RNASEH2B
Ribonuclease H2 Subunit B
Gene Information Card
| Symbol | RNASEH2B |
|---|---|
| Full Name | Ribonuclease H2 Subunit B |
| Gene Type | Protein coding |
| Chromosomal Location | 13q14.3 |
| NCBI Gene ID | 79621 ncbi.nlm.nih.gov/gene/79621 |
| Ensembl ID | ENSG00000136167 |
| UniProt ID | Q5T8P6 |
| OMIM ID | 610326 |
| HGNC ID | 25671 |
| Aliases | AGS2, DLEU8, RNASEH2B1, RNASEH2B2 |
Description
RNASEH2B encodes the B subunit of ribonuclease H2 (RNase H2), an enzyme that cleaves ribonucleotides misincorporated into DNA during replication. RNase H2 is a heterotrimeric complex composed of subunits A, B, and C. The B subunit is essential for complex stability and catalytic activity. Mutations in RNASEH2B cause Aicardi-Goutières syndrome type 2 (AGS2), a rare autoimmune disorder characterized by encephalopathy, intracranial calcifications, and elevated interferon-alpha levels.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Aicardi-Goutières syndrome 2 (AGS2) | Loss-of-function mutations impair RNase H2 activity, leading to accumulation of ribonucleotides in DNA, triggering innate immune response and interferon production. | OMIM #610181; ClinVar; multiple case reports |
| Systemic lupus erythematosus (SLE) | Rare variants in RNASEH2B may contribute to autoimmune dysregulation via similar interferon pathway activation. | OMIM; limited association studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | Medium |
| Brain (cerebellum) | 8.2 | Medium |
| Lymph node | 7.1 | Medium |
| Liver | 5.3 | Low |
| Heart | 4.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 10.1 | Embryonic kidney; high expression |
| K562 | 6.5 | Leukemia; moderate expression |
| HeLa | 5.9 | Cervical carcinoma; moderate expression |
| HepG2 | 4.2 | Hepatocellular carcinoma; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.529G>A (p.Ala177Thr) | Missense | Common in AGS2 | Reduced RNase H2 activity; associated with milder phenotype |
| c.694C>T (p.Arg232*) | Nonsense | Rare | Loss of function; severe AGS2 |
| c.1A>G (p.Met1Val) | Start loss | Rare | Complete loss of protein; severe AGS2 |
Mutation functional classification
Loss of Function (LOF)
Most pathogenic mutations in RNASEH2B are loss-of-function, leading to reduced or absent RNase H2 activity, accumulation of ribonucleotides in genomic DNA, and chronic interferon signaling.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
Not described; disease is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • Ribonuclease H2 complex (GO:0032298) | • RNA-DNA hybrid ribonuclease activity (GO:0004523) |
| • DNA replication (GO:0006260) | • Nucleus (GO:0005634) |
| • Ribonucleotide excision repair (GO:0090305) |
Pathways
• Ribonucleotide excision repair (RER) - Reactome R-HSA-73928
• DNA replication - KEGG hsa03030
Protein Summary
The RNASEH2B protein (299 amino acids) is a component of the RNase H2 heterotrimer. It does not possess catalytic activity but is required for complex assembly and stability. The protein contains a conserved domain that mediates interaction with the catalytic A subunit and the C subunit. Defects in RNASEH2B lead to impaired removal of ribonucleotides from DNA, triggering an aberrant innate immune response characteristic of Aicardi-Goutières syndrome.
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