{"id":32997,"date":"2025-04-19T13:05:17","date_gmt":"2025-04-19T13:05:17","guid":{"rendered":"https:\/\/www.europesays.com\/uk\/32997\/"},"modified":"2025-04-19T13:05:17","modified_gmt":"2025-04-19T13:05:17","slug":"report-of-a-missense-tjp2-variant-associated-to-pfic4-with-a-pronounced-phenotypic-variability-focus-on-the-structural-effects-on-the-protein-level","status":"publish","type":"post","link":"https:\/\/www.europesays.com\/uk\/32997\/","title":{"rendered":"Report of a missense TJP2 variant associated to PFIC4 with a pronounced phenotypic variability: Focus on the structural effects on the protein level"},"content":{"rendered":"
  • \n

    Amer S, Hajira A. A comprehensive review of progressive familial intrahepatic cholestasis (PFIC): genetic disorders of hepatocanalicular transporters. Gastroenterol Res. 2014;7:39.<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Vitale G, Mattiaccio A, Conti A, Turco L, Seri M, Piscaglia F, et al. Genetics in familial intrahepatic cholestasis: clinical patterns and development of liver and biliary cancers: a review of the literature. Cancers. 2022;14:3421.<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Sambrotta M, Strautnieks S, Papouli E, Rushton P, Clark BE, Parry DA, et al. Mutations in TJP2 cause progressive cholestatic liver disease. Nat Genet. 2014;46:326\u20138.<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Zhang J, Liu LL, Gong JY, Hao CZ, Qiu YL, Lu Y, et al. TJP2 hepatobiliary disorders: novel variants and clinical diversity. Hum Mutat. 2020;41:502\u201311.<\/p>\n

    Article<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Wei CS, Becher N, Friis JB, Ott P, Vogel I, Gr\u00f8nb\u00e6k H. New tight junction protein 2 variant causing progressive familial intrahepatic cholestasis type 4 in adults: A case report. World J Gastroenterol. 2020;26:550.<\/p>\n

    Article<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Carlton VE, Harris BZ, Puffenberger EG, Batta AK, Knisely AS, Robinson DL, et al. Complex inheritance of familial hypercholanemia with associated mutations in TJP2 and BAAT. Nat Genet. 2003;34:91\u201396.<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Dixon PH, Sambrotta M, Chambers J, Taylor-Harris P, Syngelaki A, Nicolaides K, et al. An expanded role for heterozygous mutations of ABCB4, ABCB11, ATP8B1, ABCC2 and TJP2 in intrahepatic cholestasis of pregnancy. Sci Rep. 2017;7. 11823.<\/p>\n

    Article<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Kornitzer GA, Alvarez F. Case report: a novel single variant TJP2 mutation in a case of benign recurrent intrahepatic cholestasis. JPGN Rep. 2021;2:e087.<\/p>\n

    Article<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Beatch M, Jesaitis LA, Gallin WJ, Goodenough DA, Stevenson BR. The tight junction protein ZO-2 contains three PDZ (PSD-95Discs-LargeZO-1) domains and an alternatively spliced region. J Biol Chem. 1996;271:25723\u20136.<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Gonzalez-Mariscal L, Bautista P, Lechuga S, Quiros M. ZO-2, a tight junction scaffold protein involved in the regulation of cell proliferation and apoptosis. Ann N Y Acad Sci. 2012;1257:133\u201341.<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Itoh M, Terada M, Sugimoto H. The zonula occludens protein family regulates the hepatic barrier system in the murine liver. Biochimica et Biophysica Acta (BBA)-Mol Basis Dis. 2021;1867:165994.<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Shinwari K, Guojun L, Deryabina SS, Bolkov MA, Tuzankina IA, Chereshnev VA. Predicting the most deleterious missense nonsynonymous single-nucleotide polymorphisms of hennekam syndrome-causing CCBE1 gene, in silico analysis. Sci World J. 2021;2021:1\u201319.<\/p>\n

