Incidental Mutation 'P0016:Rnaseh2a'
ID7604
Institutional Source Beutler Lab
Gene Symbol Rnaseh2a
Ensembl Gene ENSMUSG00000052926
Gene Nameribonuclease H2, large subunit
Synonyms2400006P09Rik
MMRRC Submission 038269-MU
Accession Numbers

NCBI RefSeq: NM_027187.3; MGI: 1916974

Is this an essential gene? Probably essential (E-score: 0.966) question?
Stock #P0016 (G1)
Quality Score
Status Validated
Chromosome8
Chromosomal Location84956610-84969767 bp(-) (GRCm38)
Type of Mutationmissense
DNA Base Change (assembly) C to G at 84959800 bp
ZygosityHeterozygous
Amino Acid Change Aspartic acid to Histidine at position 206 (D206H)
Ref Sequence ENSEMBL: ENSMUSP00000120374 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000065049] [ENSMUST00000067472] [ENSMUST00000109736] [ENSMUST00000109738] [ENSMUST00000109740] [ENSMUST00000121880] [ENSMUST00000128972] [ENSMUST00000147812] [ENSMUST00000152378]
Predicted Effect possibly damaging
Transcript: ENSMUST00000065049
AA Change: D206H

PolyPhen 2 Score 0.787 (Sensitivity: 0.85; Specificity: 0.93)
SMART Domains Protein: ENSMUSP00000066769
Gene: ENSMUSG00000052926
AA Change: D206H

DomainStartEndE-ValueType
Pfam:RNase_HII 31 242 7.1e-54 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000067472
SMART Domains Protein: ENSMUSP00000070558
Gene: ENSMUSG00000048617

DomainStartEndE-ValueType
Pfam:Folate_rec 27 203 2e-40 PFAM
low complexity region 224 234 N/A INTRINSIC
Predicted Effect probably damaging
Transcript: ENSMUST00000109736
AA Change: D206H

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000105358
Gene: ENSMUSG00000052926
AA Change: D206H

DomainStartEndE-ValueType
Pfam:RNase_HII 31 242 1.3e-51 PFAM
Predicted Effect probably damaging
Transcript: ENSMUST00000109738
AA Change: D206H

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000105360
Gene: ENSMUSG00000052926
AA Change: D206H

DomainStartEndE-ValueType
Pfam:RNase_HII 31 242 5.5e-53 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000109740
SMART Domains Protein: ENSMUSP00000105362
Gene: ENSMUSG00000048617

DomainStartEndE-ValueType
Pfam:Folate_rec 27 203 3.5e-42 PFAM
low complexity region 224 234 N/A INTRINSIC
Predicted Effect probably benign
Transcript: ENSMUST00000121880
SMART Domains Protein: ENSMUSP00000113982
Gene: ENSMUSG00000048617

DomainStartEndE-ValueType
Pfam:Folate_rec 27 203 3.5e-42 PFAM
low complexity region 224 234 N/A INTRINSIC
Predicted Effect noncoding transcript
Transcript: ENSMUST00000122931
Predicted Effect noncoding transcript
Transcript: ENSMUST00000126029
Predicted Effect possibly damaging
Transcript: ENSMUST00000128972
AA Change: D206H

PolyPhen 2 Score 0.587 (Sensitivity: 0.87; Specificity: 0.91)
SMART Domains Protein: ENSMUSP00000121864
Gene: ENSMUSG00000052926
AA Change: D206H

DomainStartEndE-ValueType
signal peptide 1 22 N/A INTRINSIC
Pfam:RNase_HII 57 268 1.4e-53 PFAM
Predicted Effect probably damaging
Transcript: ENSMUST00000147812
AA Change: D206H

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000120374
Gene: ENSMUSG00000052926
AA Change: D206H

DomainStartEndE-ValueType
Pfam:RNase_HII 31 242 1.3e-51 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000152378
SMART Domains Protein: ENSMUSP00000132841
Gene: ENSMUSG00000048617

