Sudden infant death syndrome (SIDS) susceptibility pathways (Homo sapiens)

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6275851117254271819206734, 7036, 50, 67773115840, 122887847492110411033113527924685, 61, 1242210566846840422982316853955345313524444444444819999101444410156, 121712156, 1211218, 911014412144441011410138Increased relative SIDS expressionG2989TSPhSPhPutative TRsThermoregulationNHPutative TRSPhSerotoninTransporterVagal TonePutative TRsDecreased relative SIDS expressionSleepOtherPutative TRs Slowly-Activating K+ CurrentPutative TRTRrTR: Transcriptional Regulation2+Focal AdhesionsPutative TRsCaSIDS Susceptibility PathwaysK+Putative TRAssociated with Infection and SIDSRapidly-activating K+ CurrentSoma Membrane4R/4RCardiac myocytePutative TRSPhInfant (<1 year in age)2Gi signalingcircadianNucleusPutative TRNa+Putative TRsSerotonin Signaling BrownAdiposeMiscelaneous SIDS AssociatedBrainstem neuronNerve TerminalAssociated with Energy Metabolism and SIDSIVS-191_190insAdepressionBrainStabilizationSph: SIDS Phenotype Animal ModelBradycardiaIncreased brainstem hypoplasia with SIDSHOG5477Ars2856966HeartTRrSerotonin Synthesis and MetabolismNucleusGs signalingCell MembraneSIDS associated polymorphismsIncreased long-QT with SIDSHNK+Gq signalingPutative TRsG-proteinPutative TRPutative TRsSarcoplasmic ReticulumC825Tp+Putative TR298058652515865183109MIR13APKNOX1CREB1HTR1APPARGC1BDDCRUNX3KCNQ1YBX1RESTGATA2TLX3SP1RYR2HES1GNB3THRBHSPD1NGFRYR2CAV3RESTADCYAP1HIF1AEP300DDCKCNH2 TACR1MIR16-1CHRNA4PHOX2AKCNH2REST5-HTDEAF1SSTR2CREBBPFEVNFYADLX2PPARGC1ACREB15-HTARCTCFTPH2IL6RNR3C1SP1LMX1BMEF2CIL6VIPR1ALDOAADCYAP1R1MAOANKX2-2VIPR2RESTTP73POU3F2TPH1MAOACC2D1ASP1NKX3-1SCN5ACREB1HES1ESR2CHRNB4SP1POU3F25-HTMIR210CDCA7LAVPRETPHOX2BRORAADCYAP1JUNKCNQ1FEVHTR2ANFKB1TPH2ECE1NicotineHES5IL10RESTEN1GATA3ACADMTCF3FOXM1BHLHE40C4BPLP1NFKB1ASCL1PBX1NEUROD1TNFTPH1SP1SLC6A45-HTPSSTR1HADHASP3NR3C1IL8HIF1AEGR1FluoxetineHTR1ACAV35-HIAAGlial Cell DifferentiationL-TryptophanMAZC4A1069663486510069409094411232, 98451154292398103828997281356768912226457655Putative TRsCTNNB1SOX2NANOGPOU5F155MAPK pathway121BDNFNTRK2Gi signalingGABA114GABRA164CHRM2GJA1102SNTA1Na+H+73K+KCNJ8GJA1PKC inhibitor 14-3-3Protein Kinase APRKAR2BYWHAEYWHAZPRKAR1BPRKAR2AYWHAQYWHAGPRKAR1AYWHAHYWHABPRKACBPRKACAActivation107GAP JunctionSLC9A3CASP3FMO3123G6PCGCK5916GPD1LGRIN1HADHB116HTR3ASCN3BSCN4BSSTNa+Cardiac VagalExcitation465-HTGlutamateCa2+10H2OH2OAQP4ApoptosisCPT1AIL1A37IL1B8484IL1RN43IL13120TSPYL1VEGFA117SCN5A7174DopaminePhenylalanineCHATL-DOPAPAHAcetylcholineCholineTHTyrosineDDCNOS1AP60Gq signalingMAP218TAC1MicrotubleStabilizationSLC1A3SLC25A4GlutamateSNAP25Synaptic Vesicle ReleaseGlutamateSST1818TAC1HTR3ATH85CHAT758138SLC9A3BDNFNTRK212110AQP4GRIN154SP187NFKB2JUNHDAC912MYB119CEBPB72SNTA1102GPD1LSP1JUNNR3C1REST33JUN17CREB1POU2F293CREMRESTNFKB1CHRNB2CHRNA7Serotonergic NeuronsHDAC1MBD1MECP2NFKB1CREBBPTRrTRr114GABRA1CREB1108VAMP2Extracellular SpacePutative TRsPutative TRsPutative TRsPutative TRsPutative TRsPutative TRsPutative TRsPutative TRsPutative TRsTPPPATP1A3GAPDHHSP90B1TFSPTBN1YWHAGHIF1APutative TRs11368Chronichypoxia


Description

In this model, we provide an integrated view of Sudden Infant Death Syndrome (SIDS) at the level of implicated tissues, signaling networks and genetics. The purpose of this model is to serve as an overview of research in this field and recommend new candidates for more focused or genome wide analyses. SIDS is the sudden and unexpected death of an infant (less than 1 year of age), almost always during deep sleep, where no cause of death can be found by autopsy. Factors that mediate SIDS are likely to be both biological and behavioral, such as sleeping position, environment and stress during a critical phase of infant development (http://www.nichd.nih.gov/health/topics/Sudden_Infant_Death_Syndrome.cfm). While no clear diagnostic markers currently exist, several polymorphisms have been identified which are significantly over-represented in distinct SIDS ethnic population. The large majority of these polymorphisms exist in genes associated with neuronal signaling, cardiac contraction and inflammatory response. These and other lines of evidence suggest that SIDS has a strong autonomic nervous system component (PMID:12350301, PMID: 20124538). One of the neuronal nuclei most strongly implicated in SIDS has been the raphe nucleus of the brain stem. In this nuclei there are ultrastructural, cellular and molecular changes associated with SIDS relative to controls (PMID:19342987, PMID: 20124538). This region of the brain is responsible for the large majority of neuronal serotonin produced and is functionally important in the regulation of normal cardiopulmonary activity, sleep and thermoregulation (see associated references).

Genes associated with serotonin synthesis and receptivity have some of the strongest genetic association with SIDS. Principle among these genes the serotonin biosynthetic enzyme TPH2, the serotonin transporter SLC6A4 and the serotonin receptor HTR1A. SLC6A4 exhibits decreased expression in the raphe nucleus of the medulla oblongata and polymorphisms specifically associated with SIDS (PMID:19342987). In 75% of infants with SIDS, there is decreased HTR1A expression relative to controls along with an increase in the number of raphe serotonin neurons (PMID:19342987). Over-expression of the mouse orthologue of the HTR1A gene in the juvenile mouse medulla produces an analogous phenotype to SIDS with death due to bradycardia and hypothermia (PMID:18599790). These genes as well as those involved in serotonin synthesis are predicted to be transcriptionally regulated by a common factor, FEV (human orthologue of PET-1). PET-1 knock-out results in up to a 90% loss of serotonin neurons (PMID:12546819), while polymorphisms in FEV are over-represented in African American infants with SIDS. In addition to FEV, other transcription factors implicated in the regulation of these genes (Putative transcriptional regulators (TRs)) and FEV are also listed (see associated references). In addition to serotonin, vasopressin signaling and its regulation by serotonin appear to be important in a common pathway of cardiopulmonary regulation (PMID:2058745). A protein that associates with vasopressin signaling, named pituitary adenylate cyclase-activating polypeptide (ADCYAP1), results in a SIDS like phenotype, characterized by a high increase in spontaneous neonatal death, exacerbated by hypothermia and hypoxia (PMID:14608012), when disrupted in mice. Protein for this gene is widely distributed throughout the central nervous system (CNS), including autonomic control centers (PMID:12389210). ADCYAP1 and HTR1A are both predicted to be transcriptionally regulated by REST promoter binding. Regulation of G-protein coupled signaling pathways is illustrated for these genes, however, it is not clear whether ADCYAP1 acts directly upon raphe serotonin neurons.

Another potentially important class of receptors in SIDS is nicotine. Receptors for nicotine are expressed in serotonin neurons of the raphe throughout development (PMID:18986852). Application of nicotine or cigarette smoke is sufficient to inhibit electrical activity of raphe serotonin neurons (PMID:17515803) and chronic nicotine infusion in rats decreases expression of SLC6A4 (PMID:18778441). Furthermore, nicotine exposure reduces both HTR1A and HTR2A immunoreactivity in several nuclei of the brainstem (PMID:17451658).

