MCTP2, also known as multiple C2-domains with two transmembrane regions 2, is involved in several biological functions. It plays a role in lipid droplet biogenesis as it marks special ER sites where lipid droplets and peroxisomes preferentially arise [2]. It is also implicated in intercellular signal transduction and synapse function [7]. Additionally, it is important for cardiac outflow tract development [5].

In human genetic studies, MCTP2 has been associated with various diseases. In a study of Saudi Arabian families, recessive inheritance of MCTP2-related disorders was observed, adding to the understanding of its role in genetic diseases [1]. A heterozygous mutation of MCTP2 was found in a patient with coarctation of the aorta [3]. An induced pluripotent stem cell line was generated from an aortic dissection patient carrying an MCTP2 mutation, which could be used to investigate the mechanism of aortic dissection [4]. Mutations in MCTP2 were discovered in patients with congenital prosopagnosia, revealing its role in face recognition [6]. MCTP2 gene variants were associated with schizophrenia in Scandinavian samples [7]. It was also linked to the heart rate response to exercise, falling under the category of genes related to cardiac development [8]. In diabetes research, the RGMA-MCTP2 region was associated with diabetic kidney disease [9].

In conclusion, MCTP2 is crucial for lipid droplet biogenesis, intercellular signaling, synapse function, and cardiac development. Through genetic studies in humans, it has been associated with a range of diseases including aortic coarctation, aortic dissection, congenital prosopagnosia, schizophrenia, and diabetic kidney disease. These findings help in understanding the biological functions of MCTP2 and its implications in disease mechanisms.

References:

1. Monies, Dorota, Abouelhoda, Mohamed, AlSayed, Moeenaldeen, Meyer, Brian F, Alkuraya, Fowzan S. 2017. The landscape of genetic diseases in Saudi Arabia based on the first 1000 diagnostic panels and exomes. In Human genetics, 136, 921-939. doi:10.1007/s00439-017-1821-8. https://pubmed.ncbi.nlm.nih.gov/28600779/

2. Jackson, Catherine L. 2019. Lipid droplet biogenesis. In Current opinion in cell biology, 59, 88-96. doi:10.1016/j.ceb.2019.03.018. https://pubmed.ncbi.nlm.nih.gov/31075519/

3. Liu, Y-X, Liu, L, Dong, Y, Sheng, Y, Fan, L-L. . Novel heterozygous mutation of MCTP2 gene in a patient with coarctation of the aorta. In QJM : monthly journal of the Association of Physicians, 115, 157-159. doi:10.1093/qjmed/hcab310. https://pubmed.ncbi.nlm.nih.gov/34878133/

4. Feng, Weiqi, Li, Chenxi, Li, Ying, Yang, Jue, Fan, Ruixin. 2023. Generation of an induced pluripotent stem cell line from an aortic dissection patient carrying MCTP2/c.2635T > G mutation. In Stem cell research, 68, 103058. doi:10.1016/j.scr.2023.103058. https://pubmed.ncbi.nlm.nih.gov/36868039/

5. Lalani, Seema R, Ware, Stephanie M, Wang, Xueqing, Potocki, Lorraine, Belmont, John W. 2013. MCTP2 is a dosage-sensitive gene required for cardiac outflow tract development. In Human molecular genetics, 22, 4339-48. doi:10.1093/hmg/ddt283. https://pubmed.ncbi.nlm.nih.gov/23773997/

6. Sun, Yun, Men, Weiwei, Kennerknecht, Ingo, Zhang, Wenxia, Rao, Yi. . Human genetics of face recognition: discovery of MCTP2 mutations in humans with face blindness (congenital prosopagnosia). In Genetics, 227, . doi:10.1093/genetics/iyae047. https://pubmed.ncbi.nlm.nih.gov/38547502/

7. Djurovic, Srdjan, Le Hellard, Stephanie, Kähler, Anna K, Werge, Thomas, Andreassen, Ole A. 2009. Association of MCTP2 gene variants with schizophrenia in three independent samples of Scandinavian origin (SCOPE). In Psychiatry research, 168, 256-8. doi:10.1016/j.psychres.2008.08.007. https://pubmed.ncbi.nlm.nih.gov/19223264/

8. van de Vegte, Yordi J, Tegegne, Balewgizie S, Verweij, Niek, Snieder, Harold, van der Harst, Pim. 2019. Genetics and the heart rate response to exercise. In Cellular and molecular life sciences : CMLS, 76, 2391-2409. doi:10.1007/s00018-019-03079-4. https://pubmed.ncbi.nlm.nih.gov/30919020/

9. Dahlström, Emma, Sandholm, Niina. . Progress in Defining the Genetic Basis of Diabetic Complications. In Current diabetes reports, 17, 80. doi:10.1007/s11892-017-0906-z. https://pubmed.ncbi.nlm.nih.gov/28779365/