Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are diseases that are both caused by a deletion in the same region of chromosome 15, namely 15q11-q13 (exact position chr15:22805313-28390339 (GRCh37) taken from Kirov et al. 2014 and literature cited there). Due to methylation patterns however, different genes are responsible for the two syndromes. This pathway depicts the currently known downstream molecular interactions of several of the genes involved in PWS and/or AS. For this chromosomal region, also duplications are known. The colours of the pathway sections correspond to the colours of the genes on top. Dashed lines indicate a gap between a component and the downstream pathway. A rectangle is drawn to improve the clarity of the pathway; darker colours indicate that this particular part is derived from research in other animals than humans. A detailed description of the pathway has been published by [http://www.tandfonline.com/doi/abs/10.1080/15622975.2018.1439594 Ehrhart et al.]. The published version is WP3998-94544. Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP3998 CPTAC Assay Portal] Prader Willi and Angelman syndrome Prader Willi and Angelman Syndrome Prader-Willi and Angelman syndrome Prader-Willi Prader-Willi syndrome f8b ee0 a01 b56 aae f8b e1d dce e2a bd4 eae e62 aae a2d f8b d57 b61 e82 a01 fc1 bd4 e42 cb4 b6a c93 e41 found for mouse ESCs/NCSCs bd4 b61 found for GT1-7 cells b61 found for GT1-7 cells b61 a21 f8b evidence found in Ndn(tm2Stw) mice embryos (C57BL/6J line) c34 found for PC12 cells after NGF stimulation f8b found for PC12 cells after NGF stimulation f8b found for PC12 cells after NGF stimulation f8b found for POMC neurons a2d a2d found for GABRB3(tm1Geh) mouse strain eae a2d a56 a2d f2f The effect of FEZ1 was found in mouse studies (C57BL/6J line). In mice, the function of the FEZ1 orthologue Fez1 or UNC-76 was examined. e1d e2a The effect of FEZ1 was found in mouse studies (C57BL/6J line). In mice, the function of the FEZ1 orthologue Fez1 or UNC-76 was examined. dce This function of FEZ1 was examined in Fruitflies (drosophila melanogaster), by studying the orthologue UNC-76. d57 f8b The effect of FEZ1 was found in mouse studies (C57BL/6J line). In mice, the function of the FEZ1 orthologue Fez1 or UNC-76 was examined. f8b The information in this section is derived from research in PC12 cells. Evidence for human cells is not yet available. f8b This area contains a schematic description of the HTR2C pre-RNA with its different exons. SNORD115 binds to a specific sequence in exon Va, by which it promotes the inclusion of exon Vb, and reduces the amount of RNA encoding the truncated receptor. Excluding exon Vb leads to formation of a truncated receptor. a2d 11438699 PubMed A highly conserved protein family interacting with the fragile X mental retardation protein (FMRP) and displaying selective interactions with FMRP-related proteins FXR1P and FXR2P. Proc Natl Acad Sci U S A 2001 Schenck A Bardoni B Moro A Bagni C Mandel JL 27931246 PubMed Increased alternate splicing of Htr2c in a mouse model for Prader-Willi syndrome leads disruption of 5HT_2Creceptor mediated appetite. Mol Brain 2016 27931246 PubMed Increased alternate splicing of Htr2c in a mouse model for Prader-Willi syndrome leads disruption of 5HT_2Creceptor mediated appetite. Mol Brain 2016 Garfield AS Davies JR Burke LK Furby HV Wilkinson LS Heisler LK Isles AR 10.3180/R-HSA-72163.3 DOI mRNA splicing - major pathway Reactome; R-HSA-72163.2 20023648 PubMed HERC2 coordinates ubiquitin-dependent assembly of DNA repair factors on damaged chromosomes. Nat Cell Biol 2010 Bekker-Jensen S Rendtlew Danielsen J Fugger K Gromova I Nerstedt A Lukas C Bartek J Lukas J Mailand