RAD51

protein-coding

RAD51 recombinase, the group of FA complementation groups

Gene summary

The protein encoded by this gene is a member of the RAD51 protein family. RAD51 family members are highly similar to bacterial RecA and Saccharomyces cerevisiae Rad51, and are known to be involved in the homologous recombination and repair of DNA. This protein can interact with the ssDNA-binding protein RPA and RAD52, and it is thought to play roles in homologous pairing and strand transfer of DNA. This protein is also found to interact with BRCA1 and BRCA2, which may be important for the cellular response to DNA damage. BRCA2 is shown to regulate both the intracellular localization and DNA-binding ability of this protein. Loss of these controls following BRCA2 inactivation may be a key event leading to genomic instability and tumorigenesis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2009]

Previous symbols:

RAD51A
RECA

MANE transcript

NM_002875.5

Inheritance

AD, AR

ClinVar variants

P:15U:246B:162

Top phenotype

Mirror movements 2; Fanconi anemia, complementation group R

gnomAD constraint

pLI —, LoF o/e 0.33

Max pathogenic AF

—

Genomic locus

chr15:40,694,774-40,732,340

External References & Databases

Ensembl (ENSG00000051180)

Transcript & Mutation Effects

hg38 • Region Span ~37.6 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Fanconi anemia complementation group RSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0014986

Submitter: Labcorp Genetics (formerly Invitae)

Fanconi anemia complementation group RSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0014986

Submitter: PanelApp Australia

mirror movements 2STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0013790

Submitter: Labcorp Genetics (formerly Invitae)

mirror movements 2LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0013790

Submitter: G2P

hereditary breast carcinomaNO_KNOWN

Inheritance Pattern: AD

Disease ID:MONDO:0016419

Submitter: Labcorp Genetics (formerly Invitae)

familial congenital mirror movementsSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0016558

Submitter: Orphanet

Fanconi anemiaSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0019391

Submitter: Orphanet

Fanconi anemia complementation group RMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0014986

Submitter: Ambry Genetics

mirror movements 2MODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0013790

Submitter: Ambry Genetics

hereditary breast carcinomaLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0016419

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Mirror movements 2; Fanconi anemia, complementation group RAD

Manifestation: Craniofacial; Genitourinary; Musculoskeletal; Neurologic

Intervention: General

Rationale: 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

Comments: Individuals with Fanconi anemia, complementation group R have not been described with hematologic or oncologic manifestations

Refs: 21242494; 22305526; 26253028; 26681308

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to RAD51 variants in ClinVar

10 Conditions Cataloged

Inborn genetic diseasesTotal: 349

not providedTotal: 167

not specifiedTotal: 29

RAD51-related disorderTotal: 25

Fanconi anemia complementation group RTotal: 9

Mirror movements 2Total: 6

Familial cancer of breastTotal: 5

Hereditary cancerTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002875.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	155 clinvar		157
missense	3 clinvar	8 clinvar	239 clinvar	7 clinvar		257
nonsense	1 clinvar	1 clinvar	3 clinvar			5
start loss						0
frameshift	1 clinvar	1 clinvar	1 clinvar			3
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	5	10	246	162	0	423

Highest pathogenic variant AF is 0.000022928474

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 46 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002875.5	RefSeq	NP_002866.2	9	MANE Select
ENST00000267868.8	Ensembl	ENSP00000267868.3	9	MANE Select
NM_001164269.2	RefSeq	NP_001157741.1	9	Standard
NM_001164270.2	RefSeq	NP_001157742.1	8	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
rad51	Danio rerio	Structure: nucleate erythrocyte Quality: increased size abnormal

Gene / Model

Organism

Observed Phenotype

rad51

Danio rerio

Structure: nucleate erythrocyte

Quality: increased size

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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

Biological Process

telomere maintenance via recombination
double-strand break repair via homologous recombination
DNA recombinase assembly
DNA unwinding involved in DNA replication
DNA repair

Molecular Function

recombinase activity
chromatin binding
double-stranded DNA binding
single-stranded DNA binding
protein binding

Cellular Component

nuclear chromosome
nuclear chromosome, telomeric region
chromatin
nuclear chromatin
condensed chromosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000382643
Coding exons: 9
Length: 37383
Individuals with no LoFs: 125742
Homozygous LoFs: 0
Heterozygous LoFs: 6
Defined: 125748
p: 0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.62	81	180	0.450	0.0000100	2181
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000018	0.000018	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.959

Intolerance Scores

LoFtool: 0.140
RVIS EVS: -0.14
RVIS percentile EVS: 43.29

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.963

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium