RNASEH2A

Chr 19AR

ribonuclease H2 subunit A

Also known as: AGS4, RNASEHI, RNHIA, RNHL

NCBI Gene: 10535 ENSG00000104889 UniProt: O75792 OMIM: 606034

RNASEH2A encodes the catalytic subunit of RNase HII, an endonuclease that degrades RNA in RNA:DNA hybrids and excises single ribonucleotides from DNA duplexes during DNA replication. Mutations cause Aicardi-Goutières syndrome, an autosomal recessive neuroinflammatory disorder characterized by progressive microcephaly, psychomotor retardation, intracranial calcifications, and elevated interferon-alpha levels in cerebrospinal fluid. The gene shows low constraint to loss-of-function variation (pLI 0.004, LOEUF 0.88).

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is a component of the heterotrimeric type II ribonuclease H enzyme (RNAseH2). RNAseH2 is the major source of ribonuclease H activity in mammalian cells and endonucleolytically cleaves ribonucleotides. It is predicted to remove Okazaki fragment RNA primers during lagging strand DNA synthesis and to excise single ribonucleotides from DNA-DNA duplexes. Mutations in this gene cause Aicardi-Goutieres Syndrome (AGS), a an autosomal recessive neurological disorder characterized by progressive microcephaly and psychomotor retardation, intracranial calcifications, elevated levels of interferon-alpha and white blood cells in the cerebrospinal fluid.[provided by RefSeq, Aug 2009]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Aicardi-Goutieres syndrome 4MIM #610333

Clinical highlights

Gene-disease validity (ClinGen)

RNASEH2A-related type 1 interferonopathy · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.88

LOEUF

LOF

Mechanism· G2P

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GeneReview available — RNASEH2A