Figure 4 from ENIGMA <i>CHEK2</i>gether Project: A Comprehensive Study Identifies Functionally Impaired <i>CHEK2</i> Germline Missense Variants Associated with Increased Breast Cancer Risk
Authors: Stolarova Lenka , Kleiblova Petra , Zemankova Petra , Stastna Barbora , Janatova Marketa , Soukupova Jana , Achatz Maria Isabel , Ambrosone Christine , Apostolou Paraskevi , Arun Banu K. , Auer Paul , Barnard Mollie , Bertelsen Birgitte , Matsuda Koichi , Kamatani Yoichiro , Morisaki Takayuki , Nagai Akiko , Muto Kaori , Murakami Yoshinori , Furukawa Yoichi , Yamanashi Yuji , Nakamura Yusuke , Mushiroda Taisei , Momozawa Yukihide , Tanaka Toshihiro , Ohnishi Yozo , Kubo Michiaki , Higashiue Shinichi , Kobayashi Shuzo , Minami Shiro , Yamaguhci Hiroki , Arai Hajime , Yamaji Ken , Okazaki Yasushi , Asai Satoshi , Takahashi Yasuo , Fujioka Tomoaki , Obara Wataru , Mori Seijiro , Murayama Shigeo , Nagayama Satoshi , Miki Yoshio , Masumoto Akihide , Yamada Akira , Nishizawa Yasuko , Higashiyama Masahiko , Kutsumi Hiromu , Koretsune Yukihiro , Yoshiyama Takashi , Blok Marinus J. , Boddicker Nicholas , Brunet Joan , Burnside Elizabeth S. , Calvello Mariarosaria , Campbell Ian , Chan Sock Hoai , Chen Fei , Chiang Jian Bang , Coppa Anna , Cortesi Laura , Crujeiras-González Ana , Borecka Marianna , Cerna Marta , Hovhannisyan Milena , Jelinkova Sandra , Nehasil Petr , Foretova Lenka , Machackova Eva , Krutilkova Vera , Tavandzis Spiros , Cerna Leona , Chvojka Stepan , Koudova Monika , Puchmajerova Alena , Havranek Ondrej , Novotny Jan , Vesela Kamila , Vocka Michal , Hruskova Lucie , Michalovska Renata , Schwetzova Denisa , Vlckova Zdenka , Cerna Monika , Hejnalova Marketa , Jedlickova Nikol , Subrt Ivan , Zavoral Tomas , Kosarova Marcela , Vacinova Gabriela , Janikova Maria , Kratochvilova Romana , Curtisova Vaclava , Vrtel Radek , Scheinost Ondrej , Duskova Petra , Stranecky Viktor , De Leeneer Kim , De Putter Robin , DePersia Allison , Devereux Lisa , Domchek Susan , Efremidis Anna , Engel Christoph , Ernst Corinna , Evans D. Gareth R. , Feliubadaló Lidia , Fostira Florentia , Fuentes-Ríos Olivia , Gómez-García Encarna B. , González Sara , Haiman Christopher , Hansen Thomas van Overeem , Hauke Jan , Hodge James , Hu Chunling , Huang Hongyan , Ishak Nur Diana Binte , Iwasaki Yusuke , Konstantopoulou Irene , Kraft Peter , Lacey James , Lázaro Conxi , Li Na , Lim Weng Khong , Lindstrom Sara , Lori Adriana , Martinez Elana , Martins Alexandra , Matsuda Koichi , Matullo Giuseppe , McInerny Simone , Michailidou Kyriaki , Montagna Marco , Monteiro Alvaro N.A. , Mori Luigi , Nathanson Katherine , Neuhausen Susan L. , Nevanlinna Heli , Olson Janet E. , Palmer Julie , Pasini Barbara , Patel Alpa , Piane Maria , Poppe Bruce , Radice Paolo , Renieri Alessandra , Resta Nicoletta , Richardson Marcy E. , Rosseel Toon , Ruddy Kathryn J. , Santamariña Marta , Dos Santos Elizabeth Santana , Teras Lauren , Toland Amanda E. , Trentham-Dietz Amy , Vachon Celine M. , Volk Alexander E. , Weber-Lassalle Nana , Weitzel Jeffrey N. , Wiesmuller Lisa , Winham Stacey , Yadav Siddhartha , Yannoukakos Drakoulis , Yao Song , Zampiga Valentina , Zethoven Magnus , Zhang Ze Wen , Zima Tomas , Spurdle Amanda B. , Vega Ana , Rossing Maria , Del Valle Jesús , De Nicolo Arcangela , Hahnen Eric , Claes Kathleen B.M. , Ngeow Joanne , Momozawa Yukihide , James Paul A. , Couch Fergus J. , Macurek Libor , Kleibl Zdenek 
Published: August 2023

<p>Results of KAP1 and CHK2 kinase assays for 430 successfully analyzed missense <i>CHEK2</i> variants (shown as an average relative CHK2 kinase activity). Bars are colored as functionally WT-like (green), intermediate (IM; yellow), and impaired (ID; red), respectively, with thresholds for IM variants (0.428 and 0.479) and ID variants (0.705 and 0.710) for KAP1 and CHK2 assays, respectively (dashed lines). Error bars represent standard errors of mean. Color/gray letters for protein variants indicate concordant/discordant functional assays result, respectively. Blue boxes denote conserved CHK2 domains. DNL, variants that do not localize into the nucleus.</p>