RAD52

Summary

RAD52 (RAD52 DNA repair protein, HGNC:9824) is a protein-coding gene on chromosome 12p13.33, encoding DNA repair protein RAD52 homolog (P43351). Involved in double-stranded break repair.

The protein encoded by this gene shares similarity with Saccharomyces cerevisiae Rad52, a protein important for DNA double-strand break repair and homologous recombination. This gene product was shown to bind single-stranded DNA ends, and mediate the DNA-DNA interaction necessary for the annealing of complementary DNA strands. It was also found to interact with DNA recombination protein RAD51, which suggested its role in RAD51 related DNA recombination and repair. A pseudogene of this gene is present on chromosome 2. Alternative splicing results in multiple transcript variants. Additional alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known.

Source: NCBI Gene 5893 — RefSeq curated summary.

At a glance

• GWAS associations: 12
• Clinical variants (ClinVar): 74 total
• Druggable target: yes — 24 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_134424

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9824
Approved symbol	RAD52
Name	RAD52 DNA repair protein
Location	12p13.33
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000002016
Ensembl biotype	protein_coding
OMIM	600392
Entrez	5893

Gene structure

Transcript identifiers

Ensembl transcripts: 31 — 19 protein_coding, 4 retained_intron, 4 nonsense_mediated_decay, 4 protein_coding_CDS_not_defined

ENST00000228345, ENST00000358495, ENST00000397230, ENST00000430095, ENST00000461568, ENST00000463750, ENST00000468231, ENST00000481052, ENST00000488642, ENST00000535376, ENST00000536177, ENST00000541619, ENST00000542297, ENST00000542584, ENST00000542785, ENST00000543912, ENST00000544742, ENST00000545564, ENST00000545967, ENST00000904778, ENST00000904779, ENST00000904780, ENST00000904781, ENST00000904782, ENST00000928981, ENST00000928982, ENST00000928983, ENST00000952664, ENST00000952665, ENST00000952666, ENST00000952667

RefSeq mRNA: 5 — MANE Select: NM_134424 NM_001297419, NM_001297420, NM_001297421, NM_001297422, NM_134424

CCDS: CCDS76500, CCDS76501, CCDS8507

Canonical transcript exons

ENST00000358495 — 12 exons

Exon	Start	End
ENSE00001700104	911736	913452
ENSE00001865764	949602	949694
ENSE00003467716	932975	933076
ENSE00003526447	913894	914121
ENSE00003567483	925450	925525
ENSE00003578357	931220	931321
ENSE00003609824	929819	929886
ENSE00003631369	916344	916483
ENSE00003643968	914431	914532
ENSE00003661521	916639	916820
ENSE00003665072	927145	927263
ENSE00003742687	930051	930144

Expression profiles

Bgee: expression breadth ubiquitous, 218 present calls, max score 91.93.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.4223 / max 88.8407, expressed in 1640 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
128913	3.5339	1441
128914	1.8884	1093

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	91.93	gold quality
sural nerve	UBERON:0015488	91.79	gold quality
right lobe of thyroid gland	UBERON:0001119	91.45	gold quality
mucosa of transverse colon	UBERON:0004991	91.36	gold quality
buccal mucosa cell	CL:0002336	90.66	gold quality
lower esophagus mucosa	UBERON:0035834	89.99	gold quality
right hemisphere of cerebellum	UBERON:0014890	89.62	gold quality
right ovary	UBERON:0002118	89.61	gold quality
endocervix	UBERON:0000458	89.36	gold quality
left ovary	UBERON:0002119	88.83	gold quality
left lobe of thyroid gland	UBERON:0001120	88.79	gold quality
cerebellar hemisphere	UBERON:0002245	88.64	gold quality
cerebellar cortex	UBERON:0002129	88.41	gold quality
apex of heart	UBERON:0002098	88.35	gold quality
thyroid gland	UBERON:0002046	88.19	gold quality
tibial nerve	UBERON:0001323	87.84	gold quality
body of uterus	UBERON:0009853	87.80	gold quality
metanephros cortex	UBERON:0010533	87.56	gold quality
transverse colon	UBERON:0001157	87.18	gold quality
right lobe of liver	UBERON:0001114	86.89	gold quality
ovary	UBERON:0000992	86.77	gold quality
body of pancreas	UBERON:0001150	86.71	gold quality
right frontal lobe	UBERON:0002810	86.56	gold quality
tendon of biceps brachii	UBERON:0008188	86.07	gold quality
muscle layer of sigmoid colon	UBERON:0035805	85.97	gold quality
ectocervix	UBERON:0012249	85.81	gold quality
vagina	UBERON:0000996	85.77	gold quality
muscle of leg	UBERON:0001383	85.74	gold quality
gastrocnemius	UBERON:0001388	85.66	gold quality
rectum	UBERON:0001052	85.58	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.54

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

63 targeting RAD52, 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-3613-3P	100.00	76.36	7965
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-2053	99.57	69.15	1635
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-766-3P	99.47	65.24	1811
HSA-MIR-548AV-3P	99.43	68.50	1721
HSA-MIR-4284	99.36	65.25	1293
HSA-MIR-542-3P	99.34	67.58	1270
HSA-MIR-145-3P	99.33	67.66	764