N 28074012 PubMed Reduced abundance of the E3 ubiquitin ligase E6AP contributes to decreased expression of the INK4/ARF locus in non-small cell lung cancer. Sci Signal 2017 Gamell C Gulati T Levav-Cohen Y Young RJ Do H Pilling P Takano E Watkins N Fox SB Russell P Ginsberg D Monahan BJ Wright G Dobrovic A Haupt S Solomon B Haupt Y Prader-Willi syndrome DOID:11983 Disease 21914775 PubMed Regulation of NKB pathways and their roles in the control of Kiss1 neurons in the arcuate nucleus of the male mouse. Endocrinology 2011 21914775 PubMed Regulation of NKB pathways and their roles in the control of Kiss1 neurons in the arcuate nucleus of the male mouse. Endocrinology 2011 21914775 PubMed Regulation of NKB pathways and their roles in the control of Kiss1 neurons in the arcuate nucleus of the male mouse. Endocrinology 2011 Navarro VM Gottsch ML Wu M García-Galiano D Hobbs SJ Bosch MA Pinilla L Clifton DK Dearth A Ronnekleiv OK Braun RE Palmiter RD Tena-Sempere M Alreja M Steiner RA 25002992 PubMed Leptin signaling defects in a mouse model of Prader-Willi syndrome: An orphan genetic obesity syndrome no more? Rare Dis 2013 Colmers WF Wevrick R 25957321 PubMed A new pathway in the control of the initiation of puberty: the MKRN3 gene. J Mol Endocrinol 2015 25957321 PubMed A new pathway in the control of the initiation of puberty: the MKRN3 gene. J Mol Endocrinol 2015 25957321 PubMed A new pathway in the control of the initiation of puberty: the MKRN3 gene. J Mol Endocrinol 2015 Abreu AP Macedo DB Brito VN Kaiser UB Latronico AC 8863824 PubMed Identification, molecular cloning, and distribution of a short variant of the 5-hydroxytryptamine2C receptor produced by alternative splicing. Mol Pharmacol 1996 Canton H Emeson RB Barker EL Backstrom JR Lu JT Chang MS Sanders-Bush E 27288456 PubMed Loss of Magel2 impairs the development of hypothalamic Anorexigenic circuits. Hum Mol Genet 2016 27288456 PubMed Loss of Magel2 impairs the development of hypothalamic Anorexigenic circuits. Hum Mol Genet 2016 27288456 PubMed Loss of Magel2 impairs the development of hypothalamic Anorexigenic circuits. Hum Mol Genet 2016 Maillard J Park S Croizier S Vanacker C Cook JH Prevot V Tauber M Bouret SG 22065085 PubMed A global view of the OCA2-HERC2 region and pigmentation. Hum Genet 2012 Donnelly MP Paschou P Grigorenko E Gurwitz D Barta C Lu RB Zhukova OV Kim JJ Siniscalco M New M Li H Kajuna SL Manolopoulos VG Speed WC Pakstis AJ Kidd JR Kidd KK 9153397 PubMed Regulation of serotonin-2C receptor G-protein coupling by RNA editing. Nature 1997 Burns CM Chu H Rueter SM Hutchinson LK Canton H Sanders-Bush E Emeson RB 15649943 PubMed Essential role for the Prader-Willi syndrome protein necdin in axonal outgrowth. Hum Mol Genet 2005 Lee S Walker CL Karten B Kuny SL Tennese AA O'Neill MA Wevrick R 9971736 PubMed Mammalian homologue of the Caenorhabditis elegans UNC-76 protein involved in axonal outgrowth is a protein kinase C zeta-interacting protein. J Cell Biol 1999 9971736 PubMed Mammalian homologue of the Caenorhabditis elegans UNC-76 protein involved in axonal outgrowth is a protein kinase C zeta-interacting protein. J Cell Biol 1999 9971736 PubMed Mammalian homologue of the Caenorhabditis elegans UNC-76 protein involved in axonal outgrowth is a protein kinase C zeta-interacting protein. J Cell Biol 1999 9971736 PubMed Mammalian homologue of the Caenorhabditis elegans UNC-76 protein involved in axonal outgrowth is a protein kinase C zeta-interacting protein. J Cell Biol 1999 9971736 PubMed Mammalian homologue of the Caenorhabditis elegans UNC-76 protein involved in axonal outgrowth is a protein kinase C zeta-interacting protein. J Cell Biol 1999 Kuroda S Nakagawa N Tokunaga C