In addition to CNS abnormalities, several studies have identified a critical link between cardiac arrhythmia (long QT syndrome) and SIDS (PMID:18928334). A number of genetic association studies identified functionally modifying mutations in critical cardiac channels in as many as 10% of all SIDS cases (PMID:18928334). These mutations have been predicted to predispose infants for long QT syndrome and sudden death. The highest proportion of SIDS associated mutations (both inherited and sporadic) is found in the sodium channel gene SCN5A. Examination of putative transcriptional regulators for these genes, highlights a diverse set of factors as well as a relatively common one (SP1).

Finally, several miscellaneous mutations have been identified in genes associated with inflammatory response and thermoregulation. Infection is considered a significant risk factor for SIDS (PMID:19114412). For inflammatory associated genes, such as TNF alpha, interleukin 10 and complement component 4, many of these mutations are only significant in the presence of infection and SIDS. In addition to these mutations, cerebrospinal fluid levels of IL6 are increased in SIDS cases as well as IL6R levels in the arcuate nucleus of the brain, another major site of serotonin synthesis (PMID:19396608). Genes such as ILR6 and ADCYAP1 are also associated with autoimmune disorders, thus SIDS may also be associated with autoinflammation of autonomic centers in the brain. Regulation of thermogenesis by brown adipose tissue has been proposed be an important component of SIDS, given that SIDS incidence is highest in the winter time and that animal models of SIDS demonstrate variation in body temperature. Interestingly, activation of raphe HTR1A decreases both shivering and peripheral vasoconstriction in piglets (18094064). Although a putative significant polymorphism was identified in the thermoregulator gene HSP60, this only occurred in one SIDS case. It is important to note that in the large majority of all these studies, sleeping position and smoking were among the most significant risk factors for SIDS.

In loving memory of Milo Salomonis (http://www.milosalomonis.org).

