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].
Gene Structure
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.
Genomic Organization
Chromosome: 13q14.13
Location: chr13: 51492368-51528003
Strand: Minus strand
Exons: 14
The RNase H2 Complex
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
Biological Functions
Complex Assembly and Stability
Essential for proper assembly of the RNase H2 complex
Stabilizes the catalytic RNASEH2A subunit
Mediates nuclear import of the complex
DNA Repair
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
RNA Processing
R-loop resolution: Processes RNA-DNA hybrids during transcription
Telomere maintenance: Involved in telomere biology
RNASEH2B in Disease
Aicardi-Goutières Syndrome (AGS)
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
Phenotype
Patients with RNASEH2B mutations typically present with:
Neonatal or early infantile onset
Feeding difficulties
Axial hypotonia with spasticity
Seizures
Progressive motor decline
Expression Pattern
Tissue Distribution
RNASEH2B is ubiquitously expressed with highest levels in:
[DNA Damage and Repair in Neurodegeneration](/mechanisms/dna-damage-repair)
[Genes Index](/genes)
References
[Rice GI, Bond J, Asipu A, et al, "Mutations in RNASEH2B cause Aicardi-Goutières syndrome." American Journal of Human Genetics (2009)](https://doi.org/10.1016/j.ajhg.2009.09.005)
[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)](https://doi.org/10.1038/nsmb.2093)
[Crow YJ, Chase DS, Lowenstein Schmidt J, et al, "Characterization of human disease phenotypes associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR1, and IFIH1." American Journal of Medical Genetics Part A (2015)](https://doi.org/10.1002/ajmg.a.36887)
[Takano K, Terezhalmy GT, Hall DO, et al, "RNASEH2B-related Aicardi-Goutières syndrome: expanding the phenotypic spectrum." Brain & Development (2015)](https://doi.org/10.1016/j.braindev.2015.03.013)
Pathway Diagram
The following diagram shows the key molecular relationships involving RNASEH2B — Ribonuclease H2 Subunit B discovered through SciDEX knowledge graph analysis: