04.557.470.670.590.500; C04.557.580.625.600.380.515; C04.557.580.625.600.590.500
D008579	Meningioma	C04.557.580.520; C04.557.645.520; C04.588.614.250.580.500; C10.551.240.500.500
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
D009208	Myoepithelioma	C04.557.435.585
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700
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
D012878	Skin Neoplasms	C04.588.805; C17.800.882
C562840	Breast Cancer, Familial (supp.)
C567767	Nijmegen Breakage Syndrome-Like Disorder (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725155 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

Clinical evidence (CIViC)

Drug × variant × indication: 1 predictive associations from 1 curated evidence items.

Variant	Therapy	Indication	Effect	Level	CIViC
RAD50 L1237F	Irinotecan + Checkpoint Kinase Inhibitor AZD7762	Ureter Small Cell Carcinoma	Sensitivity/Response	CIViC C	EID5829

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2299014	RAD50		0.00	0

ChEMBL bioactivities

5 potent at pChembl≥5 of 5 total, top 5 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.36	IC50	440	nM	MOLIBRESIB
5.76	Kd	1742	nM	CHEMBL5653589
5.76	ED50	1742	nM	CHEMBL5653589
5.05	Kd	8821	nM	CHEMBL3752910
5.05	ED50	8821	nM	CHEMBL3752910

PubChem BioAssay actives

3 with measured affinity, of 10 total; 3 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178777: Inhibition of RAD50 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	0.4400	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149186: Binding affinity to human RAD50 incubated for 45 mins by Kinobead based pull down assay	kd	1.7422	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149186: Binding affinity to human RAD50 incubated for 45 mins by Kinobead based pull down assay	kd	8.8208	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	4
Vorinostat	decreases expression	3
Resveratrol	affects cotreatment, decreases expression, affects binding	2
Arsenic	increases mutagenesis, decreases expression, increases abundance	2
Copper	affects cotreatment, decreases expression, affects binding	2
Rotenone	increases expression	2
Valproic Acid	decreases expression, increases expression	2
GSK-J4	decreases expression	1
FR900359	increases phosphorylation	1
pradimicin-IRD	affects response to substance, affects expression	1
testosterone enanthate	affects expression	1
methylmercuric chloride	decreases expression	1
myristicin	decreases expression	1
oxybenzone	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	decreases expression, increases oxidation, increases abundance, affects cotreatment	1
pirinixic acid	increases activity, affects binding, decreases expression	1
bisphenol A	increases expression	1
pyrithione zinc	increases expression	1
bromoacetate	decreases expression	1
cobaltous chloride	increases expression	1
fludarabine	affects cotreatment, decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
nivalenol	increases expression	1
methacrylaldehyde	affects cotreatment, decreases expression, increases oxidation, increases abundance	1
flavone	increases expression	1
ptaquiloside	decreases expression	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
tamibarotene	affects expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652228	Binding	Binding affinity to human RAD50 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

