Citations 2
Germline mutations in a G protein identify signaling cross-talk in T cells
Ham, Hyoungjun , Jing, Huie , Lamborn, Ian T. , Kober, M. , Anderson, David E. , Druey, Kirk M. , Mandl, Judith N. , Isidor, Bertrand , Freeman, Alexandra F. , Ganesan, Sundar , Karsak, Meliha , Mustillo, Peter , Teo, Juliana , Zolkipli‐Cunningham, Zarazuela , Lecoquierre, François , Schmid, Jana Pachlopnik , Kuhns, Douglas B. , Xu, Xuehua , Al–Herz, Waleed , Terhal, Paulien A., Muurinen, Mari , Barlogis, Vincent , Danielson, Jeffrey J. , Stewart, Helen , Rading, Sebastian, Keren, Boris , Pfundt, Rolph , Potocki, Lorraine , Olivier, Kenneth N., Faivre, Laurence , Wong, Melanie , Puel, Anne , Chou, Janet , Tusseau, Maud, Moutsopoulos, Niki M. , Matthews, Helen, Simons, Cas , Fink, Danielle , Kong, Heidi H. , Kabát, Juraj , Kim, Woo Sung , Bierhals, Tatjana , Meguro, Kazuyuki , Gu, Jingwen , Stoddard, Jennifer , Banos-Pinero, Benito, Slack, Maria A., Trivellin, Giampaolo , Mazel, Benoît , Li, Samuel T. , Watts, Val J. , Rodriguez-Quevedo, Maria F. , Bruel, Ange‐Line , Lehalle, Daphné , Torres, Daniel , Sullivan, Kathleen E. , Duffourd, Yannis, Similuk, Morgan , Blanc, Pierre , Jin, Tian, Geha, Raif S., Casanova, Jean‐Laurent , Mäkitie, Outi , Edery, Patrick , Germain, Ronald N. , Billadeau, Daniel D. , Zhang, Yu , Lenardo, Michael J. , Kober, Megan M , Koval, Alexey , Anderson, D Eric , Druey, Kirk M , Mandl, Judith N , Isidor, Bertrand , Ferreira, Carlos R , Freeman, Alexandra F , Karsak, Meliha , Mustillo, Peter J , Teo, Juliana , Chatron, Nicolas , Lecoquierre, Francois , Oler, Andrew J , Schmid, Jana Pachlopnik , Kuhns, Douglas B , Xu, Xuehua , Hauck, Fabian , Al-Herz, Waleed , Wagner, Matias , Terhal, Paulien A , Muurinen, Mari , Barlogis, Vincent , Loid, Petra , Keren, Boris , Pfundt, Rolph , Zarember, Kol A , Vill, Katharina , Olivier, Kenneth N , Lesca, Gaetan , Faivre, Laurence , Puel, Anne , Chou, Janet , Moutsopoulos, Niki M , Simons, Cas , Soldatos, Ariane , Masle-Farquhar, Etienne , Pittaluga, Stefania , Brink, Robert , Kong, Heidi H , Kabat, Juraj , Bierhals, Tatjana , Hsu, Amy P. , Gu, Jingwen , Trivellin, Giampaolo , Mazel, Benoît , Soomann, Maarja , Li, Samuel , Watts, Val J , Stratakis, Constantine A , Rodriguez-Quevedo, Maria F , Bruel, Ange-Line , Lipsanen-Nyman, Marita , Saultier, Paul , Lehalle, Daphne , Torres, Daniel , Barbarot, Sébastien , Neu, Axel , Similuk, Morgan N , McWalter, Kirsty , Blanc, Pierre , Bézieau, Stéphane , Geha, Raif S , Casanova, Jean Laurent , Makitie, Outi M , Edery, Patrick , Christodoulou, John , Germain, Ronald N , Goodnow, Christopher C , Sakmar, Thomas P , Billadeau, Daniel D , Kury, Sebastien , Katanaev, Vladimir L , Zhang, Yu , Lenardo, Michael J , Su, Helen C , Berchiche, Yamina A. , Wagner, Matias , Cruz, Phillip , Lesca, Gaëtan , Tusseau, Maud , Taft, Ryan J. , Pittaluga, Stefania , Baños-Piñero, Benito, Stratakis, Constantine A. , Jain, Rashmi, Bezieau, Stéphane , Jin, Tian , Kubisch, Christian , Küry, Sébastien , Su, Helen C.