Literature-anchored findings (GeneRIF, showing 40)

• The ring-shaped quaternary structure of RAD52 and the formation of higher ordered complexes of rings appear to contribute to the extreme thermal stability of RAD52. (PMID:11456495)
• reduces double-strand break-induced homologous recombination with overexpression in mammalian cells (PMID:11691922)
• differential effects of Rad52p overexpression on gene targeting and extrachromosomal homologous recombination in a human tumor cell line (PMID:11809887)
• Analysis of the human replication protein A:Rad52 complex: evidence for crosstalk between RPA32, RPA70, Rad52 and DNA (PMID:12139939)
• Crystal structure of the homologous-pairing domain from the human Rad52 recombinase in the undecameric form. (PMID:12191481)
• crystal structure of the single-strand annealing domain (PMID:12370410)
• RAD52 may play a role in transcription regulation and in targeting DNA damage on transcription active loci to recombinational repair (PMID:12372413)
• women with Ser346ter nonsense polymorphism of RAD52 not at increased risk of breast cancer in case-control study (PMID:12376524)
• coordinated WRN and RAD52 activities are involved in replication fork rescue after DNA damage (PMID:12750383)
• Rad52 facilitates homologous recognition between single-stranded DNA and duplex-DNA through a process that involves unwinding or transient unpairing of the interacting duplex via a novel three-stranded intermediate that does not lead to strand exchange. (PMID:14690434)
• the ternary complex of hRad52 and XPF/ERCC1 is the active species that processes recombination intermediates generated during the repair of DNA double strand breaks and in homology-dependent gene targeting events (PMID:14734547)
• For both yeast Rad52 and HsRad52, the yield of strand-exchange reactions was proportional to the fractional A.T content of the DNA substrates, but both enzymes catalyzed exchange with substrates that contained up to at least 50% G.C (PMID:15205482)
• formation of a stoichiometric complex between HsRad52 and single-stranded DNA was found to be critical for strand exchange activity (PMID:15205484)
• analysis of residues important for DNA binding in the full-length human Rad52 protein (PMID:15571718)
• RAD52 Y415X polymorphism is not associated with epithelial ovarian cancer in Australian women (PMID:15670896)
• purified hRad51 and hRad52 interact with each other as well as with Mini chromosome maintenance (MCM) proteins in HeLa cell extracts (PMID:15766559)
• Interestingly, presence of hRad52 restores the ability of hRad51 binding to such DNA targets as well. (PMID:16018971)
• DNA-induced disassembly of higher-order forms of Rad51 and Rad52 proteins as steps that precede protein assembly during hRad51 presynapsis on DNA, in vitro. (PMID:16367760)
• Rad52 protein functions by binding to single-stranded DNA formed as intermediates of recombination rather than by binding to the unprocessed DNA double-strand break. (PMID:17040915)
• germline mutations in RAD51, RAD51AP1, RAD51L1, RAD51L3, RAD52 and RAD54L are unlikely to be causal of an inherited predisposition to CLL. (PMID:18203022)
• Data show that DNA repair synthesis, catalyzed by human DNA polymerase eta (poleta) acting upon the priming strand of a D loop, leads to capture and annealing of the second end of a resected DSB in reactions mediated by RAD52 protein. (PMID:18313388)
• Rad52 aligns two recombining DNA molecules within the first and second DNA binding sites to stimulate the homology search and strand invasion processes. (PMID:18593704)
• model for hRad52-mediated DNA annealing where ssDNA release and dsDNA zippering are coordinated through successive rearrangement of overlapping nucleoprotein complexes (PMID:19074292)
• Of the 21 loci screened, RAD52 2259 and RAD52 GLN221GLU may be of importance to disease process and may be associated with papillary thyroid cancer risk in Saudi Arabian population. (PMID:19092295)
• Results indicate that RAD52 cooperates with OGG1 to repair oxidative DNA damage and enhances the cellular resistance to oxidative stress. (PMID:19506022)
• These data show that phosphorylated RPA promoted formation of a complex with monomeric Rad52 and caused the transfer of single stranded DNA from RPA to Rad52. (PMID:19530647)
• This study demonstrated a positive correlation between molecular beacon fluorescence intensity, RAD52 gene expression and both gamma ionising radiation and antineoplastic concentration in human TK6 cells. (PMID:19799994)
• aRPA interacted with both Rad52 and Rad51 and stimulated Rad51 strand exchange. (PMID:19996105)
• hRad52 stably binds and wraps both, protein free and replication protein A-coated ssDNA. (PMID:20081207)
• the possibility of sumoylation playing an important role in the nuclear transport of RAD52 (PMID:20190268)
• Rad52 can respond to DNA double-strand breaks and replication stalling independently of BRCA2 (PMID:21148102)
• RAD52(Y104pCMF) specifically targets and wraps ssDNA. Phosphorylation at Y104 enhances ssDNA annealing activity of RAD52 by attenuating dsDNA binding. (PMID:21804533)
• Silencing of the Rad52 gene in fractionated group of A549 cells made the cells radiosensitive. (PMID:22001234)
• The recruitment kinetics of Rad52 is slower than that of Mdc1, but exhibits the same dependence on LET (PMID:22860035)
• RAD52 is an alternative repair pathway of RAD51-mediated homologous recombination, and a target for therapy in cells deficient in the BRCA1-PALB2-BRCA2 repair pathway. (PMID:22964643)
• rs7963551 located at the hsa-let-7 binding site may alter expression of RAD52 and contribute to the development of breast cancer in Chinese women. (PMID:23188672)
• Both RAD52 variants and protein expression can predict platinum resistance, and RAD52 variants appeared to predict prognosis in cervical cancer patients. (PMID:23209746)
• Single nucleotide polymorphisms in RAD52 are associated with myelodysplastic syndromes. (PMID:23339595)
• RAD52 mutation is associated with leukemia. (PMID:23836560)
• Nuclear/chromatin PTEN mediates DNA damage repair through interacting with and modulating the activity of Rad52. (PMID:24047694)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rad52	ENSDARG00000005274
mus_musculus	Rad52	ENSMUSG00000030166
rattus_norvegicus	Rad52	ENSRNOG00000009742

