Microsomal triglyceride transfer protein: molecular genetics, functional mechanisms, and clinical significance
https://doi.org/10.52727/2078-256X-2025-21-4-453-464
Abstract
The aim of this work is to provide a comprehensive review of the structural and functional organization of the MTTP gene and the microsomal triglyceride transfer protein (MTP) it encodes, to characterize its pathogenic variants, and to describe the molecular mechanisms of their action. The MTP is a key regulator of lipid metabolism that is required for the assembly and secretion of apoB‑containing lipoproteins in hepatocytes and enterocytes. Biallelic pathogenic variants in MTTP cause abetalipoproteinemia, a rare life‑threatening disorder with progressive neurological and ophthalmological complications. Several common single nucleotide variants in this gene are associated with various metabolic disturbances. A literature review was conducted, including analysis of the gene structure and mechanisms of alternative splicing of MTTP, the domain organization of MTP, its interaction with protein disulfide isomerase, and selected pathogenic variants of this gene based on published functional studies and clinical data. An in‑depth understanding of the molecular mechanisms underlying MTP dysfunction is essential for accurate interpretation of genetic testing results, prediction of clinical phenotype, differential diagnosis, and the development of personalized therapeutic strategies for abetalipoproteinemia and related disorders.
Keywords
MTTP gene,
microsomal triglyceride transfer protein,
protein disulfide isomerase,
abetalipoproteinemia,
genetic variants
Supporting agencies: This research was conducted with the financial support of the State Budget Project FWNR2022-0021.
About the Authors
A. S. Asekritova
Government Autonomous Institution of the Republic of Sakha (Yakutia) "Republican Clinical Hospital No.3;
Federal State Autonomous Educational Institution of Higher Education «M.K. Ammosov Northeastern Federal University»
Russian Federation
Russian Federation
Alexandra S. Asekritova, head of center for predictive medicine and bioinformatics, сandidate of medical sciences, associate professor of the Department of therapy, Institute of Medicine
94, Gorkogo ыt., Yakutsk, Republic of Sakha (Yakutia), 677027
58, Belinskogo st., Yakutsk, Republic of Sakha (Yakutia), 677000
A. V. Pavlova
Government Autonomous Institution of the Republic of Sakha (Yakutia) "Republican Clinical Hospital No.3
Russian Federation
Russian Federation
Anna V. Pavlova, chief cardiologist of center for predictive medicine and bioinformatics
94, Gorkogo ыt., Yakutsk, Republic of Sakha (Yakutia), 677027
S. V. Mikhailova
Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences
Russian Federation
Russian Federation
Svetlana V. Mikhailova, researcher at the laboratory of human molecular genetics
10, Lavrentyeva ave., Novosibirsk, 630090
D. E. Ivanoshchuk
Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences
Russian Federation
Russian Federation
Dinara E. Ivanoshchuk, junior researcher at the laboratory of human molecular genetics
10, Lavrentyeva ave., Novosibirsk, 630090
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For citations:
Asekritova A.S., Pavlova A.V., Mikhailova S.V., Ivanoshchuk D.E. Microsomal triglyceride transfer protein: molecular genetics, functional mechanisms, and clinical significance. Ateroscleroz. 2025;21(4):453-464. (In Russ.) https://doi.org/10.52727/2078-256X-2025-21-4-453-464
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