EXO1

exonuclease 1, the group of Exonucleases

Basic information

Region (hg38): 1:241847966-241895148

Links

ENSG00000174371 ∙ NCBI:9156 ∙ OMIM:606063 ∙ HGNC:3511 ∙ Uniprot:Q9UQ84 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Lynch syndrome (Refuted Evidence), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the EXO1 gene.

• Inborn genetic diseases (24 variants)
• not provided (13 variants)
• not specified (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 EXO1 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	1	3
missense			24	2	3	29
nonsense						0
start loss						0
frameshift		1				1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1	1	2
non coding						0
Total	0	1	24	4	4

Highest pathogenic variant AF is 0.0000131

Variants in EXO1

This is a list of pathogenic ClinVar variants found in the EXO1 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-241850498-C-A		not specified	Uncertain significance (Aug 12, 2021)
1-241850524-C-T		EXO1-related disorder	Benign (Feb 16, 2019)
1-241850544-T-C		not specified	Uncertain significance (Feb 28, 2024)
1-241850560-AC-A			Likely pathogenic (Jan 01, 2018)
1-241850594-T-C			Likely benign (Nov 15, 2018)
1-241852289-T-C		EXO1-related disorder	Benign (Aug 13, 2019)
1-241852347-C-T		not specified	Uncertain significance (Aug 02, 2021)
1-241852356-G-A		EXO1-related disorder	Benign (Jul 12, 2019)
1-241852407-A-G		EXO1-related disorder	Benign (May 20, 2019)
1-241853401-G-A			Uncertain significance (-)
1-241853415-G-A			Likely benign (May 21, 2018)
1-241853453-C-T		not specified	Uncertain significance (Dec 17, 2023)
1-241857352-G-A		not specified	Uncertain significance (Oct 06, 2022)
1-241857374-C-G		EXO1-related disorder	Likely benign (Sep 04, 2019)
1-241857375-G-A		not specified	Uncertain significance (May 11, 2022)
1-241857397-C-T			Uncertain significance (Nov 01, 2023)
1-241857433-A-G		not specified	Uncertain significance (Dec 14, 2021)
1-241858508-A-G		EXO1-related disorder	Likely benign (Jul 10, 2019)
1-241858510-T-C		not specified	Uncertain significance (Aug 16, 2021)
1-241858517-G-T		not specified	Uncertain significance (Aug 16, 2021)
1-241858532-A-G		EXO1-related disorder	Likely benign (Jun 20, 2019)
1-241858594-C-T		not specified	Uncertain significance (Jun 22, 2021)
1-241858609-G-A		not specified	Uncertain significance (Jan 03, 2024)
1-241858663-G-T		not specified	Uncertain significance (Nov 08, 2022)
1-241858683-G-C		not specified	Uncertain significance (Dec 21, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EXO1	protein_coding	protein_coding	ENST00000366548	13	47182

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.12e-13	0.863	125279	2	467	125748	0.00187

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.03	500	439	1.14	0.0000228	5542
Missense in Polyphen		130	132.84	0.97859		1684
Synonymous	-0.859	182	168	1.08	0.00000950	1617
Loss of Function	1.92	25	37.7	0.662	0.00000205	485

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00325	0.00325
Ashkenazi Jewish	0.000498	0.000496
East Asian	0.000163	0.000163
Finnish	0.000832	0.000832
European (Non-Finnish)	0.00285	0.00283
Middle Eastern	0.000163	0.000163
South Asian	0.000589	0.000588
Other	0.00213	0.00212

dbNSFP

Source: dbNSFP

• Function: FUNCTION: 5'->3' double-stranded DNA exonuclease which may also possess a cryptic 3'->5' double-stranded DNA exonuclease activity. Functions in DNA mismatch repair (MMR) to excise mismatch- containing DNA tracts directed by strand breaks located either 5' or 3' to the mismatch. Also exhibits endonuclease activity against 5'-overhanging flap structures similar to those generated by displacement synthesis when DNA polymerase encounters the 5'-end of a downstream Okazaki fragment. Required for somatic hypermutation (SHM) and class switch recombination (CSR) of immunoglobulin genes. Essential for male and female meiosis. {ECO:0000269|PubMed:10364235, ECO:0000269|PubMed:10608837, ECO:0000269|PubMed:11809771, ECO:0000269|PubMed:11842105, ECO:0000269|PubMed:12414623, ECO:0000269|PubMed:12704184, ECO:0000269|PubMed:14636568, ECO:0000269|PubMed:14676842, ECO:0000269|PubMed:15225546, ECO:0000269|PubMed:15886194, ECO:0000269|PubMed:16143102, ECO:0000269|PubMed:9685493}.
• Pathway: Mismatch repair - Homo sapiens (human);Mismatch repair;Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta);Mismatch Repair;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;Generic Transcription Pathway;Homology Directed Repair;RNA Polymerase II Transcription;G2/M DNA damage checkpoint;G2/M Checkpoints;Cell Cycle Checkpoints;Regulation of TP53 Activity through Phosphorylation;Regulation of TP53 Activity;Transcriptional Regulation by TP53;Cell Cycle;Processing of DNA double-strand break ends;Presynaptic phase of homologous DNA pairing and strand exchange;Homologous DNA Pairing and Strand Exchange;Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha);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: 0.261

Intolerance Scores

• loftool: 0.974
• rvis_EVS: 3.14
• rvis_percentile_EVS: 99.3

Haploinsufficiency Scores

• pHI: 0.363
• hipred: Y
• hipred_score: 0.531
• ghis: 0.515

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.699

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Exo1
• 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); reproductive system phenotype; hematopoietic system phenotype; neoplasm; immune system phenotype; endocrine/exocrine gland phenotype; cellular phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: DNA replication;DNA repair;mismatch repair;DNA recombination;RNA phosphodiester bond hydrolysis, endonucleolytic;t-circle formation
• Cellular component: nucleus;nucleoplasm;plasma membrane;nuclear body
• Molecular function: DNA binding;RNA-DNA hybrid ribonuclease activity;exonuclease activity;protein binding;5'-3' exonuclease activity;5'-flap endonuclease activity;5'-3' exodeoxyribonuclease activity;single-stranded DNA 5'-3' exodeoxyribonuclease activity;metal ion binding;flap endonuclease activity;double-stranded DNA 5'-3' exodeoxyribonuclease activity