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Normal Function
The TMCO1 gene provides instructions for making a protein that forms specialized structures called channels through which positively charged calcium atoms (calcium ions) flow. The protein is found in the membrane of a cell structure called the endoplasmic reticulum, which acts as a storage center for calcium ions. When there is too much calcium in the endoplasmic reticulum, four TMCO1 proteins come together to form a channel that releases the excess calcium into the surrounding fluid inside the cell (cytoplasm).
The TMCO1 protein helps regulate the balance of calcium ions inside the endoplasmic reticulum. Calcium acts as a signal for many cellular functions including cell growth and division and gene activity. The proper balance of these ions in cells and in cell compartments is important for the development and function of various tissues and organs.
Health Conditions Related to Genetic Changes
Cerebro-facio-thoracic dysplasia
At least four TMCO1 gene mutations have been found to cause cerebro-facio-thoracic dysplasia, which is characterized by severe intellectual disability, distinctive facial features, and bone abnormalities that primarily involve the ribs and spinal bones (vertebrae). The gene mutations that cause cerebro-facio-thoracic dysplasia lead to production of abnormally short TMCO1 proteins that are likely broken down quickly. Without this protein, TMCO1 channels cannot form, and excess calcium builds up in the endoplasmic reticulum. The imbalance of calcium in this compartment disrupts development of a variety of tissues and organs, including the brain and structures in the head, face, and torso, resulting in the features of cerebro-facio-thoracic dysplasia.
More About This Health ConditionOther disorders
Genetic variations in the TMCO1 gene or in regions of the DNA that control the gene's activity are associated with the development of an eye disorder called primary open-angle glaucoma, which is a common cause of vision loss worldwide. This condition results from damage to the nerves that connect the eyes and the brain (the optic nerves) and typically develops in older adults. TMCO1 gene variations appear to be a risk factor for primary open-angle glaucoma in certain populations, including people of European descent, but not in others. How these genetic variations contribute to the condition is unknown. Additional genetic and environmental factors are thought to play a role in development of this eye disorder.
Other Names for This Gene
- TMCC4
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Alanay Y, Erguner B, Utine E, Hacariz O, Kiper PO, Taskiran EZ, Percin F, Uz E, Sagiroglu MS, Yuksel B, Boduroglu K, Akarsu NA. TMCO1 deficiency causes autosomal recessive cerebrofaciothoracic dysplasia. Am J Med Genet A. 2014 Feb;164A(2):291-304. doi: 10.1002/ajmg.a.36248. Epub 2013 Nov 5. Citation on PubMed
- Burdon KP, Macgregor S, Hewitt AW, Sharma S, Chidlow G, Mills RA, Danoy P, Casson R, Viswanathan AC, Liu JZ, Landers J, Henders AK, Wood J, Souzeau E, Crawford A, Leo P, Wang JJ, Rochtchina E, Nyholt DR, Martin NG, Montgomery GW, Mitchell P, Brown MA, Mackey DA, Craig JE. Genome-wide association study identifies susceptibility loci for open angle glaucoma at TMCO1 and CDKN2B-AS1. Nat Genet. 2011 Jun;43(6):574-8. doi: 10.1038/ng.824. Epub 2011 May 1. Citation on PubMed
- Michael Yates T, Ng OH, Offiah AC, Willoughby J, Berg JN; DDD Study; Johnson DS. Cerebrofaciothoracic dysplasia: Four new patients with a recurrent TMCO1 pathogenic variant. Am J Med Genet A. 2019 Jan;179(1):43-49. doi: 10.1002/ajmg.a.60678. Epub 2018 Dec 17. Citation on PubMed
- Pehlivan D, Karaca E, Aydin H, Beck CR, Gambin T, Muzny DM, Bilge Geckinli B, Karaman A, Jhangiani SN; Centers for Mendelian Genomics; Gibbs RA, Lupski JR. Whole-exome sequencing links TMCO1 defect syndrome with cerebro-facio-thoracic dysplasia. Eur J Hum Genet. 2014 Sep;22(9):1145-8. doi: 10.1038/ejhg.2013.291. Epub 2014 Jan 15. Citation on PubMed or Free article on PubMed Central
- van Koolwijk LM, Ramdas WD, Ikram MK, Jansonius NM, Pasutto F, Hysi PG, Macgregor S, Janssen SF, Hewitt AW, Viswanathan AC, ten Brink JB, Hosseini SM, Amin N, Despriet DD, Willemse-Assink JJ, Kramer R, Rivadeneira F, Struchalin M, Aulchenko YS, Weisschuh N, Zenkel M, Mardin CY, Gramer E, Welge-Lussen U, Montgomery GW, Carbonaro F, Young TL; DCCT/EDIC Research Group; Bellenguez C, McGuffin P, Foster PJ, Topouzis F, Mitchell P, Wang JJ, Wong TY, Czudowska MA, Hofman A, Uitterlinden AG, Wolfs RC, de Jong PT, Oostra BA, Paterson AD; Wellcome Trust Case Control Consortium 2; Mackey DA, Bergen AA, Reis A, Hammond CJ, Vingerling JR, Lemij HG, Klaver CC, van Duijn CM. Common genetic determinants of intraocular pressure and primary open-angle glaucoma. PLoS Genet. 2012;8(5):e1002611. doi: 10.1371/journal.pgen.1002611. Epub 2012 May 3. Citation on PubMed or Free article on PubMed Central
- Wang QC, Zheng Q, Tan H, Zhang B, Li X, Yang Y, Yu J, Liu Y, Chai H, Wang X, Sun Z, Wang JQ, Zhu S, Wang F, Yang M, Guo C, Wang H, Zheng Q, Li Y, Chen Q, Zhou A, Tang TS. TMCO1 Is an ER Ca(2+) Load-Activated Ca(2+) Channel. Cell. 2016 Jun 2;165(6):1454-1466. doi: 10.1016/j.cell.2016.04.051. Epub 2016 May 19. Citation on PubMed or Free article on PubMed Central
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