NRG1

Summary

Gene Symbol: NRG1
Description: neuregulin 1
Alias: ARIA, GGF, GGF2, HGL, HRG, HRG1, HRGA, MST131, MSTP131, NDF, NRG1-IT2, SMDF, pro-neuregulin-1, membrane-bound isoform, acetylcholine receptor-inducing activity, glial growth factor 2, heregulin, alpha (45kD, ERBB2 p185-activator), neu differentiation factor, pro-NRG1, sensory and motor neuron derived factor
Species: human
Products:     NRG1

Top Publications

  1. Addington A, Gornick M, Shaw P, Seal J, Gogtay N, Greenstein D, et al. Neuregulin 1 (8p12) and childhood-onset schizophrenia: susceptibility haplotypes for diagnosis and brain developmental trajectories. Mol Psychiatry. 2007;12:195-205 pubmed
    ..Since the initial report of association between neuregulin 1 (NRG1) and schizophrenia in 2002, numerous independent replications have been reported...
  2. Bao J, Lin H, Ouyang Y, Lei D, Osman A, Kim T, et al. Activity-dependent transcription regulation of PSD-95 by neuregulin-1 and Eos. Nat Neurosci. 2004;7:1250-8 pubmed
    ..This upregulation of PSD-95 expression by the Nrg-ICD-Eos complex provides a molecular basis for activity-dependent synaptic plasticity. ..
  3. Geisberg C, Wang G, Safa R, Smith H, Anderson B, Peng X, et al. Circulating neuregulin-1? levels vary according to the angiographic severity of coronary artery disease and ischemia. Coron Artery Dis. 2011;22:577-82 pubmed publisher
    ..Therefore we conclude that plasma is the optimal source for the further exploration of the biological significance of NRG-1? as a biomarker of CAD severity and ischemia. ..
  4. Ky B, Kimmel S, Safa R, Putt M, Sweitzer N, Fang J, et al. Neuregulin-1 beta is associated with disease severity and adverse outcomes in chronic heart failure. Circulation. 2009;120:310-7 pubmed publisher
    ..These findings support a role for NRG-1/ErbB signaling in human heart failure and identify serum NRG-1beta as a novel biomarker that may have clinical applications. ..
  5. Tang J, Chen W, He G, Zhou J, Gu N, Feng G, et al. Polymorphisms within 5' end of the Neuregulin 1 gene are genetically associated with schizophrenia in the Chinese population. Mol Psychiatry. 2004;9:11-2 pubmed
  6. Syed N, Reddy K, Yang D, Taveggia C, Salzer J, Maurel P, et al. Soluble neuregulin-1 has bifunctional, concentration-dependent effects on Schwann cell myelination. J Neurosci. 2010;30:6122-31 pubmed publisher
    Members of the neuregulin-1 (Nrg1) growth factor family play important roles during Schwann cell development. Recently, it has been shown that the membrane-bound type III isoform is required for Schwann cell myelination...
  7. Britsch S. The neuregulin-I/ErbB signaling system in development and disease. Adv Anat Embryol Cell Biol. 2007;190:1-65 pubmed
    ..The neuregulin family of ligands has four members: NRG1, NRG2, NRG3, and NRG4. Relatively little is known about the biological functions of the NRG2, 3, and 4 proteins...
  8. Tan W, Wang Y, Gold B, Chen J, Dean M, Harrison P, et al. Molecular cloning of a brain-specific, developmentally regulated neuregulin 1 (NRG1) isoform and identification of a functional promoter variant associated with schizophrenia. J Biol Chem. 2007;282:24343-51 pubmed
    Neuregulin 1 (NRG1) is essential for the development and function of multiple organ systems, and its dysregulation has been linked to diseases such as cancer and schizophrenia...
  9. Walss Bass C, Liu W, Lew D, Villegas R, Montero P, Dassori A, et al. A novel missense mutation in the transmembrane domain of neuregulin 1 is associated with schizophrenia. Biol Psychiatry. 2006;60:548-53 pubmed
    ..Additional analyses of an independent sample as well as detailed functional studies should be performed to determine the relevance of this novel polymorphism to the pathophysiology of schizophrenia. ..

More Information

Publications94

  1. Hong L, Wonodi I, Stine O, Mitchell B, Thaker G. Evidence of missense mutations on the neuregulin 1 gene affecting function of prepulse inhibition. Biol Psychiatry. 2008;63:17-23 pubmed
    Neuregulin 1 (NRG1) is one of the leading candidate genes in schizophrenia. Rodents with NRG1 knock-out showed significantly impaired prepulse inhibition (PPI) in the original report linking NRG1 to schizophrenia...
  2. McIntosh A, Moorhead T, Job D, Lymer G, Muñoz Maniega S, McKirdy J, et al. The effects of a neuregulin 1 variant on white matter density and integrity. Mol Psychiatry. 2008;13:1054-9 pubmed
    ..Neuregulin 1 (NRG1) is a psychosis susceptibility gene with effects on neuronal migration, axon guidance and myelination that could ..