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  83. Derry C, Benjamin C, Bladin P, le Bars D, Tochon-Danguy H, Berkovic SF, Zimmer L, Costes N, Mulligan R, Reutens D; ''Increased serotonin receptor availability in human sleep: evidence from an [18F]MPPF PET study in narcolepsy.''; Neuroimage, 2006 PubMed Europe PMC Scholia
  84. Ferrante L, Opdal SH, Vege A, Rognum TO; ''IL-1 gene cluster polymorphisms and sudden infant death syndrome.''; Hum Immunol, 2010 PubMed Europe PMC Scholia
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  86. Lavezzi AM, Casale V, Oneda R, Weese-Mayer DE, Matturri L; ''Sudden infant death syndrome and sudden intrauterine unexplained death: correlation between hypoplasia of raphé nuclei and serotonin transporter gene promoter polymorphism.''; Pediatr Res, 2009 PubMed Europe PMC Scholia
  87. Umenishi F, Verkman AS; ''Isolation and functional analysis of alternative promoters in the human aquaporin-4 water channel gene.''; Genomics, 1998 PubMed Europe PMC Scholia
  88. Nagamoto-Combs K, Piech KM, Best JA, Sun B, Tank AW; ''Tyrosine hydroxylase gene promoter activity is regulated by both cyclic AMP-responsive element and AP1 sites following calcium influx. Evidence for cyclic amp-responsive element binding protein-independent regulation.''; J Biol Chem, 1997 PubMed Europe PMC Scholia
  89. Pombo PM, Barettino D, Espliguero G, Metsis M, Iglesias T, Rodriguez-Pena A; ''Transcriptional repression of neurotrophin receptor trkB by thyroid hormone in the developing rat brain.''; J Biol Chem, 2000 PubMed Europe PMC Scholia
  90. Patel PD, Bochar DA, Turner DL, Meng F, Mueller HM, Pontrello CG; ''Regulation of tryptophan hydroxylase-2 gene expression by a bipartite RE-1 silencer of transcription/neuron restrictive silencing factor (REST/NRSF) binding motif.''; J Biol Chem, 2007 PubMed Europe PMC Scholia
  91. Klintschar M, Heimbold C; ''Association between a functional polymorphism in the MAOA gene and sudden infant death syndrome.''; Pediatrics, 2012 PubMed Europe PMC Scholia
  92. Martens LK, Kirschner KM, Warnecke C, Scholz H; ''Hypoxia-inducible factor-1 (HIF-1) is a transcriptional activator of the TrkB neurotrophin receptor gene.''; J Biol Chem, 2007 PubMed Europe PMC Scholia
  93. Dawson SJ, Yoon SO, Chikaraishi DM, Lillycrop KA, Latchman DS; ''The Oct-2 transcription factor represses tyrosine hydroxylase expression via a heptamer TAATGARAT-like motif in the gene promoter.''; Nucleic Acids Res, 1994 PubMed Europe PMC Scholia
  94. Rahim RA, Boyd PA, Ainslie Patrick WJ, Burdon RH; ''Human heat shock protein gene polymorphisms and sudden infant death syndrome.''; Arch Dis Child, 1996 PubMed Europe PMC Scholia
  95. Dergacheva O, Griffioen KJ, Wang X, Kamendi H, Gorini C, Mendelowitz D; ''5-HT(2) receptor subtypes mediate different long-term changes in GABAergic activity to parasympathetic cardiac vagal neurons in the nucleus ambiguus.''; Neuroscience, 2007 PubMed Europe PMC Scholia
  96. Kingsbury TJ, Krueger BK; ''Ca2+, CREB and krüppel: a novel KLF7-binding element conserved in mouse and human TRKB promoters is required for CREB-dependent transcription.''; Mol Cell Neurosci, 2007 PubMed Europe PMC Scholia
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  98. Nishida K, Otsu K, Hori M, Kuzuya T, Tada M; ''Cloning and characterization of the 5'-upstream regulatory region of the Ca(2+)-release channel gene of cardiac sarcoplasmic reticulum.''; Eur J Biochem, 1996 PubMed Europe PMC Scholia
  99. Yang Z, Lantz PE, Ibdah JA; ''''; , PubMed Europe PMC Scholia
  100. Van Hoecke M, Prigent-Tessier AS, Garnier PE, Bertrand NM, Filomenko R, Bettaieb A, Marie C, Beley AG; ''Evidence of HIF-1 functional binding activity to caspase-3 promoter after photothrombotic cerebral ischemia.''; Mol Cell Neurosci, 2007 PubMed Europe PMC Scholia
