Article
Bi-allelic KICS2 mutations impair KICSTOR complex-mediated mTORC1 regulation, causing intellectual disability and epilepsy.
American journal of human genetics - 6 Feb 2025
Buchert Rebecca, Burkhalter Martin D, Huridou Chrisovalantou, Sofan Linda, Roser Timo, Cremer Kirsten, Alvi Javeria Raza, Efthymiou Stephanie, Froukh Tawfiq, Gulieva Sughra, Guliyeva Ulviyya, Hamdallah Moath, Holder-Espinasse Muriel, Kaiyrzhanov Rauan, Klingler Doreen, Koko Mahmoud, Matthies Lars, Park Joohyun, Sturm Marc, Velic Ana, Spranger Stephanie, Sultan Tipu, Engels Hartmut, Lerche Holger, Houlden Henry, Pagnamenta Alistair T, Borggraefe Ingo, Weber Yvonne, Bonnen Penelope E, Maroofian Reza, Riess Olaf, Weber Jonasz J, Philipp Melanie, Haack Tobias B
Abstract excerpt
Nutrient-dependent mTORC1 regulation upon amino acid deprivation is mediated by the KICSTOR complex, comprising SZT2, KPTN, ITFG2, and KICS2, recruiting GATOR1 to lysosomes. Previously, pathogenic SZT2 and KPTN variants have been associated with autosomal recessive intellectual disability and epileptic encephalopathy. We identified bi-allelic KICS2 variants in eleven affected individuals presenting with...
Topics
- Humans
- Intellectual Disability
- Mechanistic Target of Rapamycin Complex 1
- Epilepsy
- Zebrafish
- Mutation
- Animals