  3. Lachman H, Pedrosa E, Nolan K, Glass M, Ye K, Saito T. Analysis of polymorphisms in AT-rich domains of neuregulin 1 gene in schizophrenia. Am J Med Genet B Neuropsychiatr Genet. 2006;141B:102-9 pubmed
    Linkage analysis and association studies have pointed to neuregulin 1 (NRG1) as the prime candidate for 8p-linked schizophrenia (SZ)...
  4. Munafò M, Thiselton D, Clark T, Flint J. Association of the NRG1 gene and schizophrenia: a meta-analysis. Mol Psychiatry. 2006;11:539-46 pubmed
    We investigated the association of the NRG1 gene and schizophrenia using meta-analytic techniques, combining all published data while restricting our analysis to studies investigating the most commonly reported single marker (..
  5. Stefansson H, Sigurdsson E, Steinthorsdottir V, Bjornsdottir S, Sigmundsson T, Ghosh S, et al. Neuregulin 1 and susceptibility to schizophrenia. Am J Hum Genet. 2002;71:877-92 pubmed
    ..and haplotype-association analysis, supplemented by a transmission/disequilibrium test, identifies neuregulin 1 (NRG1) as a candidate gene for schizophrenia...
  6. Shirakabe K, Wakatsuki S, Kurisaki T, Fujisawa Sehara A. Roles of Meltrin beta /ADAM19 in the processing of neuregulin. J Biol Chem. 2001;276:9352-8 pubmed
    ..Furthermore, the effects of the secretory pathway inhibitors suggested that meltrin beta participates in the intracellular processing of NRGs rather than the cleavage on the cell surface. ..
  7. Norton N, Moskvina V, Morris D, Bray N, Zammit S, Williams N, et al. Evidence that interaction between neuregulin 1 and its receptor erbB4 increases susceptibility to schizophrenia. Am J Med Genet B Neuropsychiatr Genet. 2006;141B:96-101 pubmed
    There is now strong evidence that Neuregulin 1 (NRG1) is a susceptibility gene for schizophrenia...
  8. Wang J, Miller S, Falls D. The N-terminal region of neuregulin isoforms determines the accumulation of cell surface and released neuregulin ectodomain. J Biol Chem. 2001;276:2841-51 pubmed
  9. Stefansson H, Sarginson J, Kong A, Yates P, Steinthorsdottir V, Gudfinnsson E, et al. Association of neuregulin 1 with schizophrenia confirmed in a Scottish population. Am J Hum Genet. 2003;72:83-7 pubmed
    Recently, we identified neuregulin 1 (NRG1) as a susceptibility gene for schizophrenia in the Icelandic population, by a combined linkage and association approach...
  10. Yang J, Si T, Ruan Y, Ling Y, Han Y, Wang X, et al. Association study of neuregulin 1 gene with schizophrenia. Mol Psychiatry. 2003;8:706-9 pubmed
    ..In this region, the candidate gene of interest, neuregulin 1 (NRG1), may play a role in the pathogenesis of schizophrenia...
  11. Stefanis N, Trikalinos T, Avramopoulos D, Smyrnis N, Evdokimidis I, Ntzani E, et al. Impact of schizophrenia candidate genes on schizotypy and cognitive endophenotypes at the population level. Biol Psychiatry. 2007;62:784-92 pubmed
    ..We examined the potential impact of 18 single nucleotide polymorphisms (SNPs) within the DTNBP1, NRG1, DAOA/G32, and DAAO genes, on cognition and self-rated schizotypy, in a representative population of 2243 young ..
  12. Winterer G, Konrad A, Vucurevic G, Musso F, Stoeter P, Dahmen N. Association of 5' end neuregulin-1 (NRG1) gene variation with subcortical medial frontal microstructure in humans. Neuroimage. 2008;40:712-718 pubmed publisher
    Animal data suggest that the gene neuregulin-1 (NRG1) is involved in neuronal myelination. A haplotype (deCODE) in the 5' end region of the gene was described to double the risk for schizophrenia in an Icelandic population (Stefansson, H...
  13. Hall D, Gogos J, Karayiorgou M. The contribution of three strong candidate schizophrenia susceptibility genes in demographically distinct populations. Genes Brain Behav. 2004;3:240-8 pubmed
    ..contribution of three recently identified strong candidate schizophrenia susceptibility genes; G72, neuregulin 1 (NRG1) and dystrobrevin-binding protein 1 (DTNBP1) in two independent datasets of patients with distinct genetic ..
  14. Tang W, Li B, Xu X, Zhou Z, Wu W, Tang J, et al. Aberrant high expression of NRG1 gene in Hirschsprung disease. J Pediatr Surg. 2012;47:1694-8 pubmed publisher
    ..Recent studies have indicated the potential function of neuregulin-1 (NRG1) in HSCR, which encodes the heregulins and other mitogenic ligands for the ErbB family...
  15. Cabedo H, Luna C, Fernandez A, Gallar J, Ferrer Montiel A. Molecular determinants of the sensory and motor neuron-derived factor insertion into plasma membrane. J Biol Chem. 2002;277:19905-12 pubmed
    The sensory and motor neuron-derived factor (SMDF) is a type III neuregulin that regulates development and proliferation of Schwann cells...
  16. Hahn C, Wang H, Cho D, Talbot K, Gur R, Berrettini W, et al. Altered neuregulin 1-erbB4 signaling contributes to NMDA receptor hypofunction in schizophrenia. Nat Med. 2006;12:824-8 pubmed
    Recent molecular genetics studies implicate neuregulin 1 (NRG1) and its receptor erbB in the pathophysiology of schizophrenia...
  17. Corfas G, Roy K, Buxbaum J. Neuregulin 1-erbB signaling and the molecular/cellular basis of schizophrenia. Nat Neurosci. 2004;7:575-80 pubmed
    ..Recently, the gene that encodes neuregulin-1 (NRG1) has been identified as a potential susceptibility gene for schizophrenia, and defects in the expression of erbB3, ..
  18. Nason M, Adhikari A, Bozinoski M, Gordon J, Role L. Disrupted activity in the hippocampal-accumbens circuit of type III neuregulin 1 mutant mice. Neuropsychopharmacology. 2011;36:488-96 pubmed publisher
    Neuregulin 1 (Nrg1), a schizophrenia susceptibility gene, is involved in fundamental aspects of neurodevelopment...
  19. Barakat A, Dean B, Scarr E, Evin G. Decreased Neuregulin 1 C-terminal fragment in Brodmann's area 6 of patients with schizophrenia. Schizophr Res. 2010;124:200-7 pubmed publisher
    Neuregulin 1 (NRG1) is a susceptibility gene for schizophrenia. A decrease in NRG1-ErbB4 signalling has also been associated with the disease...
  20. Georgieva L, Dimitrova A, Ivanov D, Nikolov I, Williams N, Grozeva D, et al. Support for neuregulin 1 as a susceptibility gene for bipolar disorder and schizophrenia. Biol Psychiatry. 2008;64:419-27 pubmed publisher
    There is support that Neuregulin 1 (NRG1) plays a role in susceptibility to schizophrenia but limited evidence for its involvement in bipolar disorder...
  21. Kalinowski A, Plowes N, Huang Q, Berdejo Izquierdo C, Russell R, Russell K. Metalloproteinase-dependent cleavage of neuregulin and autocrine stimulation of vascular endothelial cells. FASEB J. 2010;24:2567-75 pubmed publisher
    ..Cytokine-activated metalloproteinase cleavage of neuregulin may play an important role in autocrine activation of EC signaling pathways, contributing to key biological effects, perhaps including inflammation-associated angiogenesis. ..
  22. Krug A, Markov V, Krach S, Jansen A, Zerres K, Eggermann T, et al. The effect of Neuregulin 1 on neural correlates of episodic memory encoding and retrieval. Neuroimage. 2010;53:985-91 pubmed publisher
    Neuregulin 1 (NRG1) has been found to be associated with schizophrenia. Impaired performance in episodic memory tasks is an often replicated finding in this disorder...
  23. Cheng L, Zha Z, Lang B, Liu J, Yao X. Heregulin-beta1 promotes metastasis of breast cancer cell line SKBR3 through upregulation of Snail and induction of epithelial-mesenchymal transition. Cancer Lett. 2009;280:50-60 pubmed publisher
    b>HRG-beta1 stimulation of breast cancer cell line SKBR3 resulted in not only increased cell migration and invasion, upregulation of some mesenchymal markers, and downregulation of epithelial marker, but also upregulation of transcription ..
  24. Shibuya M, Komi E, Wang R, Kato T, Watanabe Y, Sakai M, et al. Measurement and comparison of serum neuregulin 1 immunoreactivity in control subjects and patients with schizophrenia: an influence of its genetic polymorphism. J Neural Transm (Vienna). 2010;117:887-95 pubmed publisher
    Neuregulin-1 (NRG1) gene is implicated in the etiology or neuropathology of schizophrenia, although its biological contribution to this illness is not fully understood...
  25. Li D, Collier D, He L. Meta-analysis shows strong positive association of the neuregulin 1 (NRG1) gene with schizophrenia. Hum Mol Genet. 2006;15:1995-2002 pubmed
    ..an associated haplotype in the gene neuregulin 1 (NRG1), also known as heuregulin, glial growth factor, NDF43 and ARIA. A 290 kb core at risk haplotype at the 5' end of the gene (HAP(ICE)), defined by five SNPs and two microsatellite ..
  26. Shamir A, Kwon O, Karavanova I, Vullhorst D, Leiva Salcedo E, Janssen M, et al. The importance of the NRG-1/ErbB4 pathway for synaptic plasticity and behaviors associated with psychiatric disorders. J Neurosci. 2012;32:2988-97 pubmed publisher
    ..These findings are important to better understand ErbB4's role in complex behaviors and warrant further analysis of ErbB4 mutant mice lacking the receptor in distinct neuron types. ..