Science | September 19, 2024 | Volume: 385 | Issue: 6715 | Pages: No page available
Humans with monogenic inborn errors responsible for extreme disease phenotypes can reveal essential physiological pathways. We investigated germline mutations in GNAI2 , which encodes G αi2 , a key component in heterotrimeric G protein signal transduction usually thought to regulate adenylyl cyclase–mediated cyclic adenosine monophosphate (cAMP) production. Patients with activating G αi2 mutations had clinical presentations that included impaired immunity. Mutant G αi2 impaired cell migration and augmented responses to T cell receptor (TCR) stimulation. We found that mutant G αi2 influenced TCR signaling by sequestering the guanosine triphosphatase (GTPase)–activating protein RASA2, thereby promoting RAS activation and increasing downstream extracellular signal–regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)–AKT S6 signaling to drive cellular growth and proliferation.
The Human Phenotype Ontology in 2024: phenotypes around the world
Gargano, Michael , Matentzoglu, Nicolas , Coleman, Ben , Addo-Lartey, Eunice B, Anagnostopoulos, Anna V. , Anderton, Joel , Avillach, Paul , Bagley, Anita , Bakštein, Eduard , Balhoff, James P. , Baynam, Gareth , Bertram, Holli , Bishop, Somer , Bodenstein, David F. , Botas, Pablo , Cady, J , Cameron, Rhiannon , Castellanos, F , Chan, Lauren , Cruz-Rojo, Jaime , Dahan‐Oliel, Noémi , Davids, Jon R. , Dieuleveult, Maud de , Souza, Vinícius de , Vries, Bert B.A. de , Diaz‐Byrd, Claudia , Duyzend, Michael , Elfeky, Reem , Essaid, Shahim , Fabrizzi, Carolina , Freudenberg‐Hua, Yun , Gabriel, Davera , Moses, Rachel Gore , Green, Ian, Gu, Weihong, Guthrie, Julia, Hamosh, Ada , Hanauer, Marc , Hanušová, Kateřina , He, Yongqun , Helbig, Ingo , Huang, Shangzhi, Joseph, Lisa , Keramatian, Kamyar , King, Bryan , Knoflach, Katrin , Koolen, David A. , Kraus, Megan L , Kroll, Carlo , Kusters, Maaike , Ladewig, Markus S. , Lagorce, David , Laraway, Bryan , Li, Xiarong, Lucano, Caterina , Marazita, Mary L. , Martínez‐Glez, Víctor , McHenry, Toby H, McInnis, Melvin G. , Mihulová, Michaela , Millett, Caitlin E. , Moslerová, Veronika , Narutomi, Kenji, Nevado, Julián , Nierenberg, Andrew A. , Čajbiková, Nikola Novák , Ogishima, Soichi , Olson, Daniel , Ortiz, Abigail, Nanclares, Guiomar Pérez de , Peters, Amy T. , Rapp, Christina , Rath, Ana , Rekerle, Lauren , Roberts, Angharad M. , Roy, Suzy, Sanders, Stephan , Schuetz, Catharina , Schwarz, Martin , Scott, Katie , Seelow, Dominik , Seitz, Berthold , Shen, Yiping , Similuk, Morgan , Simon, Eric S. , Singh, Balwinder , Smith, Cynthia L. , Smolinsky, Jake T , Stafford, Elizabeth , Stefancsik, Ray , Steinhaus, Robin , Strawbridge, Rebecca , Sundaramurthi, Jagadish Chandrabose , Talapova, Polina , Castano, Jair A Tenorio , Tesner, Pavel , Thomas, Rhys H. , Turnovec, Marek , Gijn, Mariëlle van , Vlčková, Markéta , Walden, Anita , Ware, James S. , Wiafe, Addo A, Wiafe, Samuel Agyei , Wiggins, Lisa D. , Williams, Andrew E. , Wu, Chen , Xiong, Hui, Yalın, Nefize , Yamamoto, Yasunori , Yatham, Lakshmi N. , Yocum, Anastasia K. , Young, Allan H. , Yüksel, Zafer , Zandi, Peter P. , Zvolský, Miroslav , Carmody, Leigh , Harris, Nomi L. , Muñoz-Torres, Mónica , Daniš, Daniel , Mungall, Chris , Haendel, Melissa , Robinson, Peter N. , Gargano, Michael A , Bagley, Anita M , Bello, Susan M , Berk, Michael , Bertram, Holli , Bishop, Somer , Blau, Hannah , Bodenstein, David F , Botas, Pablo , Boztug, Kaan , Čady, Jolana , Callahan, Tiffany J , Cameron, Rhiannon , Carbon, Seth J , Castellanos, Francisco , Caufield, J Harry , Chan, Lauren E , Chute, Christopher G , Cruz-Rojo, Jaime , Dahan-Oliel, Noémi , Davids, Jon R , de Dieuleveult, Maud , de Vries, Bert B A , de Vries, Esther , DePaulo, J Raymond , Derfalvi, Beata , Dhombres, Ferdinand , Diaz-Byrd, Claudia , Dingemans, Alexander J M , Donadille, Bruno , Duyzend, Michael , Elfeky, Reem , Essaid, Shahim , Fabrizzi, Carolina , Fico, Giovanna , Firth, Helen V , Freudenberg-Hua, Yun , Fullerton, Janice M , Gilmour, Kimberly , Giordano, Jessica , Goes, Fernando , Moses, Rachel Gore , Griese, Matthias , Groza, Tudor , Guthrie, Julia , Gyori, Benjamin , Hamosh, Ada , Hanauer, Marc , Hanušová, Kateřina , He, Yongqun , Hegde, Harshad , Helbig, Ingo , Holasová, Kateřina , Hoyt, Charles Tapley , Hurwitz, Eric , Jacobsen, Julius O B , Joseph, Lisa , Keramatian, Kamyar , King, Bryan , Knoflach, Katrin , Koolen, David A , Kraus, Megan L , Kusters, Maaike , Ladewig, Markus S , Lagorce, David , Lai, Meng-Chuan , Lapunzina, Pablo , Laraway, Bryan , Lewis-Smith, David , Lucano, Caterina , Majd, Marzieh , Marazita, Mary L , Martinez-Glez, Victor , McInnis, Melvin G , McMurry, Julie A , Mihulová, Michaela , Millett, Caitlin E , Mitchell, Philip B , Moslerová, Veronika , Nematollahi, Shahrzad , Nevado, Julian , Nierenberg, Andrew A , Čajbiková, Nikola Novák , Nurnberger, John I , Ogishima, Soichi , Olson, Daniel , Ortiz, Abigail , Pachajoa, Harry , Perez de Nanclares, Guiomar , Peters, Amy T , Putman, Tim , Rath, Ana , Reese, Justin , Rekerle, Lauren , Sanders, Stephan J , Schuetz, Catharina , Schulte, Eva , Schulze, Thomas , Schwarz, Martin , Scott, Katie , Seelow, Dominik , Seitz, Berthold , Similuk, Morgan N , Simon, Eric S , Singh, Balwinder , Smedley, Damian , Smith, Cynthia L , Smolinsky, Jake T , Sperry, Sarah , Stafford, Elizabeth , Stefancsik, Ray , Steinhaus, Robin , Strawbridge, Rebecca , Sundaramurthi, Jagadish Chandrabose , Talapova, Polina , Tenorio Castano, Jair A , Tesner, Pavel , Thomas, Rhys H , Thurm, Audrey , Turnovec, Marek , van Gijn, Marielle E , Vasilevsky, Nicole A , Vlčková, Markéta , Walden, Anita , Wang, Kai , Wapner, Ron , Ware, James S , Wiafe, Samuel A , Wiggins, Lisa D , Williams, Andrew , Wyrwoll, Margot J , Yalin, Nefize , Yamamoto, Yasunori , Yatham, Lakshmi N , Yocum, Anastasia K , Young, Allan H , Yüksel, Zafer , Zandi, Peter P , Zankl, Andreas , Zarante, Ignacio , Zvolský, Miroslav , Toro, Sabrina , Carmody, Leigh C , Harris, Nomi L , Munoz-Torres, Monica C , Danis, Daniel , Mungall, Christopher J , Köhler, Sebastian , Haendel, Melissa , Robinson, Peter N , Berk, Michael , Chute, Christopher G. , Fico, Giovanna , Fullerton, Janice M. , Giordano, Jessica L. , Jiang, Xiaofeng , Lai, Meng‐Chuan , Schulte, Eva C. , Smedley, Damian , Sperry, Sarah H. , Xiong, Hui
Nucleic Acids Research | October 19, 2023 | Volume: 52 | Issue: D1 | Pages: D1333-D1346
Abstract The Human Phenotype Ontology (HPO) is a widely used resource that comprehensively organizes and defines the phenotypic features of human disease, enabling computational inference and supporting genomic and phenotypic analyses through semantic similarity and machine learning algorithms. The HPO has widespread applications in clinical diagnostics and translational research, including genomic diagnostics, gene-disease discovery, and cohort analytics. In recent years, groups around the world have developed translations of the HPO from English to other languages, and the HPO browser has been internationalized, allowing users to view HPO term labels and in many cases synonyms and definitions in ten languages in addition to English. Since our last report, a total of 2239 new HPO terms and 49235 new HPO annotations were developed, many in collaboration with external groups in the fields of psychiatry, arthrogryposis, immunology and cardiology. The Medical Action Ontology (MAxO) is a new effort to model treatments and other measures taken for clinical management. Finally, the HPO consortium is contributing to efforts to integrate the HPO and the GA4GH Phenopacket Schema into electronic health records (EHRs) with the goal of more standardized and computable integration of rare disease data in EHRs.