  101. Weese-Mayer DE, Berry-Kravis EM, Zhou L, Maher BS, Curran ME, Silvestri JM, Marazita ML; ''Sudden infant death syndrome: case-control frequency differences at genes pertinent to early autonomic nervous system embryologic development.''; Pediatr Res, 2004 PubMed Europe PMC Scholia
  102. Cheng J, Van Norstrand DW, Medeiros-Domingo A, Valdivia C, Tan BH, Ye B, Kroboth S, Vatta M, Tester DJ, January CT, Makielski JC, Ackerman MJ; ''Alpha1-syntrophin mutations identified in sudden infant death syndrome cause an increase in late cardiac sodium current.''; Circ Arrhythm Electrophysiol, 2009 PubMed Europe PMC Scholia
  103. Fukuchi M, Tabuchi A, Tsuda M; ''Transcriptional regulation of neuronal genes and its effect on neural functions: cumulative mRNA expression of PACAP and BDNF genes controlled by calcium and cAMP signals in neurons.''; J Pharmacol Sci, 2005 PubMed Europe PMC Scholia
  104. Toliver-Kinsky T, Wood T, Perez-Polo JR; ''Nuclear factor kappaB/p49 is a negative regulatory factor in nerve growth factor-induced choline acetyltransferase promoter activity in PC12 cells.''; J Neurochem, 2000 PubMed Europe PMC Scholia
  105. Maddodi N, Bhat KM, Devi S, Zhang SC, Setaluri V; ''Oncogenic BRAFV600E induces expression of neuronal differentiation marker MAP2 in melanoma cells by promoter demethylation and down-regulation of transcription repressor HES1.''; J Biol Chem, 2010 PubMed Europe PMC Scholia
  106. Lemonde S, Rogaeva A, Albert PR; ''Cell type-dependent recruitment of trichostatin A-sensitive repression of the human 5-HT1A receptor gene.''; J Neurochem, 2004 PubMed Europe PMC Scholia
  107. Broadbelt KG, Rivera KD, Paterson DS, Duncan JR, Trachtenberg FL, Paulo JA, Stapels MD, Borenstein NS, Belliveau RA, Haas EA, Stanley C, Krous HF, Steen H, Kinney HC; ''Brainstem deficiency of the 14-3-3 regulator of serotonin synthesis: a proteomics analysis in the sudden infant death syndrome.''; Mol Cell Proteomics, 2012 PubMed Europe PMC Scholia
  108. Hu Y, Lund IV, Gravielle MC, Farb DH, Brooks-Kayal AR, Russek SJ; ''Surface expression of GABAA receptors is transcriptionally controlled by the interplay of cAMP-response element-binding protein and its binding partner inducible cAMP early repressor.''; J Biol Chem, 2008 PubMed Europe PMC Scholia
  109. Cummings KJ, Klotz C, Liu WQ, Weese-Mayer DE, Marazita ML, Cooper ME, Berry-Kravis EM, Tobias R, Goldie C, Bech-Hansen NT, Wilson RJ; ''Sudden infant death syndrome (SIDS) in African Americans: polymorphisms in the gene encoding the stress peptide pituitary adenylate cyclase-activating polypeptide (PACAP).''; Acta Paediatr, 2009 PubMed Europe PMC Scholia
  110. Goudet G, Delhalle S, Biemar F, Martial JA, Peers B; ''Functional and cooperative interactions between the homeodomain PDX1, Pbx, and Prep1 factors on the somatostatin promoter.''; J Biol Chem, 1999 PubMed Europe PMC Scholia
  111. Sawaguchi T, Patricia F, Kadhim H, Groswasser J, Sottiaux M, Nishida H, Kahn A; ''The correlation between microtubule-associated protein 2 in the brainstem of SIDS victims and physiological data on sleep apnea.''; Early Hum Dev, 2003 PubMed Europe PMC Scholia
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  113. Côté F, Schussler N, Boularand S, Peirotes A, Thévenot E, Mallet J, Vodjdani G; ''Involvement of NF-Y and Sp1 in basal and cAMP-stimulated transcriptional activation of the tryptophan hydroxylase (TPH ) gene in the pineal gland.''; J Neurochem, 2002 PubMed Europe PMC Scholia
  114. Broadbelt KG, Paterson DS, Belliveau RA, Trachtenberg FL, Haas EA, Stanley C, Krous HF, Kinney HC; ''Decreased GABAA receptor binding in the medullary serotonergic system in the sudden infant death syndrome.''; J Neuropathol Exp Neurol, 2011 PubMed Europe PMC Scholia
  115. Shang LL, Sanyal S, Pfahnl AE, Jiao Z, Allen J, Liu H, Dudley SC Jr; ''NF-kappaB-dependent transcriptional regulation of the cardiac scn5a sodium channel by angiotensin II.''; Am J Physiol Cell Physiol, 2008 PubMed Europe PMC Scholia
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History