  27. Wang F, Jiang T, Sun Z, Teng S, Luo X, Zhu Z, et al. Neuregulin 1 genetic variation and anterior cingulum integrity in patients with schizophrenia and healthy controls. J Psychiatry Neurosci. 2009;34:181-6 pubmed
    Neuregulin1 (NRG1) influences the development of white matter connectivity and is implicated in genetic susceptibility to schizophrenia. The cingulum bundle is a white matter structure implicated in schizophrenia...
  28. Harrison P, Law A. Neuregulin 1 and schizophrenia: genetics, gene expression, and neurobiology. Biol Psychiatry. 2006;60:132-40 pubmed
    Neuregulin 1 (NRG1) is a leading schizophrenia susceptibility gene...
  29. Huang H, Chin S, Ginestier C, Bardou V, Adélaïde J, Iyer N, et al. A recurrent chromosome breakpoint in breast cancer at the NRG1/neuregulin 1/heregulin gene. Cancer Res. 2004;64:6840-4 pubmed
    ..We previously reported that five breast cancer cell lines have chromosome translocations that break in the NRG1 gene and that could cause abnormal NRG1 expression...
  30. Thomson P, Christoforou A, Morris S, Adie E, Pickard B, Porteous D, et al. Association of Neuregulin 1 with schizophrenia and bipolar disorder in a second cohort from the Scottish population. Mol Psychiatry. 2007;12:94-104 pubmed
    ..It spans a approximately 136 kb region that includes the coding sequence of the sensory and motor neuron derived factor (SMDF) isoform and 3' exons of all other known NRG1 isoforms...
  31. Bakker S, Hoogendoorn M, Selten J, Verduijn W, Pearson P, Sinke R, et al. Neuregulin 1: genetic support for schizophrenia subtypes. Mol Psychiatry. 2004;9:1061-3 pubmed
  32. Williams N, Preece A, Spurlock G, Norton N, Williams H, Zammit S, et al. Support for genetic variation in neuregulin 1 and susceptibility to schizophrenia. Mol Psychiatry. 2003;8:485-7 pubmed
    ..6%; P=0.019). Our results therefore replicate the Icelandic findings in an out-bred Northern European population, although they suggest that the risk conferred by the haplotype is small. ..
  33. Duan J, Martinez M, Sanders A, Hou C, Krasner A, Schwartz D, et al. Neuregulin 1 (NRG1 ) and schizophrenia: analysis of a US family sample and the evidence in the balance. Psychol Med. 2005;35:1599-610 pubmed
    ..A gene from this region, neuregulin 1 (NRG1 ), known to be involved with glutamatergic function, has been found to be associated in some studied samples...
  34. Wilson T, Lee D, Berry L, Shames D, Settleman J. Neuregulin-1-mediated autocrine signaling underlies sensitivity to HER2 kinase inhibitors in a subset of human cancers. Cancer Cell. 2011;20:158-72 pubmed publisher
    ..These cells were found to depend on a neuregulin-1 (NRG1)-mediated autocrine loop driving HER3 activation, which can be disrupted by lapatinib...
  35. Bertram I, Bernstein H, Lendeckel U, Bukowska A, Dobrowolny H, Keilhoff G, et al. Immunohistochemical evidence for impaired neuregulin-1 signaling in the prefrontal cortex in schizophrenia and in unipolar depression. Ann N Y Acad Sci. 2007;1096:147-56 pubmed
    ..Reduced NRG-1alpha protein concentrations were found in brains of schizophrenics after Western blot analysis. The diminished expression of NRG-1alpha strongly supports an early neurodevelopmental component to schizophrenia. ..
  36. Hall J, Whalley H, Job D, Baig B, McIntosh A, Evans K, et al. A neuregulin 1 variant associated with abnormal cortical function and psychotic symptoms. Nat Neurosci. 2006;9:1477-8 pubmed
    b>NRG1, encoding neuregulin 1, is a susceptibility gene for schizophrenia, but no functional mutation causally related to the disorder has yet been identified...
  37. Tang C, Ngan E, Tang W, So M, Cheng G, Miao X, et al. Mutations in the NRG1 gene are associated with Hirschsprung disease. Hum Genet. 2012;131:67-76 pubmed publisher
    ..association study conducted on Chinese HSCR patients, we identified a new HSCR contributing locus, neuregulin 1 (NRG1; 8p12), a gene known to be involved in the development of the ENS...
  38. Shamir A, Buonanno A. Molecular and cellular characterization of Neuregulin-1 type IV isoforms. J Neurochem. 2010;113:1163-76 pubmed publisher
    Numerous genetic studies associated the Neuregulin 1 (NRG1) Icelandic haplotype (HAP(ice)), and its single nucleotide polymorphism SNP8NRG243177 [T/T], with schizophrenia...
