Gene Symbol: RNASEH2B
Description: ribonuclease H2 subunit B
Alias: AGS2, DLEU8, ribonuclease H2 subunit B, Aicardi-Goutieres syndrome 2 protein, RNase H2 subunit B, deleted in lymphocytic leukemia 8, ribonuclease HI subunit B
Species: human
Products:     RNASEH2B

Top Publications

  1. Crow Y, Leitch A, Hayward B, Garner A, Parmar R, Griffith E, et al. Mutations in genes encoding ribonuclease H2 subunits cause Aicardi-Goutières syndrome and mimic congenital viral brain infection. Nat Genet. 2006;38:910-6 pubmed
    ..Our findings demonstrate a role for ribonuclease H in human neurological disease and suggest an unanticipated relationship between ribonuclease H2 and the antiviral immune response that warrants further investigation. ..
  2. Chon H, Vassilev A, DePamphilis M, Zhao Y, Zhang J, Burgers P, et al. Contributions of the two accessory subunits, RNASEH2B and RNASEH2C, to the activity and properties of the human RNase H2 complex. Nucleic Acids Res. 2009;37:96-110 pubmed publisher
    ..In contrast, the RNASEH2B and RNASEH2C subunits from human and Saccharomyces cerevisiae share very little homology, although they both form ..
  3. Tonduti D, Izzo G, D Arrigo S, Riva D, Moroni I, Zorzi G, et al. Spontaneous MRI improvement and absence of cerebral calcification in Aicardi-Goutières syndrome: Diagnostic and disease-monitoring implications. Mol Genet Metab. 2019;: pubmed publisher
    ..We reviewed clinical and MRI findings in three young RNASEH2B-mutated patients studied with serial CT and MRI studies...
  4. Mottaghi Dastjerdi N, Soltany Rezaee Rad M, Sepehrizadeh Z, Roshandel G, Ebrahimifard F, Setayesh N. Identification of novel genes involved in gastric carcinogenesis by suppression subtractive hybridization. Hum Exp Toxicol. 2015;34:3-11 pubmed publisher
    ..The genes were ribosomal protein L18A, RNase H2 subunit B, SEC13, eukaryotic translation initiation factor 4A1, tetraspanin 8, cytochrome c oxidase subunit 2, NADH ..
  5. Wang C, Wang G, Feng X, Shepherd P, Zhang J, Tang M, et al. Genome-wide CRISPR screens reveal synthetic lethality of RNASEH2 deficiency and ATR inhibition. Oncogene. 2019;38:2451-2463 pubmed publisher
    ..Notably, RNASEH2 deficiency is frequently found in prostate adenocarcinoma; we found decreased RNASEH2B protein levels in prostate adenocarcinoma patient-derived xenograft (PDX) samples...
  6. Ji T, Wang J, Li H, Zhao L, Sang Y, Wu Y. [Clinical and genetic analysis of a family with Aicardi-Goutières syndrome and literature review]. Zhonghua Er Ke Za Zhi. 2014;52:822-7 pubmed
    ..TREX1 [38% (96/252) ] and RNASEH2B [23% (58/252)]are the most common pathogenic genes...
  7. Travaglini L, Aiello C, Stregapede F, D Amico A, Alesi V, Ciolfi A, et al. The impact of next-generation sequencing on the diagnosis of pediatric-onset hereditary spastic paraplegias: new genotype-phenotype correlations for rare HSP-related genes. Neurogenetics. 2018;19:111-121 pubmed publisher
    ..number of pathogenic variants were disclosed in POLR3A, FA2H, DDHD2, ATP2B4, ENTPD1, ERLIN2, CAPN1, ALS2, ADAR1, RNASEH2B, TUBB4A, ATL1, and KIF1A...
  8. Crow Y, Chase D, Lowenstein Schmidt J, Szynkiewicz M, Forte G, Gornall H, et al. Characterization of human disease phenotypes associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR, and IFIH1. Am J Med Genet A. 2015;167A:296-312 pubmed publisher
    Aicardi-Goutières syndrome is an inflammatory disease occurring due to mutations in any of TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR or IFIH1. We report on 374 patients from 299 families with mutations in these seven genes...
