4p16.3 copy number variation (Homo sapiens)

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7, 8, 229, 10, 18613, 14, 26242, 12, 19-2154153, 275121, 6, 1116, 17, 23616, 17, 23253, 27Function unknownPossibly involved in neurodevelopmentProtein degradationRNA polymerase II elongation of transcriptionChondrocyte proliferation, differentiation, and apoptosisError-prone DNA polymerase that often misincorporatesdT regardless of template sequenceDopamine uptakechr4:1,552,030Function unknownMay play an important role in neural developmentbut details unknownStabilization of the kinetochorefibers of the mitotic spindlePlays an essential role in adipogenesis, by regulating expression of genes involvedin pre-adipocyte differentiationTMEM129H3F3AC4orf48Linker histone H1 and H5 familyNAT8LL-aspartateFGFR3MAPK1CKAP5protonNELF negative elongation factor complexNELFBSLBPPOLNCBLFGF2ERI1PI3K-AKT1 signaling pathwayK+FAM53ANELFABCS1LLETM1MAPK3NELFESCARNA22Ca2+N-acetyl-L-aspartateUBE2J2NSD2CLTCL1TACC3Core histone H2A/H2B/H3/H4MIR943MethamphetamineNELFCDAcetyl-CoAFRS2PLCG1GRB2SOS1PIK3R1GAB1Inositol 1,4,5-trisphosphateTACC3TMEM129FRS2PH3F3AMMNELFACBLPPLCG1PFunction unknownCa2+protonprotonK+protonCatalysisBindingMethylatedLEGENDInhibitionPhosphorylatedConversionStimulationPMchr4:2,091,303Core histone H2A/H2B/H3/H4Linker histone H1 and H5 family7, 8, 229, 10, 18


Description

The Wolf-Hirschhorn syndrome is a rare genetic disorder caused by a microdeletion in the chromosomal region 4p16.3. Typical symptoms are a distinct facial morphology, intellectual disability, psychiatric disorders, seizures, and heart defects. The chromosomal position chr4:1,552,030-2,091,303 (GCRh37) was taken from Kirov et al. 2014 and literature cited there (10.1016/j.biopsych.2013.07.022).