  39. Dutt A, McDonald C, Dempster E, Prata D, Shaikh M, Williams I, et al. The effect of COMT, BDNF, 5-HTT, NRG1 and DTNBP1 genes on hippocampal and lateral ventricular volume in psychosis. Psychol Med. 2009;39:1783-97 pubmed publisher
    ..epidemiological studies support an overlap between schizophrenia and bipolar disorder, and COMT, BDNF, 5-HTT, NRG1 and DTNBP1 genes have been implicated in the aetiology of both these disorders...
  40. Schmechtig A, Vassos E, Kumari V, Hutton S, Collier D, Morris R, et al. Association of Neuregulin 1 rs3924999 genotype with antisaccades and smooth pursuit eye movements. Genes Brain Behav. 2010;9:621-7 pubmed publisher
    Neuregulin 1 (NRG1) has been identified as one of the leading candidate genes for schizophrenia. However, its functional mechanisms and its effects on neurocognition remain unclear...
  41. Sliwkowski M, Schaefer G, Akita R, Lofgren J, Fitzpatrick V, Nuijens A, et al. Coexpression of erbB2 and erbB3 proteins reconstitutes a high affinity receptor for heregulin. J Biol Chem. 1994;269:14661-5 pubmed
    The heregulin/neu differentiation factor gene products were purified and cloned based on their ability to stimulate the phosphorylation of a 185-kDa protein in human breast carcinoma cell lines known to express erbB2...
  42. Munafo M, Attwood A, Flint J. Neuregulin 1 genotype and schizophrenia. Schizophr Bull. 2008;34:9-12 pubmed
    The neuregulin 1 (NRG1) gene has been the subject of considerable excitement within the psychiatric genetics literature since it was originally identified as a potential susceptibility locus for schizophrenia...
  43. Singer E, Landgraf R, Horan T, Slamon D, Eisenberg D. Identification of a heregulin binding site in HER3 extracellular domain. J Biol Chem. 2001;276:44266-74 pubmed
    ..We show that the EGF-like domain of heregulin (hrg) binds to domains I and II of HER3, in contrast to the EGF receptor, for which prior studies have shown that a ..
  44. Tang C, Tang W, So M, Miao X, Leung B, Yip B, et al. Fine mapping of the NRG1 Hirschsprung's disease locus. PLoS ONE. 2011;6:e16181 pubmed publisher
    ..association study, we uncovered a ?350 kb HSCR-associated region encompassing part of the neuregulin-1 gene (NRG1)...
  45. Walss Bass C, Raventos H, Montero A, Armas R, Dassori A, Contreras S, et al. Association analyses of the neuregulin 1 gene with schizophrenia and manic psychosis in a Hispanic population. Acta Psychiatr Scand. 2006;113:314-21 pubmed
    ..Further studies in the CVCR and other Latin American populations should be performed in order to corroborate these findings. ..
  46. Bian Y, Sun M, Silver M, Ho K, Marchionni M, Caggiano A, et al. Neuregulin-1 attenuated doxorubicin-induced decrease in cardiac troponins. Am J Physiol Heart Circ Physiol. 2009;297:H1974-83 pubmed publisher
    Neuregulin-1 (NRG1) is a potential therapeutic agent for the treatment of doxorubicin (Dox)-induced heart failure. NRG1, however, activates the erbB2 receptor, which is frequently overexpressed in breast cancers...
  47. Mata I, Perez Iglesias R, Roiz Santiáñez R, Tordesillas Gutierrez D, Gonzalez Mandly A, Vazquez Barquero J, et al. A neuregulin 1 variant is associated with increased lateral ventricle volume in patients with first-episode schizophrenia. Biol Psychiatry. 2009;65:535-40 pubmed publisher
    ..Neuregulin 1 gene (NRG1) is a candidate gene for schizophrenia, and its protein has different roles in nervous system development and ..
  48. Schaefer G, Fitzpatrick V, Sliwkowski M. Gamma-heregulin: a novel heregulin isoform that is an autocrine growth factor for the human breast cancer cell line, MDA-MB-175. Oncogene. 1997;15:1385-94 pubmed
    A novel neuregulin isoform, termed gamma-HRG, was cloned and characterized from the human breast cancer cell line, MDA-MB-175...
  49. Zhao Y, Sawyer D, Baliga R, Opel D, Han X, Marchionni M, et al. Neuregulins promote survival and growth of cardiac myocytes. Persistence of ErbB2 and ErbB4 expression in neonatal and adult ventricular myocytes. J Biol Chem. 1998;273:10261-9 pubmed
    Neuregulins (i.e. neuregulin-1 (NRG1), also called neu differentiation factor, heregulin, glial growth factor, and acetylcholine receptor-inducing activity) are known to induce growth and differentiation of epithelial, glial, neuronal, ..
  50. Velanac V, Unterbarnscheidt T, Hinrichs W, Gummert M, Fischer T, Rossner M, et al. Bace1 processing of NRG1 type III produces a myelin-inducing signal but is not essential for the stimulation of myelination. Glia. 2012;60:203-17 pubmed publisher
    Myelin sheath thickness is precisely adjusted to axon caliber, and in the peripheral nervous system, neuregulin 1 (NRG1) type III is a key regulator of this process...
