RAD51B

Summary

RAD51B (RAD51 paralog B, HGNC:9822) is a protein-coding gene on chromosome 14q24.1, encoding DNA repair protein RAD51 homolog 2 (O15315). Involved in the homologous recombination repair (HRR) pathway of double-stranded DNA breaks arising during DNA replication or induced by DNA-damaging agents. In precision oncology, RAD51B Mutation confers sensitivity to Olaparib in Castration-resistant Prostate Carcinoma (CIViC Level A). It is a selective cancer dependency (DepMap: 11.0% of cell lines).

The protein encoded by this gene is a member of the RAD51 protein family. RAD51 family members are evolutionarily conserved proteins essential for DNA repair by homologous recombination. This protein has been shown to form a stable heterodimer with the family member RAD51C, which further interacts with the other family members, such as RAD51, XRCC2, and XRCC3. Overexpression of this gene was found to cause cell cycle G1 delay and cell apoptosis, which suggested a role of this protein in sensing DNA damage. Rearrangements between this locus and high mobility group AT-hook 2 (HMGA2, GeneID 8091) have been observed in uterine leiomyomata.

Source: NCBI Gene 5890 — RefSeq curated summary.

At a glance

• Gene–disease (curated): primary ovarian failure (Limited, GenCC)
• GWAS associations: 91
• Clinical variants (ClinVar): 633 total — 1 likely-pathogenic
• Precision-oncology evidence (CIViC): 1 curated variant–drug association
• Cancer dependency (DepMap): dependent in 11.0% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency little evidence, triplosensitivity no evidence
• MANE Select transcript: NM_133510

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9822
Approved symbol	RAD51B
Name	RAD51 paralog B
Location	14q24.1
Locus type	gene with protein product
Status	Approved
Aliases	REC2, hREC2, R51H2
Ensembl gene	ENSG00000182185
Ensembl biotype	protein_coding
OMIM	602948
Entrez	5890

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 13 protein_coding_CDS_not_defined, 8 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000460526, ENST00000468382, ENST00000469165, ENST00000471583, ENST00000474051, ENST00000478014, ENST00000479335, ENST00000485181, ENST00000487270, ENST00000487861, ENST00000488612, ENST00000492236, ENST00000497460, ENST00000553334, ENST00000553595, ENST00000553734, ENST00000554183, ENST00000554244, ENST00000554575, ENST00000555782, ENST00000555907, ENST00000556251, ENST00000557045, ENST00000711050

RefSeq mRNA: 12 — MANE Select: NM_133510 NM_001321809, NM_001321810, NM_001321812, NM_001321814, NM_001321815, NM_001321817, NM_001321818, NM_001321819, NM_001321821, NM_002877, NM_133509, NM_133510

CCDS: CCDS81815, CCDS9789, CCDS9790

Canonical transcript exons

ENST00000471583 — 11 exons

Exon	Start	End
ENSE00001306179	67825464	67825577
ENSE00001313228	67835080	67835196
ENSE00001518458	67823542	67823627
ENSE00001901116	67819779	67819853
ENSE00001902707	68477648	68478093
ENSE00003480597	68291884	68291980
ENSE00003487010	68468172	68468250
ENSE00003563425	68411424	68411527
ENSE00003579281	67887021	67887204
ENSE00003596749	67865003	67865139
ENSE00003622212	67885869	67885988

Expression profiles

Bgee: expression breadth ubiquitous, 193 present calls, max score 95.74.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.2404 / max 209.1073, expressed in 1479 samples.

FANTOM5 promoters (16 alternative TSS)

Promoter ID	TPM avg	Samples expressed
140249	1.9732	1048
140248	1.6673	897
207265	0.1792	47
140268	0.1192	52
140257	0.0674	13
140256	0.0513	10
140253	0.0423	17
140262	0.0325	6
140259	0.0260	5
140252	0.0223	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	95.74	gold quality
buccal mucosa cell	CL:0002336	90.85	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.14	gold quality
adrenal tissue	UBERON:0018303	85.76	gold quality
secondary oocyte	CL:0000655	85.31	gold quality
body of uterus	UBERON:0009853	85.20	gold quality
ventricular zone	UBERON:0003053	84.96	gold quality
calcaneal tendon	UBERON:0003701	84.25	gold quality
gall bladder	UBERON:0002110	83.62	gold quality
corpus callosum	UBERON:0002336	83.16	gold quality
colonic epithelium	UBERON:0000397	82.98	gold quality
left ovary	UBERON:0002119	82.92	gold quality
minor salivary gland	UBERON:0001830	82.23	gold quality
monocyte	CL:0000576	81.69	gold quality
right ovary	UBERON:0002118	81.68	gold quality
saliva-secreting gland	UBERON:0001044	81.32	gold quality
mononuclear cell	CL:0000842	81.02	gold quality
leukocyte	CL:0000738	80.84	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.79	gold quality
tonsil	UBERON:0002372	80.47	gold quality
ovary	UBERON:0000992	80.27	gold quality
bone marrow cell	CL:0002092	80.11	gold quality
smooth muscle tissue	UBERON:0001135	80.00	gold quality
ganglionic eminence	UBERON:0004023	79.99	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	79.70	gold quality
mouth mucosa	UBERON:0003729	79.55	gold quality
ectocervix	UBERON:0012249	78.90	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	78.68	gold quality
stromal cell of endometrium	CL:0002255	78.33	gold quality
skin of abdomen	UBERON:0001416	77.47	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	44.56
E-HCAD-35	yes	10.63
E-ANND-3	no	7.03