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Bibliography

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  1. Arun P, Moffett JR, Namboodiri AM; ''Evidence for mitochondrial and cytoplasmic N-acetylaspartate synthesis in SH-SY5Y neuroblastoma cells.''; Neurochem Int, 2009 PubMed Europe PMC Scholia
  2. Kuo AJ, Cheung P, Chen K, Zee BM, Kioi M, Lauring J, Xi Y, Park BH, Shi X, Garcia BA, Li W, Gozani O; ''NSD2 links dimethylation of histone H3 at lysine 36 to oncogenic programming.''; Mol Cell, 2011 PubMed Europe PMC Scholia
  3. Cheeseman LP, Harry EF, McAinsh AD, Prior IA, Royle SJ; ''Specific removal of TACC3-ch-TOG-clathrin at metaphase deregulates kinetochore fiber tension.''; J Cell Sci, 2013 PubMed Europe PMC Scholia
  4. Endele S, Nelkenbrecher C, Bördlein A, Schlickum S, Winterpacht A; ''C4ORF48, a gene from the Wolf-Hirschhorn syndrome critical region, encodes a putative neuropeptide and is expressed during neocortex and cerebellar development.''; Neurogenetics, 2011 PubMed Europe PMC Scholia
  5. van de Weijer ML, Bassik MC, Luteijn RD, Voorburg CM, Lohuis MA, Kremmer E, Hoeben RC, LeProust EM, Chen S, Hoelen H, Ressing ME, Patena W, Weissman JS, McManus MT, Wiertz EJ, Lebbink RJ; ''A high-coverage shRNA screen identifies TMEM129 as an E3 ligase involved in ER-associated protein degradation.''; Nat Commun, 2014 PubMed Europe PMC Scholia
  6. Ariyannur PS, Moffett JR, Manickam P, Pattabiraman N, Arun P, Nitta A, Nabeshima T, Madhavarao CN, Namboodiri AM; ''Methamphetamine-induced neuronal protein NAT8Lis the NAA biosynthetic enzyme: implications for specialized acetyl coenzyme A metabolism in the CNS.''; Brain Res, 2010 PubMed Europe PMC Scholia
  7. Zheng L, Dominski Z, Yang XC, Elms P, Raska CS, Borchers CH, Marzluff WF; ''Phosphorylation of stem-loop binding protein (SLBP) on two threonines triggers degradation of SLBP, the sole cell cycle-regulated factor required for regulation of histone mRNA processing, at the end of S phase.''; Mol Cell Biol, 2003 PubMed Europe PMC Scholia
  8. Wang ZF, Whitfield ML, Ingledue TC 3rd, Dominski Z, Marzluff WF; ''The protein that binds the 3' end of histone mRNA: a novel RNA-binding protein required for histone pre-mRNA processing.''; Genes Dev, 1996 PubMed Europe PMC Scholia
  9. Kaiyrzhanov R, Mohammed SEM, Maroofian R, Husain RA, Catania A, Torraco A, Alahmad A, Dutra-Clarke M, Grønborg S, Sudarsanam A, Vogt J, Arrigoni F, Baptista J, Haider S, Feichtinger RG, Bernardi P, Zulian A, Gusic M, Efthymiou S, Bai R, Bibi F, Horga A, Martinez-Agosto JA, Lam A, Manole A, Rodriguez DP, Durigon R, Pyle A, Albash B, Dionisi-Vici C, Murphy D, Martinelli D, Bugiardini E, Allis K, Lamperti C, Reipert S, Risom L, Laugwitz L, Di Nottia M, McFarland R, Vilarinho L, Hanna M, Prokisch H, Mayr JA, Bertini ES, Ghezzi D, Østergaard E, Wortmann SB, Carrozzo R, Haack TB, Taylor RW, Spinazzola A, Nowikovsky K, Houlden H; ''Bi-allelic LETM1 variants perturb mitochondrial ion homeostasis leading to a clinical spectrum with predominant nervous system involvement.''; Am J Hum Genet, 2022 PubMed Europe PMC Scholia
  10. Austin S, Mekis R, Mohammed SEM, Scalise M, Wang WA, Galluccio M, Pfeiffer C, Borovec T, Parapatics K, Vitko D, Dinhopl N, Demaurex N, Bennett KL, Indiveri C, Nowikovsky K; ''TMBIM5 is the Ca(2+) /H(+) antiporter of mammalian mitochondria.''; EMBO Rep, 2022 PubMed Europe PMC Scholia
  11. Wiame E, Tyteca D, Pierrot N, Collard F, Amyere M, Noel G, Desmedt J, Nassogne MC, Vikkula M, Octave JN, Vincent MF, Courtoy PJ, Boltshauser E, van Schaftingen E; ''Molecular identification of aspartate N-acetyltransferase and its mutation in hypoacetylaspartia.''; Biochem J, 2009 PubMed Europe PMC Scholia