  51. Li T, Stefansson H, Gudfinnsson E, Cai G, Liu X, Murray R, et al. Identification of a novel neuregulin 1 at-risk haplotype in Han schizophrenia Chinese patients, but no association with the Icelandic/Scottish risk haplotype. Mol Psychiatry. 2004;9:698-704 pubmed
    To determine if neuregulin 1 (NRG1) is associated with schizophrenia in Asian populations, we investigated a Han Chinese population using both a family trio design and a case-control design...
  52. Weickert C, Tiwari Y, Schofield P, Mowry B, Fullerton J. Schizophrenia-associated HapICE haplotype is associated with increased NRG1 type III expression and high nucleotide diversity. Transl Psychiatry. 2012;2:e104 pubmed publisher
    Excitement and controversy have followed neuregulin (NRG1) since its discovery as a putative schizophrenia susceptibility gene; however, the mechanism of action of the associated risk haplotype (HapICE) has not been identified, and ..
  53. Kampman O, Anttila S, Illi A, Saarela M, Rontu R, Mattila K, et al. Neuregulin genotype and medication response in Finnish patients with schizophrenia. Neuroreport. 2004;15:2517-20 pubmed
    ..We also analyzed NRG1 genotype with regard to age at onset and between responders and non-responders to conventional antipsychotics...
  54. Fricker F, Lago N, Balarajah S, Tsantoulas C, Tanna S, Zhu N, et al. Axonally derived neuregulin-1 is required for remyelination and regeneration after nerve injury in adulthood. J Neurosci. 2011;31:3225-33 pubmed publisher
    Neuregulin-1 (NRG1) plays a crucial role in axoglial signaling during the development of the peripheral nervous system, but its importance in adulthood after peripheral nerve injury remains unclear...
  55. Kanakry C, Li Z, Nakai Y, Sei Y, Weinberger D. Neuregulin-1 regulates cell adhesion via an ErbB2/phosphoinositide-3 kinase/Akt-dependent pathway: potential implications for schizophrenia and cancer. PLoS ONE. 2007;2:e1369 pubmed
    Neuregulin-1 (NRG1) is a putative schizophrenia susceptibility gene involved extensively in central nervous system development as well as cancer invasion and metastasis...
  56. Keri S, Kiss I, Seres I, Kelemen O. A polymorphism of the neuregulin 1 gene (SNP8NRG243177/rs6994992) affects reactivity to expressed emotion in schizophrenia. Am J Med Genet B Neuropsychiatr Genet. 2009;150B:418-20 pubmed publisher
    ..These results raise the possibility that there is a significant gene by environment interaction regarding SNP8NRG243177/rs6994992 and psychosocial stress. ..
  57. Barnes A, Isohanni M, Barnett J, Pietiläinen O, Veijola J, Miettunen J, et al. Neuregulin-1 genotype is associated with structural differences in the normal human brain. Neuroimage. 2012;59:2057-61 pubmed publisher
    ..These results suggest that this genetic variant may mediate risk for schizophrenia, in part, through its effect on brain structure in these regions. ..
  58. Yonezawa M, Wada K, Tatsuguchi A, Akamatsu T, Gudis K, Seo T, et al. Heregulin-induced VEGF expression via the ErbB3 signaling pathway in colon cancer. Digestion. 2009;80:215-25 pubmed publisher
    Heregulin (HRG/NRG) ligation to erbB3/4 promotes their respective heterodimerization with erbB2, and consequent erbB2 tyrosine phosphorylation...
  59. Smyrnis N, Kattoulas E, Stefanis N, Avramopoulos D, Stefanis C, Evdokimidis I. Schizophrenia-related neuregulin-1 single-nucleotide polymorphisms lead to deficient smooth eye pursuit in a large sample of young men. Schizophr Bull. 2011;37:822-31 pubmed publisher
    Neuregulin-1 (NRG1) variations have been shown to modulate schizophrenia candidate endophenotypes related to brain structure and function...
  60. Liu X, Bates R, Yin D, Shen C, Wang F, Su N, et al. Specific regulation of NRG1 isoform expression by neuronal activity. J Neurosci. 2011;31:8491-501 pubmed publisher
    Neuregulin 1 (NRG1) is a trophic factor that has been implicated in neural development, neurotransmission, and synaptic plasticity...
  61. Marchionni M, Goodearl A, Chen M, Bermingham McDonogh O, Kirk C, Hendricks M, et al. Glial growth factors are alternatively spliced erbB2 ligands expressed in the nervous system. Nature. 1993;362:312-8 pubmed
    ..These factors are probably important in the development and regeneration of the nervous system. ..
  62. Vermeer P, Einwalter L, Moninger T, Rokhlina T, Kern J, Zabner J, et al. Segregation of receptor and ligand regulates activation of epithelial growth factor receptor. Nature. 2003;422:322-6 pubmed
    ..This model also suggests a mechanism for abnormal receptor activation in diseases with increased epithelial permeability. ..