Protein

Protein identifiers

DNA repair protein RAD52 homolog — P43351 (reviewed: P43351)

All UniProt accessions (6): E9PF95, P43351, F5GX32, F5GX95, F5H1K5, Q5DR82

UniProt curated annotations — full annotation on UniProt →

Function. Involved in double-stranded break repair. Plays a central role in genetic recombination and DNA repair by promoting the annealing of complementary single-stranded DNA and by stimulation of the RAD51 recombinase.

Subunit / interactions. The full-length protein forms heptameric rings. Interacts with ABL1. Interacts with RPA2; the interaction is direct and associates RAD52 with the RPA complex. Interacts with RAD51AP1.

Subcellular location. Nucleus.

Post-translational modifications. Phosphorylated upon DNA damage by ABL1, and probably by ATM or ATR.

Miscellaneous. Unable to interact with isoform alpha, may act as dominant negative. Unable to interact with isoform alpha, may act as dominant negative. Unable to interact with isoform alpha, may act as dominant negative.

Similarity. Belongs to the RAD52 family.

Isoforms (4)

UniProt ID	Names	Canonical?
P43351-1	alpha	yes
P43351-2	beta
P43351-3	gamma
P43351-4	delta

RefSeq proteins (5): NP_001284348, NP_001284349, NP_001284350, NP_001284351, NP_602296* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004585	DNA_recomb/repair_Rad52	Family
IPR007232	Rad52_Rad59_Rad22	Family
IPR041247	Rad52_fam	Family
IPR042525	Rad52_Rad59_Rad22_sf	Homologous_superfamily

Pfam: PF04098

UniProt features (44 total): helix 9, splice variant 6, strand 6, mutagenesis site 5, modified residue 4, sequence variant 3, region of interest 3, compositionally biased region 3, sequence conflict 2, chain 1, DNA-binding region 1, turn 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
8BJM	ELECTRON MICROSCOPY	2.2
8RJW	ELECTRON MICROSCOPY	2.3
5JRB	X-RAY DIFFRACTION	2.4
8TKQ	ELECTRON MICROSCOPY	2.5
1H2I	X-RAY DIFFRACTION	2.7
1KN0	X-RAY DIFFRACTION	2.85
8RIL	ELECTRON MICROSCOPY	2.9
5XS0	X-RAY DIFFRACTION	3
8RJ3	ELECTRON MICROSCOPY	3.2
8H1P	ELECTRON MICROSCOPY	3.48
5XRZ	X-RAY DIFFRACTION	3.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P43351-F1	70.52	0.47

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 (4): 318, 335, 104, 199

Mutagenesis-validated functional residues (5):

Position	Phenotype
55	abolishes ssdna-binding.
65	moderately defective in both ss and dsdna-binding.
152	abolishes ssdna-binding.
153	moderately defective in both ss and dsdna-binding.
156	moderately defective in both ss and dsdna-binding.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-3108214	SUMOylation of DNA damage response and repair proteins
R-HSA-5685938	HDR through Single Strand Annealing (SSA)
R-HSA-5685939	HDR through MMEJ (alt-NHEJ)

MSigDB gene sets: 210 (showing top): TGCACTT_MIR519C_MIR519B_MIR519A, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, KAUFFMANN_DNA_REPAIR_GENES, GOBP_REGULATION_OF_DNA_REPAIR, KEGG_HOMOLOGOUS_RECOMBINATION, BROWNE_HCMV_INFECTION_48HR_DN, KRASNOSELSKAYA_ILF3_TARGETS_DN, GOBP_NUCLEOTIDE_EXCISION_REPAIR, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_DNA_DAMAGE_RESPONSE, SHIN_B_CELL_LYMPHOMA_CLUSTER_1, TSENG_IRS1_TARGETS_DN, SCHLOSSER_SERUM_RESPONSE_DN, GOBP_MITOTIC_RECOMBINATION, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_STRESS

GO Biological Process (11): double-strand break repair via homologous recombination (GO:0000724), DNA recombinase assembly (GO:0000730), double-strand break repair (GO:0006302), DNA recombination (GO:0006310), mitotic recombination (GO:0006312), DNA double-strand break processing involved in repair via single-strand annealing (GO:0010792), cellular response to oxidative stress (GO:0034599), double-strand break repair via single-strand annealing (GO:0045002), regulation of nucleotide-excision repair (GO:2000819), DNA repair (GO:0006281), DNA damage response (GO:0006974)