  9. Veronesi G, Aude Garcia C, Kieffer I, Gallon T, Delangle P, Herlin Boime N, et al. Exposure-dependent Ag+ release from silver nanoparticles and its complexation in AgS2 sites in primary murine macrophages. Nanoscale. 2015;7:7323-30 pubmed publisher
    ..41 ± 0.03 Å and 2.38 ± 0.01 Å in acute and chronic exposure respectively, compatible with digonal AgS2 coordination. Glutathione is identified as the most likely putative ligand for Ag(+)...

More Information


  1. Wang Y, Fang R, Yuan Y, Hu M, Zhou Y, Zhao J. Identification of host proteins interacting with the integrin-like A domain of Toxoplasma gondii micronemal protein MIC2 by yeast-two-hybrid screening. Parasit Vectors. 2014;7:543 pubmed publisher
    ..identified: they are LAMTOR1 (late endosomal/lysosomal adaptor, MAPK and mTOR activator 1) and RNaseH2B (ribonuclease H2 subunit B)...
  2. Crow Y, Zaki M, Abdel Hamid M, Abdel Salam G, Boespflug Tanguy O, Cordeiro N, et al. Mutations in ADAR1, IFIH1, and RNASEH2B presenting as spastic paraplegia. Neuropediatrics. 2014;45:386-93 pubmed publisher
    ..spastic paraplegia were identified with mutations in either ADAR1 (one patient), IFIH1 (one patient), or RNASEH2B (three patients from two families)...
  3. Bubeck D, Reijns M, Graham S, Astell K, Jones E, Jackson A. PCNA directs type 2 RNase H activity on DNA replication and repair substrates. Nucleic Acids Res. 2011;39:3652-66 pubmed publisher
    ..of Archaeoglobus fulgidus RNase HII in complex with PCNA, and human PCNA bound to a C-terminal peptide of RNASEH2B. In the archaeal structure, three binding modes are observed as the enzyme rotates about a flexible hinge while ..
  4. Zimmermann M, Murina O, Reijns M, Agathanggelou A, Challis R, Tarnauskaitė Ž, et al. CRISPR screens identify genomic ribonucleotides as a source of PARP-trapping lesions. Nature. 2018;559:285-289 pubmed publisher
    ..are a hitherto unappreciated source of PARP-trapping DNA lesions, and that the frequent deletion of RNASEH2B in metastatic prostate cancer and chronic lymphocytic leukaemia could provide an opportunity to exploit these ..
  5. Cuadrado E, Michailidou I, van Bodegraven E, Jansen M, Sluijs J, Geerts D, et al. Phenotypic variation in Aicardi-Goutières syndrome explained by cell-specific IFN-stimulated gene response and cytokine release. J Immunol. 2015;194:3623-33 pubmed publisher
    ..syndrome (AGS) is a monogenic inflammatory encephalopathy caused by mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR1, or MDA5...
  6. Abdel Salam G, Abdel Hamid M, Mohammad S, Abdel Ghafar S, Soliman D, El Bassyouni H, et al. Aicardi-Goutières syndrome: unusual neuro-radiological manifestations. Metab Brain Dis. 2017;32:679-683 pubmed publisher
    ..The diagnosis of AGS was confirmed by sequence analysis, which identified a previously reported homozygous RNASEH2B mutation, c.554 T > G (p.V185G). Parents were heterozygous for the same mutation...
  7. La Piana R, Uggetti C, Roncarolo F, Vanderver A, Olivieri I, Tonduti D, et al. Neuroradiologic patterns and novel imaging findings in Aicardi-Goutières syndrome. Neurology. 2016;86:28-35 pubmed publisher
    ..identified: deep white matter cysts, associated with TREX1 mutations, and delayed myelination, associated with RNASEH2B mutations and early age at onset...
  8. Pokatayev V, Hasin N, Chon H, Cerritelli S, Sakhuja K, Ward J, et al. RNase H2 catalytic core Aicardi-Goutières syndrome-related mutant invokes cGAS-STING innate immune-sensing pathway in mice. J Exp Med. 2016;213:329-36 pubmed publisher
    ..G37S homozygotes are perinatal lethal, in contrast to the early embryonic lethality previously reported for Rnaseh2b- or Rnaseh2c-null mice...
  9. Buers I, Rice G, Crow Y, Rutsch F. MDA5-Associated Neuroinflammation and the Singleton-Merten Syndrome: Two Faces of the Same Type I Interferonopathy Spectrum. J Interferon Cytokine Res. 2017;37:214-219 pubmed publisher
    ..6 different genes were described to be associated with Aicardi-Goutières syndrome, specifically-TREX1, RNASEH2A, RNASEH2B, RNASEH2C, ADAR, and SAMHD1...
