9.B.228. The TMEM18 (TMEM18) Family An intergenic region of human chromosome 2 (2p25.3) harbors genetic variants which are among those most strongly and reproducibly associated with obesity. The gene closest to these variants is TMEM18. Tmem18 expression in the murine hypothalamic paraventricular nucleus (PVN) was altered by changes in the nutritional state (Larder et al. 2017). Germline loss of Tmem18 in mice resulted in increased body weight, which was exacerbated by a high fat diet and driven by increased food intake. Selective overexpression of Tmem18 in the PVN of wild-type mice reduced food intake and also increased energy expenditure. Larder et al. 2017 provided evidence that TMEM18 has four, not three, transmembrane domains and that it physically interacts with key components of the nuclear pore complex. Their data support the hypothesis that TMEM18 itself, acting within the central nervous system, is a plausible mediator of the impact of adjacent genetic variation on human adiposity. TMEM18 in the spermatozoa of rats under calorie restriction were positively correlated with sperm concentration, while testes' TMEM18 expression was also positively correlated with sperm vitality and negatively correlated with insulin resistance (Correia et al. 2022).
References:
Correia, A.S., S.C. Pereira, T. Morais, A.D. Martins, M.P. Monteiro, M.G. Alves, and P.F. Oliveira. (2022). Obesity-Related Genes Expression in Testes and Sperm Parameters Respond to GLP-1 and Caloric Restriction. Biomedicines 10:.
Larder, R., M.F.M. Sim, P. Gulati, R. Antrobus, Y.C.L. Tung, D. Rimmington, E. Ayuso, J. Polex-Wolf, B.Y.H. Lam, C. Dias, D.W. Logan, S. Virtue, F. Bosch, G.S.H. Yeo, V. Saudek, S. O'Rahilly, and A.P. Coll. (2017). Obesity-associated gene TMEM18 has a role in the central control of appetite and body weight regulation. Proc. Natl. Acad. Sci. USA 114: 9421-9426.
Examples:
TC#	Name	Organismal Type	Example
9.B.228.1.1	*TMEM18 of 140 aas and 4 TMSs. It shows a concerved motif with TC# 2.A.1.40.1: 48- YRLQ-GH-LCL-IL -62. Implicated in obesety of mice (Larder et al.* 2017).**		TMEM18 of Homo sapiens

9.B.228.1.2	TMEM18 of 3 or 4 TMSs.		*TMEM18 of Arabidopsis thaliana* (Mouse-ear cress)**

9.B.228.1.3	Uncharacterized protein of 159 aas and 3 TMSs.		*UP of Galdieria sulphuraria* (Red alga)**

9.B.228.1.4	Uncharacterized protein of 206 aas and 3 TMSs.		UP of Trypanosoma cruzi

9.B.228.1.5	Uncharacterized protein of 205 aas and 4 TMSs.		UP of Leishmania major

9.B.228.1.6	Uncharacterized protein of 159 aas and 3 TMSs.		UP of Tulasnella calospora