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TLDc family genes mutations in severe neurological human disorders
https://doi.org/10.25557/2073-7998.2026.07.12-21
Abstract
Neurological disorders represent a broad group of human pathological conditions of varied severity, ranging from rare epileptic seizures and hearing loss to severe central nervous system pathologies. Numerous mutations in various genes linked to human neurological disorders have been described, and one of the examples are mutations in OXR1 and TBC1D24 genes, members of a highly conserved TLDc gene family. TLDc family members are found in eukaryotic genomes and are characterised by presence of conserved TLDc domain with unknown molecular function. It has been shown that TLDc family members play an important role in protection against oxidative stress, especially in the cells of the central nervous system, and regulate the function of vesicular ATPase, thus altering the intraluminal pH of vesicular organelles. Numerous mutations in the TBC1D24 gene have been identified in patients with various epilepsy types, hearing loss, as well as rare multisystem DOORS syndrome. During the last few years approximately ten patients with OXR1 mutations have also been described – their severe condition is characterised by microcephaly, neurodegeneration and profound developmental delay among other symptomes. This review briefly characterises TLDc protein family members’ functions and associated with their disturbance phenotypes of model organisms, and in details discusses the role of TLDc genes mutations in human diseases.
Supporting agencies: The study was carried out with the financial support of the Russian Science Foundation, project 25-14-00373.
About the Authors
V. S. Fadeev
V.A. Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences (EIMB RAS)
Russian Federation
Russian Federation
32 bldg 1 Vavilova str., Moscow, 119991
Y. Y. Silaeva
V.A. Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences (EIMB RAS)
Russian Federation
Russian Federation
32 bldg 1 Vavilova str., Moscow, 119991
D. M. Dolmatova
V.A. Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences (EIMB RAS)
Russian Federation
Russian Federation
32 bldg 1 Vavilova str., Moscow, 119991
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Fadeev V.S., Silaeva Y.Y., Dolmatova D.M. TLDc family genes mutations in severe neurological human disorders. Medical Genetics. 2026;25(7):12-21. (In Russ.) https://doi.org/10.25557/2073-7998.2026.07.12-21
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