View all...
CompareRevisionActionTimeUserComment
129309view13:49, 26 March 2024MkutmonOntology Term : 'disease pathway' added !
128759view13:07, 21 February 2024EweitzUpgrade disease node
124910view09:44, 31 December 2022EgonwOne last encoding issue
124909view09:19, 31 December 2022EgonwOne more fixed character encoding issue
124908view09:18, 31 December 2022EgonwFixed character encoding issues
124907view08:49, 31 December 2022EgonwConverted into a translation
117178view09:58, 18 May 2021EweitzModified title
113813view13:58, 26 November 2020Finterlysmall graphical update
106830view13:31, 17 September 2019MaintBotHMDB identifier normalization
105829view23:06, 15 August 2019Khanspersmodified description
101924view17:05, 17 November 2018EgonwRemoved whitespace in PubMed identifiers.
96990view11:22, 25 April 2018Fehrhartinteractions to graphical lines
96989view10:00, 25 April 2018Fehrhartinteractions to graphical lines
96988view09:55, 25 April 2018Fehrhartinteractions to graphical lines
96900view14:21, 18 April 2018FehrhartInteractions to graphical lines
96897view14:09, 18 April 2018FehrhartInteractions to graphical lines
96896view14:04, 18 April 2018FehrhartConverted interactions to graphical lines
96895view13:58, 18 April 2018FehrhartConverted interactions to graphical lines
92921view11:36, 17 July 2017EgonwReplaced a CAS of a salt with that of the parent compound.
86078view09:59, 29 June 2016MirellaKalafatiModified title
80056view09:31, 3 May 2015LarsEijssenCorrected spelling error: serotinergic -> serotonergic
78533view10:30, 7 January 2015MaintBotadded missing graphIds
74443view07:26, 20 April 2014EgonwFixed a PubMed ID.
73552view18:27, 30 January 2014EgonwH2O not H20....
70114view19:12, 12 July 2013MaintBotupdated to 2013 schema
68050view12:25, 29 June 2013EgonwFixed a few identifier issues.
68049view12:21, 29 June 2013EgonwFixed char encoding issues in references.
67641view11:43, 26 June 2013DdiglesOntology Term : 'serotonin signaling pathway' added !
59166view18:29, 22 February 2013MaintBotUpdated Ensembl data source
55364view18:39, 13 December 2012NsalomonisPeriodical save, work in progress
55358view18:18, 13 December 2012NsalomonisSpecify description
55355view18:08, 13 December 2012NsalomonisPeriodical save, work in progress
55354view17:58, 13 December 2012NsalomonisPeriodical save, work in progress
55353view17:47, 13 December 2012NsalomonisPeriodical save, work in progress
55352view17:32, 13 December 2012NsalomonisSpecify description
52941view21:29, 24 October 2012NsalomonisSpecify description
52817view01:50, 23 October 2012NsalomonisSpecify description
52816view00:16, 23 October 2012Nsalomonistest-without-DNA
52726view03:39, 20 October 2012NsalomonisSpecify description
52723view03:12, 20 October 2012NsalomonisSpecify description
52722view03:02, 20 October 2012NsalomonisSpecify description
52721view00:57, 20 October 2012NsalomonisSpecify description
52720view00:55, 20 October 2012NsalomonisSpecify description
52719view00:32, 20 October 2012NsalomonisSpecify description
52718view00:20, 20 October 2012NsalomonisSpecify description
52715view23:35, 19 October 2012NsalomonisSpecify description
52714view23:29, 19 October 2012NsalomonisSpecify description
52713view23:27, 19 October 2012NsalomonisSpecify description
52712view23:25, 19 October 2012NsalomonisSpecify description
52711view23:23, 19 October 2012NsalomonisSpecify description

