The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

RAI1  -  retinoic acid induced 1

Homo sapiens

Synonyms: DKFZP434A139, KIAA1820, MGC12824, Retinoic acid-induced protein 1, SMCR, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of RAI1

  • FISH analysis of the PACs allowed determination of the position of the transcripts with respect to the SMS critical region and the presumptive chromosomal breakpoint in medulloblastomas [1].
  • In addition, variation in the RAI1 gene was analyzed in 30 spinocerebellar ataxia (SCA2) patients and normal individuals to show the possible influence on the age at onset [2].
  • Phenotypic comparison between patients with deletions and patients with RAI1 mutations show that 21 of 30 SMS features are the result of haploinsufficiency of RAI1, whereas cardiac anomalies, speech and motor delay, hypotonia, short stature, and hearing loss are associated with 17p11.2 deletions rather than RAI1 mutations (P<.05) [3].
  • CONCLUSIONS: Haploinsufficiency of the RAI1 gene is associated with most features of SMS, including craniofacial, behavioural, and neurological signs and symptoms [4].
  • Decreased expression of N-myc precedes retinoic acid-induced morphological differentiation of human neuroblastoma [5].

Psychiatry related information on RAI1


High impact information on RAI1


Chemical compound and disease context of RAI1


Biological context of RAI1

  • It is not clear if the entire SMS phenotype can be accounted for by RAI1 haploinsufficiency, nor has the precise function of RAI1 been delineated [17].
  • Recently, point mutations in the retinoic acid induced 1 (RAI1) gene, which lies within the SMS critical interval, were identified in three patients with many SMS features in whom no deletion was detected [17].
  • Bioinformatics analyses of RAI1 and comparative genomics between human and mouse orthologues revealed a zinc finger-like plant homeo domain (PHD) at the carboxyl terminus that is conserved in the trithorax group of chromatin-based transcription regulators [17].
  • Haploinsufficiency of one of them, RAI1, seems to be responsible for the neurobehavioural, craniofacial and otolaryngological features of the syndrome, but not for short stature, commonly seen in SMS patients with chromosome deletion, implying the role of other genes in the 17p11.2 region [18].
  • However, we identified a 5-year-old girl with an apparent SMS phenotype who was a compound heterozygote for an RAI1 missense mutation inherited from her father and a polyglutamine repeat of 18 copies, representing the largest known CAG repeat in this gene, inherited from her mother [19].

Anatomical context of RAI1


Associations of RAI1 with chemical compounds

  • This result implicates RAI1 as a possible contributor to SCA2 neurodegeneration and raises the possibility that other CAG-containing proteins may play a role in the pathogenesis of other polyglutamine disorders [25].
  • The deletion of a single cytosine occurs in a heptameric C-tract (CCCCCCC), the longest mononucleotide repeat in the RAI1 coding region [19].
  • However, the v-myc-associated block of phorbol 12-myristate 13-acetate-, 1 alpha,25-dihydroxycholecalciferol-, and retinoic acid-induced differentiation retinoic acid-induced differentiation can be overcome by adding interferon gamma as a costimulatory factor [26].
  • (iii) When allowances are made for the time required for the synthesis of the retinoic acid-induced protein, the time course of retinoic acid suppression of interferon production is superimposable on the time course of actinomycin D suppression because the slopes are parallel [27].
  • In this study, we demonstrate the nature of retinoid receptors involved in retinoic acid-induced expression of CD38 protein in the human myeloblastic leukemia cell line HL-60 [28].

Regulatory relationships of RAI1


Other interactions of RAI1

  • We present two patients with SMS who have interstitial deletions at 17p11.2 but are not deleted for currently available commercial FISH probes that include FLII; both patients have deletions that are demonstrated with probes containing the RAI1 gene [34].
  • Molecular analyses determined that the der(17) contains RAI1 but not PMP22 [35].
  • RAI1 point mutations, CAG repeat variation, and SNP analysis in non-deletion Smith-Magenis syndrome [19].
  • OBJECTIVE: Analysis of four individuals with features consistent with SMS for variations in RAI1, using a polymerase chain reaction and sequencing strategy [4].
  • C/EBPbeta: a major PML-RARA-responsive gene in retinoic acid-induced differentiation of APL cells [36].

Analytical, diagnostic and therapeutic context of RAI1

  • Molecular cloning and characterization of human RAI1, a gene associated with schizophrenia [37].
  • Following treatment, NQ was lower in all-trans retinoic acid-induced complete remission (CR) than chemotherapy-induced CR (P =.018) and at first test after consolidation chemotherapy (P =.037) [38].
  • Antigenicities of intact PMN, HL-60, and retinoic acid-induced HL-60 (r.a.-HL-60) were studied by flow cytofluorometry [39].
  • Pancreatic enzyme secretion, gall bladder contraction, and cholecystokinin response after a Lundh meal were completely inhibited by SMS, while pancreatic enzyme secretion elicited by intravenous injection of secretin and pancreozymin was suppressed by 80 percent [40].
  • On day 7 after intravenous infusion of 2 x 10(11) particles of both AdV-SMS1 and AdV-SMS2 into mice, liver SMS1 and SMS2 mRNA levels as well as SMS activity were significantly increased (2.5-, 2.7-, 2.1-, and 2.3-fold, respectively; P < 0.001) [41].


  1. Transcription mapping in a medulloblastoma breakpoint interval and Smith-Magenis syndrome candidate region: identification of 53 transcriptional units and new candidate genes. Seranski, P., Heiss, N.S., Dhorne-Pollet, S., Radelof, U., Korn, B., Hennig, S., Backes, E., Schmidt, S., Wiemann, S., Schwarz, C.E., Lehrach, H., Poustka, A. Genomics (1999) [Pubmed]
  2. Modulation of age at onset in Huntington's disease and spinocerebellar ataxia type 2 patients originated from eastern India. Chattopadhyay, B., Ghosh, S., Gangopadhyay, P.K., Das, S.K., Roy, T., Sinha, K.K., Jha, D.K., Mukherjee, S.C., Chakraborty, A., Singhal, B.S., Bhattacharya, A.K., Bhattacharyya, N.P. Neurosci. Lett. (2003) [Pubmed]
  3. Genotype-phenotype correlation in Smith-Magenis syndrome: evidence that multiple genes in 17p11.2 contribute to the clinical spectrum. Girirajan, S., Vlangos, C.N., Szomju, B.B., Edelman, E., Trevors, C.D., Dupuis, L., Nezarati, M., Bunyan, D.J., Elsea, S.H. Genet. Med. (2006) [Pubmed]
  4. RAI1 variations in Smith-Magenis syndrome patients without 17p11.2 deletions. Girirajan, S., Elsas, L.J., Devriendt, K., Elsea, S.H. J. Med. Genet. (2005) [Pubmed]
  5. Decreased expression of N-myc precedes retinoic acid-induced morphological differentiation of human neuroblastoma. Thiele, C.J., Reynolds, C.P., Israel, M.A. Nature (1985) [Pubmed]
  6. Retinoic acid induced differentiated neuroblastoma cells show increased expression of the beta A4 amyloid gene of Alzheimer's disease and an altered splicing pattern. König, G., Masters, C.L., Beyreuther, K. FEBS Lett. (1990) [Pubmed]
  7. Critical period for retinoic acid-induced developmental abnormalities of the vitreous in mouse fetuses. Ozeki, H., Shirai, S., Ikeda, K., Ogura, Y. Exp. Eye Res. (1999) [Pubmed]
  8. Mutations in RAI1 associated with Smith-Magenis syndrome. Slager, R.E., Newton, T.L., Vlangos, C.N., Finucane, B., Elsea, S.H. Nat. Genet. (2003) [Pubmed]
  9. Retinoic acid-induced apoptosis in leukemia cells is mediated by paracrine action of tumor-selective death ligand TRAIL. Altucci, L., Rossin, A., Raffelsberger, W., Reitmair, A., Chomienne, C., Gronemeyer, H. Nat. Med. (2001) [Pubmed]
  10. Distinct roles of the co-activators p300 and CBP in retinoic-acid-induced F9-cell differentiation. Kawasaki, H., Eckner, R., Yao, T.P., Taira, K., Chiu, R., Livingston, D.M., Yokoyama, K.K. Nature (1998) [Pubmed]
