RAD51
RAD51 recombinase, the group of FA complementation groups
Basic information
Region (hg38): 15:40694774-40732340
Previous symbols: [ "RAD51A", "RECA" ]
Links
Phenotypes
GenCC
Source:
- hereditary breast carcinoma (No Known Disease Relationship), mode of inheritance: AD
- mirror movements 2 (Limited), mode of inheritance: AD
- Fanconi anemia (Supportive), mode of inheritance: AR
- familial congenital mirror movements (Supportive), mode of inheritance: AD
- mirror movements 2 (Moderate), mode of inheritance: AD
- Fanconi anemia complementation group R (Moderate), mode of inheritance: AD
- hereditary breast carcinoma (Limited), mode of inheritance: AD
- Fanconi anemia complementation group R (Strong), mode of inheritance: AD
- mirror movements 2 (Strong), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Mirror movements 2; Fanconi anemia, complementation group R | AD | General | Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing | Craniofacial; Genitourinary; Musculoskeletal; Neurologic | 21242494; 22305526; 26253028; 26681308 |
| Individuals with Fanconi anemia, complementation group R have not been described with hematologic or oncologic manifestations |
ClinVar
This is a list of variants' phenotypes submitted to
- Inborn_genetic_diseases (346 variants)
- not_provided (141 variants)
- RAD51-related_disorder (18 variants)
- not_specified (14 variants)
- Fanconi_anemia_complementation_group_R (7 variants)
- Mirror_movements_2 (6 variants)
- Familial_cancer_of_breast (5 variants)
- Hereditary_cancer (3 variants)
- Hereditary_cancer-predisposing_syndrome (1 variants)
- Ovarian_cancer (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the RAD51 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000002875.5. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 152 | 154 | ||||
| missense | 229 | 245 | ||||
| nonsense | 4 | |||||
| start loss | 1 | 1 | ||||
| frameshift | 4 | |||||
| splice donor/acceptor (+/-2bp) | 1 | |||||
| Total | 4 | 9 | 234 | 161 | 1 |
Highest pathogenic variant AF is 0.0000229285
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| RAD51 | protein_coding | protein_coding | ENST00000382643 | 9 | 37383 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.0266 | 0.971 | 125742 | 0 | 6 | 125748 | 0.0000239 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.62 | 81 | 180 | 0.450 | 0.0000100 | 2181 |
| Missense in Polyphen | 11 | 60.038 | 0.18322 | 724 | ||
| Synonymous | -0.626 | 71 | 64.6 | 1.10 | 0.00000370 | 693 |
| Loss of Function | 2.68 | 6 | 18.4 | 0.326 | 0.00000116 | 217 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000904 | 0.0000904 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.0000462 | 0.0000462 |
| European (Non-Finnish) | 0.0000176 | 0.0000176 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000327 | 0.0000327 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Plays an important role in homologous strand exchange, a key step in DNA repair through homologous recombination (HR) (PubMed:28575658). Binds to single and double-stranded DNA and exhibits DNA-dependent ATPase activity. Catalyzes the recognition of homology and strand exchange between homologous DNA partners to form a joint molecule between a processed DNA break and the repair template. Binds to single-stranded DNA in an ATP-dependent manner to form nucleoprotein filaments which are essential for the homology search and strand exchange (PubMed:26681308). Part of a PALB2-scaffolded HR complex containing BRCA2 and RAD51C and which is thought to play a role in DNA repair by HR. Plays a role in regulating mitochondrial DNA copy number under conditions of oxidative stress in the presence of RAD51C and XRCC3. Also involved in interstrand cross-link repair (PubMed:26253028). {ECO:0000269|PubMed:12205100, ECO:0000269|PubMed:12442171, ECO:0000269|PubMed:18417535, ECO:0000269|PubMed:20231364, ECO:0000269|PubMed:20348101, ECO:0000269|PubMed:20413593, ECO:0000269|PubMed:23509288, ECO:0000269|PubMed:23754376, ECO:0000269|PubMed:26253028, ECO:0000269|PubMed:26681308, ECO:0000269|PubMed:28575658}.;
- Disease
