RAD52

protein-coding

RAD52 homolog, DNA repair protein

Gene summary

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. [provided by RefSeq, Jul 2014]

MANE transcript

NM_134424.4

Inheritance

—

ClinVar variants

U:41B:6

Top phenotype

Congenital myasthenic syndrome 19

gnomAD constraint

pLI —, LoF o/e 0.76

Max pathogenic AF

—

Genomic locus

chr12:911,736-990,053

External References & Databases

Ensembl (ENSG00000002016)

Transcript & Mutation Effects

hg38 • Region Span ~78.3 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to RAD52 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 38

not providedTotal: 5

Congenital myasthenic syndrome 19Total: 1

RAD52-related disorderTotal: 1

Pilocytic astrocytomaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_134424.4. 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				1 clinvar		1
missense			35 clinvar	3 clinvar	1 clinvar	39
nonsense			1 clinvar		1 clinvar	2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	41	4	2	47

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 68 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_134424.4	RefSeq	NP_602296.2	11	MANE Select
ENST00000358495.8	Ensembl	ENSP00000351284.3	11	MANE Select
NM_001297419.1	RefSeq	NP_001284348.1	11	Standard
NM_001297420.1	RefSeq	NP_001284349.1	7	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
rad52	Danio rerio	Structure: double-strand break repair via single-strand annealing Quality: decreased frequency abnormal

Gene / Model

Organism

Observed Phenotype

rad52

Danio rerio

Structure: double-strand break repair via single-strand annealing

Quality: decreased frequency

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Homologous recombination - Homo sapiens (human)
miRNA Regulation of DNA Damage Response
miRNAs involved in DNA damage response
Homologous recombination
DNA Damage Response

Biological Process

double-strand break repair via homologous recombination
DNA recombinase assembly
double-strand break repair
DNA recombination
mitotic recombination

Molecular Function

DNA binding
single-stranded DNA binding
protein binding
identical protein binding

Cellular Component

nucleus
nucleoplasm
protein-containing complex
protein-DNA complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000358495
Coding exons: 11
Length: 77977
Individuals with no LoFs: 125625
Homozygous LoFs: 1
Heterozygous LoFs: 121
Defined: 125747
p: 0.000485

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.551	222	246	0.901	0.0000143	2714
Missense (PolyPhen)		55	71.259	0.77183		809
Synonymous	-0.0152	100	99.8	1.00	0.00000640	808
Loss of Function	1.14	19	25.1	0.756	0.00000139	270

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.0023	0.0023	notable
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00012	0.00011	rare
South Asian	0.00088	0.00085	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: 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. {ECO:0000269|PubMed:12379650, ECO:0000269|PubMed:8702565}.;

Recessive Scores

pRec: 0.415

Intolerance Scores

LoFtool: 0.859
RVIS EVS: 0.51
RVIS percentile EVS: 80.1

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.735

Gene Damage Prediction

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