Pleiotropic role of TRAF7 in skull-base meningiomas and congenital heart disease

Ketu Mishra-Gorur, Tanyeri Barak, Leon D. Kaulen, Octavian Henegariu, Sheng Chih Jin, Stephanie Marie Aguilera, Ezgi Yalbir, Gizem Goles, Sayoko Nishimura, Danielle Miyagishima, Lydia Djenoune, Selin Altinok, Devendra K. Rai, Stephen Viviano, Andrew Prendergast, Cynthia Zerillo, Kent Ozcan, Burcin Baran, Leman Sencar, Nukte GocYanki Yarman, A. Gulhan Ercan-Sencicek, Kaya Bilguvar, Richard P. Lifton, Jennifer Moliterno, Angeliki Louvi, Shiaulou Yuan, Engin Deniz, Martina Brueckner, Murat Gunel

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


While somatic variants of TRAF7 (Tumor necrosis factor receptor-associated factor 7) underlie anterior skull-base meningiomas, here we report the inherited mutations of TRAF7 that cause congenital heart defects. We show that TRAF7 mutants operate in a dominant manner, inhibiting protein function via heterodimerization with wild-type protein. Further, the shared genetics of the two disparate pathologies can be traced to the common origin of forebrain meninges and cardiac outflow tract from the TRAF7-expressing neural crest. Somatic and inherited mutations disrupt TRAF7-IFT57 interactions leading to cilia degradation. TRAF7-mutant meningioma primary cultures lack cilia, and TRAF7 knockdown causes cardiac, craniofacial, and ciliary defects in Xenopus and zebrafish, suggesting a mechanistic convergence for TRAF7-driven meningiomas and developmental heart defects.

Original languageEnglish
Article numbere2214997120
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number16
StatePublished - Apr 18 2023


  • TRAF7
  • cilia
  • congenital heart defect
  • meningioma


Dive into the research topics of 'Pleiotropic role of TRAF7 in skull-base meningiomas and congenital heart disease'. Together they form a unique fingerprint.

Cite this