6 cell lines: 5 cancer cell line, 1 telomerase immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8NJ	Abcam HCT 116 RAD50 KO	Cancer cell line	Male
CVCL_B9AX	Abcam MCF-7 RAD50 KO	Cancer cell line	Female
CVCL_B9QV	Abcam A-549 RAD50 KO	Cancer cell line	Male
CVCL_C4N7	NT-36	Cancer cell line	Male
CVCL_KT97	HeLa SilenciX Rad50	Cancer cell line	Female
CVCL_VL08	F239hTert	Telomerase immortalized cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02562170	PHASE4	COMPLETED	Protexa® Versus TiLoopBra® in Immediate Breast Reconstruction- A Pilot Study
NCT00190697	PHASE4	COMPLETED	A Study of LY353381 (Arzoxifene) for Patients Who Benefitted From This Drug in Other Oncology Trials and Wished to Continue Treatment
NCT00277160	PHASE4	COMPLETED	A Study of Primary Prophylaxis With Neulasta (Pegfilgrastim) Versus Secondary Prophylaxis After Chemotherapy in Elderly Subjects (>/= 65 Years Old) With Cancer
NCT00727961	PHASE4	COMPLETED	A Study to Evaluate Efficacy and Tolerance of Caelyx in Patients With Epithelial Ovarian Cancer. (Study P04072)(COMPLETED)
NCT00740116	PHASE4	COMPLETED	Tranexamic Acid in Surgery of Advanced Ovarian Cancer
NCT00817479	PHASE4	COMPLETED	Tumor Gene Expression in Women With Ovarian Cancer
NCT01432015	PHASE4	COMPLETED	Fosaprepitant Versus Aprepitant in the Prevention of Chemotherapy Induced Nausea and Vomiting
NCT01706120	PHASE4	UNKNOWN	Study of Clinical and Biological Prognostic Factors in Patients With Ovarian Cancer Receiving Carboplatin +Paclitaxel With Bevacizumab
NCT01932125	PHASE4	COMPLETED	An Interventional Study of Avastin (Bevacizumab) in Patients With Advanced/Metastatic Epithelial Ovarian Cancer, Fallopian Tube Cancer or Primary Peritoneal Cancer
NCT01953107	PHASE4	COMPLETED	Oral Iron vs. Placebo in Newly Diagnosed Gynecologic Oncology Patients Who Are Surgical Candidates.
NCT02035345	PHASE4	TERMINATED	Slowed Carboplatin Infusion for Ovarian Cancer Patients Receiving Carboplatin Re-Treatment
NCT02243059	PHASE4	WITHDRAWN	Magnetic Resonance Imaging for Lymph Node Staging in Ovarian Cancer
NCT03164980	PHASE4	TERMINATED	QoL-Comparison Between Trabectedin/PLD and Pt-based Therapy in Patients With Pt-sensitive Recurrent Ovarian Cancer
NCT03384511	PHASE4	COMPLETED	The Use of 18F-ALF-NOTA-PRGD2 PET/CT Scan to Predict the Efficacy and Adverse Events of Apatinib in Malignancies.
NCT03543462	PHASE4	COMPLETED	Diaphragmatic Resection And Gynecological Ovarian Neoplasm
NCT03752216	PHASE4	COMPLETED	NIraparib and Quality of LifE is a Longitudinal Study Evaluating in Real Life the Tolerability of Niraparib.
NCT03858166	PHASE4	TERMINATED	Efficacy and Safety of PEG-rhG-CSF Secondary Prophylaxis vs. Therapeutic Administration in Patients With Ovarian Cancer
NCT04024254	PHASE4	COMPLETED	A Study of Serum Folate Levels in Patients Treated With Olaparib
NCT04330040	PHASE4	COMPLETED	Prospective Multicentre Phase-IV Clinical Trial of Olaparib in Indian Patients With Ovarian and Metastatic Breast Cancer
NCT04352439	PHASE4	COMPLETED	Aspirin for Prevention of Venous Thromboembolism Among Ovarian Cancer Patients Receiving Neoadjuvant Chemotherapy
NCT05187208	PHASE4	UNKNOWN	PARP Inhibitor Oral Maintenance in Low-Risk Ovarian Cancer
NCT05606692	PHASE4	RECRUITING	Influences of Propofol and Sevoflurane Anesthesia in Ovarian Cancer (Anesthetics)
NCT05926336	PHASE4	RECRUITING	The Effects of Using Different Anesthetics on the Prognosis of Primary Tumors and Its Mechanism of Action
NCT06412120	PHASE4	RECRUITING	Study Evaluating Safety, Tolerability, and Metabolism of Niraparib
NCT06871787	PHASE4	NOT_YET_RECRUITING	Near-Infrared Fluorescence Imaging With Indocyanine Green to Evaluate Bowel Anastomoses in Gynecologic Oncology Surgery
NCT06887933	PHASE4	NOT_YET_RECRUITING	A Trial to Evaluate the Safety of Niraparib Tablets in Adult Female Participants With Advanced or Relapsed Epithelial Ovarian Cancer
NCT07469202	PHASE4	NOT_YET_RECRUITING	CYTALUX Dose Extension Study
NCT00673335	PHASE3	COMPLETED	Letrozole in Preventing Breast Cancer in Postmenopausal Women With a BRCA1 or BRCA2 Mutation
NCT00685256	PHASE3	COMPLETED	Standard Genetic Counseling With or Without a Decision Guide in Improving Communication Between Mothers Undergoing BRCA1/2 Testing and Their Minor-Age Children
NCT03162276	PHASE3	UNKNOWN	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT00001806	PHASE3	COMPLETED	Methods in Education for Breast Cancer Genetics
NCT00002477	PHASE3	UNKNOWN	Adjuvant Chemotherapy Compared With Observation in Treating Patients With Resected Early Stage Ovarian Epithelial Cancer
NCT00002568	PHASE3	COMPLETED	Combination Chemotherapy With or Without Surgery in Treating Patients With Stage III Ovarian Epithelial Cancer
NCT00002641	PHASE3	COMPLETED	Surgery With or Without Chemotherapy in Treating Patients With Soft Tissue Sarcoma
NCT00002717	PHASE3	COMPLETED	Paclitaxel and Cisplatin in Treating Patients With Stage III or Stage IV Ovarian Cancer or Primary Peritoneal Cancer
NCT00002764	PHASE3	COMPLETED	Surgery With or Without Combination Chemotherapy in Treating Patients With Lung Metastases From Soft Tissue Sarcoma
NCT00002819	PHASE3	TERMINATED	Chemotherapy With or Without Peripheral Stem Cell Transplantation in Treating Patients With Persistent Ovarian Epithelial Cancer
NCT00002894	PHASE3	COMPLETED	Platinum-based Chemotherapy With or Without Paclitaxel in Treating Patients With Relapsed Ovarian Cancer
NCT00002895	PHASE3	COMPLETED	Early Chemotherapy Based on CA 125 Level Alone Compared With Delayed Chemotherapy in Treating Patients With Recurrent Ovarian Epithelial , Fallopian Tube, or Primary Peritoneal Cancer
NCT00003120	PHASE3	COMPLETED	S9701 Paclitaxel in Treating Patients With Advanced Ovarian, Fallopian Tube, or Primary Peritoneal Cancer in Remission