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GTF3A, MYC, TFAP2A, TP53

miRNA regulators (miRDB)

54 targeting RAD51B, 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-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-3663-3P	99.84	70.39	798
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-6757-3P	99.63	66.88	1089
HSA-MIR-298	99.63	67.56	1916
HSA-MIR-6832-5P	99.58	64.82	1132
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-4708-3P	99.51	67.99	870
HSA-MIR-513C-5P	99.50	68.42	1730
HSA-MIR-514B-5P	99.50	68.19	1766
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-8064	99.45	66.92	875

Functional genomics

ClinGen dosage: haploinsufficiency 1 (little evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 11.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• This work describes the in vitro and in vivo identification of the RAD51B/RAD51C heterocomplex (PMID:11744692)
• involved in the frequently occurring t(6;14) (p21;q23–>q24) in pulmonary chondroid hamartomas (PMID:11978964)
• Rad51B and Rad51C function through interactions with the human Rad51 recombinase and play a crucial role in the homologous recombinational repair pathway (PMID:12427746)
• Rad51B protein may have a specific function in Holliday junction processing in the homologous recombinational repair pathway in humans (PMID:12441335)
• a fragment of Rad51B containing amino acid residues 1-75 interacts with the C-terminus and linker of Rad51C, residues 79-376, and this region of Rad51C also interacts with mRad51D and Xrcc3 (PMID:14704354)
• motif in the N-terminus of Rad51B serves as an NLS that allows Rad51B to localize to the nucleus independent of Rad51C or BRCA2 (PMID:15701685)
• EVL protein is a novel recombination factor that may be required for repairing specific DNA lesions, and that may cause tumor malignancy by its inappropriate expression. (PMID:19329439)
• A multistage genome-wide association study in breast cancer identifies two new risk alleles at 1p11.2 and 14q24.1 (RAD51L1). (PMID:19330030)
• BCR/ABL fragments were used for identifying the sites of BCR/ABL interaction with RAD51B (PMID:19657362)
• polymorphisms in and haplotypes of the RAD51L1 gene, which is involved in the double-strand break repair pathway, modulate gamma-radiation-induced mutagen sensitivity. (PMID:20610542)
• findings support the notion that DNA repair genes, in particular RAD51L1, play a role in nasopharyngeal carcinoma etiology and development (PMID:21368091)
• our results suggest that RAD51L1 is unlikely to represent a high-penetrance breast cancer susceptibility gene. (PMID:21533530)
• rs11249433 at 1p.11.2, and two highly correlated single-nucleotide polymorphisms rs999737 and rs10483813 (r(2)= 0.98) at 14q24.1 (RAD51L1), for up to 46 036 invasive breast cancer cases and 46 930 controls from 39 studies, were genotyped. (PMID:21852249)
• Single Nucleotide Polymorphisms in RAD51L1 gene is associated with glioblastoma. (PMID:22017238)
• Single nucleotide polymorphism in RAD51L1 is associated with breast cancer. (PMID:22454379)
• SNP in RAD51B at 14q24.1 was significantly associated with male breast cancer risk (PMID:23001122)
• Study observed centrosome defects in the absence of XRCC3. While RAD51B and RAD51C act early in homologous recombination, XRCC3 functions jointly with GEN1 later in the pathway at the stage of Holliday junction resolution. (PMID:23108668)
• The HsRAD51B-HsRAD51C complex plays a role in stabilizing the HsRAD51 nucleoprotein filament during the presynaptic phase of homologous recombination. (PMID:23810717)
• This study provides robust evidence for an association of rheumatoid arthritis susceptibility with genes involved in B cell differentiation (BACH2) and DNA repair (RAD51B). (PMID:24022229)
• It confirms that RAD51 paralog mutations confer breast and ovarian cancer predisposition and are rare events. (PMID:24139550)
• Data indicate that complement factor H (CFH) R1210C and common variants in COL8A1 and RAD51B plus six genes contribute predictive information for advanced macular degeneration (AMD) beyond macular and behavioral phenotypes. (PMID:24498017)
• the risk of developing AMD exhibits dose dependency as well as an epistatic combined effect in rs17105278 T>C and rs4902566 C>T carriers and that the elevated risk for rs17105278 T>C carriers may be due to decreased transcription of RAD51B. (PMID:24526414)
• Relative excess risk of breast cancer due to interaction between RAD51L1 single-nucleotide polymorphism and BMI. (PMID:25255808)
• a novel germ line RAD51B nonsense mutation, and reduced expression of RAD51B in melanoma cells indicating inactivation of RAD51B (PMID:25600502)
• Mutations in epithelial ovarian cancer cases were more frequent in RAD51C (14 occurrences, 0.41%) and RAD51D (12 occurrences, 0.35%) than in RAD51B (two occurrences, 0.06%). (PMID:26261251)
• The aim of the present study was to evaluate the relationship between prostate cancer risk and the presence of single nucleotide polymorphisms in the genes involved in Homologous recombination repair, RAD51, RAD51B, XRCC2 and XRCC3. (PMID:26339569)
• common variation is significantly associated with familial breast cancer risk (PMID:27149063)
• our study suggested that miRNA-binding site genetic variants of RAD51B may modify the susceptibility to cervical cancer, which is important to identify individuals with differential risk for this malignancy and to improve the effectiveness of preventive intervention. (PMID:27334422)
• over-expression of RAD51B promoted cell proliferation, aneuploidy, and drug resistance, while RAD51B knockdown led to G1 arrest and sensitized cells to 5-fluorouracil (PMID:27651161)
• hypermethylation of homologous recombination DNA repair genes including RAD51B and XRCC3 is associated with an inflamed phenotype in squamous cell cancers of the head and neck, lung and cervix. (PMID:27683114)
• We successfully identified a common variant, rs911263, as being significantly associated with the disease status . In addition, this SNP was shown to be related to erosion, a clinical assessment of disease severity in RA (P = 2.89 x 10(-5), OR = 0.52). These findings shed light on the role of RAD51B in the onset and severity of Rheumatoid arthritis (RA). (PMID:28361912)
• Here we provide three coherent sets of isogenic mutants, both in transformed and non-transformed human cells. Importantly, using these mutant lines, we report the unanticipated result that RAD51B has a less crucial role in homologous recombination than the other four paralogs, and find that all RAD51 paralogs are critically important for early functions during homologous recombination (PMID:31584931)
• Sequential role of RAD51 paralog complexes in replication fork remodeling and restart. (PMID:32669601)
• TBX15 rs98422, DNM3 rs1011731, RAD51B rs8017304, and rs2588809 Gene Polymorphisms and Associations With Pituitary Adenoma. (PMID:33622874)
• Serum Levels of ARMS2, COL8A1, RAD51B, and VEGF and their Correlations in Age-related Macular Degeneration. (PMID:34060991)
• RAD51B Harbors Germline Mutations Associated With Pancreatic Ductal Adenocarcinoma. (PMID:35737913)
• Structure and function of the RAD51B-RAD51C-RAD51D-XRCC2 tumour suppressor. (PMID:37344587)
• Structural insights into BCDX2 complex function in homologous recombination. (PMID:37344589)
• Uterine leiomyoma with RAD51B::NUDT3 fusion: a report of 2 cases. (PMID:37466765)
• Sarcomas With RAD51B Fusions Are Associated With a Heterogeneous Phenotype. (PMID:38141829)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rad51b	ENSDARG00000037046
mus_musculus	Rad51b	ENSMUSG00000059060
rattus_norvegicus	Rad51b	ENSRNOG00000059245

