TMEM18 explained

Transmembrane protein 18 also known as TMEM18 is a protein which in humans is encoded by the TMEM18 gene.^[1]

Function

TMEM18 seems to affect energy levels through insulin and glucagon signaling, and in flies, its downregulation induces a metabolic state resembling type-II diabetes^[2]

Overexpression of the TMEM18 protein increases the migration capacity of neural stem cells while inactivation of TMEM18 results in almost complete loss of migration activity.^[3]

The TMEM18 gene is ubiquitously expressed in both mammalian and fly tissues,^[2] which suggests a basic cellular function. In the mouse brain, it is found in the majority of all cells, but is more abundant in neurons than other cell types.

Clinical significance

Genetic variants in the proximity of the TMEM18 gene are associated with obesity,^{[4] [5] [6] [7] [8]} insulin levels, and blood sugar levels ^[2]

Evolutionary history

The TMEM18 gene has a long evolutionary history as it is present in both plants and animals.^[2] The TMEM18 protein's amino acid sequence is well conserved, which suggests that it has retained its function since the divergence of human and plants. The gene seems to have been lost in two separate lineages, but is not found duplicated in any analyzed genomes. Hence, it is not essential for eukaryotic organisms, but there appears to be selection against multiple copies of the TMEM18 gene.^[2]

Further reading

• Bauer F, Elbers CC, Adan RA, etal . Obesity genes identified in genome-wide association studies are associated with adiposity measures and potentially with nutrient-specific food preference . Am. J. Clin. Nutr. . 90 . 4 . 951–959 . 2009 . 19692490 . 10.3945/ajcn.2009.27781 . free .
• Trynka G, Zhernakova A, Romanos J, etal . Coeliac disease-associated risk variants in TNFAIP3 and REL implicate altered NF-kappaB signalling . Gut . 58 . 8 . 1078–1083 . 2009 . 19240061 . 10.1136/gut.2008.169052 . 17111427 .
• Haupt A, Thamer C, Heni M, etal . Novel Obesity Risk Loci Do Not Determine Distribution of Body Fat Depots: A Whole-body MRI/MRS study . Obesity (Silver Spring) . 18. 6. 1212–1217 . 2009 . 19910938 . 10.1038/oby.2009.413 . free .
• Willer CJ, Speliotes EK, Loos RJ, etal . Six new loci associated with body mass index highlight a neuronal influence on body weight regulation . Nat. Genet. . 41 . 1 . 25–34 . 2009 . 19079261 . 10.1038/ng.287 . 2695662 .
• Li S, Zhao JH, Luan J, etal . Cumulative effects and predictive value of common obesity-susceptibility variants identified by genome-wide association studies . Am. J. Clin. Nutr. . 91 . 1 . 184–190 . 2010 . 19812171 . 10.3945/ajcn.2009.28403 . free .
• Brandys MK, van Elburg AA, Loos RJ, etal . Are recently identified genetic variants regulating BMI in the general population associated with anorexia nervosa? . Am. J. Med. Genet. B Neuropsychiatr. Genet. . 153B . 2 . 695–699 . 2010 . 19746409 . 10.1002/ajmg.b.31026 . 45793585 .
• Renström F, Payne F, Nordström A, etal . Replication and extension of genome-wide association study results for obesity in 4923 adults from northern Sweden . Hum. Mol. Genet. . 18 . 8 . 1489–1496 . 2009 . 19164386 . 10.1093/hmg/ddp041 . 2664142 .
• Hotta K, Nakamura M, Nakamura T, etal . Association between obesity and polymorphisms in SEC16B, TMEM18, GNPDA2, BDNF, FAIM2 and MC4R in a Japanese population . J. Hum. Genet. . 54 . 12 . 727–731 . 2009 . 19851340 . 10.1038/jhg.2009.106 . free .
• Thorleifsson G, Walters GB, Gudbjartsson DF, etal . Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity . Nat. Genet. . 41 . 1 . 18–24 . 2009 . 19079260 . 10.1038/ng.274 . 764409 .

Notes and References

1. Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–16903 lpl. December 2002 . 12477932 . 139241 . 10.1073/pnas.242603899 . 2002PNAS...9916899M . free .
2. Wiemerslage L, Gohel PA, Maestri G, Hilmarsson TG, Mickael M, Fredriksson R, Williams MJ, Schioth HB . The Drosophila ortholog of TMEM18 regulates insulin and glucagon-like signaling. . J Endocrinol . 2016 . 27029472 . 10.1530/JOE-16-0040 . 229 . 3 . 233–243. free .
3. Jurvansuu J, Zhao Y, Leung DS, Boulaire J, Yu YH, Ahmed S, Wang S . Transmembrane protein 18 enhances the tropism of neural stem cells for glioma cells . Cancer Res. . 68 . 12 . 4614–4622 . June 2008 . 18559506 . 10.1158/0008-5472.CAN-07-5291 . free .
4. Almén MS, Jacobsson JA, Shaik JH, Olszewski PK, Cedernaes J, Alsiö J,Sreedharan S, Levine AS, Fredriksson R, Marcus C, Schiöth HB. The obesity gene, TMEM18, is of ancient origin, found in majority of neuronal cells in all major brain regions and associated with obesity in severely obese children. BMC Med. Genet. . 11 . 58 . April 2010 . 20380707 . 2858727. 10.1186/1471-2350-11-58 . free.
5. Thorleifsson G, Walters GB, Gudbjartsson DF, etal . Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity . Nat. Genet. . 41 . 1 . 18–24 . January 2009 . 19079260 . 10.1038/ng.274. 764409 .
6. Willer CJ, Speliotes EK, Loos RJ, etal . Six new loci associated with body mass index highlight a neuronal influence on body weight regulation . Nat. Genet. . 41 . 1 . 24–34 . January 2009 . 19079261 . 10.1038/ng.287. 2695662 .
7. Zhao J, Bradfield JP, Li M, etal . The role of obesity-associated loci identified in genome wide association studies in the determination of pediatric BMI . Obesity (Silver Spring) . 17. 12. 2254–2257. May 2009 . 19478790 . 10.1038/oby.2009.159 . 2860782.
8. Renström F, Payne F, Nordström A, Brito EC, Rolandsson O, Hallmans G, Barroso I, Nordström P, Franks PW . Replication and extension of genome-wide association study results for obesity in 4923 adults from northern Sweden . Hum. Mol. Genet. . 18 . 8 . 1489–1496 . April 2009 . 19164386 . 2664142 . 10.1093/hmg/ddp041 .