  11. Cloning and expression of a developmentally regulated protein that induces mitogenic and neurite outgrowth activity. Li, Y.S., Milner, P.G., Chauhan, A.K., Watson, M.A., Hoffman, R.M., Kodner, C.M., Milbrandt, J., Deuel, T.F. Science (1990) [Pubmed]
  12. Mammalian Rcd1 is a novel transcriptional cofactor that mediates retinoic acid-induced cell differentiation. Hiroi, N., Ito, T., Yamamoto, H., Ochiya, T., Jinno, S., Okayama, H. EMBO J. (2002) [Pubmed]
  13. Integrin phosphorylation is modulated during the differentiation of F-9 teratocarcinoma stem cells. Dahl, S.C., Grabel, L.B. J. Cell Biol. (1989) [Pubmed]
  14. Effects of liarozole, a new antitumoral compound, on retinoic acid-induced inhibition of cell growth and on retinoic acid metabolism in MCF-7 human breast cancer cells. Wouters, W., van Dun, J., Dillen, A., Coene, M.C., Cools, W., De Coster, R. Cancer Res. (1992) [Pubmed]
  15. Identification of a novel class of retinoic acid receptor beta-selective retinoid antagonists and their inhibitory effects on AP-1 activity and retinoic acid-induced apoptosis in human breast cancer cells. Li, Y., Hashimoto, Y., Agadir, A., Kagechika, H., Zhang, X. J. Biol. Chem. (1999) [Pubmed]
  16. Transcriptional activation of Gs alpha expression by retinoic acid and parathyroid hormone-related protein in F9 teratocarcinoma cells. Chan, S.D., Strewler, G.J., Nissenson, R.A. J. Biol. Chem. (1990) [Pubmed]
  17. Mutations of RAI1, a PHD-containing protein, in nondeletion patients with Smith-Magenis syndrome. Bi, W., Saifi, G.M., Shaw, C.J., Walz, K., Fonseca, P., Wilson, M., Potocki, L., Lupski, J.R. Hum. Genet. (2004) [Pubmed]
  18. Smith-Magenis syndrome and growth hormone deficiency. Spadoni, E., Colapietro, P., Bozzola, M., Marseglia, G.L., Repossi, L., Danesino, C., Larizza, L., Maraschio, P. Eur. J. Pediatr. (2004) [Pubmed]
  19. RAI1 point mutations, CAG repeat variation, and SNP analysis in non-deletion Smith-Magenis syndrome. Bi, W., Saifi, G.M., Girirajan, S., Shi, X., Szomju, B., Firth, H., Magenis, R.E., Potocki, L., Elsea, S.H., Lupski, J.R. Am. J. Med. Genet. A (2006) [Pubmed]
  20. Appearance of a new nucleosomal protein during differentiation of human leukemia (HL-60) cells. Chou, R.H., Chervenick, P.A., Barch, D.R. Science (1984) [Pubmed]
  21. Cloning and expression of AP-2, a cell-type-specific transcription factor that activates inducible enhancer elements. Williams, T., Admon, A., Lüscher, B., Tjian, R. Genes Dev. (1988) [Pubmed]
  22. Retinoic acid receptor expression vector inhibits differentiation of F9 embryonal carcinoma cells. Espeseth, A.S., Murphy, S.P., Linney, E. Genes Dev. (1989) [Pubmed]
  23. GA-binding protein and p300 are essential components of a retinoic acid-induced enhanceosome in myeloid cells. Resendes, K.K., Rosmarin, A.G. Mol. Cell. Biol. (2006) [Pubmed]
  24. Changing the differentiation program of hematopoietic cells: retinoic acid-induced shift of eosinophil-committed cells to neutrophils. Paul, C.C., Mahrer, S., Tolbert, M., Elbert, B.L., Wong, I., Ackerman, S.J., Baumann, M.A. Blood (1995) [Pubmed]
  25. CAG repeat length in RAI1 is associated with age at onset variability in spinocerebellar ataxia type 2 (SCA2). Hayes, S., Turecki, G., Brisebois, K., Lopes-Cendes, I., Gaspar, C., Riess, O., Ranum, L.P., Pulst, S.M., Rouleau, G.A. Hum. Mol. Genet. (2000) [Pubmed]