  10. Al Mutairi F, Alfadhel M, Nashabat M, El Hattab A, Ben Omran T, Hertecant J, et al. Phenotypic and Molecular Spectrum of Aicardi-Goutières Syndrome: A Study of 24 Patients. Pediatr Neurol. 2018;78:35-40 pubmed publisher
    ..2%). Homozygous mutations were identified in RNASEH2B (54.2%), RNASEH2A (20.8%), RNASEH2C (8.3%), SAMHD1 (8.3%), TREX1 (4.2%), and heterozygous mutations in IFIH1 (4...
  11. Rump P, Jazayeri O, van Dijk Bos K, Johansson L, van Essen A, Verheij J, et al. Whole-exome sequencing is a powerful approach for establishing the etiological diagnosis in patients with intellectual disability and microcephaly. BMC Med Genomics. 2016;9:7 pubmed publisher
    ..Two unrelated patients had mutations in the ASPM gene. In seven other patients we found mutations in RAB3GAP1, RNASEH2B, KIF11, ERCC8, CASK, DYRK1A and BRCA2. In one of the sib-pairs, mutations were found in the RTTN gene...
  12. Nagler M, Palkowitsch L, Rading S, Moepps B, Karsak M. Cannabinoid receptor 2 expression modulates Gβ(1)γ(2) protein interaction with the activator of G protein signalling 2/dynein light chain protein Tctex-1. Biochem Pharmacol. 2016;99:60-72 pubmed publisher
    The activator of G protein signalling AGS2 (Tctex-1) forms protein complexes with Gβγ, and controls cell proliferation by regulating cell cycle progression...
  13. Armangue T, Orsini J, Takanohashi A, Gavazzi F, Conant A, Ulrick N, et al. Neonatal detection of Aicardi Goutières Syndrome by increased C26:0 lysophosphatidylcholine and interferon signature on newborn screening blood spots. Mol Genet Metab. 2017;122:134-139 pubmed publisher
    ..All five AGS patients with negative IFN signature at birth had RNASEH2B mutations. Consistency of agreement between IFN signature in neonatal and post-natal samples was high (0.85)...
  14. Feng S, Cao Z. Is the role of human RNase H2 restricted to its enzyme activity?. Prog Biophys Mol Biol. 2016;121:66-73 pubmed publisher
    ..Thirdly, the subunit proteins RNASEH2A and RNASEH2B respectively, not related to the RNase H2 enzymatic activities, have been shown to play a certain role in the ..
  15. Lim Y, Sanz L, Xu X, Hartono S, Chédin F. Genome-wide DNA hypomethylation and RNA:DNA hybrid accumulation in Aicardi-Goutières syndrome. elife. 2015;4: pubmed publisher
    ..endogenous nucleic acid species owing to mutations in nucleic acid-degrading enzymes TREX1 (AGS1), RNase H2 (AGS2, 3 and 4), and SAMHD1 (AGS5)...
  16. Ortiz Madinaveitia S, Conejo Moreno D, López Pisón J, Peña Segura J, Serrano Madrid M, Durán Palacios I, et al. [Phenotypic variations in Aicardi-Goutieres syndrome caused by RNASEH2B gene mutations: report of two new cases]. Rev Neurol. 2016;62:165-9 pubmed
    ..Two cases are described in detail below caused by RNASEH2B gene mutation, one of which displays a mutation no described to date...
  17. Bossini Castillo L, de Kovel C, Kallberg H, van t Slot R, Italiaander A, Coenen M, et al. A genome-wide association study of rheumatoid arthritis without antibodies against citrullinated peptides. Ann Rheum Dis. 2015;74:e15 pubmed publisher
    ..Our study shed light on the influence of the HLA region in ACPA-negative RA and identified a suggestive risk locus for this condition. ..
  18. Livingston J, Crow Y. Neurologic Phenotypes Associated with Mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR1, and IFIH1: Aicardi-Goutières Syndrome and Beyond. Neuropediatrics. 2016;47:355-360 pubmed
    ..following seven genes may result in the classical AGS phenotype: TREX1 (AGS1), RNASEH2A (AGS2), RNASEH2B (AGS3), RNASEH2C (AGS4), SAMHD1 (AGS5), ADAR1 (AGS6), and IFIH1 (AGS7)...