Paralogs (6): RAD51 (ENSG00000051180), DMC1 (ENSG00000100206), RAD51C (ENSG00000108384), XRCC3 (ENSG00000126215), RAD51D (ENSG00000185379), XRCC2 (ENSG00000196584)

Protein

Protein identifiers

DNA repair protein RAD51 homolog 2 — O15315 (reviewed: O15315)

Alternative names: RAD51 homolog B, RAD51-like protein 1

All UniProt accessions (6): O15315, C9J5S9, C9JYJ0, F8WAY6, G3V4W9, H0YJI5

UniProt curated annotations — full annotation on UniProt →

Function. Involved in the homologous recombination repair (HRR) pathway of double-stranded DNA breaks arising during DNA replication or induced by DNA-damaging agents. May promote the assembly of presynaptic RAD51 nucleoprotein filaments. Binds single-stranded DNA and double-stranded DNA and has DNA-dependent ATPase activity. Part of the RAD51 paralog protein complex BCDX2 which acts in the BRCA1-BRCA2-dependent HR pathway. Upon DNA damage, BCDX2 acts downstream of BRCA2 recruitment and upstream of RAD51 recruitment. BCDX2 binds predominantly to the intersection of the four duplex arms of the Holliday junction and to junction of replication forks. The BCDX2 complex was originally reported to bind single-stranded DNA, single-stranded gaps in duplex DNA and specifically to nicks in duplex DNA. The BCDX2 subcomplex RAD51B:RAD51C exhibits single-stranded DNA-dependent ATPase activity suggesting an involvement in early stages of the HR pathway.