  12. Zhuang L, Jang Y, Park YK, Lee JE, Jain S, Froimchuk E, Broun A, Liu C, Gavrilova O, Ge K; ''Depletion of Nsd2-mediated histone H3K36 methylation impairs adipose tissue development and function.''; Nat Commun, 2018 PubMed Europe PMC Scholia
  13. Huang E, Qu D, Huang T, Rizzi N, Boonying W, Krolak D, Ciana P, Woulfe J, Klein C, Slack RS, Figeys D, Park DS; ''PINK1-mediated phosphorylation of LETM1 regulates mitochondrial calcium transport and protects neurons against mitochondrial stress.''; Nat Commun, 2017 PubMed Europe PMC Scholia
  14. Jiang D, Zhao L, Clapham DE; ''Genome-wide RNAi screen identifies Letm1 as a mitochondrial Ca2+/H+ antiporter.''; Science, 2009 PubMed Europe PMC Scholia
  15. Lee YS, Gao Y, Yang W; ''How a homolog of high-fidelity replicases conducts mutagenic DNA synthesis.''; Nat Struct Mol Biol, 2015 PubMed Europe PMC Scholia
  16. Narita T, Yamaguchi Y, Yano K, Sugimoto S, Chanarat S, Wada T, Kim DK, Hasegawa J, Omori M, Inukai N, Endoh M, Yamada T, Handa H; ''Human transcription elongation factor NELF: identification of novel subunits and reconstitution of the functionally active complex.''; Mol Cell Biol, 2003 PubMed Europe PMC Scholia
  17. Zollino M, Lecce R, Fischetto R, Murdolo M, Faravelli F, Selicorni A, Buttè C, Memo L, Capovilla G, Neri G; ''Mapping the Wolf-Hirschhorn syndrome phenotype outside the currently accepted WHS critical region and defining a new critical region, WHSCR-2.''; Am J Hum Genet, 2003 PubMed Europe PMC Scholia
  18. De Marchi U, Santo-Domingo J, Castelbou C, Sekler I, Wiederkehr A, Demaurex N; ''NCLX protein, but not LETM1, mediates mitochondrial Ca2+ extrusion, thereby limiting Ca2+-induced NAD(P)H production and modulating matrix redox state.''; J Biol Chem, 2014 PubMed Europe PMC Scholia
  19. Li Y, Trojer P, Xu CF, Cheung P, Kuo A, Drury WJ 3rd, Qiao Q, Neubert TA, Xu RM, Gozani O, Reinberg D; ''The target of the NSD family of histone lysine methyltransferases depends on the nature of the substrate.''; J Biol Chem, 2009 PubMed Europe PMC Scholia
  20. Tisi D, Chiarparin E, Tamanini E, Pathuri P, Coyle JE, Hold A, Holding FP, Amin N, Martin AC, Rich SJ, Berdini V, Yon J, Acklam P, Burke R, Drouin L, Harmer JE, Jeganathan F, van Montfort RL, Newbatt Y, Tortorici M, Westlake M, Wood A, Hoelder S, Heightman TD; ''Structure of the Epigenetic Oncogene MMSET and Inhibition by N-Alkyl Sinefungin Derivatives.''; ACS Chem Biol, 2016 PubMed Europe PMC Scholia
  21. Zanoni P, Steindl K, Sengupta D, Joset P, Bahr A, Sticht H, Lang-Muritano M, van Ravenswaaij-Arts CMA, Shinawi M, Andrews M, Attie-Bitach T, Maystadt I, Belnap N, Benoit V, Delplancq G, de Vries BBA, Grotto S, Lacombe D, Larson A, Mourmans J, Õunap K, Petrilli G, Pfundt R, Ramsey K, Blok LS, Tsatsaris V, Vitobello A, Faivre L, Wheeler PG, Wevers MR, Wojcik M, Zweier M, Gozani O, Rauch A; ''Loss-of-function and missense variants in NSD2 cause decreased methylation activity and are associated with a distinct developmental phenotype.''; Genet Med, 2021 PubMed Europe PMC Scholia
  22. Martin F, Schaller A, Eglite S, Schümperli D, Müller B; ''The gene for histone RNA hairpin binding protein is located on human chromosome 4 and encodes a novel type of RNA binding protein.''; EMBO J, 1997 PubMed Europe PMC Scholia
  23. Yamaguchi Y, Takagi T, Wada T, Yano K, Furuya A, Sugimoto S, Hasegawa J, Handa H; ''NELF, a multisubunit complex containing RD, cooperates with DSIF to repress RNA polymerase II elongation.''; Cell, 1999 PubMed Europe PMC Scholia
