@article{85281,
  author = {Victoria Patterson and Farid Ullah and Laura Bryant and John Griffin and Alpa Sidhu and Sheila Saliganan and Mackenzie Blaile and Margarita Saenz and Rosemarie Smith and Sara Ellingwood and Dorothy Grange and Xuyun Hu and Maimaiti Mireguli and Yanfei Luo and Yiping Shen and Maureen Mulhern and Elaine Zackai and Alyssa Ritter and Kosaki Izumi and Julia Hoefele and Matias Wagner and Korbinian Riedhammer and Barbara Seitz and Nathaniel Robin and Dana Goodloe and Cyril Mignot and Boris Keren and Helen Cox and Joanna Jarvis and Maja Hempel and Cynthia Gibson and Frederic Mau-Them and Antonio Vitobello and Ange-Line Bruel and Arthur Sorlin and Sarju Mehta and Lucy Raymond and Kelly Gilmore and Bradford Powell and Karen Weck and Chumei Li and Anneke van Silfhout and Thea Giacomini and Maria Mancardi and Andrea Accogli and Vincenzo Salpietro and Federico Zara and Neeta Vora and Erica Davis and Rebecca Burdine and Elizabeth Bhoj},
  title = {Abrogation of MAP4K4 protein function causes congenital anomalies in humans and zebrafish.},
  abstract = {<p>We report 21 families displaying neurodevelopmental differences and multiple congenital anomalies while bearing a series of rare variants in (). MAP4K4 has been implicated in many signaling pathways including c-Jun N-terminal and RAS kinases and is currently under investigation as a druggable target for multiple disorders. Using several zebrafish models, we demonstrate that these human variants are either loss-of-function or dominant-negative alleles and show that decreasing Map4k4 activity causes developmental defects. Furthermore, MAP4K4 can restrain hyperactive RAS signaling in early embryonic stages. Together, our data demonstrate that MAP4K4 negatively regulates RAS signaling in the early embryo and that variants identified in affected humans abrogate its function, establishing as a causal locus for individuals with syndromic neurodevelopmental differences.</p>},
  year = {2023},
  journal = {Science advances},
  volume = {9},
  pages = {eade0631},
  month = {04/2023},
  issn = {2375-2548},
  doi = {10.1126/sciadv.ade0631},
  language = {eng},
}