External references

DataNodes

View all...
NameTypeDatabase referenceComment
5-HIAAMetaboliteHMDB0000763 (HMDB)
5-HTMetaboliteHMDB0000259 (HMDB)
5-HTPMetaboliteHMDB0000472 (HMDB)
ACADMGeneProduct34 (Entrez Gene)
ADCYAP1GeneProduct116 (Entrez Gene)
ADCYAP1R1GeneProduct117 (Entrez Gene)
ALDOAGeneProductENSG00000149925 (Ensembl)
AQP4GeneProductENSG00000171885 (Ensembl)
ARGeneProduct367 (Entrez Gene)
ASCL1GeneProduct429 (Entrez Gene)
ATP1A3GeneProductENSG00000105409 (Ensembl)
AVPGeneProduct551 (Entrez Gene)
AcetylcholineMetabolite51-84-3 (CAS)
BDNFGeneProductENSG00000176697 (Ensembl)
BHLHE40GeneProductENSG00000134107 (Ensembl)
C4AGeneProduct720 (Entrez Gene)
C4BGeneProduct721 (Entrez Gene)
CASP3GeneProductENSG00000164305 (Ensembl)
CAV3GeneProduct859 (Entrez Gene)
CC2D1AGeneProduct54862 (Entrez Gene)
CDCA7LGeneProduct55536 (Entrez Gene)
CEBPBGeneProductENSG00000172216 (Ensembl)
CHATGeneProductENSG00000070748 (Ensembl)
CHRM2GeneProduct1129 (Entrez Gene)
CHRNA4GeneProduct1137 (Entrez Gene)
CHRNA7GeneProductENSG00000175344 (Ensembl)
CHRNB2GeneProduct1141 (Entrez Gene)
CHRNB4GeneProduct1143 (Entrez Gene)
CPT1AGeneProductENSG00000110090 (Ensembl)
CREB1GeneProduct1385 (Entrez Gene)
CREB1GeneProductENSG00000118260 (Ensembl)
CREBBPGeneProductENSG00000005339 (Ensembl)
CREMGeneProductENSG00000095794 (Ensembl)
CTCFGeneProduct10664 (Entrez Gene)
CTNNB1GeneProductENSG00000168036 (Ensembl)
CholineMetabolite62-49-7 (CAS)
Chronic hypoxiaQ105688 (Wikidata)
DDCGeneProduct1644 (Entrez Gene)
DEAF1GeneProduct10522 (Entrez Gene)
DLX2GeneProductENSG00000115844 (Ensembl)
DopamineMetabolite62-31-7 (CAS)
ECE1GeneProduct1889 (Entrez Gene)
EGR1GeneProductENSG00000120738 (Ensembl)
EN1GeneProduct2019 (Entrez Gene)
EP300GeneProduct2033 (Entrez Gene)
ESR2GeneProduct2100 (Entrez Gene)
FEVGeneProduct54738 (Entrez Gene)
FMO3GeneProductENSG00000007933 (Ensembl)
FOXM1GeneProduct2305 (Entrez Gene)
FluoxetineMetabolite54910-89-3 (CAS)
G6PCGeneProductENSG00000131482 (Ensembl)
GABAMetaboliteHMDB0000112 (HMDB)
GABRA1GeneProduct2554 (Entrez Gene)
GAPDHGeneProductENSG00000111640 (Ensembl)
GATA2GeneProduct2624 (Entrez Gene)
GATA3GeneProduct2625 (Entrez Gene)
GCKGeneProductENSG00000106633 (Ensembl)
GJA1GeneProductENSG00000152661 (Ensembl)
GNB3GeneProduct2784 (Entrez Gene)
GPD1LGeneProductENSG00000152642 (Ensembl)
GRIN1GeneProductENSG00000176884 (Ensembl)
Glial Cell DifferentiationPathwayWP2276 (WikiPathways)
GlutamateMetaboliteHMDB0004135 (HMDB)
HADHAGeneProduct3030 (Entrez Gene)
HADHBGeneProductENSG00000138029 (Ensembl)
HDAC1GeneProductENSG00000116478 (Ensembl)
HDAC9GeneProductENSG00000048052 (Ensembl)
HES1GeneProduct3280 (Entrez Gene)
HES1GeneProductENSG00000114315 (Ensembl)
HES5GeneProduct388585 (Entrez Gene)
HIF1AGeneProductENSG00000100644 (Ensembl)
HSP90B1GeneProductENSG00000166598 (Ensembl)
HSPD1GeneProduct3329 (Entrez Gene)
HTR1AGeneProduct3350 (Entrez Gene)
HTR2AGeneProduct3356 (Entrez Gene)
HTR3AGeneProductENSG00000166736 (Ensembl)
IL10GeneProduct3586 (Entrez Gene)
IL13GeneProductENSG00000169194 (Ensembl)
IL1AGeneProductENSG00000115008 (Ensembl)
IL1BGeneProductENSG00000125538 (Ensembl)
IL1RNGeneProductENSG00000136689 (Ensembl)
IL6GeneProduct3569 (Entrez Gene)
IL6RGeneProduct3570 (Entrez Gene)
IL8GeneProduct3576 (Entrez Gene)
JUNGeneProductENSG00000177606 (Ensembl)
KCNH2 GeneProduct3757 (Entrez Gene)
KCNH2GeneProduct3757 (Entrez Gene)
KCNJ8GeneProduct3764 (Entrez Gene)
KCNQ1GeneProduct3784 (Entrez Gene)
L-DOPAMetabolite59-92-7 (CAS)
L-TryptophanMetaboliteHMDB0000929 (HMDB)
LMX1BGeneProduct4010 (Entrez Gene)
MAOAGeneProduct4128 (Entrez Gene)
MAP2GeneProductENSG00000078018 (Ensembl)
MAZGeneProductENSG00000103495 (Ensembl)