- DISEASE: Breast cancer (BC) [MIM:114480]: A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case. {ECO:0000269|PubMed:10807537, ECO:0000269|PubMed:25539919}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Mirror movements 2 (MRMV2) [MIM:614508]: A disorder characterized by contralateral involuntary movements that mirror voluntary ones. While mirror movements are occasionally found in young children, persistence beyond the age of 10 is abnormal. Mirror movements occur more commonly in the upper extremities. {ECO:0000269|PubMed:22305526}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Fanconi anemia, complementation group R (FANCR) [MIM:617244]: A disorder affecting all bone marrow elements and resulting in anemia, leukopenia and thrombopenia. It is associated with cardiac, renal and limb malformations, dermal pigmentary changes, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage) and defective DNA repair. {ECO:0000269|PubMed:26253028, ECO:0000269|PubMed:26681308}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Fanconi anemia pathway - Homo sapiens (human);Homologous recombination - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Pancreatic cancer - Homo sapiens (human);miRNA Regulation of DNA Damage Response;Homologous recombination;ATM Signaling Pathway;Rac1-Pak1-p38-MMP-2 pathway;DNA Damage Response;HDR through Single Strand Annealing (SSA);HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA);DNA Repair;Gene expression (Transcription);DNA Double-Strand Break Repair;role of brca1 brca2 and atr in cancer susceptibility;Transcriptional Regulation by E2F6;Generic Transcription Pathway;Homology Directed Repair;RNA Polymerase II Transcription;p73 transcription factor network;atm signaling pathway;BARD1 signaling events;ATR signaling pathway;Presynaptic phase of homologous DNA pairing and strand exchange;Homologous DNA Pairing and Strand Exchange;Resolution of D-loop Structures through Holliday Junction Intermediates;Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA);Resolution of D-Loop Structures;HDR through Homologous Recombination (HRR)
(Consensus)
Recessive Scores
- pRec
- 0.959
Intolerance Scores
- loftool
- 0.140
- rvis_EVS
- -0.14
- rvis_percentile_EVS
- 43.29
Haploinsufficiency Scores
- pHI
- 1.00
- hipred
- Y
- hipred_score
- 0.827
- ghis
- 0.648
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- E
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.963
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Rad51
- Phenotype
- mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); embryo phenotype; growth/size/body region phenotype; cellular phenotype;
Zebrafish Information Network
- Gene name
- rad51
- Affected structure
- nucleate erythrocyte
- Phenotype tag
- abnormal
- Phenotype quality
- increased size
Gene ontology
- Biological process
- telomere maintenance via recombination;double-strand break repair via homologous recombination;DNA recombinase assembly;DNA unwinding involved in DNA replication;DNA repair;DNA recombination;mitotic recombination;cellular response to DNA damage stimulus;reciprocal meiotic recombination;regulation of double-strand break repair via homologous recombination;telomere maintenance via telomere lengthening;replication fork processing;interstrand cross-link repair;strand invasion;positive regulation of DNA ligation;protein homooligomerization;meiotic cell cycle;chromosome organization involved in meiotic cell cycle;negative regulation of G0 to G1 transition;cellular response to ionizing radiation;cellular response to camptothecin;mitotic recombination-dependent replication fork processing
- Cellular component
- nuclear chromosome;nuclear chromosome, telomeric region;chromatin;nuclear chromatin;condensed chromosome;condensed nuclear chromosome;lateral element;nucleus;nucleoplasm;nucleolus;cytoplasm;mitochondrion;mitochondrial matrix;microtubule organizing center;cytosol;PML body;protein-containing complex;site of double-strand break;perinuclear region of cytoplasm
- Molecular function
- recombinase activity;chromatin binding;double-stranded DNA binding;single-stranded DNA binding;protein binding;ATP binding;protein C-terminus binding;DNA-dependent ATPase activity;enzyme binding;identical protein binding;single-stranded DNA-dependent ATPase activity;DNA polymerase binding