Subunit / interactions. Part of the BCDX2 complex consisting of RAD51B, RAD51C, RAD51D and XRCC2; the complex has a ring-like structure arranged into a flat disc around a central channel. The BCDX2 subcomplex RAD51B:RAD51C interacts with RAD51. Interacts with SWSAP1; involved in homologous recombination repair. Interacts with HELQ.

Subcellular location. Nucleus.

Tissue specificity. Expressed in a wide range of tissues.

Post-translational modifications. Phosphorylated on tyrosine residues by BCR-ABL.

Disease relevance. A chromosomal aberration involving RAD51B is found in pulmonary chondroid hamartoma. Translocation t(6;14)(p21;q23-24) with HMGA1. A chromosomal aberration involving RAD51B is found in uterine leiomyoma. Translocation t(12;14)(q15;q23-24) with HMGA2.

Similarity. Belongs to the RecA family. RAD51 subfamily.

Isoforms (5)

UniProt ID	Names	Canonical?
O15315-3	1	yes
O15315-1	2, RAD51L1a
O15315-2	3, RAD51L1b
O15315-4	4
O15315-5	5

RefSeq proteins (12): NP_001308738, NP_001308739, NP_001308741, NP_001308743, NP_001308744, NP_001308746, NP_001308747, NP_001308748, NP_001308750, NP_002868, NP_598193, NP_598194* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003593	AAA+_ATPase	Domain
IPR013632	Rad51_C	Domain
IPR016467	DNA_recomb/repair_RecA-like	Family
IPR020588	RecA_ATP-bd	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR030548	RAD51B	Family
IPR058766	HHH_XRCC3_RAD51B	Domain

Pfam: PF08423, PF26169

UniProt features (25 total): sequence variant 8, helix 6, splice variant 4, chain 1, region of interest 1, mutagenesis site 1, sequence conflict 1, binding site 1, turn 1, site 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
8OUZ	ELECTRON MICROSCOPY	2.2
8FAZ	ELECTRON MICROSCOPY	2.3
9Q2A	ELECTRON MICROSCOPY	2.67
8GBJ	ELECTRON MICROSCOPY	3.11
8OUY	ELECTRON MICROSCOPY	3.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15315-F1	79.50	0.58

Functional residue map

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

Catalytic / active sites (1): 252–253 (breakpoint for translocation to form hmga2-rad51b)

Ligand- & substrate-binding residues (1): 108–115

Mutagenesis-validated functional residues (1):

Position	Phenotype
326	abolishes interaction with bcr-abl sh3 domain.

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-5685942	HDR through Homologous Recombination (HRR)
R-HSA-5693554	Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)
R-HSA-5693568	Resolution of D-loop Structures through Holliday Junction Intermediates
R-HSA-5693579	Homologous DNA Pairing and Strand Exchange
R-HSA-5693616	Presynaptic phase of homologous DNA pairing and strand exchange
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-9709603	Impaired BRCA2 binding to PALB2
R-HSA-983231	Factors involved in megakaryocyte development and platelet production

MSigDB gene sets: 300 (showing top): GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, TAATAAT_MIR126, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_POSITIVE_REGULATION_OF_MITOTIC_CELL_CYCLE, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_GROWTH, AACYNNNNTTCCS_UNKNOWN, KAUFFMANN_DNA_REPAIR_GENES, GGGTGGRR_PAX4_03, CAGCTG_AP4_Q5, KEGG_HOMOLOGOUS_RECOMBINATION, AACWWCAANK_UNKNOWN, GOBP_REGULATION_OF_CELL_CYCLE_G2_M_PHASE_TRANSITION, GOBP_POSITIVE_REGULATION_OF_CELL_CYCLE_G2_M_PHASE_TRANSITION

GO Biological Process (10): double-strand break repair via homologous recombination (GO:0000724), blastocyst growth (GO:0001832), DNA repair (GO:0006281), DNA recombination (GO:0006310), reciprocal meiotic recombination (GO:0007131), positive regulation of cell population proliferation (GO:0008284), positive regulation of G2/M transition of mitotic cell cycle (GO:0010971), somite development (GO:0061053), in utero embryonic development (GO:0001701), DNA damage response (GO:0006974)

