Alt. symbols: RNASEHI | RNHIA | RNHL | AGS4

Approved name: ribonuclease H2 subunit A
Alt. names: ribonuclease H2, large subunit, Aicardi-Goutieres syndrome 4, ribonuclease H2, subunit A

Location: 19p13.13: 12806584 - 12813640 (+)
Gene type: protein_coding, 6 transcripts.

Scores: LoFtool: 0.254000 | pLI: 0.05007913 | LOEUF: 0.880

HGNC: 18518

NCBI: 10535, RefSeq: NG_012662.1

Ensembl: ENSG00000104889.7

LRG_278 | Status: public

OMIM: 606034

Expression | ProteinAtlas

The RNASEH2A gene encodes a subunit of the RNase H2 complex. This complex is a ribonuclease, that is, an enzyme that helps break down RNA molecules. In particular, the RNase H2 complex normally helps break down RNA-DNA hybrid molecules (one strand of RNA is combined with one strand of DNA) when these are no longer needed. RNA-DNA hybrids are formed in all cells during DNA replication. The RNase H2 complex is also thought to be involved in error repair, and other cellular processes, including helping to prevent inappropriate immune system activation.

Biallelic mutations in RNASEH2A cause Aicardi-Goutieres syndrome 4 (AGS4) [MIM:610333]. AGS is an autosomal recessive and genetically heterogeneous encephalopathy characterized in its most severe form by cerebral atrophy, leukodystrophy, intracranial calcifications, chronic cerebrospinal fluid (CSF) lymphocytosis, increased CSF alpha-interferon (IFNA1), and negative serologic investigations for common prenatal infections (Ali et al., 2006). AGS is phenotypically similar to in utero viral infecti on. Severe neurologic dysfunction becomes clinically apparent in infancy, and manifests as progressive microcephaly, spasticity, dystonic posturing, profound psychomotor retardation, and often death in early childhood. Outside the nervous system, thrombocytopenia, hepatosplenomegaly, and elevated hepatic transaminases along with intermittent fever may also erroneously suggest an infective process. More than 40 pathogenic mutations in the RNASEH2A gene have been identified in people with AGS. RNASEH2A mutations lead to a dysfunctional RNase H2 complex, which may disrupt transcription, DNA replication, DNA repair, apoptosis, or other processes. Such disruptions are thought to lead to the accumulation of unneeded DNA and RNA in cells. These DNA and RNA fragments may be mistaken for the genetic material of viral invaders, triggering immune system reactions in multiple body systems that cause encephalopathy, skin lesions and the other clinical manifestations characteristic of AGS. [Load More]