MRE11

MRE11 homolog, double strand break repair nuclease, the group of BRCA1 C complex|MRN complex|MicroRNA protein coding host genes

Basic information

Region (hg38): 11:94415569-94493885

Previous symbols: [ "MRE11A" ]

Links

ENSG00000020922 ∙ NCBI:4361 ∙ OMIM:600814 ∙ HGNC:7230 ∙ Uniprot:P49959 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• ataxia-telangiectasia-like disorder 1 (Supportive), mode of inheritance: AR
• ataxia-telangiectasia-like disorder 1 (Definitive), mode of inheritance: AR
• ataxia-telangiectasia-like disorder 1 (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: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Breast cancer, susceptibility to	AD	Oncologic	Awareness of the risk of malignancy may allow early surveillance, preventive measures, and early diagnosis and treatment of disease	Dermatologic; Neurologic; Oncologic; Ophthalmologic	8445618; 8684395; 10612394; 11196167; 11371508; 15269180; 15574463; 17932350; 19383352; 19584272; 19732584; 20087742; 21227757; 21799032; 22006311; 22863007; 24332946; 24549055; 24894818
Individuals with Ataxia-telangiectasia-like disorder 1 may be at increased risk for malignancy, though the data are unclear

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MRE11 gene.

• Hereditary cancer-predisposing syndrome (1358 variants)
• Ataxia-telangiectasia-like disorder (866 variants)
• Ataxia-telangiectasia-like disorder 1 (313 variants)
• not provided (236 variants)
• not specified (64 variants)
• Hereditary breast ovarian cancer syndrome (50 variants)
• MRE11-related condition (11 variants)
• Ovarian cancer (5 variants)
• Inborn genetic diseases (3 variants)
• See cases (2 variants)
• Breast carcinoma (2 variants)
• Malignant tumor of urinary bladder (2 variants)
• Premature ovarian insufficiency (1 variants)
• Colonic neoplasm (1 variants)
• - (1 variants)
• Depression;Dementia;Parkinsonism;Dystonic disorder (1 variants)
• Depression;Dementia;Dystonic disorder;Parkinsonism (1 variants)
• Neoplasm of ovary (1 variants)
• Renal transitional cell carcinoma (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MRE11 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			2	336	1	339
missense		3	903	14	2	922
nonsense	24	15	1			40
start loss		1	1			2
frameshift	39	27	4			70
inframe indel			12			12
splice donor/acceptor (+/-2bp)	2	45	2			49
splice region			53	42	1	96
non coding			66	144	60	270
Total	65	91	991	494	63

Highest pathogenic variant AF is 0.0000263

Variants in MRE11

This is a list of pathogenic ClinVar variants found in the MRE11 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-94417394-C-T		Malignant tumor of urinary bladder	other (-)
11-94417421-C-G		Ataxia-telangiectasia-like disorder 1	Uncertain significance (Jan 13, 2018)
11-94417422-T-C		Ataxia-telangiectasia-like disorder 1	Uncertain significance (Jan 13, 2018)
11-94417425-G-A		Ataxia-telangiectasia-like disorder 1	Uncertain significance (Jan 13, 2018)
11-94417426-T-A		Ataxia-telangiectasia-like disorder 1	Benign (Jan 13, 2018)
11-94417463-T-C		Ataxia-telangiectasia-like disorder 1	Benign (Jan 13, 2018)
11-94417467-T-C		Ataxia-telangiectasia-like disorder 1	Uncertain significance (Jan 12, 2018)
11-94417594-T-A		Ataxia-telangiectasia-like disorder 1	Uncertain significance (Jan 12, 2018)
11-94417624-T-C		Ataxia-telangiectasia-like disorder 1	Benign (Oct 29, 2020)
11-94417659-A-G		Ataxia-telangiectasia-like disorder 1	Benign (Sep 27, 2017)
11-94417673-G-A		Ataxia-telangiectasia-like disorder 1	Uncertain significance (Jan 13, 2018)
11-94417681-T-C		Ataxia-telangiectasia-like disorder 1	Likely benign (Jan 12, 2018)
11-94417801-C-A		Ataxia-telangiectasia-like disorder 1	Uncertain significance (Jan 13, 2018)
11-94417805-A-G		Ataxia-telangiectasia-like disorder 1	Uncertain significance (Jan 13, 2018)
11-94417829-T-C		Ataxia-telangiectasia-like disorder 1	Uncertain significance (Jan 13, 2018)
11-94417867-C-G		Ataxia-telangiectasia-like disorder 1	Uncertain significance (Jan 12, 2018)
11-94417947-T-G		Ataxia-telangiectasia-like disorder 1	Uncertain significance (Jan 13, 2018)
11-94417955-T-A		Ataxia-telangiectasia-like disorder 1	Uncertain significance (Jan 12, 2018)
11-94418019-A-G		Ataxia-telangiectasia-like disorder 1	Uncertain significance (Jan 13, 2018)
11-94418058-T-C		Ataxia-telangiectasia-like disorder 1	Benign (Jan 12, 2018)
11-94418072-A-G		Ataxia-telangiectasia-like disorder 1	Benign (Sep 27, 2017)
11-94418192-C-A		Ataxia-telangiectasia-like disorder 1	Uncertain significance (Jan 13, 2018)
11-94418225-G-A		Ataxia-telangiectasia-like disorder 1	Uncertain significance (Jan 13, 2018)
11-94418349-G-A		Ataxia-telangiectasia-like disorder 1	Uncertain significance (Jan 12, 2018)
11-94418359-C-G		Ataxia-telangiectasia-like disorder 1	Benign (Jan 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MRE11	protein_coding	protein_coding	ENST00000323929	19	74180