    Article<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Behairy MY, Abdelrahman AA, Abdallah HY, Ibrahim EEDA, Sayed AA, Azab MM. In silico analysis of missense variants of the C1qA gene related to infection and autoimmune diseases. J Taibah Univ Med Sci. 2022;17:1074\u201382.<\/p>\n

    PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Poon KS. In silico analysis of BRCA1 and BRCA2 missense variants and the relevance in molecular genetic testing. Sci Rep. 2021;11. 11114.<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Mansouri M, El Haddoumi G, Bendani H, Boumajdi N, Hakmi M, Abbou H, et al. In silico analyses of all STAT3 missense variants leading to explore divergent AD-HIES clinical phenotypes. Evolut Bioinforma. 2023;19. 11769343231169374.<\/p>\n

    Article<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Doyle DA, Lee A, Lewis J, Kim E, Sheng M, MacKinnon R. Crystal structures of a complexed and peptide-free membrane protein\u2013binding domain: molecular basis of peptide recognition by PDZ. Cell. 1996;85:1067\u201376.<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Rosina E, Pezzani L, Pezzoli L, Marchetti D, Bellini M, Pilotta A, et al. Atypical, composite, or blended phenotypes: how different molecular mechanisms could associate in double-diagnosed patients. Genes. 2022;13:1275.<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Walters-Sen LC, Hashimoto S, Thrush DL, Reshmi S, Gastier-Foster JM, Astbury C, et al. Variability in pathogenicity prediction programs: impact on clinical diagnostics. Mol Genet Genom Med. 2015;3:99\u2013110.<\/p>\n

    Article<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Thusberg J, Olatubosun A, Vihinen M. Performance of mutation pathogenicity prediction methods on missense variants. Hum Mutat. 2011;32:358\u201368.<\/p>\n

    Article<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Wang D, Li J, Wang Y, Wang E. A comparison on predicting functional impact of genomic variants. NAR genomics Bioinforma. 2022;4. lqab122.<\/p>\n

    Article<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Dou J, Vorobieva AA, Sheffler W, Doyle LA, Park H, Bick MJ, et al. De novo design of a fluorescence-activating \u03b2-barrel. Nature. 2018;561:485\u201391.<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Tokuriki N, Tawfik DS. Stability effects of mutations and protein evolvability. Curr Opin Struct Biol. 2009;19:596\u2013604.<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Idicula-Thomas S, Balaji PV. Correlation between the structural stability and aggregation propensity of proteins. silico Biol. 2007;7:225\u201337.<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Dudola D, Hinsenkamp A, G\u00e1sp\u00e1ri Z. Ensemble-Based analysis of the dynamic allostery in the PSD-95 PDZ3 domain in relation to the general variability of PDZ structures. Int J Mol Sci. 2020;21:8348.<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Heinemann U, Schuetz A. Structural features of tight-junction proteins. Int J Mol Sci. 2019;20:6020.<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    MacGowan SA, Madeira F, Britto-Borges T, Schmittner MS, Cole C, Barton GJ. Human missense variation is constrained by domain structure and highlights functional and pathogenic residues. BioRxiv. 2017;127050.<\/p>\n<\/li>\n

  • \n

    Iqbal S, P\u00e9rez-Palma E, Jespersen JB, May P, Hoksza D, Heyne HO, et al. Comprehensive characterization of amino acid positions in protein structures reveals molecular effect of missense variants. Proc Natl Acad Sci. 2020;117:28201\u201311.<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Lipi\u0144ski P, Ciara E, Jurkiewicz D, Pollak A, Wypch\u0142o M, P\u0142oski R, et al. Targeted next-generation sequencing in diagnostic approach to monogenic cholestatic liver disorders\u2014single-center experience. Front Pediatr. 2020;8:414.<\/p>\n

    Article<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Tang J, Tan M, Deng Y, Tang H, Shi H, Li M, et al. Two novel pathogenic variants of TJP2 gene and the underlying molecular mechanisms in progressive familial intrahepatic cholestasis type 4 patients. Front Cell Dev Biol. 2021;9. 661599.<\/p>\n