DomainStartEndE-ValueType
Pfam:Folate_rec 2 172 2.8e-38 PFAM
low complexity region 193 203 N/A INTRINSIC
Meta Mutation Damage Score 0.2077 question?
Coding Region Coverage
  • 1x: 85.6%
  • 3x: 81.0%
  • 10x: 66.8%
  • 20x: 50.1%
Validation Efficiency 96% (97/101)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] 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]
Allele List at MGI

All alleles(33) : Targeted(1) Gene trapped(32)

Other mutations in this stock
Total: 18 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
1700123K08Rik A T 5: 138,562,938 L154* probably null Het
4930432E11Rik T C 7: 29,563,112 noncoding transcript Het
Arap3 T A 18: 37,984,348 T892S probably benign Het
Ctnnd2 G A 15: 30,966,938 V987I probably benign Het
Dennd6b T C 15: 89,186,977 I351V probably benign Het
Kif27 G A 13: 58,303,452 Q1021* probably null Het
Klb G A 5: 65,379,923 W865* probably null Het
Mbd1 C T 18: 74,274,538 R130* probably null Het
Mroh7 T A 4: 106,707,857 probably null Het
Myo16 C T 8: 10,400,596 probably benign Het
Rbm22 T A 18: 60,570,770 probably benign Het
Slain1 A G 14: 103,685,674 T187A probably benign Het
Slamf6 A G 1: 171,936,501 T154A probably damaging Het
Traip A G 9: 107,968,656 D316G possibly damaging Het
Ttn T C 2: 76,811,183 D5196G probably damaging Het
Ubr5 C T 15: 38,000,578 V1569M probably damaging Het
Zfp750 T A 11: 121,513,978 K24* probably null Het
Zfp799 T C 17: 32,819,357 E645G possibly damaging Het
Other mutations in Rnaseh2a
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL01318:Rnaseh2a APN 8 84965123 unclassified probably benign
IGL01773:Rnaseh2a APN 8 84965138 missense probably damaging 1.00
IGL02606:Rnaseh2a APN 8 84960094 missense probably damaging 1.00
R1521:Rnaseh2a UTSW 8 84965858 critical splice donor site probably null
R2270:Rnaseh2a UTSW 8 84965419 missense probably benign 0.03
R4226:Rnaseh2a UTSW 8 84960073 missense possibly damaging 0.72
R4227:Rnaseh2a UTSW 8 84960073 missense possibly damaging 0.72
R4763:Rnaseh2a UTSW 8 84965392 missense probably benign 0.02
R5344:Rnaseh2a UTSW 8 84958106 unclassified probably benign
R8000:Rnaseh2a UTSW 8 84966049 unclassified probably benign
R8354:Rnaseh2a UTSW 8 84965147 missense probably benign
R8454:Rnaseh2a UTSW 8 84965147 missense probably benign
RF008:Rnaseh2a UTSW 8 84960058 nonsense probably null
Protein Function and Prediction

RNase H2 is an enzyme that hydrolyzes the RNA strand from RNA/DNA hybrids during DNA replication, transcription, and telomere elongation (1).  RNase H2 also can cleave the 5′-phosphodiester bond of one or more ribonucleotides embedded in a DNA duplex (2).  RNaseH2a is one of three subunits within the  eukaryotic RNase H2 complex (3).

Background

Mutations in RNASEH2A are linked to Aicardi-Goutieres syndrome (OMIM # 610333), an autosomal recessive encephalopathy characterized in its most severe form by cerebral atrophy, leukodystrophy, intracranial calcifications, chronic cerebrospinal fluid (CSF) lymphocytosis, increased CSF alpha-interferon, and negative serologic investigations for common prenatal infections (4). AGS is phenotypically similar to congenital viral brain infection (5). 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 (6).

References
Posted On2012-10-05
Science WriterAnne Murray