MBD1GeneProductENSG00000141644 (Ensembl)
MECP2GeneProductENSG00000169057 (Ensembl)
MEF2CGeneProductENSG00000081189 (Ensembl)
MIR13AGeneProductENSG00000208009 (Ensembl)
MIR16-1GeneProduct406950 (Entrez Gene)
MIR210GeneProductENSG00000199038 (Ensembl)
MYBGeneProductENSG00000118513 (Ensembl)
NANOGGeneProductENSG00000111704 (Ensembl)
NEUROD1GeneProductENSG00000162992 (Ensembl)
NFKB1GeneProduct4790 (Entrez Gene)
NFKB1GeneProductENSG00000109320 (Ensembl)
NFKB2GeneProductENSG00000077150 (Ensembl)
NFYAGeneProduct4800 (Entrez Gene)
NGFGeneProductENSG00000134259 (Ensembl)
NKX2-2GeneProduct4821 (Entrez Gene)
NKX3-1GeneProduct4824 (Entrez Gene)
NOS1APGeneProductENSG00000198929 (Ensembl)
NR3C1GeneProduct2908 (Entrez Gene)
NR3C1GeneProductENSG00000113580 (Ensembl)
NTRK2GeneProduct4915 (Entrez Gene)
NicotineMetaboliteHMDB0001934 (HMDB)
PAHGeneProduct5053 (Entrez Gene)
PBX1GeneProductENSG00000185630 (Ensembl)
PHOX2AGeneProduct401 (Entrez Gene)
PHOX2BGeneProduct8929 (Entrez Gene)
PKNOX1GeneProductENSG00000160199 (Ensembl)
PLP1GeneProductENSG00000123560 (Ensembl)
POU2F2GeneProductENSG00000028277 (Ensembl)
POU3F2GeneProduct5454 (Entrez Gene)
POU5F1GeneProductENSG00000204531 (Ensembl)
PPARGC1AGeneProduct10891 (Entrez Gene)
PPARGC1BGeneProduct133522 (Entrez Gene)
PRKACAGeneProduct5566 (Entrez Gene)
PRKACBGeneProduct5567 (Entrez Gene)
PRKAR1AGeneProduct5573 (Entrez Gene) KAP0 HUMAN
PRKAR1BGeneProduct5575 (Entrez Gene)
PRKAR2AGeneProduct5576 (Entrez Gene)
PRKAR2BGeneProduct5577 (Entrez Gene)
PhenylalanineMetabolite63-91-2 (CAS)
RESTGeneProduct5978 (Entrez Gene)
RESTGeneProductENSG00000084093 (Ensembl)
RETGeneProduct5979 (Entrez Gene)
RORAGeneProduct6095 (Entrez Gene)
RUNX3GeneProductENSG00000020633 (Ensembl)
RYR2GeneProduct6262 (Entrez Gene)
SCN3BGeneProductENSG00000166257 (Ensembl)
SCN4BGeneProductENSG00000177098 (Ensembl)
SCN5AGeneProduct6331 (Entrez Gene)
SLC1A3GeneProductENSG00000079215 (Ensembl)
SLC25A4GeneProductENSG00000151729 (Ensembl)
SLC6A4GeneProduct6532 (Entrez Gene) Contains an alternative promoter in the first and possibly second intron.
SLC9A3GeneProduct6550 (Entrez Gene)
SNAP25GeneProductENSG00000132639 (Ensembl)
SNTA1GeneProduct6640 (Entrez Gene)
SOX2GeneProductENSG00000181449 (Ensembl)
SP1GeneProduct6667 (Entrez Gene)
SP1GeneProductENSG00000185591 (Ensembl)
SP3GeneProductENSG00000172845 (Ensembl)
SPTBN1GeneProductENSG00000115306 (Ensembl)
SSTGeneProductENSG00000157005 (Ensembl)
SSTR1GeneProductENSG00000139874 (Ensembl)
SSTR2GeneProductENSG00000180616 (Ensembl)
TAC1GeneProductENSG00000006128 (Ensembl)
TACR1GeneProductENSG00000115353 (Ensembl)
TCF3GeneProductENSG00000071564 (Ensembl)
TFGeneProductENSG00000091513 (Ensembl)
THGeneProductENSG00000180176 (Ensembl)
THRBGeneProductENSG00000151090 (Ensembl)
TLX3GeneProduct30012 (Entrez Gene)
TNFGeneProduct7124 (Entrez Gene)
TP73GeneProductENSG00000078900 (Ensembl)
TPH1GeneProduct7166 (Entrez Gene)
TPH2GeneProduct121278 (Entrez Gene)
TPPPGeneProductENSG00000171368 (Ensembl)
TSPYL1GeneProductENSG00000189241 (Ensembl)
TyrosineMetabolite60-18-4 (CAS)
VAMP2GeneProductENSG00000220205 (Ensembl)
VEGFAGeneProductENSG00000112715 (Ensembl)
VIPR1GeneProduct7433 (Entrez Gene)
VIPR2GeneProduct7434 (Entrez Gene)
YBX1GeneProduct4904 (Entrez Gene)
YWHABGeneProduct7529 (Entrez Gene)
YWHAEGeneProduct7531 (Entrez Gene)
YWHAGGeneProduct7532 (Entrez Gene)
YWHAGGeneProductENSG00000170027 (Ensembl)
YWHAHGeneProduct7533 (Entrez Gene)
YWHAQGeneProduct10971 (Entrez Gene)
YWHAZGeneProduct7534 (Entrez Gene) PMID: 9861170 PMID: 1317796

Annotated Interactions

No annotated interactions

Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP706"
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