TMEM70 gene

transmembrane protein 70

Normal Function

The TMEM70 gene provides instructions for making a protein called transmembrane protein 70. This protein is found in cell structures called mitochondria, which convert the energy from food into a form that cells can use. Transmembrane protein 70 is thought to play an important role in assembling and stabilizing a group of proteins called complex V. Complex V is the last of five complexes that carry out a multistep process called oxidative phosphorylation, through which cells derive much of their energy. Complex V is involved in the final step of oxidative phosphorylation. Specifically, one segment of complex V allows positively charged particles, called protons, to flow across a specialized membrane inside mitochondria. Another segment of complex V uses the energy created by this proton flow to convert a molecule called adenosine diphosphate (ADP) to adenosine triphosphate (ATP), which is used by the cell as energy.

Transmembrane protein 70 is also thought to be involved in the assembly of complex I, which is the first mitochondrial complex involved in oxidative phosphorylation.

Health Conditions Related to Genetic Changes

Mitochondrial complex V deficiency

At least 12 mutations in the TMEM70 gene have been identified in people who have mitochondrial complex V deficiency, a disorder with a wide variety of signs and symptoms. A few of these gene mutations are particular to people of Roma or Arab descent, and account for the majority of mitochondrial complex V deficiency cases caused by TMEM70 gene mutations. This disorder can also be caused by mutations in other genes.

The signs and symptoms of mitochondrial complex V deficiency are most prominent in organs and tissues that require a large amount of energy, such as the brain and heart. Abnormal brain function (encephalopathy) and other neurological problems can occur. Another common feature of mitochondrial complex V deficiency, especially when caused by TMEM70 gene mutations, is hypertrophic cardiomyopathy. This condition is characterized by thickening (hypertrophy) of the heart (cardiac) muscle that can lead to heart failure. TMEM70 gene mutations alter transmembrane protein 70 and impair its ability to perform its function in complex V assembly. As a result, the amount of complex V in cells is reduced. The resulting impairment of oxidative phosphorylation and energy production leads to the signs and symptoms of mitochondrial complex V deficiency.

More About This Health Condition

Other Names for This Gene

FLJ20533
MC5DN2
transmembrane protein 70, mitochondrial isoform a
transmembrane protein 70, mitochondrial isoform b

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Tests of TMEM70

Scientific Articles on PubMed

PubMed

Catalog of Genes and Diseases from OMIM

TRANSMEMBRANE PROTEIN 70; TMEM70

Gene and Variant Databases

References

Diodato D, Invernizzi F, Lamantea E, Fagiolari G, Parini R, Menni F, Parenti G, Bollani L, Pasquini E, Donati MA, Cassandrini D, Santorelli FM, Haack TB, Prokisch H, Ghezzi D, Lamperti C, Zeviani M. Common and Novel TMEM70 Mutations in a Cohort of Italian Patients with Mitochondrial Encephalocardiomyopathy. JIMD Rep. 2015;15:71-8. doi: 10.1007/8904_2014_300. Epub 2014 Apr 17. Citation on PubMed or Free article on PubMed Central
Guerrero-Castillo S, Baertling F, Kownatzki D, Wessels HJ, Arnold S, Brandt U, Nijtmans L. The Assembly Pathway of Mitochondrial Respiratory Chain Complex I. Cell Metab. 2017 Jan 10;25(1):128-139. doi: 10.1016/j.cmet.2016.09.002. Epub 2016 Oct 6. Citation on PubMed
Hejzlarova K, Mracek T, Vrbacky M, Kaplanova V, Karbanova V, Nuskova H, Pecina P, Houstek J. Nuclear genetic defects of mitochondrial ATP synthase. Physiol Res. 2014;63(Suppl 1):S57-71. doi: 10.33549/physiolres.932643. Citation on PubMed
Magner M, Dvorakova V, Tesarova M, Mazurova S, Hansikova H, Zahorec M, Brennerova K, Bzduch V, Spiegel R, Horovitz Y, Mandel H, Eminoglu FT, Mayr JA, Koch J, Martinelli D, Bertini E, Konstantopoulou V, Smet J, Rahman S, Broomfield A, Stojanovic V, Dionisi-Vici C, van Coster R, Morava E, Sperl W, Zeman J, Honzik T. TMEM70 deficiency: long-term outcome of 48 patients. J Inherit Metab Dis. 2015 May;38(3):417-26. doi: 10.1007/s10545-014-9774-8. Epub 2014 Oct 18. Erratum In: J Inherit Metab Dis. 2015 May;38(3):583-4. doi: 10.1007/s10545-015-9833-9.. Morava-Kozicz, Eva [corrected to Morava, Eva]. Citation on PubMed
Spiegel R, Khayat M, Shalev SA, Horovitz Y, Mandel H, Hershkovitz E, Barghuti F, Shaag A, Saada A, Korman SH, Elpeleg O, Yatsiv I. TMEM70 mutations are a common cause of nuclear encoded ATP synthase assembly defect: further delineation of a new syndrome. J Med Genet. 2011 Mar;48(3):177-82. doi: 10.1136/jmg.2010.084608. Epub 2010 Dec 8. Citation on PubMed
Torraco A, Verrigni D, Rizza T, Meschini MC, Vazquez-Memije ME, Martinelli D, Bianchi M, Piemonte F, Dionisi-Vici C, Santorelli FM, Bertini E, Carrozzo R. TMEM70: a mutational hot spot in nuclear ATP synthase deficiency with a pivotal role in complex V biogenesis. Neurogenetics. 2012 Nov;13(4):375-86. doi: 10.1007/s10048-012-0343-8. Epub 2012 Sep 18. Citation on PubMed

Genomic Location

The TMEM70 gene is found on chromosome 8.

MEDICAL ENCYCLOPEDIA

Understanding Genetics

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