  63. Steinthorsdottir V, Stefansson H, Ghosh S, Birgisdottir B, Bjornsdottir S, Fasquel A, et al. Multiple novel transcription initiation sites for NRG1. Gene. 2004;342:97-105 pubmed
    The large neuregulin 1 gene (NRG1) has been mapped to a 1.125 Mb region on chromosome 8p11-21. Three major forms of NRG1 (types I-III), all with distinct amino-termini encoded by unique 5'-exons, have been described...
  64. Orr Urtreger A, Trakhtenbrot L, Ben Levy R, Wen D, Rechavi G, Lonai P, et al. Neural expression and chromosomal mapping of Neu differentiation factor to 8p12-p21. Proc Natl Acad Sci U S A. 1993;90:1867-71 pubmed
    b>Neu differentiation factor (NDF/heregulin) is a 44-kDa glycoprotein that interacts with the Neu/ErbB-2 receptor tyrosine kinase to increase its phosphorylation on tyrosine residues...
  65. Esper R, Pankonin M, Loeb J. Neuregulins: versatile growth and differentiation factors in nervous system development and human disease. Brain Res Rev. 2006;51:161-75 pubmed
    ..of the neuregulin signaling system comes in part from a large number of alternatively-spliced forms of the NRG1 gene that can produce both soluble and membrane-bound forms...
  66. Talmage D. Mechanisms of neuregulin action. Novartis Found Symp. 2008;289:74-84; discussion 84-93 pubmed
    Neuregulin 1 (Nrg1) and ErbB receptor tyrosine kinase signalling is essential for the formation and proper functioning of multiple organ systems and inappropriate Nrgl/ErbB signalling severely compromises health, contributing to such ..
  67. Garcia Barcelo M, Tang C, Ngan E, Lui V, Chen Y, So M, et al. Genome-wide association study identifies NRG1 as a susceptibility locus for Hirschsprung's disease. Proc Natl Acad Sci U S A. 2009;106:2694-9 pubmed publisher
    ..associations in plausible candidate genes were found for 2 SNPs located in intron 1 of the neuregulin1 gene (NRG1) on 8p12, with rs16879552 and rs7835688 yielding odds ratios of 1.68 [CI(95%):(1.40, 2.00), P = 1...
  68. Keri S. Genes for psychosis and creativity: a promoter polymorphism of the neuregulin 1 gene is related to creativity in people with high intellectual achievement. Psychol Sci. 2009;20:1070-3 pubmed publisher
    ..Intriguingly, the highest creative achievements and creative-thinking scores were found in people who carried the T/T genotype, which was previously shown to be related to psychosis risk and altered prefrontal activation. ..
  69. Zhao X, Shi Y, Tang J, Tang R, Yu L, Gu N, et al. A case control and family based association study of the neuregulin1 gene and schizophrenia. J Med Genet. 2004;41:31-4 pubmed
  70. Zhang L, Fletcher Turner A, Marchionni M, Apparsundaram S, Lundgren K, Yurek D, et al. Neurotrophic and neuroprotective effects of the neuregulin glial growth factor-2 on dopaminergic neurons in rat primary midbrain cultures. J Neurochem. 2004;91:1358-68 pubmed
    Glial growth factor-2 (GGF2) and other neuregulin (NRG) isoforms have been shown to play important roles in survival, migration, and differentiation of certain neural and non-neural cells...
  71. Bousman C, Yung A, Pantelis C, Ellis J, Chavez R, Nelson B, et al. Effects of NRG1 and DAOA genetic variation on transition to psychosis in individuals at ultra-high risk for psychosis. Transl Psychiatry. 2013;3:e251 pubmed publisher
    Prospective studies have suggested genetic variation in the neuregulin 1 (NRG1) and D-amino-acid oxidase activator (DAOA) genes may assist in differentiating high-risk individuals who will or will not transition to psychosis...
  72. Sheng Q, Liu X, Fleming E, Yuan K, Piao H, Chen J, et al. An activated ErbB3/NRG1 autocrine loop supports in vivo proliferation in ovarian cancer cells. Cancer Cell. 2010;17:298-310 pubmed publisher
    ..tyrosine kinase in ovarian cancer cell lines by RNAi, we found that an autocrine signal-transducing loop involving NRG1 and activated ErbB3 operates in a subset of primary ovarian cancers and ovarian cancer cell lines...
  73. Wang X, Jolicoeur E, Conte N, Chaffanet M, Zhang Y, Mozziconacci M, et al. gamma-heregulin is the product of a chromosomal translocation fusing the DOC4 and HGL/NRG1 genes in the MDA-MB-175 breast cancer cell line. Oncogene. 1999;18:5718-21 pubmed
    ..chromosomes and the MDA-MB-175 cell line contains a chromosomal translocation that leads to the fusion of DOC4 and HGL, on chromosomes 11 and 8, respectively...
