RAD50
RAD50 double strand break repair protein, the group of BRCA1 C complex|MRN complex
Basic information
Region (hg38): 5:132556019-132646349
Links
Phenotypes
GenCC
Source:
- Nijmegen breakage syndrome-like disorder (Limited), mode of inheritance: AR
- Nijmegen breakage syndrome-like disorder (Limited), mode of inheritance: AR
- Nijmegen breakage syndrome-like disorder (Strong), mode of inheritance: AR
- hereditary breast carcinoma (Refuted Evidence), mode of inheritance: AD
- familial ovarian cancer (Refuted Evidence), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Breast cancer, susceptibility to; Nijmegen breakage syndrome-like disorder | AD/AR | Audiologic/Otolaryngologic; Cardiovascular; Oncologic | In Breast cancer, susceptibility to, awareness may allow surveillance, preventive measures, and early diagnosis and treatment of disease; Nijmegen breakage syndrome-like disorder has been described as involving sensorineural hearing loss, and early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; An individual with Nijmegen breakage syndrome-like disorder has been described with arrhythmias, and awareness may allow early diagnosis and management of cardiac sequelae | Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Dermatologic; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic | 14684699; 16474176; 1887849; 19092773; 19409520; 20571869; 21356067; 21799032; 22006311; 22048815; 22476849; 24549055; 24894818; 32212377 |
ClinVar
This is a list of variants' phenotypes submitted to
- Hereditary cancer-predisposing syndrome (299 variants)
- Nijmegen breakage syndrome-like disorder (22 variants)
- not provided (7 variants)
- Breast and/or ovarian cancer (3 variants)
- Breast carcinoma (1 variants)
- Neoplasm of the skin (1 variants)
- Familial cancer of breast (1 variants)
- Hepatocellular carcinoma (1 variants)
- RAD50-related disorder (1 variants)
- Hereditary breast ovarian cancer syndrome (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the RAD50 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 | 817 | 829 | ||||
| missense | 2184 | 10 | 2197 | |||
| nonsense | 107 | 36 | 151 | |||
| start loss | 7 | |||||
| frameshift | 191 | 40 | 15 | 246 | ||
| inframe indel | 37 | 39 | ||||
| splice donor/acceptor (+/-2bp) | 76 | 88 | ||||
| splice region | 9 | 100 | 116 | 11 | 236 | |
| non coding | 39 | 362 | 54 | 455 | ||
| Total | 301 | 158 | 2303 | 1191 | 59 |
Highest pathogenic variant AF is 0.000140
Variants in RAD50
This is a list of pathogenic ClinVar variants found in the RAD50 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 5-132556665-C-T | Benign (Apr 09, 2019) | |||
| 5-132556973-G-A | not provided (-) | |||
| 5-132557041-C-A | not provided (-) | |||
| 5-132557287-G-G | not specified | Benign (Oct 23, 2013) | ||
| 5-132557320-C-T | Uncertain significance (Feb 29, 2024) | |||
| 5-132557322-A-G | Hereditary cancer-predisposing syndrome | Uncertain significance (Nov 14, 2022) | ||
| 5-132557324-C-T | Hereditary cancer-predisposing syndrome | Uncertain significance (Mar 05, 2018) | ||
| 5-132557325-A-G | Hereditary cancer-predisposing syndrome | Likely pathogenic (Nov 12, 2021) | ||
| 5-132557327-G-A | Hereditary cancer-predisposing syndrome • Nijmegen breakage syndrome-like disorder | Pathogenic/Likely pathogenic (Aug 01, 2024) | ||
| 5-132557328-T-A | Hereditary cancer-predisposing syndrome | Uncertain significance (Dec 31, 2023) | ||
| 5-132557328-T-C | Hereditary cancer-predisposing syndrome | Uncertain significance (Feb 03, 2023) | ||
| 5-132557328-T-G | Hereditary cancer-predisposing syndrome | Uncertain significance (Jun 22, 2022) | ||
| 5-132557329-C-T | Hereditary cancer-predisposing syndrome | Conflicting classifications of pathogenicity (Aug 27, 2018) | ||
| 5-132557330-C-T | Hereditary cancer-predisposing syndrome | Likely benign (Jul 12, 2022) | ||
| 5-132557331-C-T | Hereditary cancer-predisposing syndrome | Uncertain significance (Dec 10, 2023) | ||
| 5-132557332-G-A | Hereditary cancer-predisposing syndrome | Uncertain significance (Apr 08, 2021) | ||
| 5-132557332-G-T | Hereditary cancer-predisposing syndrome | Uncertain significance (Apr 25, 2023) | ||
| 5-132557333-G-A | Hereditary cancer-predisposing syndrome | Likely benign (Dec 29, 2023) | ||
| 5-132557333-G-C | Hereditary cancer-predisposing syndrome | Likely benign (Mar 17, 2024) | ||
| 5-132557334-A-G | Hereditary cancer-predisposing syndrome | Uncertain significance (Sep 10, 2023) | ||
| 5-132557336-C-A | Hereditary cancer-predisposing syndrome | Likely benign (Sep 24, 2023) | ||
| 5-132557336-C-T | Hereditary cancer-predisposing syndrome | Likely benign (Jan 29, 2020) | ||
| 5-132557336-CG-TT | Hereditary cancer-predisposing syndrome | Likely pathogenic (Feb 14, 2020) | ||
| 5-132557337-G-A | Hereditary cancer-predisposing syndrome | Uncertain significance (Nov 30, 2023) | ||
| 5-132557337-GA-G | Hereditary cancer-predisposing syndrome | Pathogenic (Mar 22, 2022) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| RAD50 | protein_coding | protein_coding | ENST00000265335 | 25 | 88603 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 3.44e-27 | 0.716 | 125214 | 0 | 534 | 125748 | 0.00213 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.25 | 587 | 679 | 0.865 | 0.0000357 | 8776 |
| Missense in Polyphen | 163 | 185.44 | 0.87899 | 2257 | ||
