RNASEH1

Protein identityUniProt · HPA

UniProt accession

O60930

Gene

RNASEH1

Ensembl

ENSG00000171865

Chromosome

2

Canonical length

286 aa

Protein class

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

Subcellular location

Nucleoplasm,Cytosol

Secretome location

Intracellular and membrane

OverviewNCBI Gene

This gene encodes an endonuclease that specifically degrades the RNA of RNA-DNA hybrids and plays a key role in DNA replication and repair. Alternate in-frame start codon initiation results in the production of alternate isoforms that are directed to the mitochondria or to the nucleus. The production of the mitochondrial isoform is modulated by an upstream open reading frame (uORF). Mutations in this gene have been found in individuals with progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 2. Alternative splicing results in additional coding and non-coding transcript variants. Pseudogenes of this gene have been defined on chromosomes 2 and 17. [provided by RefSeq, Jul 2017]

Canonical amino-acid sequenceUniProt

286 residues, UniProt reviewed canonical sequence.

>O60930|RNASEH1
     1  MSWLLFLAHR VALAALPCRR GSRGFGMFYA VRRGRKTGVF LTWNECRAQV DRFPAARFKK
    61  FATEDEAWAF VRKSASPEVS EGHENQHGQE SEAKASKRLR EPLDGDGHES AEPYAKHMKP
   121  SVEPAPPVSR DTFSYMGDFV VVYTDGCCSS NGRRRPRAGI GVYWGPGHPL NVGIRLPGRQ
   181  TNQRAEIHAA CKAIEQAKTQ NINKLVLYTD SMFTINGITN WVQGWKKNGW KTSAGKEVIN
   241  KEDFVALERL TQGMDIQWMH VPGHSGFIGN EEADRLAREG AKQSED

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against RNASEH1 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)

0.4

Highest tissue expression

16 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about RNASEH1.

Disease | AllUniProt

Conditions RNASEH1 is implicated in, by any mechanism.

• Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 2 (PEOB2) MIM:616479

Disease | GeneticClinVar

6 pathogenic / likely-pathogenic of 240 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 2
• Inborn genetic diseases
• Possible mitochondrial disorder - nuclear genes

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)

0.74

gnomAD pLI

0.01

gnomAD missense Z

0.11

DepMap mean gene effect

-0.05

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 8% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

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

Molecular functions

• magnesium ion binding
• nucleic acid binding
• RNA binding
• RNA nuclease activity
• RNA-DNA hybrid ribonuclease activity

Cellular components

• mitochondrial matrix
• mitochondrion

Protein domainsUniProt · Pfam · InterPro

• Ribonuclease H domain
• Large ribosomal subunit protein bL9/RNase H1, N-terminal
• Ribonuclease H1, N-terminal
• Ribonuclease H-like superfamily
• Ribonuclease H superfamily
• Ribonuclease H1, N-terminal domain superfamily
• RNase H
• Ribonuclease H1 N-terminal domain
• Ribonuclease H1, eukaryote
• Ribonuclease H

KeywordsUniProt

• Cytoplasm
• Endonuclease
• Hydrolase
• Magnesium
• Metal-binding
• Nuclease
• Primary mitochondrial disease
• Progressive external ophthalmoplegia