| Symbol |
RNASEH2B |
| Full Name |
Ribonuclease H2 Subunit B |
| Chromosome |
13q14.13 |
| NCBI Gene |
79684 |
| Ensembl |
ENSG00000137713 |
| OMIM |
610296 |
| UniProt |
Q9Y2Q9 |
| Diseases |
[Aicardi-Goutières Syndrome](/diseases/aicardi-goutieres-syndrome) |
| Expression |
Ubiquitously expressed; high expression in brain, testis, thyroid |
RNASEH2B (Ribonuclease H2 Subunit B) is a gene located on chromosome 13q14.13 that encodes a non-catalytic subunit of the RNase H2 complex. Together with RNASEH2A (catalytic subunit) and RNASEH2C, RNASEH2B forms the heterotrimeric RNase H2 enzyme essential for DNA repair and genome stability. Mutations in RNASEH2B cause Aicardi-Goutières syndrome (AGS), a severe neurodevelopmental disorder characterized by early-onset encephalopathy and elevated interferon signature [1][2].
The RNASEH2B gene spans approximately 35 kb and consists of 14 exons. The gene encodes a 517-amino acid protein that serves as a scaffold for the RNase H2 complex.
- Chromosome: 13q14.13
- Location: chr13: 51492368-51528003
- Strand: Minus strand
- Exons: 14
RNase H2 is a heterotrimeric complex:
- RNASEH2A: Catalytic subunit with RNase H activity
- RNASEH2B: Non-catalytic subunit, critical for complex stability and localization
- RNASEH2C: Non-catalytic subunit, aids in assembly
RNASEH2B is the largest subunit and is essential for proper complex formation and cellular localization.
¶ Protein Structure and Function
¶ Domain Architecture
RNASEH2B contains:
- N-terminal region: Mediates interaction with RNASEH2A
- Central domain: Scaffold for complex formation
- C-terminal region: Binds RNASEH2C and is involved in nuclear localization
¶ Complex Assembly and Stability
- Essential for proper assembly of the RNase H2 complex
- Stabilizes the catalytic RNASEH2A subunit
- Mediates nuclear import of the complex
- Ribonucleotide removal: Supports RNase H2's role in removing misincorporated ribonucleotides from DNA
- Genome stability: Prevents accumulation of ribonucleotides in genomic DNA
- DNA damage response: Participates in DNA repair signaling pathways
- R-loop resolution: Processes RNA-DNA hybrids during transcription
- Telomere maintenance: Involved in telomere biology
RNASEH2B mutations account for approximately 40% of AGS cases, making it the most common genetic cause. Clinical features include:
- Progressive encephalopathy (onset in first year of life)
- Microcephaly
- Intracranial calcifications (particularly in basal ganglia)
- Leukodystrophy
- Severe developmental delay
- Elevated type I interferon signature
Common pathogenic variants:
- P181L, Y177C, D180G (missense)
- Various splice-site mutations
- Deletions and frameshifts
Patients with RNASEH2B mutations typically present with:
- Neonatal or early infantile onset
- Feeding difficulties
- Axial hypotonia with spasticity
- Seizures
- Progressive motor decline
RNASEH2B is ubiquitously expressed with highest levels in:
- Brain (cortex, cerebellum)
- Testis
- Thyroid
- Adrenal gland
- Heart
- Primarily nuclear
- Enriched in nucleolus
- Associates with chromatin
RNASEH2B expression is regulated by:
- Cell cycle
- DNA damage responses
- Transcriptional programs
- JAK inhibitors: Suppress interferon signature
- Antiretroviral therapy: Some nucleoside analogs may help
- Supportive care: Management of seizures, feeding difficulties
- Understanding genotype-phenotype correlations
- Developing gene replacement therapies
- Exploring interferon-targeted treatments
- RNASEH2B mutations are the most common cause of Aicardi-Goutières syndrome. Brain, 2009.
- Structure of the human RNase H2 complex. Nature Structural & Molecular Biology, 2011.
- Genotype-phenotype correlations in Aicardi-Goutières syndrome. Journal of Medical Genetics, 2021.