TMEM18

Transmembrane protein 18 also known as TMEM18 is a protein which in humans is encoded by the TMEM18 gene.[3]

TMEM18
Identifiers
Aliases	TMEM18, transmembrane protein 18, lncND
External IDs	OMIM: 613220 HomoloGene: 138333 GeneCards: TMEM18
Gene location (Human) Chr. Chromosome 2 (human)[1] Band 2p25.3 Start 663,877 bp[1] End 677,406 bp[1]
Gene ontology Molecular function • DNA binding Cellular component • cytoplasm • integral component of membrane • not the membrane • membrane • cell nucleus Biological process • cell migration • transcription, DNA-templated Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	129787	n/a
Ensembl	ENSG00000151353	n/a
UniProt	Q96B42	n/a
RefSeq (mRNA)	NM_152834 NM_001352680 NM_001352681	n/a
RefSeq (protein)	NP_690047 NP_001339609 NP_001339610	n/a
Location (UCSC)	Chr 2: 0.66 – 0.68 Mb	n/a
PubMed search	[2]	n/a
Wikidata
View/Edit Human

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[4]

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.[5]

The TMEM18 gene is ubiquitously expressed in both mammalian and fly tissues,[4] 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.[6]

Clinical significance

Genetic variants in the proximity of the TMEM18 gene are associated with obesity,[6][7][8][9][10] insulin levels, and blood sugar levels [4]

Evolutionary history

The TMEM18 gene has a long evolutionary history as it is present in both plants and animals.[4][6] 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.[4]

References

1. GRCh38: Ensembl release 89: ENSG00000151353 - Ensembl, May 2017
2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
3. Strausberg RL, Feingold EA, Grouse LH, et al. (December 2002). "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. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
4. Wiemerslage L, Gohel PA, Maestri G, Hilmarsson TG, Mickael M, Fredriksson R, Williams MJ, Schioth HB (2016). "The Drosophila ortholog of TMEM18 regulates insulin and glucagon-like signaling". J Endocrinol. 229 (3): 233–243. doi:10.1530/JOE-16-0040. PMID 27029472.
5. Jurvansuu J, Zhao Y, Leung DS, Boulaire J, Yu YH, Ahmed S, Wang S (June 2008). "Transmembrane protein 18 enhances the tropism of neural stem cells for glioma cells". Cancer Res. 68 (12): 4614–4622. doi:10.1158/0008-5472.CAN-07-5291. PMID 18559506.
6. Almén MS, Jacobsson JA, Shaik JH, Olszewski PK, Cedernaes J, Alsiö J, Sreedharan S, Levine AS, Fredriksson R, Marcus C, Schiöth HB (April 2010). "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. doi:10.1186/1471-2350-11-58. PMC 2858727. PMID 20380707.
7. Thorleifsson G, Walters GB, Gudbjartsson DF, et al. (January 2009). "Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity". Nat. Genet. 41 (1): 18–24. doi:10.1038/ng.274. PMID 19079260. S2CID 764409.
8. Willer CJ, Speliotes EK, Loos RJ, et al. (January 2009). "Six new loci associated with body mass index highlight a neuronal influence on body weight regulation". Nat. Genet. 41 (1): 24–34. doi:10.1038/ng.287. PMC 2695662. PMID 19079261.
9. Zhao J, Bradfield JP, Li M, et al. (May 2009). "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. doi:10.1038/oby.2009.159. PMC 2860782. PMID 19478790.
10. Renström F, Payne F, Nordström A, Brito EC, Rolandsson O, Hallmans G, Barroso I, Nordström P, Franks PW (April 2009). "Replication and extension of genome-wide association study results for obesity in 4923 adults from northern Sweden". Hum. Mol. Genet. 18 (8): 1489–1496. doi:10.1093/hmg/ddp041. PMC 2664142. PMID 19164386.

Further reading

• Bauer F, Elbers CC, Adan RA, et al. (2009). "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. doi:10.3945/ajcn.2009.27781. PMID 19692490.
• Trynka G, Zhernakova A, Romanos J, et al. (2009). "Coeliac disease-associated risk variants in TNFAIP3 and REL implicate altered NF-kappaB signalling". Gut. 58 (8): 1078–1083. doi:10.1136/gut.2008.169052. PMID 19240061. S2CID 17111427.
• Haupt A, Thamer C, Heni M, et al. (2009). "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. doi:10.1038/oby.2009.413. PMID 19910938.
• Willer CJ, Speliotes EK, Loos RJ, et al. (2009). "Six new loci associated with body mass index highlight a neuronal influence on body weight regulation". Nat. Genet. 41 (1): 25–34. doi:10.1038/ng.287. PMC 2695662. PMID 19079261.
• Li S, Zhao JH, Luan J, et al. (2010). "Cumulative effects and predictive value of common obesity-susceptibility variants identified by genome-wide association studies". Am. J. Clin. Nutr. 91 (1): 184–190. doi:10.3945/ajcn.2009.28403. PMID 19812171.
• Brandys MK, van Elburg AA, Loos RJ, et al. (2010). "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. doi:10.1002/ajmg.b.31026. PMID 19746409. S2CID 45793585.
• Renström F, Payne F, Nordström A, et al. (2009). "Replication and extension of genome-wide association study results for obesity in 4923 adults from northern Sweden". Hum. Mol. Genet. 18 (8): 1489–1496. doi:10.1093/hmg/ddp041. PMC 2664142. PMID 19164386.
• Hotta K, Nakamura M, Nakamura T, et al. (2009). "Association between obesity and polymorphisms in SEC16B, TMEM18, GNPDA2, BDNF, FAIM2 and MC4R in a Japanese population". J. Hum. Genet. 54 (12): 727–731. doi:10.1038/jhg.2009.106. PMID 19851340.
• Thorleifsson G, Walters GB, Gudbjartsson DF, et al. (2009). "Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity". Nat. Genet. 41 (1): 18–24. doi:10.1038/ng.274. PMID 19079260. S2CID 764409.