GO Molecular Function (10): DNA binding (GO:0003677), double-stranded DNA binding (GO:0003690), single-stranded DNA binding (GO:0003697), ATP binding (GO:0005524), ATP-dependent activity, acting on DNA (GO:0008094), ATP-dependent DNA damage sensor activity (GO:0140664), nucleotide binding (GO:0000166), four-way junction DNA binding (GO:0000400), protein binding (GO:0005515), ATP hydrolysis activity (GO:0016887)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), replication fork (GO:0005657), Rad51B-Rad51C-Rad51D-XRCC2 complex (GO:0033063)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Resolution of D-Loop Structures	2
Defective homologous recombination repair (HRR) due to PALB2 loss of function	2
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	1
HDR through Homologous Recombination (HRR)	1
Homologous DNA Pairing and Strand Exchange	1
Diseases of DNA Double-Strand Break Repair	1
Defective homologous recombination repair (HRR) due to BRCA2 loss of function	1
Hemostasis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA metabolic process	2
DNA binding	2
ATP-dependent activity	2
cellular anatomical structure	2
recombinational repair	1
double-strand break repair	1
blastocyst development	1
developmental growth	1
DNA damage response	1
meiosis I	1
reciprocal homologous recombination	1
meiotic cell cycle process	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
G2/M transition of mitotic cell cycle	1
regulation of G2/M transition of mitotic cell cycle	1
positive regulation of mitotic cell cycle phase transition	1
positive regulation of cell cycle G2/M phase transition	1
embryo development	1
epithelium development	1
chordate embryonic development	1
cellular response to stress	1
nucleic acid binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ATP hydrolysis activity	1
catalytic activity, acting on DNA	1
ATP-dependent activity, acting on DNA	1
DNA damage sensor activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
DNA secondary structure binding	1
binding	1
ribonucleoside triphosphate phosphatase activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
chromosome	1
DNA recombinase mediator complex	1
nuclear protein-containing complex	1

Protein interactions and networks

STRING

2852 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RAD51B	K7EN88	K7EN88	999
RAD51B	RAD51D	O75771	991
RAD51B	XRCC2	O43543	990
RAD51B	RAD51C	O43502	988
RAD51B	RAD1	O60671	958
RAD51B	BRCA2	P51587	851
RAD51B	F5H6H0	F5H6H0	821
RAD51B	PALB2	Q86YC2	756
RAD51B	TOX3	O15405	746
RAD51B	BRCA1	P38398	741
RAD51B	RAD54L	Q92698	740
RAD51B	RAD52	P43351	733
RAD51B	BARD1	Q99728	722
RAD51B	XRCC3	O43542	713
RAD51B	CCNB1IP1	Q9NPC3	709

IntAct

56 interactions, top by confidence:

A	B	Type	Score
RAD51C	RAD51B	psi-mi:“MI:0915”(physical association)	0.940
RAD51C	RAD51B	psi-mi:“MI:0914”(association)	0.940
RAD51B	RAD51C	psi-mi:“MI:0914”(association)	0.940
RAD51B	RAD51C	psi-mi:“MI:0915”(physical association)	0.940
RAD51D	RAD51B	psi-mi:“MI:0914”(association)	0.850
RAD51D	RAD51B	psi-mi:“MI:0915”(physical association)	0.850
XRCC2	RAD51B	psi-mi:“MI:0914”(association)	0.720
ARL4C	RGS12	psi-mi:“MI:0914”(association)	0.640
FAM9B	RAD51B	psi-mi:“MI:0915”(physical association)	0.560
RAD51B	FAM9B	psi-mi:“MI:0915”(physical association)	0.560
RAD51B	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
RAD51B	RPAIN	psi-mi:“MI:0915”(physical association)	0.560
H1-0	RAD51B	psi-mi:“MI:0407”(direct interaction)	0.560
RAD51B	SWSAP1	psi-mi:“MI:0915”(physical association)	0.520

BioGRID (85): FAM9B (Two-hybrid), RAD51B (Affinity Capture-MS), RAD51B (Affinity Capture-MS), RAD51B (Affinity Capture-MS), RAD51B (Affinity Capture-MS), RAD51B (Affinity Capture-MS), RAD51B (Affinity Capture-MS), RAD51B (Affinity Capture-MS), RAD51B (Affinity Capture-Western), RAD51B (Affinity Capture-MS), RAD51B (Affinity Capture-RNA), RAD51B (Co-localization), RAD51B (Two-hybrid), RAD51B (Affinity Capture-MS), RAD51B (Proximity Label-MS)

ESM2 similar proteins: A2AIG8, A6NFX1, O15315, O35083, O35719, O35790, O43502, O54783, O54804, O55229, O73884, P16442, P20417, P35790, P35821, P47802, Q01134, Q08DW9, Q27HK4, Q2TBS1, Q3T9M1, Q3U129, Q4R3I0, Q4R766, Q4R7M4, Q5E9H2, Q5E9T4, Q5SUV1, Q5SX19, Q5VYX0, Q6GV29, Q86XW9, Q8BVM4, Q8CIW5, Q8N2K0, Q8NBA8, Q8QGV6, Q8R2J9, Q8TCT0, Q924H5

Diamond homologs: A3CXI2, A4FYL0, A4WN87, A4YCN4, A5UKT8, A6VJS2, A8EZW1, A8F2Q0, A8GY17, B0R636, B6YXT4, B8BM09, C3MRI1, C3MY77, C3MZK6, C3N7M8, C3NFU5, C3PLP0, C4K1F5, C4KIT6, C5A2F7, C6A0N1, O15315, O27728, O28184, O29269, O35719, O43502, O57859, O73948, O93748, P0CW60, P0CW61, P0CW91, P0CW92, P37384, P38953, P41079, P81415, P95547

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
RAD51B	“form complex”	RAD51B/RAD51C	binding