    Article<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Z\u00f6llner J, Finer S, Linton KJ, van Heel DA, Williamson C, Dixon PH. Rare variant contribution to cholestatic liver disease in a South Asian population in the United Kingdom. Sci Rep. 2023;13. 8120.<\/p>\n

    Article<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Zhou S, Hertel PM, Finegold MJ, Wang L, Kerkar N, Wang J, et al. Hepatocellular carcinoma associated with tight-junction protein 2 deficiency. Hepatology. 2015;62:1914\u20136.<\/p>\n

    Article<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Rajabi S, Dastmalchi R, Dehghan MH, Eftekharian A, Aghazadeh E, Ghaderian SMH. TJP2 Gene Mutation c. G1012A May Responsible for Congenital Hearing Loss with Incomplete Penetrance in An Iranian Pedigree. J Genet Resour. 2019;5:143\u20138.<\/p>\n


    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Zhang J, Guo S, Mei TL, Zhou J, Guan DX, Wang GL. Novel mutation of the TJP2 gene in a Chinese child with progressive cholestatic liver disease coexistent with hearing impairment. Hepatobiliary Pancreat Dis Int. 2021;20:198\u2013200.<\/p>\n

    Article<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Gong R, Li S. Extraction of human genomic DNA from whole blood using a magnetic microsphere method. Int J Nanomed. 2014;9:3781\u20139.<\/p>\n<\/li>\n

  • \n

    Khabou B, Mahjoub B, Barbu V, Balhoudi N, Wardani A, Sfar MT, et al. Phenotypic variability in Tunisian PFIC3 patients harboring a complex genotype with a differential clinical outcome of UDCA treatment. Clin Chim Acta. 2018;486:122\u20138.<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Rentzsch P, Witten D, Cooper GM, Shendure J, Kircher M. CADD: predicting the deleteriousness of variants throughout the human genome. Nucleic acids Res. 2019;47:D886\u2013D894.<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Case DA, Cheatham TE III, Darden T, Gohlke H, Luo R, Merz KM Jr, et al. The Amber biomolecular simulation programs. J Comput Chem. 2005;26:1668\u201388.<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Roe DR, Cheatham TE III. PTRAJ and CPPTRAJ: software for processing and analysis of molecular dynamics trajectory data. J Chem theory Comput. 2013;9:3084\u201395.<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    McGibbon RT, Beauchamp KA, Harrigan MP, Klein C, Swails JM, Hern\u00e1ndez CX, et al. MDTraj: a modern open library for the analysis of molecular dynamics trajectories. Biophys J. 2015;109:1528\u201332.<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Mirza N, Bharadwaj R, Malhotra S, Sibal A. Progressive familial intrahepatic cholestasis type 4 in an Indian child: presentation, initial course and novel compound heterozygous mutation. BMJ Case Rep CP. 2020;13:e234193.<\/p>\n

    Article<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n","protected":false},"excerpt":{"rendered":"Amer S, Hajira A. A comprehensive review of progressive familial intrahepatic cholestasis (PFIC): genetic disorders of hepatocanalicular transporters.…\n","protected":false},"author":2,"featured_media":32998,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[3846],"tags":[13450,17907,3972,19391,267,3969,19314,19389,19390,70,16,15],"class_list":{"0":"post-32997","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-genetics","8":"tag-computational-biology-and-bioinformatics","9":"tag-gene-expression","10":"tag-gene-function","11":"tag-gene-therapy","12":"tag-genetics","13":"tag-human-genetics","14":"tag-molecular-medicine","15":"tag-next-generation-sequencing","16":"tag-paediatrics","17":"tag-science","18":"tag-uk","19":"tag-united-kingdom"},"share_on_mastodon":{"url":"https:\/\/pubeurope.com\/@uk\/114364777935079472","error":""},"_links":{"self":[{"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/posts\/32997","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/comments?post=32997"}],"version-history":[{"count":0,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/posts\/32997\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/media\/32998"}],"wp:attachment":[{"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/media?parent=32997"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/categories?post=32997"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/tags?post=32997"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}