  74. Liu X, Baker E, Eyre H, Sutherland G, Zhou M. Gamma-heregulin: a fusion gene of DOC-4 and neuregulin-1 derived from a chromosome translocation. Oncogene. 1999;18:7110-4 pubmed
    ..We conclude, therefore, that gamma-heregulin is not a native isoform of the neuregulin-1 gene, but a novel growth factor that may contribute to tumour cell proliferation. ..
  75. Atlas E, Cardillo M, Mehmi I, Zahedkargaran H, Tang C, Lupu R. Heregulin is sufficient for the promotion of tumorigenicity and metastasis of breast cancer cells in vivo. Mol Cancer Res. 2003;1:165-75 pubmed
    ..Heregulin (HRG) is a pleiotropic growth factor that binds to the erbB family of receptors, which are correlated with breast cancer ..
  76. Petryshen T, Middleton F, Kirby A, Aldinger K, Purcell S, Tahl A, et al. Support for involvement of neuregulin 1 in schizophrenia pathophysiology. Mol Psychiatry. 2005;10:366-74, 328 pubmed
    ..More recently, significant association with a candidate gene on 8p12, neuregulin 1 (NRG1), has been reported in several European and Chinese samples...
  77. Hashimoto R, Straub R, Weickert C, Hyde T, Kleinman J, Weinberger D. Expression analysis of neuregulin-1 in the dorsolateral prefrontal cortex in schizophrenia. Mol Psychiatry. 2004;9:299-307 pubmed
    ..Subtle abnormalities in the expression patterns of NRG-1 mRNA isoforms in DLPFC may be associated with schizophrenia. ..
  78. Law A, Lipska B, Weickert C, Hyde T, Straub R, Hashimoto R, et al. Neuregulin 1 transcripts are differentially expressed in schizophrenia and regulated by 5' SNPs associated with the disease. Proc Natl Acad Sci U S A. 2006;103:6747-52 pubmed
    Genetic variation in neuregulin 1 (NRG1) is associated with schizophrenia. The disease-associated SNPs are noncoding, and their functional implications remain unknown...
  79. Papiol S, Begemann M, Rosenberger A, Friedrichs H, Ribbe K, Grube S, et al. A phenotype-based genetic association study reveals the contribution of neuregulin1 gene variants to age of onset and positive symptom severity in schizophrenia. Am J Med Genet B Neuropsychiatr Genet. 2011;156B:340-5 pubmed publisher
    ..the risk of developing schizophrenia has been repeatedly associated with specific variants of the neuregulin1 (NRG1) gene. However, the role of NRG1 in the etiology of schizophrenia has remained unclear...
  80. Corvin A, Morris D, McGhee K, Schwaiger S, Scully P, Quinn J, et al. Confirmation and refinement of an 'at-risk' haplotype for schizophrenia suggests the EST cluster, Hs.97362, as a potential susceptibility gene at the Neuregulin-1 locus. Mol Psychiatry. 2004;9:208-13 pubmed
    Two recent association studies have implicated the neuregulin-1 gene (NRG1) at chromosome 8p21-22 as a susceptibility gene for schizophrenia...
  81. Holmes W, Sliwkowski M, Akita R, Henzel W, Lee J, Park J, et al. Identification of heregulin, a specific activator of p185erbB2. Science. 1992;256:1205-10 pubmed
    ..A 45-kilodalton protein heregulin-alpha (HRG-alpha) that specifically induced phosphorylation of p185erbB2 was purified from the conditioned medium of a human ..
  82. Odiete O, Hill M, Sawyer D. Neuregulin in cardiovascular development and disease. Circ Res. 2012;111:1376-85 pubmed publisher
    ..In this review, we bring together this growing literature on NRG-1 and its significance in cardiovascular development and disease. ..
  83. Walker R, Christoforou A, Thomson P, McGhee K, Maclean A, Mühleisen T, et al. Association analysis of Neuregulin 1 candidate regions in schizophrenia and bipolar disorder. Neurosci Lett. 2010;478:9-13 pubmed publisher
    ..Neuregulin 1 (NRG1) is a leading candidate gene for SCZ, and has recently been implicated in BPD...
  84. Thiselton D, Webb B, Neale B, Ribble R, O Neill F, Walsh D, et al. No evidence for linkage or association of neuregulin-1 (NRG1) with disease in the Irish study of high-density schizophrenia families (ISHDSF). Mol Psychiatry. 2004;9:777-83; image 729 pubmed
    The neuregulin-1 gene (NRG1) at chromosome 8p21-22 has been implicated as a schizophrenia susceptibility gene in Icelandic, Scottish, Irish and mixed UK populations...
  85. Panutsopulos D, Arvanitis D, Tsatsanis C, Papalambros E, Sigala F, Spandidos D. Expression of heregulin in human coronary atherosclerotic lesions. J Vasc Res. 2005;42:463-74 pubmed
    ..The aim of the present study was to determine whether heregulin (HRG) is associated with human coronary artery disease...