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
Meiotic recombination	5	40.5×	2e-06

GO biological processes:

GO term	Partners	Fold	FDR
double-strand break repair via homologous recombination	6	36.0×	2e-06

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	356
Likely benign	188
Benign	59

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
4759309	NM_133510.4(RAD51B):c.772C>T (p.Gln258Ter)	Likely pathogenic

SpliceAI

5568 predictions. Top by Δscore:

Variant	Effect	Δscore
14:67823511:A:AG	acceptor_gain	1.0000
14:67823511:AT:A	acceptor_gain	1.0000
14:67823511:ATG:A	acceptor_gain	1.0000
14:67823512:T:A	acceptor_gain	1.0000
14:67823512:T:G	acceptor_gain	1.0000
14:67823513:G:A	acceptor_gain	1.0000
14:67823531:T:A	acceptor_gain	1.0000
14:67823532:G:A	acceptor_gain	1.0000
14:67853963:G:GT	donor_gain	1.0000
14:67865136:AAAGG:A	donor_loss	1.0000
14:67865138:AGGTA:A	donor_loss	1.0000
14:67865139:GGT:G	donor_loss	1.0000
14:67865140:G:GC	donor_loss	1.0000
14:67865141:T:A	donor_loss	1.0000
14:67885861:A:AG	acceptor_gain	1.0000
14:67885862:C:G	acceptor_gain	1.0000
14:67885864:CACAG:C	acceptor_loss	1.0000
14:67885866:C:G	acceptor_gain	1.0000
14:67885867:A:AG	acceptor_gain	1.0000
14:67885867:AGACT:A	acceptor_gain	1.0000
14:67885868:G:GA	acceptor_gain	1.0000
14:67885868:GA:G	acceptor_gain	1.0000
14:67885868:GAC:G	acceptor_gain	1.0000
14:67885868:GACT:G	acceptor_gain	1.0000
14:67885868:GACTG:G	acceptor_gain	1.0000
14:67885987:AGGTA:A	donor_loss	1.0000
14:67885989:G:GG	donor_gain	1.0000
14:67885989:GTATG:G	donor_loss	1.0000
14:67885990:T:G	donor_loss	1.0000
14:67887016:TATAG:T	acceptor_loss	1.0000

AlphaMissense

2255 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:67887079:T:C	S211P	0.998
14:67865041:T:G	C118W	0.997
14:67865051:A:C	S122R	0.997
14:67865053:C:A	S122R	0.997
14:67865053:C:G	S122R	0.997
14:68411468:T:A	W300R	0.997
14:68411468:T:C	W300R	0.997
14:67865028:A:T	K114I	0.996
14:67865031:C:T	T115I	0.995
14:67865039:T:C	C118R	0.995
14:67865040:G:A	C118Y	0.995
14:67887185:C:A	A246D	0.995
14:68291885:T:A	V253D	0.995
14:68291898:T:A	N257K	0.995
14:68291898:T:G	N257K	0.995
14:67887184:G:C	A246P	0.994
14:67865025:G:A	G113E	0.993
14:67887077:A:C	D210A	0.993
14:67887077:A:T	D210V	0.993
14:68411470:G:C	W300C	0.993
14:68411470:G:T	W300C	0.993
14:68411490:G:C	R307P	0.993
14:68411493:T:C	L308P	0.993
14:67865126:T:C	F147L	0.992
14:67865128:T:A	F147L	0.992
14:67865128:T:G	F147L	0.992
14:67885871:T:C	L152P	0.992
14:67885882:G:C	A156P	0.992
14:67825492:T:C	L38P	0.991
14:67865029:A:C	K114N	0.991

dbSNP variants (sampled 300 via entrez): RS1000000796 (14:68404883 A>G), RS1000006967 (14:68499239 A>C,G), RS1000009466 (14:68163943 A>G), RS1000010636 (14:68393072 C>G), RS1000012963 (14:68346533 A>C), RS1000013102 (14:67926819 C>A,T), RS1000016067 (14:67993065 A>G), RS1000033723 (14:68404533 A>G), RS1000034346 (14:68489981 G>A), RS1000037726 (14:67887694 T>C,G), RS1000041125 (14:68348830 C>T), RS1000042139 (14:68019291 A>G,T), RS1000042143 (14:68440494 C>T), RS1000044186 (14:68616900 C>G), RS1000044922 (14:68075516 A>G)

Disease associations

OMIM: gene MIM:602948 | disease phenotypes: MIM:114480

GenCC curated gene-disease

Disease	Classification	Inheritance
primary ovarian failure	Limited	Autosomal recessive

Mondo (5): hereditary breast ovarian cancer syndrome (MONDO:0003582), hereditary neoplastic syndrome (MONDO:0015356), hereditary breast carcinoma (MONDO:0016419), diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype (MONDO:0858939), primary ovarian failure (MONDO:0005387)