| Synonymous | -0.859 | 239 | 223 | 1.07 | 0.0000104 | 2246 |
| Loss of Function | 2.48 | 54 | 77.6 | 0.696 | 0.00000440 | 928 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00406 | 0.00398 |
| Ashkenazi Jewish | 0.000605 | 0.000595 |
| East Asian | 0.00253 | 0.00250 |
| Finnish | 0.00554 | 0.00551 |
| European (Non-Finnish) | 0.00161 | 0.00158 |
| Middle Eastern | 0.00253 | 0.00250 |
| South Asian | 0.00215 | 0.00213 |
| Other | 0.00278 | 0.00277 |
dbNSFP
Source:
- Function
- FUNCTION: Component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis. The complex possesses single-strand endonuclease activity and double-strand- specific 3'-5' exonuclease activity, which are provided by MRE11. RAD50 may be required to bind DNA ends and hold them in close proximity. This could facilitate searches for short or long regions of sequence homology in the recombining DNA templates, and may also stimulate the activity of DNA ligases and/or restrict the nuclease activity of MRE11 to prevent nucleolytic degradation past a given point (PubMed:11741547, PubMed:9590181, PubMed:9705271, PubMed:9651580). The complex may also be required for DNA damage signaling via activation of the ATM kinase (PubMed:15064416). In telomeres the MRN complex may modulate t-loop formation (PubMed:10888888). {ECO:0000269|PubMed:10888888, ECO:0000269|PubMed:11741547, ECO:0000269|PubMed:15064416, ECO:0000269|PubMed:9590181, ECO:0000269|PubMed:9651580, ECO:0000269|PubMed:9705271}.;
- Disease
- DISEASE: Nijmegen breakage syndrome-like disorder (NBSLD) [MIM:613078]: A disorder similar to Nijmegen breakage syndrome and characterized by chromosomal instability, radiation sensitivity, microcephaly, growth retardation, short stature and bird-like face. Immunodeficiency is absent. {ECO:0000269|PubMed:19409520}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Homologous recombination - Homo sapiens (human);Cellular senescence - Homo sapiens (human);Non-homologous end-joining - Homo sapiens (human);miRNA Regulation of DNA Damage Response;Homologous recombination;DDX1 as a regulatory component of the Drosha microprocessor;ATM Signaling Network in Development and Disease;Non-homologous end joining;DNA Damage Response;HDR through Single Strand Annealing (SSA);HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA);HDR through MMEJ (alt-NHEJ);DNA Repair;Gene expression (Transcription);Nonhomologous End-Joining (NHEJ);DNA Double-Strand Break Repair;role of brca1 brca2 and atr in cancer susceptibility;Generic Transcription Pathway;DNA Damage/Telomere Stress Induced Senescence;Cellular Senescence;Homology Directed Repair;Cellular responses to stress;RNA Polymerase II Transcription;G2/M DNA damage checkpoint;G2/M Checkpoints;Cell Cycle Checkpoints;Cellular responses to external stimuli;Fanconi anemia pathway;Regulation of TP53 Activity through Phosphorylation;Regulation of TP53 Activity;Transcriptional Regulation by TP53;Sensing of DNA Double Strand Breaks;Cell Cycle;Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks;DNA Double Strand Break Response;Regulation of Telomerase;BARD1 signaling events;Processing of DNA double-strand break ends;ATM 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
- 0.586
Intolerance Scores
- loftool
- 0.987
- rvis_EVS
- -0.5
- rvis_percentile_EVS
- 21.84
Haploinsufficiency Scores
- pHI
- 0.754
- hipred
- N
- hipred_score
- 0.492
- ghis
- 0.611
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.958
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Rad50
- Phenotype
- cellular phenotype; endocrine/exocrine gland phenotype; neoplasm; growth/size/body region phenotype; hematopoietic system 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); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); reproductive system phenotype; digestive/alimentary phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; liver/biliary system phenotype; embryo phenotype; pigmentation phenotype;
Gene ontology
- Biological process
- regulation of mitotic recombination;telomere maintenance via recombination;telomere maintenance;double-strand break repair via homologous recombination;DNA double-strand break processing;DNA replication;DNA repair;double-strand break repair;double-strand break repair via nonhomologous end joining;DNA recombination;cellular response to DNA damage stimulus;telomere maintenance via telomerase;reciprocal meiotic recombination;viral process;telomere capping;telomeric 3' overhang formation;positive regulation of protein autophosphorylation;positive regulation of telomere maintenance;DNA duplex unwinding;positive regulation of kinase activity;nucleoside monophosphate phosphorylation;chromosome organization involved in meiotic cell cycle;nucleic acid phosphodiester bond hydrolysis;negative regulation of telomere capping
- Cellular component
- nuclear chromosome, telomeric region;nuclear chromatin;condensed nuclear chromosome;nucleoplasm;membrane;Mre11 complex;site of double-strand break
- Molecular function
- single-stranded DNA endodeoxyribonuclease activity;DNA binding;double-stranded telomeric DNA binding;ATP-dependent DNA helicase activity;adenylate kinase activity;protein binding;ATP binding;3'-5' exonuclease activity;protein binding, bridging;single-stranded telomeric DNA binding;metal ion binding;G-quadruplex DNA binding