medgenМедицинская генетикаMedical Genetics2073-7998Publishing House «Genius Media» LLC10.25557/2073-7998.2026.07.12-21medgen-3508Research ArticleНАУЧНЫЙ ОБЗОРREVIEWРоль генов семейства TLDc в тяжелых неврологических заболеваниях человекаTLDc family genes mutations in severe neurological human disordersФадеевВ. С.FadeevV. S.

119991, г. Москва ,ул. Вавилова, д. 32, стр. 1

32 bldg 1 Vavilova str., Moscow, 119991

lis_vit@rambler.ruСилаеваЮ. Ю.SilaevaY. Y.

119991, г. Москва, ул. Вавилова, д. 32, стр. 1

32 bldg 1 Vavilova str., Moscow, 119991

ДолматоваД. М.DolmatovaD. M.

119991, г. Москва, ул. Вавилова, д. 32, стр. 1

32 bldg 1 Vavilova str., Moscow, 119991

Институт молекулярной биологии им. В.А. Энгельгардта (ИМБ РАН)РоссияV.A. Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences (EIMB RAS)Russian Federation2026100820262571221Copyright © Фадеев В.С., Силаева Ю.Ю., Долматова Д.М., 20262026Фадеев В.С., Силаева Ю.Ю., Долматова Д.М.Fadeev V.S., Silaeva Y.Y., Dolmatova D.M.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.medgen-journal.ru/jour/article/view/3508

Неврологические заболевания человека представляют собой обширную группу заболеваний разной степени тяжести, от редких эпилептических приступов и нарушений слуха до тяжелых поражений центральной нервной системы. На данный момент описано большое число генов, мутации в которых приводят к развитию неврологических нарушений, и ярким примером являются гены OXR1 и TBC1D24, члены высококонсервативного семейства TLDc. Гены этого семейства обнаружены у всех эукариотических организмов и характеризуются наличием консервативного TLDc домена с неизвестной молекулярной функцией. Было показано, что все гены семейства TLDc играют важную роль в защите от окислительного стресса, в особенности в клетках центральной нервной системы, а также способны регулировать функцию везикулярной АТФазы, влияя на внутрипросветный pH в различных мембранных органеллах. На сегодняшний день описано большое количество пациентов с патогенными вариантами в гене TBC1D24, приводящими к различным формам эпилепсии, потере слуха, а также тяжелым синдромам, таким как DOORS. За последние несколько лет было также описано несколько пациентов с патогенными вариантами в гене OXR1 с тяжелыми неврологическими нарушениями, включающими микроцефалию, нейродегенерацию и глубокую задержку психического развития. В данном обзоре кратко изложены функции белков данного семейства и ассоциированные с нарушением их функции фенотипы модельных организмов, а также подробно разбирается связь различных вариантов в генах семейства TLDc с заболеваниями человека.

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.

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The authors declare that there are no conflicts of interest present.