  24. Tan D, Marzluff WF, Dominski Z, Tong L; ''Structure of histone mRNA stem-loop, human stem-loop binding protein, and 3'hExo ternary complex.''; Science, 2013 PubMed Europe PMC Scholia
  25. Tamai S, Iida H, Yokota S, Sayano T, Kiguchiya S, Ishihara N, Hayashi J, Mihara K, Oka T; ''Characterization of the mitochondrial protein LETM1, which maintains the mitochondrial tubular shapes and interacts with the AAA-ATPase BCS1L.''; J Cell Sci, 2008 PubMed Europe PMC Scholia
  26. Tsai MF, Jiang D, Zhao L, Clapham D, Miller C; ''Functional reconstitution of the mitochondrial Ca2+/H+ antiporter Letm1.''; J Gen Physiol, 2014 PubMed Europe PMC Scholia
  27. Booth DG, Hood FE, Prior IA, Royle SJ; ''A TACC3/ch-TOG/clathrin complex stabilises kinetochore fibres by inter-microtubule bridging.''; EMBO J, 2011 PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
127455view18:38, 3 October 2023KhanspersUpdated legend from interactions to graphical lines
127068view09:11, 27 July 2023FehrhartModified description
127067view09:06, 27 July 2023FehrhartOntology Term : 'disease pathway' added !
127066view09:04, 27 July 2023Fehrhartcorrection and updates
127065view08:45, 27 July 2023Fehrhartcorrection and updates
126852view10:07, 27 June 2023Ewoud
126577view15:02, 4 June 2023Ewoudfiller
126576view14:58, 4 June 2023Ewoudfiller
126529view11:43, 25 May 2023EwoudNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
GeneProduct
Acetyl-CoAMetaboliteCHEBI:57288 (ChEBI)
BCS1LGeneProductENSG00000074582 (Ensembl)
C4orf48GeneProductENSG00000243449 (Ensembl)
CBLGeneProductENSG00000110395 (Ensembl)
CKAP5GeneProductENSG00000175216 (Ensembl)
CLTCL1GeneProductENSG00000070371 (Ensembl)
Ca2+MetaboliteCHEBI:29108 (ChEBI)
Core histone H2A/H2B/H3/H4ProteinPF00125 (Pfam)
ERI1GeneProductENSG00000104626 (Ensembl)
FAM53AGeneProductENSG00000174137 (Ensembl)
FGF2GeneProductENSG00000138685 (Ensembl)
FGFR3GeneProductENSG00000068078 (Ensembl)
FRS2GeneProductENSG00000166225 (Ensembl)
GAB1GeneProductENSG00000109458 (Ensembl)
GRB2GeneProductENSG00000177885 (Ensembl)
H3F3AGeneProduct3020 (Entrez Gene)
Inositol 1,4,5-trisphosphateMetaboliteCHEBI:16595 (ChEBI)
K+MetaboliteCHEBI:29103 (ChEBI)
L-aspartateMetaboliteCHEBI:29991 (ChEBI)
LETM1GeneProductENSG00000168924 (Ensembl)
Linker histone H1 and H5 familyProteinPF00538 (Pfam)
MAPK1GeneProductENSG00000100030 (Ensembl)
MAPK3GeneProductENSG00000102882 (Ensembl)
MIR943GeneProductENSG00000284587 (Ensembl)
MethamphetamineMetaboliteCHEBI:6809 (ChEBI)
N-acetyl-L-aspartateMetaboliteCHEBI:16953 (ChEBI)
NAT8LGeneProductENSG00000185818 (Ensembl)
NELF negative elongation factor complexComplexCPX-6267
NELFAGeneProductENSG00000185049 (Ensembl)
NELFBGeneProductENSG00000188986 (Ensembl)
NELFCDGeneProductENSG00000101158 (Ensembl)
NELFEGeneProductENSG00000204356 (Ensembl)
NSD2GeneProductENSG00000109685 (Ensembl)
PI3K-AKT1 signaling pathwayPathwaymap04151 (KEGG Pathway)
PIK3R1GeneProductENSG00000145675 (Ensembl)
PLCG1GeneProductENSG00000124181 (Ensembl)
POLNGeneProductENSG00000130997 (Ensembl)
SCARNA22GeneProductENSG00000249784 (Ensembl)
SLBPGeneProductENSG00000163950 (Ensembl)
SOS1GeneProductENSG00000115904 (Ensembl)
TACC3GeneProductENSG00000013810 (Ensembl)
TMEM129GeneProductENSG00000168936 (Ensembl)
UBE2J2GeneProductENSG00000160087 (Ensembl)
protonMetaboliteCHEBI:24636 (ChEBI)

Annotated Interactions

SourceTargetTypeDatabase referenceComment
N-acetyl-L-aspartatemim-conversion14165 (Rhea)
NAT8Lmim-catalysis14165 (Rhea)
Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP5365"
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