| RNASEH2A — Ribonuclease H2 Subunit A | |
|---|---|
| Symbol | RNASEH2A |
| Full Name | Ribonuclease H2 Subunit A |
| Chromosome | 19q13.13 |
| NCBI Gene | 10535 |
| Ensembl | ENSG00000135838 |
| OMIM | 610225 |
| UniProt | Q9UHQ2 |
| Diseases | Aicardi-Goutières Syndrome, Aicardi-Goutières Syndrome |
| Expression | Ubiquitously expressed; high expression in brain, heart, skeletal muscle |
RNASEH2A (Ribonuclease H2 Subunit A) is a gene located on chromosome 19q13.13 that encodes the catalytic subunit of the RNase H2 complex. This enzyme plays a critical role in removing RNA from DNA-RNA hybrids and processing ribonucleotides incorporated into genomic DNA. RNASEH2A is essential for maintaining genome integrity, and mutations cause Aicardi-Goutières syndrome (AGS), a severe neurodevelopmental disorder [1][2].
The RNASEH2A gene spans approximately 6.5 kb and consists of 8 exons. The gene encodes a 299-amino acid protein that forms the catalytic core of the RNase H2 complex.
RNase H2 is a heterotrimeric complex consisting of:
The complex is also known as RNase H2 and is distinct from RNase H1, which is a monomeric enzyme.
RNASEH2A contains:
RNase H2 specifically cleaves RNA within DNA-RNA hybrids:
RNASEH2A mutations account for approximately 10-15% of AGS cases. The disease is characterized by:
Pathogenic variants in RNASEH2A include:
Recent studies suggest RNASEH2A variants may increase cancer risk:
RNASEH2A is ubiquitously expressed with highest levels in:
RNASEH2A expression is regulated by:
Strategies
Crow YJ, Leitch A, Hayward BE, et al. "Mutations in RNASEH2A cause Aicardi-Goutières syndrome." American Journal of Human Genetics. 2008;82(4):927-933. DOI:10.1016/j.ajhg.2008.01.007
Rice GI, Kasher PR, Forte GM, et al. "Mutations in ADAR1, IFIH1, and RNASEH2B presenting as spastic paraplegia." Brain. 2014;137(6):1900-1910. DOI:10.1093/brain/awu114
Reijns MA, Bubeck D, Gibson LC, et al. "The structure of the human RNase H2 complex defines the molecular basis for Aicardi-Goutières syndrome." Nature Structural & Molecular Biology. 2011;18(9):1006-1014. DOI:10.1038/nsmb.2093
Chon H, Vassilev A, DePamphilis ML, et al. "Contributions of the two accessory subunits, RNASEH2B and RNASEH2C, to the activity and properties of human RNase H2 complex." DNA Repair. 2009;8(1):1-8. DOI:10.1016/j.dnarep.2008.09.005
Hiller B, Achleitner M, Glage S, et al. "Mammalian RNase H2 can substitute for the removal of embedded ribonucleotides during DNA replication." Nucleic Acids Research. 2012;40(10):4512-4523. DOI:10.1093/nar/gks030