GO Molecular Function (4): DNA binding (GO:0003677), single-stranded DNA binding (GO:0003697), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), protein-containing complex (GO:0032991), protein-DNA complex (GO:0032993)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
SUMO E3 ligases SUMOylate target proteins	1
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	1
Homology Directed Repair	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
double-strand break repair	2
DNA metabolic process	2
recombinational repair	1
double-strand break repair via synthesis-dependent strand annealing	1
protein-DNA complex assembly	1
DNA repair complex assembly	1
DNA repair	1
DNA recombination	1
DNA double-strand break processing	1
double-strand break repair via single-strand annealing	1
response to oxidative stress	1
cellular response to chemical stress	1
regulation of DNA repair	1
nucleotide-excision repair	1
DNA damage response	1
cellular response to stress	1
nucleic acid binding	1
DNA binding	1
protein binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
cellular_component	1
protein-containing complex	1

Protein interactions and networks

STRING

1866 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RAD52	RAD51	Q06609	999
RAD52	ATRX	P46100	993
RAD52	BRCA2	P51587	991
RAD52	WRN	Q14191	969
RAD52	BRCA1	P38398	961
RAD52	RAD18	Q9NS91	958
RAD52	RAD54B	Q9Y620	951
RAD52	ERCC1	P07992	935
RAD52	RPA2	P15927	934
RAD52	XRCC3	O43542	910
RAD52	MUS81	Q96NY9	902
RAD52	RAD54L	Q92698	900
RAD52	EXO1	Q9UQ84	897
RAD52	UBE2V2	Q15819	883
RAD52	RDM1	Q8NG50	877

IntAct

71 interactions, top by confidence:

A	B	Type	Score
RPA2	RPA1	psi-mi:“MI:0914”(association)	0.960
RPA1	RPA2	psi-mi:“MI:0914”(association)	0.960
RPA3	RPA2	psi-mi:“MI:0914”(association)	0.930
RAD52	RAD52	psi-mi:“MI:0915”(physical association)	0.820
RAD52	RAD52	psi-mi:“MI:0407”(direct interaction)	0.820
WRN	RAD52	psi-mi:“MI:0915”(physical association)	0.680
WRN	RAD52	psi-mi:“MI:0407”(direct interaction)	0.680
RAD52	WRN	psi-mi:“MI:0407”(direct interaction)	0.680
RAD52	WRN	psi-mi:“MI:0915”(physical association)	0.680
RAD52	WRN	psi-mi:“MI:0403”(colocalization)	0.680
RAD51	RAD52	psi-mi:“MI:0915”(physical association)	0.630
RAD52	RPA3	psi-mi:“MI:0915”(physical association)	0.620
KPNA3	RAD52	psi-mi:“MI:0915”(physical association)	0.560
RAD52	MEOX1	psi-mi:“MI:0915”(physical association)	0.560
RAD52	DCP1A	psi-mi:“MI:0915”(physical association)	0.560
RAD52	NFYC	psi-mi:“MI:0915”(physical association)	0.560
RAD52	RDM1	psi-mi:“MI:0915”(physical association)	0.560
RAD52	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
RAD52	PAX5	psi-mi:“MI:0915”(physical association)	0.560
KPNA5	RAD52	psi-mi:“MI:0915”(physical association)	0.560
RAD52	PLK3	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (120): RAD52 (Biochemical Activity), RAD52 (Affinity Capture-Western), RAD52 (Affinity Capture-MS), RAD52 (Affinity Capture-MS), RAD52 (Biochemical Activity), RAD52 (Biochemical Activity), RAD52 (Biochemical Activity), RAD52 (Biochemical Activity), RAD52 (Affinity Capture-RNA), RAD51 (Affinity Capture-Western), RAD52 (Affinity Capture-Western), RAD52 (Proximity Label-MS), RAD52 (Proximity Label-MS), RAD52 (Co-crystal Structure), RPA1 (FRET)

ESM2 similar proteins: A0A0G2L7I0, A0A0R4IWG9, A5D979, B8QB46, D3ZVU1, F6UH96, G3X912, O70445, O88700, P43351, Q08E13, Q08EN7, Q1LVK9, Q22557, Q53WJ1, Q5SPR8, Q5TKR9, Q5ZLE9, Q65Z40, Q6A037, Q6DJS0, Q6GQJ2, Q6IE81, Q6INS5, Q6ZPI0, Q71M44, Q7T308, Q7Y1C4, Q7Y1C5, Q7Z5K2, Q7ZVP1, Q7ZXG4, Q803U7, Q8BMD7, Q8BZ21, Q8K298, Q8N5U6, Q8RWK8, Q8VID5, Q8WML3

Diamond homologs: O42905, P06778, P36592, P39022, P41768, P43351, P43352, Q12223, Q6BJ51, Q6FSW2, Q756F4, Q757G7, Q8NK72, Q96UP6, Q9HEU2, Q9HGI2, Q6FWE1

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
ABL1	“up-regulates activity”	RAD52	phosphorylation
BCR-ABL	“up-regulates activity”	RAD52	phosphorylation
RAD52	up-regulates	DNA_repair

