EXO1 (Exonuclease 1) Gene: Structure, Function, and Clinical Significance
A comprehensive overview of the EXO1 gene, its protein product, associated diseases, expression patterns, and mutations.
Gene Information Card
| Symbol | EXO1 |
|---|---|
| Full Name | Exonuclease 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 1q43 |
| NCBI Gene ID | 9156 ncbi.nlm.nih.gov/gene/9156 |
| Ensembl ID | ENSG00000186335 |
| UniProt ID | Q9UQ84 |
| OMIM ID | 606063 |
| HGNC ID | 3511 |
| Aliases | HEX1, hExoI, Exo1, MBD4-interacting protein |
Description
EXO1 encodes a 5' to 3' exonuclease that plays a critical role in DNA replication, repair, and recombination. It participates in mismatch repair (MMR), double-strand break repair (DSBR), and meiotic recombination. EXO1 interacts with MMR proteins (MSH2, MLH1) and is involved in removing mismatched nucleotides. Mutations in EXO1 are associated with increased cancer susceptibility, particularly hereditary non-polyposis colorectal cancer (Lynch syndrome) and other cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Lynch syndrome (HNPCC) | Germline mutations in EXO1 impair mismatch repair, leading to microsatellite instability and increased risk of colorectal and other cancers. | ClinVar, OMIM |
| Colorectal cancer | Somatic mutations and reduced expression of EXO1 contribute to genomic instability and tumor progression. | COSMIC, ClinVar |
| Endometrial cancer | EXO1 mutations and altered expression are observed, linked to defective DNA repair. | COSMIC, ClinVar |
| Ovarian cancer | EXO1 alterations may contribute to DNA repair deficiency and tumorigenesis. | COSMIC |
| Breast cancer | EXO1 variants have been studied for association with increased risk, though evidence is still emerging. | ClinVar, COSMIC |
| Prostate cancer | EXO1 expression changes and mutations have been reported, potentially affecting DNA repair capacity. | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 22.4 | High |
| Bone marrow | 15.2 | Medium |
| Lymph node | 12.8 | Medium |
| Spleen | 11.5 | Medium |
| Colon | 8.3 | Low |
| Small intestine | 7.9 | Low |
| Stomach | 6.1 | Low |
| Liver | 4.2 | Low |
| Kidney | 3.8 | Low |
| Lung | 3.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 | 18.5 | Leukemia cell line; high expression |
| HeLa | 12.3 | Cervical cancer; moderate expression |
| A549 | 9.8 | Lung carcinoma; moderate expression |
| MCF7 | 7.2 | Breast cancer; low expression |
| HepG2 | 5.6 | Liver cancer; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1765A>G (p.Lys589Glu) | Missense | Rare | May affect protein function; reported in Lynch syndrome |
| c.2042C>T (p.Pro681Leu) | Missense | Rare | Potential pathogenic variant; associated with cancer risk |
| c.2576G>A (p.Arg859Gln) | Missense | Rare | Uncertain significance; possibly damaging |
| c.3113G>A (p.Arg1038His) | Missense | Rare | Reported in cancer cases; functional impact unclear |
| c.3765_3766del (p.Glu1255fs) | Frameshift | Very rare | Loss-of-function; likely pathogenic |
Mutation functional classification
Loss of Function (LOF)
Most EXO1 mutations are loss-of-function, impairing exonuclease activity and DNA repair, leading to genomic instability and cancer predisposition.
Gain of Function (GOF)
No clear gain-of-function mutations have been documented; EXO1 is primarily a tumor suppressor.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects by interfering with protein-protein interactions in MMR complexes, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • 5'-3' exonuclease activity | • DNA binding |
| • protein binding | • mismatch repair |
| • DNA recombination | • DNA repair |
| • meiotic recombination | • nucleus |
| • chromosome |
Pathways
• Mismatch Repair (MMR)
• Double-Strand Break Repair (Homologous Recombination)
• Meiotic Recombination
• Base Excision Repair (interaction)
Protein Summary
EXO1 is a 846-amino acid protein with a conserved exonuclease domain. It functions as a 5' to 3' exonuclease, processing DNA ends during repair and recombination. It interacts with MMR proteins (MSH2, MLH1) and is essential for removing mismatched nucleotides. EXO1 also plays a role in telomere maintenance and immunoglobulin class switch recombination. Its expression is cell-cycle regulated and highest in proliferating tissues.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| EXO1 Knockout HEK293 Cell Line | EDJ-KQ6480 | Human | 9156 | Details Get a Quote |
| REXO1 Knockout HEK293 Cell Line | EDJ-KQ15040 | Human | 57455 | Details Get a Quote |
| REXO1 Knockout HeLa Cell Line | EDJ-KQ44336 | Human | 57455 | Details Get a Quote |
| EXO1 Knockout A-549 Cell Line | EDJ-KQ30592 | Human | 9156 | Details Get a Quote |
| EXO1 Knockout HCT 116 Cell Line | EDJ-KQ30593 | Human | 9156 | Details Get a Quote |
| EXO1 Knockout HeLa Cell Line | EDJ-KQ30594 | Human | 9156 | Details Get a Quote |
| REXO1 Knockout A-549 Cell Line | EDJ-KQ45590 | Human | 57455 | Details Get a Quote |
| REXO1 Knockout HCT 116 Cell Line | EDJ-KQ45591 | Human | 57455 | Details Get a Quote |
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