RNASEH1
Ribonuclease H1, a key enzyme for RNA/DNA hybrid cleavage and mitochondrial DNA replication
Gene Information Card
| Symbol | RNASEH1 |
|---|---|
| Full Name | ribonuclease H1 |
| Gene Type | protein-coding |
| Chromosomal Location | 2p25.3 |
| NCBI Gene ID | 246243 ncbi.nlm.nih.gov/gene/246243 |
| Ensembl ID | ENSG00000115956 |
| UniProt ID | O60930 |
| OMIM ID | 604123 |
| HGNC ID | 18366 |
| Aliases | RNH1, RNH, RNASEH, RNASEHI, H1RNA |
Description
RNASEH1 encodes ribonuclease H1, an endonuclease that specifically cleaves the RNA moiety of RNA/DNA hybrids. The enzyme is essential for removing RNA primers during mitochondrial DNA replication and for maintaining genomic stability by resolving R-loops. RNASEH1 localizes to both the nucleus and mitochondria. Loss-of-function mutations cause autosomal recessive progressive external ophthalmoplegia with mitochondrial DNA deletions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 2 (PEOB2) | Biallelic loss-of-function mutations in RNASEH1 impair mitochondrial ribonuclease H1 activity, leading to defective RNA primer removal during mtDNA replication, resulting in multiple mtDNA deletions and mitochondrial dysfunction. | OMIM #616479; ClinVar; PMID: 25620205 |
| Mitochondrial DNA depletion syndrome (rare) | Severe RNASEH1 deficiency may cause mtDNA depletion in affected tissues, though evidence is limited to case reports. | ClinVar; PMID: 25620205 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 15.2 | Medium |
| Heart | 9.8 | Low |
| Skeletal muscle | 8.5 | Low |
| Brain | 6.3 | Low |
| Liver | 5.1 | Low |
| Kidney | 4.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 12.4 | Embryonic kidney cells |
| HeLa | 10.1 | Cervical carcinoma cells |
| K562 | 8.3 | Leukemia cells |
| HepG2 | 6.9 | Hepatocellular carcinoma cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.815G>A (p.Arg272His) | Missense | Rare (found in PEO families) | Loss of RNase H activity; associated with PEOB2 |
| c.814C>T (p.Arg272Cys) | Missense | Rare | Loss of RNase H activity; associated with PEOB2 |
| c.1A>G (p.Met1?) | Start loss | Rare | Complete loss of protein; associated with PEOB2 |
| c.556C>T (p.Arg186*) | Nonsense | Rare | Premature truncation; loss of function |
Mutation functional classification
Loss of Function (LOF)
Biallelic missense, nonsense, or start-loss mutations that abolish or severely reduce RNase H1 catalytic activity or protein stability, leading to mitochondrial DNA replication defects and multiple mtDNA deletions.
Gain of Function (GOF)
No gain-of-function mutations reported for RNASEH1.
Dominant Negative (DN)
No dominant-negative mutations reported; disease inheritance is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • RNA-DNA hybrid ribonuclease activity (GO:0004523) | • nucleic acid binding (GO:0003676) |
| • mitochondrion (GO:0005739) | • nucleus (GO:0005634) |
| • RNA catabolic process (GO:0006401) | • mitochondrial DNA replication (GO:0006264) |
| • RNA phosphodiester bond hydrolysis | • endonucleolytic (GO:0090502) |
Pathways
• Mitochondrial DNA replication (Reactome: R-HSA-983231)
• Resolution of R-loops (Reactome: R-HSA-5696398)
Protein Summary
Ribonuclease H1 (RNASEH1) is a 286-amino acid protein that cleaves RNA in RNA/DNA hybrids. It contains an N-terminal mitochondrial targeting sequence and a C-terminal RNase H domain. The enzyme is critical for removing RNA primers during mitochondrial DNA replication and for resolving R-loops in nuclear DNA. Loss of function leads to accumulation of mitochondrial DNA deletions and progressive external ophthalmoplegia.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RNASEH1 Knockout HEK293 Cell Line | EDC07624 | Human | 246243 | Details Get a Quote |
| RNASEH1 Knockout A-549 Cell Line | EDJ-KQ39864 | Human | 246243 | Details Get a Quote |
| RNASEH1 Knockout HCT 116 Cell Line | EDJ-KQ39865 | Human | 246243 | Details Get a Quote |
| RNASEH1 Knockout HeLa Cell Line | EDJ-KQ39866 | Human | 246243 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
