RNASEH2A

Protein identityUniProt · HPA

UniProt accession

O75792

Gene

RNASEH2A

Ensembl

ENSG00000104889

Chromosome

19

Canonical length

299 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Potential drug targets, Predicted intracellular proteins

Subcellular location

Nucleoplasm,Cytosol

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

299 residues, UniProt reviewed canonical sequence.

>O75792|RNASEH2A
     1  MDLSELERDN TGRCRLSSPV PAVCRKEPCV LGVDEAGRGP VLGPMVYAIC YCPLPRLADL
    61  EALKVADSKT LLESERERLF AKMEDTDFVG WALDVLSPNL ISTSMLGRVK YNLNSLSHDT
   121  ATGLIQYALD QGVNVTQVFV DTVGMPETYQ ARLQQSFPGI EVTVKAKADA LYPVVSAASI
   181  CAKVARDQAV KKWQFVEKLQ DLDTDYGSGY PNDPKTKAWL KEHVEPVFGF PQFVRFSWRT
   241  AQTILEKEAE DVIWEDSASE NQEGLRKITS YFLNEGSQAR PRSSHRYFLE RGLESATSL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against RNASEH2A can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.31

Highest tissue expression

26 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about RNASEH2A.

Disease | AllUniProt

Conditions RNASEH2A is implicated in, by any mechanism.

• Aicardi-Goutieres syndrome 4 (AGS4) MIM:610333

Disease | GeneticClinVar

44 pathogenic / likely-pathogenic of 563 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Aicardi-Goutieres syndrome 4
• Aicardi Goutieres syndrome
• RNASEH2A-related disorder
• Inborn genetic diseases
• RNASEH2A-related type 1 interferonopathy

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.88

gnomAD pLI

0

gnomAD missense Z

0.19

DepMap mean gene effect

-0.23

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• DNA replication
• DNA replication, removal of RNA primer
• mismatch repair
• RNA catabolic process

Molecular functions

• metal ion binding
• RNA binding
• RNA nuclease activity
• RNA-DNA hybrid ribonuclease activity

Cellular components

• cytosol
• nucleoplasm
• ribonuclease H2 complex

Protein domainsUniProt · Pfam · InterPro

• Ribonuclease H-like superfamily
• Ribonuclease H superfamily
• Ribonuclease HII/HIII
• Ribonuclease H2, subunit A
• Ribonuclease HII, helix-loop-helix cap domain superfamily
• Ribonuclease HII/HIII domain
• Ribonuclease HII

KeywordsUniProt

• Acetylation
• Aicardi-Goutieres syndrome
• Endonuclease
• Hydrolase
• Metal-binding
• Nuclease
• Nucleus
• Phosphoprotein

InteractionsUniProt · HPA

Protein binding partners of RNASEH2A in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• RNASEH2B
• RNASEH2C