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 29 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
Impaired BRCA2 binding to RAD51	6	84.2×	1e-08
HDR through Single Strand Annealing (SSA)	6	79.9×	1e-08
Presynaptic phase of homologous DNA pairing and strand exchange	6	74.2×	1e-08
HDR through Homologous Recombination (HRR)	6	51.9×	1e-07
G2/M DNA damage checkpoint	6	32.8×	1e-06
Regulation of TP53 Activity through Phosphorylation	6	32.1×	1e-06
Processing of DNA double-strand break ends	6	31.1×	1e-06
Meiotic recombination	5	29.5×	2e-05

GO biological processes:

GO term	Partners	Fold	FDR
base-excision repair	5	86.7×	5e-07
double-strand break repair via homologous recombination	7	40.5×	1e-07
DNA repair	6	14.2×	1e-04
DNA damage response	7	13.9×	4e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	29
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2412 predictions. Top by Δscore:

Variant	Effect	Δscore
12:914120:CT:C	acceptor_gain	1.0000
12:914122:C:CC	acceptor_gain	1.0000
12:914429:A:AC	donor_gain	1.0000
12:914430:C:CC	donor_gain	1.0000
12:914543:C:CT	acceptor_gain	1.0000
12:914544:A:T	acceptor_gain	1.0000
12:916342:AC:A	donor_gain	1.0000
12:916343:CC:C	donor_gain	1.0000
12:916349:CT:C	donor_gain	1.0000
12:916358:G:C	donor_gain	1.0000
12:916818:CAA:C	acceptor_gain	1.0000
12:916821:C:CC	acceptor_gain	1.0000
12:925523:CTC:C	acceptor_gain	1.0000
12:925526:C:CC	acceptor_gain	1.0000
12:925534:A:T	acceptor_gain	1.0000
12:930140:CACAC:C	acceptor_gain	1.0000
12:930142:CAC:C	acceptor_gain	1.0000
12:930145:C:CA	acceptor_loss	1.0000
12:930145:C:CC	acceptor_gain	1.0000
12:931317:TGGCA:T	acceptor_gain	1.0000
12:931319:GCAC:G	acceptor_loss	1.0000
12:931320:CA:C	acceptor_gain	1.0000
12:931322:C:CA	acceptor_loss	1.0000
12:931322:C:CC	acceptor_gain	1.0000
12:931331:C:CT	acceptor_gain	1.0000
12:931331:C:T	acceptor_gain	1.0000
12:931332:A:T	acceptor_gain	1.0000
12:933075:CT:C	acceptor_gain	1.0000
12:933076:TC:T	acceptor_loss	1.0000
12:933077:C:CC	acceptor_gain	1.0000

AlphaMissense

2727 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:925505:C:T	G163E	1.000
12:925517:C:A	G159V	1.000
12:925517:C:T	G159E	1.000
12:927156:C:A	K152N	1.000
12:927156:C:G	K152N	1.000
12:927163:C:T	G150E	1.000
12:927164:C:A	G150W	1.000
12:927176:C:G	A146P	1.000
12:927180:C:A	K144N	1.000
12:927180:C:G	K144N	1.000
12:929882:A:C	F95L	1.000
12:929882:A:T	F95L	1.000
12:929884:A:G	F95L	1.000
12:930079:C:A	W84C	1.000
12:930079:C:G	W84C	1.000
12:930081:A:G	W84R	1.000
12:930081:A:T	W84R	1.000
12:925505:C:A	G163V	0.999
12:925506:C:G	G163R	0.999
12:925506:C:T	G163R	0.999
12:925518:C:A	G159W	0.999
12:925518:C:G	G159R	0.999
12:925518:C:T	G159R	0.999
12:927148:A:G	L155P	0.999
12:927148:A:T	L155H	0.999
12:927152:C:G	A154P	0.999
12:927154:C:G	R153P	0.999
12:927158:T:C	K152E	0.999
12:927160:A:G	L151P	0.999
12:927164:C:G	G150R	0.999

dbSNP variants (sampled 300 via entrez): RS1000017604 (12:947236 G>C), RS1000043742 (12:933375 T>C), RS1000060489 (12:918761 GGCAGTGACT>G), RS1000132308 (12:920830 C>T), RS1000192714 (12:978434 T>A), RS1000210916 (12:967991 A>G,T), RS1000270358 (12:982516 C>A,T), RS1000285652 (12:943928 G>A), RS1000300623 (12:946155 A>G), RS1000328580 (12:931618 C>G), RS1000332128 (12:916200 T>A,C), RS1000375458 (12:988810 G>A,T), RS1000380542 (12:976944 G>C), RS1000389749 (12:951653 C>T), RS1000391321 (12:937834 T>G)

Disease associations

OMIM: gene MIM:600392 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): pilocytic astrocytoma (MONDO:0016691)

Orphanet (1): Pilocytic astrocytoma (Orphanet:251612)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST001638_1	Lung cancer	6.000000e-07
GCST004617_142	Eosinophil percentage of granulocytes	1.000000e-10
GCST004623_57	Neutrophil percentage of granulocytes	1.000000e-09
GCST004746_36	Small cell lung carcinoma	7.000000e-06
GCST005951_70	Body mass index	1.000000e-11
GCST006624_67	Systolic blood pressure	3.000000e-12
GCST007267_128	Systolic blood pressure	5.000000e-08
GCST011011_1	Youthful appearance (self-reported)	4.000000e-08
GCST012490_419	Femur bone mineral density x serum urate levels interaction	2.000000e-08
GCST90002385_220	High light scatter reticulocyte count	4.000000e-09
GCST90002386_316	High light scatter reticulocyte percentage of red cells	4.000000e-10
GCST90002387_116	Immature fraction of reticulocytes	2.000000e-11