  19. Ali M, Highet L, Lacombe D, Goizet C, King M, Tacke U, et al. A second locus for Aicardi-Goutieres syndrome at chromosome 13q14-21. J Med Genet. 2006;43:444-50 pubmed
    ..Our results demonstrate significant linkage to a second AGS locus (AGS2) at chromosome 13q14-21 with a maximum multipoint heterogeneity logarithm of the odds (LOD) score of 5...
  20. Deng H, Zheng W, Jankovic J. Genetics and molecular biology of brain calcification. Ageing Res Rev. 2015;22:20-38 pubmed publisher
    ..The aim of the review is to highlight clinical disorders associated with brain calcification and provide summary of current knowledge of diagnosis, genetics, and pathogenesis of brain calcification. ..
  21. Crow Y, Livingston J. Aicardi-Goutières syndrome: an important Mendelian mimic of congenital infection. Dev Med Child Neurol. 2008;50:410-6 pubmed publisher
    ..development and occasionally associated with remarkably preserved neurological function, most frequently due to RNASEH2B mutations...
  22. Beyer U, Brand F, Martens H, Weder J, Christians A, Elyan N, et al. Rare ADAR and RNASEH2B variants and a type I interferon signature in glioma and prostate carcinoma risk and tumorigenesis. Acta Neuropathol. 2017;134:905-922 pubmed publisher
    ..yielded rare, simultaneously heterozygous variants in the Aicardi-Goutières syndrome (AGS) genes ADAR and RNASEH2B co-segregating with the tumor phenotype...
  23. Ostergaard E, Joensen F, Sundberg K, Duno M, Hansen F, Batbayli M, et al. A novel RNASEH2B splice site mutation responsible for Aicardi-Goutieres syndrome in the Faroe Islands. Acta Paediatr. 2012;101:e509-13 pubmed publisher
    ..6 Mb region of homozygosity on chromosome 13, which included RNASEH2B, where a splice site mutation c.322-3C>G was identified...
  24. Izzotti A, Longobardi M, Cartiglia C, Anzuini F, Arrigo P, Fazzi E, et al. Different mutations in three prime repair exonuclease 1 and ribonuclease H2 genes affect clinical features in Aicardi-Goutieres syndrome. J Child Neurol. 2012;27:51-60 pubmed publisher
  25. Svingen L, Goheen M, Godfrey R, Wahl C, Baker E, Gahl W, et al. Late diagnosis and atypical brain imaging of Aicardi-Goutières syndrome: are we failing to diagnose Aicardi-Goutières syndrome-2?. Dev Med Child Neurol. 2017;59:1307-1311 pubmed publisher
    ..Both were homozygous for the common pathogenic RNASEH2B allele (c.529G>A, p.Ala177Thr)...
  26. Kuster A, Arnoux J, Barth M, Lamireau D, Houcinat N, Goizet C, et al. Diagnostic approach to neurotransmitter monoamine disorders: experience from clinical, biochemical, and genetic profiles. J Inherit Metab Dis. 2018;41:129-139 pubmed publisher
    ..Other mutated genes included: ADAR, RNASEH2B, RNASET2, SLC7A2-IT1 A/B lncRNA, and EXOSC3 involved in nuclear and cytoplasmic metabolism; RanBP2 and CASK ..
  27. Kind B, Muster B, Staroske W, Herce H, Sachse R, Rapp A, et al. Altered spatio-temporal dynamics of RNase H2 complex assembly at replication and repair sites in Aicardi-Goutières syndrome. Hum Mol Genet. 2014;23:5950-60 pubmed publisher
    ..We found that AGS-associated mutations alter complex formation, recruitment efficiency and exchange kinetics at sites of DNA replication and repair suggesting that impaired ribonucleotide removal contributes to AGS pathogenesis. ..
  28. Figiel M, Chon H, Cerritelli S, Cybulska M, Crouch R, Nowotny M. The structural and biochemical characterization of human RNase H2 complex reveals the molecular basis for substrate recognition and Aicardi-Goutières syndrome defects. J Biol Chem. 2011;286:10540-50 pubmed publisher
    ..Our model indicates that the difference in substrate preference stems from the different position of the crucial tyrosine residue involved in substrate binding and recognition. ..
  29. Crozat K, Vivier E, Dalod M. Crosstalk between components of the innate immune system: promoting anti-microbial defenses and avoiding immunopathologies. Immunol Rev. 2009;227:129-49 pubmed publisher