RNASEH2C
Ribonuclease H2 Subunit C
Gene Information Card
| Symbol | RNASEH2C |
|---|---|
| Full Name | Ribonuclease H2 Subunit C |
| Gene Type | Protein coding |
| Chromosomal Location | 11q13.1 |
| NCBI Gene ID | 84153 ncbi.nlm.nih.gov/gene/84153 |
| Ensembl ID | ENSG00000149257 |
| UniProt ID | Q8TDP1 |
| OMIM ID | 610330 |
| HGNC ID | 24116 |
| Aliases | AGS3, AYP1, RNASEH2C, RNASEHIIC |
Description
The RNASEH2C gene encodes subunit C of ribonuclease H2 (RNase H2), a heterotrimeric enzyme that cleaves ribonucleotides misincorporated into DNA during replication. RNase H2 is the major source of ribonuclease H activity in human cells and is essential for genome stability. Mutations in RNASEH2C are associated with Aicardi-Goutières syndrome type 3 (AGS3), a severe autoimmune disorder characterized by encephalopathy, intracranial calcifications, and elevated interferon-alpha levels.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Aicardi-Goutières syndrome 3 (AGS3) | Loss-of-function mutations impair RNase H2 activity, leading to accumulation of RNA:DNA hybrids and activation of innate immune response via cytosolic nucleic acid sensors. | OMIM #610329; ClinVar pathogenic variants |
| Systemic lupus erythematosus (SLE) | Rare variants in RNASEH2C may contribute to autoimmune dysregulation through defective removal of ribonucleotides from DNA. | PubMed association studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | Medium |
| Lymph node | 10.2 | Medium |
| Brain (cortex) | 8.9 | Medium |
| Liver | 6.3 | Low |
| Heart | 5.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 14.0 | High expression |
| K562 | 9.5 | Medium expression |
| HeLa | 8.2 | Medium expression |
| HepG2 | 6.0 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.205C>T (p.Arg69Trp) | Missense | Unknown | Loss of RNase H2 activity; associated with AGS3 |
| c.494G>A (p.Arg165His) | Missense | Unknown | Impaired subunit interaction; pathogenic in AGS3 |
| c.1A>G (p.Met1Val) | Start loss | Rare | Complete loss of protein; severe AGS3 phenotype |
Mutation functional classification
Loss of Function (LOF)
Most AGS3-associated mutations reduce or abolish RNase H2 catalytic activity, leading to accumulation of ribonucleotides in genomic DNA and chronic interferon signaling.
Gain of Function (GOF)
Not reported.
Dominant Negative (DN)
Not established; disease is typically autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • RNA-DNA hybrid ribonuclease activity (GO:0004523) | • ribonuclease H2 complex (GO:0032299) |
| • nucleus (GO:0005634) | • DNA replication (GO:0006260) |
| • RNA catabolic process (GO:0006401) |
Pathways
• RNase H2 pathway (Reactome: R-HSA-73928)
• Removal of RNA primer from Okazaki fragments (Reactome: R-HSA-69091)
Protein Summary
RNASEH2C encodes the 164-amino acid subunit C of RNase H2, which is required for complex assembly and stability. The protein interacts with subunits A and B to form the active heterotrimer. Subunit C does not contain the catalytic site but is essential for substrate binding and enzymatic activity. Defects in this subunit disrupt the entire RNase H2 complex, leading to genomic instability and autoimmune disease.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RNASEH2C Knockout HEK293 Cell Line | EDJ-KQ51810 | Human | 84153 | Details Get a Quote |
| RNASEH2C Knockout HeLa Cell Line | EDJ-KQ57540 | Human | 84153 | Details Get a Quote |
| RNASEH2C Knockout A-549 Cell Line | EDJ-KQ66038 | Human | 84153 | Details Get a Quote |
| RNASEH2C Knockout HCT 116 Cell Line | EDJ-KQ74462 | Human | 84153 | Details Get a Quote |