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0007996	eosinophil percentage of granulocytes
EFO:0007994	neutrophil percentage of granulocytes
EFO:0004340	body mass index
EFO:0006335	systolic blood pressure
EFO:0004531	urate measurement
EFO:0007986	reticulocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2362978 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

24 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 492,979 (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
CHEMBL1026	FENOLDOPAM MESYLATE	4	2,560
CHEMBL1200654	BENOXINATE HYDROCHLORIDE	4	2,199
CHEMBL1200757	PANCURONIUM BROMIDE	4	7,213
CHEMBL1200916	THIORIDAZINE HYDROCHLORIDE	4	14,243
CHEMBL1201154	PROCHLORPERAZINE EDISYLATE	4	1,206
CHEMBL1516474	TEGASEROD MALEATE	4	1,823
CHEMBL1642	IMATINIB MESYLATE	4	70,143
CHEMBL2110372	RANITIDINE HYDROCHLORIDE	4	8,866
CHEMBL2146123	METHACYCLINE HYDROCHLORIDE	4	2,985
CHEMBL3187985	APOMORPHINE HYDROCHLORIDE	4	5,278
CHEMBL405110	METHYLENE BLUE ANHYDROUS	4	113,934
CHEMBL422	TRIFLUOPERAZINE	4	20,044
CHEMBL43128	PRIMAQUINE PHOSPHATE	4	2,032
CHEMBL567	PERPHENAZINE	4	21,883
CHEMBL790	CHLORHEXIDINE	4	85,053
CHEMBL2003538	CETYLPYRIDINIUM CHLORIDE	3	3,733
CHEMBL297453	EPIGALOCATECHIN GALLATE	3	22,804
CHEMBL1237046	ROLITETRACYCLINE	2	336
CHEMBL22077	HYCANTHONE	2	2,210
CHEMBL221753	BENZETHONIUM CHLORIDE	2	104,434
CHEMBL337702	OXIDOPAMINE	2
CHEMBL46874	PINAFIDE	2
CHEMBL583912	(-)-EPICATECHIN	2
CHEMBL12089	BERBERINE CHLORIDE	1

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs11226	Toxicity	4	cisplatin;cyclophosphamide	Ovarian Neoplasms

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs11226	RAD52	4	-0.25	1	cisplatin;cyclophosphamide
rs2277869	RAD52, WNK1		0.00	0

ChEMBL bioactivities

416 potent at pChembl≥5 of 754 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.59	IC50	255	nM	EPICATECHIN GALLATE
6.57	AC50	271	nM	CHEMBL124006
6.56	AC50	278	nM	CHEMBL1413740
6.56	IC50	277	nM	EPIGALOCATECHIN GALLATE
6.50	AC50	320	nM	CHEMBL72964
6.44	AC50	360	nM	CHEMBL1734563
6.43	AC50	372	nM	CHEMBL1470728
6.30	AC50	501	nM	CHEMBL1731759
6.30	AC50	506	nM	CHEMBL1789983
6.30	IC50	500	nM	CORILAGIN
6.29	AC50	513	nM	CHEMBL1901645
6.25	AC50	558	nM	CHEMBL335782
6.25	IC50	563	nM	QUINALIZARIN
6.24	AC50	574	nM	CHEMBL1789994
6.23	AC50	590	nM	CHEMBL1731722
6.18	AC50	655	nM	CHEMBL72504
6.17	AC50	683	nM	CHEMBL1888857
6.16	AC50	689	nM	CHEMBL1536569
6.15	AC50	708	nM	CHEMBL1200847
6.13	AC50	739	nM	CHEMBL1888824
6.11	AC50	782	nM	CHEMBL493863
6.11	IC50	779	nM	OXIDOPAMINE
6.10	AC50	801	nM	CHEMBL1571682
6.10	AC50	792	nM	CHEMBL1432498
6.07	AC50	846	nM	CHEMBL1699532
6.07	AC50	849	nM	CHEMBL1592706
6.07	IC50	849	nM	CHEMBL4592344
6.06	AC50	870	nM	CHEMBL1711432
6.04	AC50	914	nM	CHEMBL1721330
6.04	IC50	913	nM	GOSSYPETIN
6.03	AC50	939	nM	CHEMBL1971727
6.03	AC50	931	nM	CHEMBL1414834
6.03	AC50	936	nM	METHYLENE BLUE ANHYDROUS
6.03	IC50	938	nM	CHEMBL1609107
6.02	AC50	952	nM	CHEMBL1868173
6.01	AC50	977	nM	CHEMBL1501307
5.98	AC50	1040	nM	CHEMBL1725136
5.97	AC50	1060	nM	CHEMBL1579644
5.97	AC50	1070	nM	CHEMBL1407955
5.97	AC50	1070	nM	CHEMBL1906617
5.97	IC50	1060	nM	CHEMBL4096162
5.96	AC50	1110	nM	CHEMBL1377932
5.96	IC50	1100	nM	CHEMBL109037
5.95	AC50	1120	nM	CHEMBL1391330
5.94	AC50	1150	nM	CHEMBL1535375
5.94	AC50	1140	nM	CHEMBL1904111
5.93	AC50	1180	nM	CHEMBL478754
5.91	AC50	1230	nM	CHEMBL1734101
5.90	AC50	1270	nM	CHEMBL580076
5.90	AC50	1270	nM	CHEMBL3391727

