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Autosomal recessive variants in TUBGCP2 alter the γ-tubulin ring complex leading to neurodevelopmental disease

Lookup NU author(s): Sunitha Balaraju, Dr Ana TopfORCiD, Professor Rita HorvathORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2020 The Author(s). Microtubules help building the cytoskeleton of neurons and other cells. Several components of the gamma-tubulin (γ-tubulin) complex have been previously reported in human neurodevelopmental diseases. We describe two siblings from a consanguineous Turkish family with dysmorphic features, developmental delay, brain malformation, and epilepsy carrying a homozygous mutation (p.Glu311Lys) in TUBGCP2 encoding the γ-tubulin complex 2 (GCP2) protein. This variant is predicted to disrupt the electrostatic interaction of GCP2 with GCP3. In primary fibroblasts carrying the variant, we observed a faint delocalization of γ-tubulin during the cell cycle but normal GCP2 protein levels. Through mass spectrometry, we observed dysregulation of multiple proteins involved in the assembly and organization of the cytoskeleton and the extracellular matrix, controlling cellular adhesion and of proteins crucial for neuronal homeostasis including axon guidance. In summary, our functional and proteomic studies link TUBGCP2 and the γ-tubulin complex to the development of the central nervous system in humans.© 2020 The Author(s)Biological Sciences; Neuroscience; Molecular Neuroscience; Clinical Neuroscience; Systems Biology; Protemics

Publication metadata

Author(s): Gungor S, Oktay Y, Hiz S, Aranguren-Ibanez A, Kalafatcilar I, Yaramis A, Karaca E, Yis U, Sonmezler E, Ekinci B, Aslan M, Yilmaz E, Ozgor B, Balaraju S, Szabo N, Laurie S, Beltran S, MacArthur DG, Hathazi D, Topf A, Roos A, Lochmuller H, Vernos I, Horvath R

Publication type: Article

Publication status: Published

Journal: iScience

Year: 2021

Volume: 24

Issue: 1

Pages: 101948

Print publication date: 22/01/2021

Online publication date: 14/12/2020

Acceptance date: 11/12/2020

Date deposited: 22/08/2023

ISSN (electronic): 2589-0042

Publisher: Elsevier Inc.


DOI: 10.1016/j.isci.2020.101948

Data Access Statement: All genetic data have been deposited in the EGA database and in RD-CONNECT under the following ID numbers: patient 1: E497133, patient 2: E477343, mother: E615258, father: E739679, unaffected sibling: E191145. These data can be made available after an authentication process.


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Funder referenceFunder name
201064/Z/16/ZWellcome Trust
203105/Z/16/ZWellcome Trust
109915/Z/15/ZWellcome Trust
Evelyn Trust
European Research Council
Lily Foundation
MR/N025431/1Medical Research Council (MRC)
Medical Research Council
MR/N027302/1Medical Research Council (MRC)
MR/S005021/1Medical Research Council (MRC)
Turkish Scientific and Research Council (TÜBITAK)
Wellcome Trust