Tatematsu K Tanizawa K 29499229 PubMed γ-Tubulin has a conserved intrinsic property of self-polymerization into double stranded filaments and fibrillar networks. Biochim Biophys Acta Mol Cell Res 2018 Chumová J Trögelová L Kourová H Volc J Sulimenko V Halada P Ku�era O Benada O Kuchařová A Klebanovych A Dráber P Daniel G Binarová P 22694955 PubMed The imprinted NPAP1/C15orf2 gene in the Prader-Willi syndrome region encodes a nuclear pore complex associated protein. Hum Mol Genet 2012 Neumann LC Markaki Y Mladenov E Hoffmann D Buiting K Horsthemke B 29425059 PubMed Prader-Willi Syndrome and Angelman Syndrome: Visualisation of the molecular pathways for two chromosomal disorders World J Biol Psychiatry 2018 Ehrhart F Janssen KJM Coort SL Evelo CT Curfs LMG2 9108119 PubMed Mice devoid of gamma-aminobutyrate type A receptor beta3 subunit have epilepsy, cleft palate, and hypersensitive behavior. Proc Natl Acad Sci U S A 1997 9108119 PubMed Mice devoid of gamma-aminobutyrate type A receptor beta3 subunit have epilepsy, cleft palate, and hypersensitive behavior. Proc Natl Acad Sci U S A 1997 Homanics GE DeLorey TM Firestone LL Quinlan JJ Handforth A Harrison NL Krasowski MD Rick CE Korpi ER Mäkelä R Brilliant MH Hagiwara N Ferguson C Snyder K Olsen RW 15649943 PubMed Essential role for the Prader-Willi syndrome protein necdin in axonal outgrowth Hum Mol Genet 2005 Lee S Walker CL Karten B Kuny SL Tennese AA O'Neill MA Wevrick R 23341784 PubMed Magel2 is required for leptin-mediated depolarization of POMC neurons in the hypothalamic arcuate nucleus in mice. PLoS Genet 2013 23341784 PubMed Magel2 is required for leptin-mediated depolarization of POMC neurons in the hypothalamic arcuate nucleus in mice. PLoS Genet 2013 Mercer RE Michaelson SD Chee MJ Atallah TA Wevrick R Colmers WF disease pathway PW:0000013 Pathway Ontology 28009282 PubMed Beyond Epilepsy and Autism: Disruption of GABRB3 Causes Ocular Hypopigmentation. Cell Rep 2016 28009282 PubMed Beyond Epilepsy and Autism: Disruption of GABRB3 Causes Ocular Hypopigmentation. Cell Rep 2016 28009282 PubMed Beyond Epilepsy and Autism: Disruption of GABRB3 Causes Ocular Hypopigmentation. Cell Rep 2016 28009282 PubMed Beyond Epilepsy and Autism: Disruption of GABRB3 Causes Ocular Hypopigmentation. Cell Rep 2016 Delahanty RJ Zhang Y Bichell TJ Shen W Verdier K Macdonald RL Xu L Boyd K Williams J Kang JQ PubMed Mammalian homologue of the Caenorhabditis elegans UNC-76 protein involved in axonal outgrowth is a protein kinase C zeta-interacting protein. J Cell Biol 1999 9971736 PubMed Mammalian homologue of the Caenorhabditis elegans UNC-76 protein involved in axonal outgrowth is a protein kinase C zeta-interacting protein. J Cell Biol 1999 9971736 PubMed Angelman syndrome DOID:1932 Disease 18930956 PubMed Necdin, a Prader-Willi syndrome candidate gene, regulates gonadotropin-releasing hormone neurons during development. Hum Mol Genet 2009 18930956 PubMed Necdin, a Prader-Willi syndrome candidate gene, regulates gonadotropin-releasing hormone neurons during development. Hum Mol Genet 2009 18930956 PubMed Necdin, a Prader-Willi syndrome candidate gene, regulates gonadotropin-releasing hormone neurons during development. Hum Mol Genet 2009 Miller NL Wevrick R Mellon PL 8019699 PubMed Insulin structure and stability. Pharm Biotechnol 1993 8019699 PubMed Insulin structure and stability. Pharm Biotechnol 1993 Brange J Langkjoer L 27941249 PubMed Deficiency in prohormone convertase PC1 impairs prohormone processing in Prader-Willi Syndrome J Clin Invest 2017 27941249 PubMed Deficiency in prohormone convertase PC1 impairs prohormone processing in Prader-Willi Syndrome J Clin Invest 2017 Burnett LC LeDuc CA Sulsona CR Paull D et al