RAD51

RAD51 recombinase, the group of FA complementation groups

Basic information

Region (hg38): 15:40694773-40732340

Previous symbols: [ "RAD51A", "RECA" ]

Links

ENSG00000051180 ∙ NCBI:5888 ∙ OMIM:179617 ∙ HGNC:9817 ∙ Uniprot:Q06609 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 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: CGD

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 ClinVar and linked to the RAD51 gene.

• Inborn genetic diseases (255 variants)
• not provided (95 variants)
• not specified (13 variants)
• RAD51-related condition (4 variants)
• Fanconi anemia complementation group R (4 variants)
• Hereditary cancer (3 variants)
• Mirror movements 2 (3 variants)
• Familial cancer of breast (2 variants)
• RAD51-related disorders (1 variants)
• Breast cancer, susceptibility to, in BRCA1 and BRCA2 carriers (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				110		110
missense		4	153	12	1	170
nonsense	1		3	1		5
start loss				1		1
frameshift		1	1			2
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1	4	2	7
non coding			1	14	26	41
Total	1	5	158	138	27

Highest pathogenic variant AF is 0.00000657

Variants in RAD51

This is a list of pathogenic ClinVar variants found in the RAD51 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
15-40695220-G-C			Benign (Jul 20, 2018)
15-40695221-C-T			Benign (Jun 23, 2018)
15-40695330-G-C		Breast cancer, susceptibility to, in BRCA1 and BRCA2 carriers	Benign (Jun 22, 2018)
15-40695367-G-T			Benign (Jun 22, 2018)
15-40695527-C-T			Benign (Jun 22, 2018)
15-40698757-T-TA		Hereditary cancer	Likely benign (Jan 23, 2024)
15-40698764-A-C		Inborn genetic diseases	Likely benign (Feb 28, 2023)
15-40698765-A-G			Uncertain significance (Aug 03, 2023)
15-40698766-T-C		Inborn genetic diseases	Uncertain significance (Apr 25, 2023)
15-40698767-G-A		Inborn genetic diseases	Uncertain significance (Aug 07, 2022)
15-40698768-C-A		Inborn genetic diseases	Uncertain significance (Mar 11, 2023)
15-40698773-G-T		Inborn genetic diseases	Uncertain significance (Dec 15, 2021)
15-40698778-T-C			Uncertain significance (Jun 09, 2023)
15-40698786-A-G		Inborn genetic diseases	Uncertain significance (Oct 05, 2021)
15-40698790-C-G		Inborn genetic diseases	Uncertain significance (Feb 01, 2022)
15-40698790-C-T		Inborn genetic diseases	Uncertain significance (Nov 03, 2023)
15-40698791-A-C		Inborn genetic diseases	Likely benign (Jun 20, 2022)
15-40698793-A-G		Inborn genetic diseases	Uncertain significance (Sep 14, 2023)
15-40698801-G-C		Inborn genetic diseases	Uncertain significance (Mar 05, 2024)
15-40698806-A-G		Inborn genetic diseases	Likely benign (Sep 13, 2021)
15-40698811-AAAGCTTTGGCCCACAA-TATCTTCTT		RAD51-related disorder	Likely pathogenic (Sep 15, 2022)
15-40698813-A-G		Inborn genetic diseases	Uncertain significance (Jul 17, 2021)
15-40698821-C-T		Inborn genetic diseases	Likely benign (Jul 09, 2020)
15-40698827-A-G		Inborn genetic diseases	Likely benign (Nov 01, 2021)
15-40698828-C-G		Inborn genetic diseases	Uncertain significance (Jan 26, 2023)

GnomAD

Source: gnomAD

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: dbNSFP

• 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