Orphanet (3): Hereditary breast and/or ovarian cancer syndrome (Orphanet:145), Inherited cancer-predisposing syndrome (Orphanet:140162), Hereditary breast cancer (Orphanet:227535)

HPO phenotypes

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

GWAS associations

91 associations (top):

Study	Trait	p-value
GCST000365_3	Breast cancer	2.000000e-07
GCST000610_3	Primary tooth development (number of teeth)	3.000000e-08
GCST000817_162	Height	8.000000e-09
GCST001010_15	Primary biliary cholangitis	2.000000e-11
GCST001337_41	Platelet count	2.000000e-10
GCST001373_2	Breast cancer (survival)	1.000000e-07
GCST001373_3	Breast cancer (survival)	3.000000e-07
GCST001690_2	Breast cancer (male)	3.000000e-13
GCST001762_183	Obesity-related traits	5.000000e-06
GCST001884_8	Age-related macular degeneration	9.000000e-11
GCST001937_21	Breast cancer	1.000000e-10
GCST001937_59	Breast cancer	3.000000e-19
GCST001942_16	Prostate cancer	3.000000e-10
GCST002263_7	Acute urticaria and angioedema (non-steroidal anti-inflammatory drug-induced)	6.000000e-06
GCST002318_96	Rheumatoid arthritis	8.000000e-11
GCST002318_97	Rheumatoid arthritis	5.000000e-08
GCST003129_20	Primary biliary cholangitis	2.000000e-09
GCST003155_17	Systemic lupus erythematosus	6.000000e-10
GCST003156_20	Systemic lupus erythematosus	2.000000e-06
GCST003219_33	Advanced age-related macular degeneration	2.000000e-10
GCST003219_34	Advanced age-related macular degeneration	1.000000e-06
GCST003588_19	Cancer (pleiotropy)	3.000000e-10
GCST003987_23	Asthma	2.000000e-08
GCST003999_16	Nose size	5.000000e-08
GCST004599_166	Mean platelet volume	5.000000e-15
GCST004601_175	Red blood cell count	3.000000e-15
GCST004602_205	Mean corpuscular volume	4.000000e-12
GCST004603_135	Platelet count	3.000000e-30
GCST004607_97	Plateletcrit	7.000000e-19
GCST004610_138	White blood cell count	5.000000e-12

EFO canonical traits (32, from GWAS)

EFO ID	Trait name
EFO:0004267	biliary liver cirrhosis
EFO:0004309	platelet count
EFO:0000714	survival time
EFO:0000482	event free survival time
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0005533	response to non-steroidal anti-inflammatory
EFO:1001492	atrophic macular degeneration
EFO:1001515	ovarian endometrioid carcinoma
EFO:1001516	ovarian serous carcinoma
EFO:0004305	erythrocyte count
EFO:0007985	platelet crit
EFO:0004833	neutrophil count
EFO:0004842	eosinophil count
EFO:0007987	granulocyte count
EFO:0005090	basophil count
EFO:0004527	mean corpuscular hemoglobin
EFO:0004723	coronary artery calcification
EFO:0004653	response to TNF antagonist
EFO:0005413	joint damage measurement
EFO:0009270	heel bone mineral density
EFO:0003924	hair color
EFO:0009933	Thyroid preparation use measurement
EFO:0009658	adverse effect
EFO:0004847	age at onset
EFO:0007992	basophil percentage of leukocytes
EFO:0004348	hematocrit
EFO:0004587	lymphocyte count
EFO:0007989	monocyte percentage of leukocytes
EFO:0010701	mean reticulocyte volume
EFO:0007874	gut microbiome measurement

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
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
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750
C562840	Breast Cancer, Familial (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

Clinical evidence (CIViC)

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

Variant	Therapy	Indication	Effect	Level	CIViC
RAD51B Mutation	Olaparib	Castration-resistant Prostate Carcinoma	Sensitivity/Response	CIViC A	EID11212

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	5
Benzo(a)pyrene	affects methylation, decreases expression	4
Aflatoxin B1	decreases expression, increases methylation	3
bisphenol A	affects cotreatment, increases methylation, decreases methylation, increases expression	2
Tobacco Smoke Pollution	decreases methylation, decreases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	affects cotreatment, decreases methylation	1
aminomethylphosphonic acid (AMPA)	increases expression	1
methylmercuric chloride	decreases expression	1
lasiocarpine	decreases expression	1
methyleugenol	decreases expression	1
myristicin	decreases expression	1
VX-agent	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
ptaquiloside	decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	decreases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
scriptaid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, decreases expression, increases expression	1
Fulvestrant	affects cotreatment, increases methylation, decreases methylation	1
Vorinostat	increases expression	1

