DNA2
DNA Replication Helicase/Nuclease 2
Gene Information Card
| Symbol | DNA2 |
|---|---|
| Full Name | DNA replication helicase/nuclease 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 10q21.3 |
| NCBI Gene ID | 1763 ncbi.nlm.nih.gov/gene/1763 |
| Ensembl ID | ENSG00000138346 |
| UniProt ID | P51530 |
| OMIM ID | 601810 |
| HGNC ID | 2940 |
| Aliases | DNA2L, FLJ12020, hDNA2 |
Description
DNA2 encodes a conserved helicase/nuclease involved in DNA replication, repair, and mitochondrial DNA maintenance. The protein processes Okazaki fragments during lagging-strand synthesis, participates in double-strand break repair via resection, and maintains mitochondrial genome integrity. Mutations in DNA2 are associated with mitochondrial disorders and cancer susceptibility.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 6 (PEOA6) | Dominant-negative or loss-of-function mutations impair mitochondrial DNA replication and repair, leading to multiple mtDNA deletions. | OMIM #615156; ClinVar |
| Mitochondrial DNA depletion syndrome 15 (MTDPS15) | Biallelic loss-of-function mutations reduce mitochondrial DNA copy number due to defective replication. | OMIM #618479; ClinVar |
| Breast cancer | Somatic mutations and altered expression may contribute to genomic instability and tumorigenesis. | COSMIC; NCBI PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 14.7 | Medium |
| Bone marrow | 10.2 | Medium |
| Lymph node | 8.5 | Medium |
| Brain | 6.3 | Low |
| Liver | 5.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 12.3 | Cervical cancer cell line |
| K562 | 9.8 | Leukemia cell line |
| HEK293 | 8.4 | Embryonic kidney cell line |
| HepG2 | 6.7 | Liver cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1298G>A (p.Arg433Gln) | Missense | Rare | Impaired helicase activity; associated with PEOA6 |
| c.1525C>T (p.Arg509Trp) | Missense | Rare | Reduced nuclease activity; linked to MTDPS15 |
| c.2269C>T (p.Arg757Cys) | Missense | Rare | Dominant-negative effect; PEOA6 |
| c.2392C>T (p.Arg798Trp) | Missense | Rare | Loss of function; MTDPS15 |
Mutation functional classification
Loss of Function (LOF)
Biallelic missense or truncating mutations reduce or abolish helicase/nuclease activity, leading to mtDNA depletion.
Gain of Function (GOF)
Not reported for DNA2.
Dominant Negative (DN)
Heterozygous missense mutations (e.g., p.Arg433Gln, p.Arg757Cys) interfere with wild-type DNA2 function, causing PEOA6.
View complete mutation data：
Gene Ontology (GO)
Pathways
• DNA replication (Reactome: R-HSA-69306)
• Resolution of D-loop structures (Reactome: R-HSA-5693571)
• Mitochondrial DNA replication (Reactome: R-HSA-1592230)
• Homology directed repair (Reactome: R-HSA-5693532)
Protein Summary
DNA2 is a 1060-amino acid protein with both 5'->3' helicase and 5'->3' exonuclease/endonuclease activities. It localizes to the nucleus and mitochondria. The protein contains an N-terminal nuclease domain and a C-terminal helicase domain. It interacts with flap endonuclease 1 (FEN1) and replication protein A (RPA) to process Okazaki fragments and resect DNA ends during repair. Mitochondrial DNA2 is essential for mtDNA replication and maintenance.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID |
|---|