  26. Interferon gamma abrogates the differentiation block in v-myc-expressing U-937 monoblasts. Oberg, F., Larsson, L.G., Anton, R., Nilsson, K. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  27. Retinoic acid (vitamin A acid) induced transcriptional control of interferon production. Blalock, J.E., Gifford, G.E. Proc. Natl. Acad. Sci. U.S.A. (1977) [Pubmed]
  28. Involvement of retinoic acid receptor-alpha-mediated signaling pathway in induction of CD38 cell-surface antigen. Mehta, K., McQueen, T., Manshouri, T., Andreeff, M., Collins, S., Albitar, M. Blood (1997) [Pubmed]
  29. Oncogenic potential of the transcription factor LYL1 in acute myeloblastic leukemia. Meng, Y.S., Khoury, H., Dick, J.E., Minden, M.D. Leukemia (2005) [Pubmed]
  30. Retinoic acid-induced apoptosis and regression of a refractory Epstein-Barr virus-containing T cell lymphoma expressing multidrug-resistance phenotypes. Su, I.J., Cheng, A.L., Tsai, T.F., Lay, J.D. Br. J. Haematol. (1993) [Pubmed]
  31. CDK2/4 regulate retinoic acid-induced G1 arrest in hepatocellular carcinoma cells. Jung, H.Y., Park, S.H., Yoo, Y.D., Kim, J.S., Kim, Y.H. Hepatol. Res. (2005) [Pubmed]
  32. FMS (CSF-1 receptor) prolongs cell cycle and promotes retinoic acid-induced hypophosphorylation of retinoblastoma protein, G1 arrest, and cell differentiation. Yen, A., Sturgill, R., Varvayanis, S., Chern, R. Exp. Cell Res. (1996) [Pubmed]
  33. Retinoic acid-induced CD38 expression in HL-60 myeloblastic leukemia cells regulates cell differentiation or viability depending on expression levels. Lamkin, T.J., Chin, V., Varvayanis, S., Smith, J.L., Sramkoski, R.M., Jacobberger, J.W., Yen, A. J. Cell. Biochem. (2006) [Pubmed]
  34. Diagnostic FISH probes for del(17)(p11.2p11.2) associated with Smith-Magenis syndrome should contain the RAI1 gene. Vlangos, C.N., Wilson, M., Blancato, J., Smith, A.C., Elsea, S.H. Am. J. Med. Genet. A (2005) [Pubmed]
  35. Trisomy 17p10-p12 due to mosaic supernumerary marker chromosome: delineation of molecular breakpoints and clinical phenotype, and comparison to other proximal 17p segmental duplications. Yatsenko, S.A., Treadwell-Deering, D., Krull, K., Lewis, R.A., Glaze, D., Stankiewicz, P., Lupski, J.R., Potocki, L. Am. J. Med. Genet. A (2005) [Pubmed]
  36. C/EBPbeta: a major PML-RARA-responsive gene in retinoic acid-induced differentiation of APL cells. Duprez, E., Wagner, K., Koch, H., Tenen, D.G. EMBO J. (2003) [Pubmed]
  37. Molecular cloning and characterization of human RAI1, a gene associated with schizophrenia. Toulouse, A., Rochefort, D., Roussel, J., Joober, R., Rouleau, G.A. Genomics (2003) [Pubmed]
  38. Quantitative real-time RT-PCR analysis of PML-RAR alpha mRNA in acute promyelocytic leukemia: assessment of prognostic significance in adult patients from intergroup protocol 0129. Gallagher, R.E., Yeap, B.Y., Bi, W., Livak, K.J., Beaubier, N., Rao, S., Bloomfield, C.D., Appelbaum, F.R., Tallman, M.S., Slack, J.L., Willman, C.L. Blood (2003) [Pubmed]
  39. Glycolipid antigens of human polymorphonuclear neutrophils and the inducible HL-60 myeloid leukemia line. Symington, F.W., Hedges, D.L., Hakomori, S. J. Immunol. (1985) [Pubmed]
  40. Effect of somatostatin analogue (SMS 201-995, Sandostatin) on pancreatic secretion in humans. Creutzfeldt, W., Lembcke, B., Fölsch, U.R., Schleser, S., Koop, I. Am. J. Med. (1987) [Pubmed]
  41. Adenovirus-mediated overexpression of sphingomyelin synthases 1 and 2 increases the atherogenic potential in mice. Dong, J., Liu, J., Lou, B., Li, Z., Ye, X., Wu, M., Jiang, X.C. J. Lipid Res. (2006) [Pubmed]
WikiGenes - Universities