Cellosaurus cell lines

6 cell lines: 4 cancer cell line, 2 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TI34	HAP1 RAD51B (-)	Cancer cell line	Male
CVCL_VR78	U2OS#18-RAD51B-8	Cancer cell line	Female
CVCL_VR79	U2OS#18-RAD51B-8/B+	Cancer cell line	Female
CVCL_W912	LAM1	Cancer cell line	Male
CVCL_XX01	HEK293-DR-GFP-RAD51B-9	Transformed cell line	Female
CVCL_XX06	HEK293-DR-GFP-RAD51B-9/B+	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00417066	PHASE4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	PHASE4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	PHASE4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	PHASE4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	PHASE4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	PHASE4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
NCT02562170	PHASE4	COMPLETED	Protexa® Versus TiLoopBra® in Immediate Breast Reconstruction- A Pilot Study
NCT00140998	PHASE3	COMPLETED	Estrogen Treatment (Oral vs. Patches) in Turner Syndrome
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
NCT00001951	PHASE2	COMPLETED	Hormone Replacement in Young Women With Premature Ovarian Failure
NCT00370019	PHASE2	WITHDRAWN	Effects of an Estrogen Replacement Therapy Skin Patch on Ovulation in Women With Premature Ovarian Failure
NCT00429494	PHASE2	COMPLETED	GnRH Analogue for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients
NCT03816852	PHASE2	SUSPENDED	The Safety and Efficiency Study of Mesenchymal Stem Cell (19#iSCLife®-POI) in Premature Ovarian Insufficiency
NCT04536467	PHASE2	UNKNOWN	Prevention of Chemotherapy-Induced Ovarian Failure With Goserelin in Premenopausal Lymphoma Patients
NCT06117982	PHASE2	COMPLETED	The Impact of Granulocyte Colony Stimulating Factor on Premature Ovarian Insufficiency
NCT00253539	PHASE2	COMPLETED	Arzoxifene or Tamoxifen in Preventing Breast Cancer in Premenopausal Women at High Risk for Breast Cancer
NCT00305695	PHASE2	COMPLETED	Zoledronate or Observation in Maintaining Bone Mineral Density in Patients Who Are Undergoing Surgery to Remove Both Ovaries
NCT00321633	PHASE2	COMPLETED	Carboplatin or Docetaxel in Treating Women With Metastatic Genetic Breast Cancer
NCT01333748	PHASE2	COMPLETED	Search Allelic Imbalance of Expression of BRCA Genes in Hereditary Risk of Breast and/or Ovarian Cancer
NCT01367639	PHASE2	COMPLETED	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT02912104	PHASE1	COMPLETED	A Therapeutic Trial of Human Amniotic Epithelial Cells Transplantation for Primary Ovarian Failure
NCT03178695	PHASE1	COMPLETED	Inovium Ovarian Rejuvenation Trials
NCT04815213	PHASE1	ACTIVE_NOT_RECRUITING	The Use of Expandeded Mesenchymal Stromal Cells (MSC) in Premature Ovarian Failure (POF) in Adult Humans
NCT05138367	PHASE1	COMPLETED	Effects of UCA-PSCs in Women With POF
NCT06132542	PHASE1	UNKNOWN	Autologous ADMSC Transplantation in Patients With POI
NCT00535119	PHASE1	COMPLETED	Veliparib, Carboplatin, and Paclitaxel in Treating Patients With Advanced Solid Cancer
NCT00892736	PHASE1	COMPLETED	Veliparib in Treating Patients With Malignant Solid Tumors That Do Not Respond to Previous Therapy
NCT07223034	PHASE1	RECRUITING	A Study of 177Lu-PSMA-617 in People With Gliomas
NCT00948857	PHASE2/PHASE3	TERMINATED	Dehydroepiandrosterone (DHEA) Treatment and Premature Ovarian Failure (POF)
NCT04031456	PHASE2/PHASE3	RECRUITING	Autologous PRP Infusion May Restore Ovarian Function and May Promote Folliculogenesis in POI Patients
NCT02043743	PHASE1/PHASE2	UNKNOWN	Autologous Stem Cells Transplantation in Patients With Idiopathic and Drug Induced Premature Ovarian Failure
NCT02062931	PHASE1/PHASE2	UNKNOWN	Autologous Mesenchymal Stem Cells Transplantation In Women With Premature Ovarian Failure
NCT02151890	PHASE1/PHASE2	COMPLETED	Pregnancy After Stem Cell Transplantation in Premature Ovarian Failure
NCT02372474	PHASE1/PHASE2	COMPLETED	It is a Real The First Baby Of Autologous Stem Cell Therapy in Premature Ovarian Failure
NCT02603744	PHASE1/PHASE2	UNKNOWN	Autologous Adipose Derived Mesenchymal Stromal Cells Transplantation in Women With Premature Ovarian Failure (POF)
NCT02644447	PHASE1/PHASE2	COMPLETED	Transplantation of HUC-MSCs With Injectable Collagen Scaffold for POF
NCT03069209	PHASE1/PHASE2	UNKNOWN	Autologous Bone Marrow-Derived Stem Cell Transplantation in Patients With Premature Ovarian Failure (POF)
NCT03985462	PHASE1/PHASE2	WITHDRAWN	Very Small Embryonic-like Stem Cells for Ovary