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.26e-12	0.980	125633	0	115	125748	0.000457

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.130	378	385	0.981	0.0000202	4714
Missense in Polyphen		89	105.63	0.84258		1389
Synonymous	-0.966	138	124	1.11	0.00000624	1263
Loss of Function	2.40	26	43.0	0.605	0.00000240	498

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000775	0.000775
Ashkenazi Jewish	0.0000994	0.0000992
East Asian	0.000435	0.000435
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000530	0.000528
Middle Eastern	0.000435	0.000435
South Asian	0.000686	0.000686
Other	0.000652	0.000652

dbNSFP

Source: dbNSFP

• 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:9651580, PubMed:9590181, PubMed:9705271, PubMed:11741547, PubMed:29670289). 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:29670289, ECO:0000269|PubMed:9590181, ECO:0000269|PubMed:9705271}.
• Disease: DISEASE: Ataxia-telangiectasia-like disorder 1 (ATLD1) [MIM:604391]: A rare disorder characterized by progressive cerebellar ataxia, dysarthria, abnormal eye movements, and absence of telangiectasia. ATLD patients show normal levels of total IgG, IgA and IgM, although there may be reduced levels of specific functional antibodies. At the cellular level, ATLD exhibits hypersensitivity to ionizing radiation and radioresistant DNA synthesis. {ECO:0000269|PubMed:10612394}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=Defects in MRE11 can be a cause of nephronophthisis- related ciliopathies (NPHP-RC), a group of recessive diseases that affect kidney, retina and brain. A homozygous truncating mutation MRE11 has been found in patients with cerebellar vermis hypoplasia, ataxia and dysarthria. {ECO:0000269|PubMed:22863007}.
• 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;STING mediated induction of host immune responses;RNA Polymerase II Transcription;G2/M DNA damage checkpoint;G2/M Checkpoints;Cell Cycle Checkpoints;Innate Immune System;Immune System;IRF3-mediated induction of type I IFN;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;Cytosolic sensors of pathogen-associated DNA ;Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks;DNA Double Strand Break Response;Regulation of Telomerase;Validated transcriptional targets of deltaNp63 isoforms;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: 0.503

Intolerance Scores

• rvis_EVS: 0.04
• rvis_percentile_EVS: 57.41

Haploinsufficiency Scores

• pHI: 0.999
• hipred: Y
• hipred_score: 0.715
• ghis: 0.626

Essentials

• essential_gene_gene_trap: H

Mouse Genome Informatics

• Gene name: Mre11a
• Phenotype: embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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); reproductive system phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); neoplasm; immune system phenotype; cellular phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: regulation of mitotic 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;sister chromatid cohesion;mitotic G2 DNA damage checkpoint;synapsis;reciprocal meiotic recombination;cell population proliferation;viral process;intra-S DNA damage checkpoint;telomeric 3' overhang formation;positive regulation of protein autophosphorylation;positive regulation of telomere maintenance;positive regulation of type I interferon production;DNA duplex unwinding;negative regulation of DNA endoreduplication;positive regulation of kinase activity;meiotic DNA double-strand break formation;negative regulation of apoptotic process;mitochondrial double-strand break repair via homologous recombination;DNA strand resection involved in replication fork processing
• Cellular component: chromosome, telomeric region;nuclear chromosome, telomeric region;nucleus;nucleoplasm;cytoplasm;cytosol;PML body;Mre11 complex;site of double-strand break
• Molecular function: single-stranded DNA endodeoxyribonuclease activity;DNA binding;double-stranded DNA binding;ATP-dependent DNA helicase activity;nuclease activity;endodeoxyribonuclease activity;protein binding;protein C-terminus binding;3'-5'-exodeoxyribonuclease activity;3'-5' exonuclease activity;5'-3' exonuclease activity;manganese ion binding;identical protein binding;cadherin binding