RNASEH2C (Ribonuclease H2 Subunit C) is a gene located on chromosome 17q11.2 that encodes the smallest subunit of the RNase H2 complex. This protein plays a supporting role in the assembly and function of the RNase H2 enzyme, which is critical for DNA repair by removing misincorporated ribonucleotides from genomic DNA. Mutations in RNASEH2C cause Aicardi-Goutières syndrome (AGS), a severe early-onset neurodevelopmental disorder [1].
Gene Structure
The RNASEH2C gene spans approximately 4 kb and consists of 4 exons. The gene encodes a 164-amino acid protein that functions as a structural component of the RNase H2 complex.
Genomic Organization
Chromosome: 17q11.2
Location: chr17: 27878779-27882841
Strand: Minus strand
Exons: 4
The RNase H2 Complex
The RNase H2 complex is composed of three subunits:
RNASEH2A (299 aa): Catalytic subunit
RNASEH2B (517 aa): Largest non-catalytic subunit
RNASEH2C (164 aa): Smallest subunit, essential for complex stability
Protein Structure and Function
Domain Architecture
RNASEH2C is a small protein with:
N-terminal region: Critical for complex formation
Central region: Structural support
C-terminal region: Interacts with RNASEH2B
Biological Functions
Complex Assembly
Essential for proper assembly of the RNase H2 heterotrimer
Stabilizes the interaction between RNASEH2A and RNASEH2B
Required for nuclear localization of the complex
DNA Repair
Supports RNase H2's catalytic activity in removing ribonucleotides
Maintains genome stability
Prevents accumulation of ribonucleotides in DNA
RNASEH2C in Disease
Aicardi-Goutières Syndrome (AGS)
RNASEH2C mutations account for approximately 5-10% of AGS cases. Clinical features include:
Early-onset encephalopathy
Intracranial calcifications
Leukodystrophy
Elevated type I interferon signature
Developmental regression
Pathogenic variants identified:
A177T, R69W (missense mutations)
Splice-site mutations
Rare truncating mutations
Expression Pattern
Tissue Distribution
RNASEH2C is ubiquitously expressed with highest levels in:
[DNA Damage and Repair in Neurodegeneration](/mechanisms/dna-damage-repair)
[Genes Index](/genes)
References
[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)
[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)
[Livingston JH, Shenoy A, Lin JP, et al, "RNASEH2C mutations: expanding the phenotype of Aicardi-Goutières syndrome." American Journal of Medical Genetics Part A (2014)](https://doi.org/10.1002/ajmg.a.36673)