PubChem BioAssay actives

16 with measured affinity, of 27 total; 16 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
[(2R,3R)-5,7-dihydroxy-2-(3,4,5-trihydroxyphenyl)-3,4-dihydro-2H-chromen-3-yl] 3,4,5-trihydroxybenzoate	1743766: Inhibition of 6His-tagged human RD52 assessed as reduction in RD52 binding to Cy3-dT30-Cy5 ssDNA incubated for 30 mins by FRET assay	ic50	0.2770	uM
2-amino-3-(2,4,5-trihydroxyphenyl)propanoic acid	1743764: Inhibition of FAM-conjugated ssDNA binding to His-tagged wild type RAD52 (unknown origin) expressed in Rosetta2(DE3)/pLysS cells measured after 30 mins by fluorescence polarization assay	ic50	1.1000	uM
[(10S,11R,12R,13S,15R)-3,4,5,11,12,21,22,23-octahydroxy-8,18-dioxo-9,14,17-trioxatetracyclo[17.4.0.02,7.010,15]tricosa-1(23),2,4,6,19,21-hexaen-13-yl] 3,4,5-trihydroxybenzoate	1743766: Inhibition of 6His-tagged human RD52 assessed as reduction in RD52 binding to Cy3-dT30-Cy5 ssDNA incubated for 30 mins by FRET assay	ic50	1.5000	uM
(2R,3R)-2-(3,4,5-trihydroxyphenyl)-3,4-dihydro-2H-chromene-3,5,7-triol	1743766: Inhibition of 6His-tagged human RD52 assessed as reduction in RD52 binding to Cy3-dT30-Cy5 ssDNA incubated for 30 mins by FRET assay	ic50	1.8000	uM
3-[(2-methoxyphenyl)sulfamoyl]-4-methylbenzoic acid	2066594: Inhibition of RAD52 (unknown origin) by FRET analysis	ic50	2.0000	uM
1-[2-(1H-indol-3-yl)-2-oxoethyl]-3-nitropyridin-2-one	2066594: Inhibition of RAD52 (unknown origin) by FRET analysis	ic50	2.0000	uM
3-(furan-2-yl)-4-propan-2-yloxycyclobut-3-ene-1,2-dione	1743764: Inhibition of FAM-conjugated ssDNA binding to His-tagged wild type RAD52 (unknown origin) expressed in Rosetta2(DE3)/pLysS cells measured after 30 mins by fluorescence polarization assay	ic50	5.0000	uM
5-[(3-carboxy-4-hydroxyphenyl)-(3-carboxy-4-oxocyclohexa-2,5-dien-1-ylidene)methyl]-2-hydroxybenzoic acid	1743764: Inhibition of FAM-conjugated ssDNA binding to His-tagged wild type RAD52 (unknown origin) expressed in Rosetta2(DE3)/pLysS cells measured after 30 mins by fluorescence polarization assay	ic50	5.0000	uM
2,4-bis(1H-pyrrol-2-ylmethylideneamino)phenol	1743764: Inhibition of FAM-conjugated ssDNA binding to His-tagged wild type RAD52 (unknown origin) expressed in Rosetta2(DE3)/pLysS cells measured after 30 mins by fluorescence polarization assay	ic50	5.0000	uM
[(4-oxocyclohexa-2,5-dien-1-ylidene)amino] 2,5-dichlorobenzenesulfonate	1743764: Inhibition of FAM-conjugated ssDNA binding to His-tagged wild type RAD52 (unknown origin) expressed in Rosetta2(DE3)/pLysS cells measured after 30 mins by fluorescence polarization assay	ic50	5.0000	uM
1-[2-(diethylamino)ethyl]-3-[2-(4-ethylpiperazin-1-yl)-4-methylquinolin-6-yl]thiourea	1743765: Inhibition of human RAD52 assessed as reduction in DNA annealing using tailed ds-DNA 337-F/1337-BHQ1 by fluorescence-quenching assay	ic50	5.0000	uM
7-(8-formyl-1,6,7-trihydroxy-3-methyl-5-propan-2-ylnaphthalen-2-yl)-2,3,8-trihydroxy-6-methyl-4-propan-2-ylnaphthalene-1-carbaldehyde	1743764: Inhibition of FAM-conjugated ssDNA binding to His-tagged wild type RAD52 (unknown origin) expressed in Rosetta2(DE3)/pLysS cells measured after 30 mins by fluorescence polarization assay	ic50	5.0000	uM
3-(1-methylpyrrol-2-yl)prop-2-enoic acid	1743764: Inhibition of FAM-conjugated ssDNA binding to His-tagged wild type RAD52 (unknown origin) expressed in Rosetta2(DE3)/pLysS cells measured after 30 mins by fluorescence polarization assay	ic50	5.0000	uM
5-[(1-methylpyrrol-2-yl)methylidene]-2-sulfanylidene-1,3-diazinane-4,6-dione	1743764: Inhibition of FAM-conjugated ssDNA binding to His-tagged wild type RAD52 (unknown origin) expressed in Rosetta2(DE3)/pLysS cells measured after 30 mins by fluorescence polarization assay	ic50	5.0000	uM
5-[(E)-3-(furan-2-yl)prop-2-enylidene]-2-sulfanylidene-1,3-diazinane-4,6-dione	1743764: Inhibition of FAM-conjugated ssDNA binding to His-tagged wild type RAD52 (unknown origin) expressed in Rosetta2(DE3)/pLysS cells measured after 30 mins by fluorescence polarization assay	ic50	5.0000	uM
4-[(E)-1H-1,2,4-triazol-5-yliminomethyl]benzoic acid	1743764: Inhibition of FAM-conjugated ssDNA binding to His-tagged wild type RAD52 (unknown origin) expressed in Rosetta2(DE3)/pLysS cells measured after 30 mins by fluorescence polarization assay	ic50	5.0000	uM

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, decreases expression, increases abundance, increases expression	3
Etoposide	decreases reaction, increases expression	2
Methyl Methanesulfonate	increases expression	2
triphenyl phosphate	affects expression	1
bisphenol A	affects methylation	1
beta-lapachone	decreases expression	1
arsenite	affects binding, decreases reaction	1
manganese chloride	increases abundance, increases expression	1
1,2,5,6-dibenzanthracene	increases expression	1
di-n-butylphosphoric acid	affects expression	1
2-palmitoylglycerol	increases expression	1
abrine	increases expression	1
bisphenol S	affects cotreatment, decreases expression	1
Arsenic	increases abundance, increases expression	1
Benzo(a)pyrene	increases methylation	1
Dexamethasone	affects cotreatment, decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Manganese	increases abundance, increases expression	1
Rotenone	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
Cyclosporine	increases methylation	1
Aflatoxin B1	increases methylation	1
Antirheumatic Agents	increases expression	1
Okadaic Acid	decreases expression	1

ChEMBL screening assays

44 unique, capped per target: 40 binding, 3 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2354285	Functional	PubChem BioAssay. FRET-based HTS for detection of RAD52 Inhibitors Measured in Biochemical System Using Plate Reader - 7018-01_Inhibitor_Dose_CherryPick_Activity. (Class of assay: confirmatory)	PubChem BioAssay data set
CHEMBL4417894	Binding	Inhibition of RAD52 (unknown origin) assessed as effect on ssDNA annealing using ssDNA oligonucleotide by fluorescence-quenching assay	Inhibitors of RAD52 Recombination Protein and Methods Using Same
CHEMBL4417905	ADMET	Effect on RAD52 (unknown origin) expressed in BCR-ABL1-positive and BRCA1-deficient mouse 32Dcl3 cells expressing GFP-RAD52 assessed as induction of RAD52 foci formation by AlexaFluor-594 staining based inverted fluorescence microscopy	Inhibitors of RAD52 Recombination Protein and Methods Using Same

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B5DC	U2OS RAD52 KO clone #1	Cancer cell line	Female
CVCL_B5DD	U2OS RAD52 KO clone #2	Cancer cell line	Female
CVCL_B5DE	U2OS RAD52 KO clone #3	Cancer cell line	Female
CVCL_TI35	HAP1 RAD52 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03975829	PHASE4	RECRUITING	Pediatric Long-Term Follow-up and Rollover Study
NCT02372409	PHASE2	TERMINATED	Using MRI-Guided Laser Heat Ablation to Induce Disruption of the Peritumoral Blood Brain Barrier to Enhance Delivery and Efficacy of Treatment of Pediatric Brain Tumors
NCT02684058	PHASE2	COMPLETED	Study of Efficacy and Safety of Dabrafenib in Combination With Trametinib in Pediatric Patients With BRAF V600 Mutation Positive LGG or Relapsed or Refractory HGG Tumors
NCT04985604	PHASE2	TERMINATED	Tovorafenib (DAY101) Monotherapy for Patients With Melanoma and Other Solid Tumors
NCT04541082	PHASE1	RECRUITING	Phase I Study of Oral ONC206 in Recurrent and Rare Primary Central Nervous System Neoplasms
NCT07121829	PHASE1	TERMINATED	Tovorafenib (DAY101) or in Combination With Pimasertib for Participants With Melanoma and Other Solid Tumors
NCT01837862	PHASE1/PHASE2	COMPLETED	A Phase I Study of Mebendazole for the Treatment of Pediatric Gliomas
NCT04065776	Not specified	RECRUITING	Evaluation of Hippocampal-Avoidance Using Proton Therapy in Low-Grade Glioma
NCT05934630	Not specified	TERMINATED	Testing Cerebrospinal Fluid for Cell-free Tumor DNA in Children, Adolescents, and Young Adults With Brain Tumors
NCT06915649	Not specified	RECRUITING	Exploration and Evaluation of Amygdalo-Hippocampectomy According to Prof. Coubes’ Technique: An Anatomical, Clinical, and Educational Approach