Encyclopedia
Translocase of inner mitochondrial membrane 8A: The TIMM8A gene provides instructions for making a protein that is found inside mitochondria, which are structures within cells that convert the energy from food into a form that cells can use.
- genes
1. Normal Function
The TIMM8A gene provides instructions for making a protein that is found inside mitochondria, which are structures within cells that convert the energy from food into a form that cells can use. Mitochondria have two membranes, an outer membrane and an inner membrane, which are separated by a fluid-filled area called the intermembrane space. The TIMM8A protein is found in the intermembrane space, where it forms a complex (a group of proteins that work together) with a very similar protein called TIMM13. This complex transports other proteins across the intermembrane space to the mitochondrial inner membrane.
2. Health Conditions Related to Genetic Changes
2.1. Deafness-dystonia-optic neuronopathy syndrome
At least 20 mutations in the TIMM8A gene have been found to cause deafness-dystonia-optic neuronopathy (DDON) syndrome. Most of these mutations result in the absence of functional TIMM8A protein inside the mitochondria, which prevents the formation of the TIMM8A/TIMM13 complex. Researchers believe that the lack of this complex leads to abnormal transport of proteins across the intermembrane space, although it is unclear how abnormal protein transport affects the function of the mitochondria and causes the signs and symptoms of DDON syndrome.
Some people with DDON syndrome have large DNA deletions that remove the entire TIMM8A gene and one end of a neighboring gene known as BTK. Mutations in the BTK gene cause X-linked agammaglobulinemia (XLA), which is characterized by an increased susceptibility to infections. Individuals with large DNA deletions that include the TIMM8A gene and the BTK gene have the signs and symptoms of both DDON syndrome and XLA.
3. Other Names for This Gene
- DDP
- DDP1
- deafness/dystonia peptide
- DFN1
- MGC12262
- TIM8A_HUMAN
- translocase of inner mitochondrial membrane 8 homolog A
- translocase of inner mitochondrial membrane 8 homolog A (yeast)
This entry is adapted from the peer-reviewed paper https://medlineplus.gov/genetics/gene/timm8a
References
- Arai T, Zhao M, Kanegane H, van Zelm MC, Futatani T, Yamada M, Ariga T, OchsHD, Miyawaki T, Oh-ishi T. Genetic analysis of contiguous X-chromosome deletionsyndrome encompassing the BTK and TIMM8A genes. J Hum Genet. 2011Aug;56(8):577-82. doi: 10.1038/jhg.2011.61.
- Binder J, Hofmann S, Kreisel S, Wöhrle JC, Bäzner H, Krauss JK, Hennerici MG, Bauer MF. Clinical and molecular findings in a patient with a novel mutation inthe deafness-dystonia peptide (DDP1) gene. Brain. 2003 Aug;126(Pt 8):1814-20.
- Engl G, Florian S, Tranebjærg L, Rapaport D. Alterations in expression levels of deafness dystonia protein 1 affect mitochondrial morphology. Hum Mol Genet.2012 Jan 15;21(2):287-99. doi: 10.1093/hmg/ddr458.
- Ha AD, Parratt KL, Rendtorff ND, Lodahl M, Ng K, Rowe DB, Sue CM, Hayes MW,Tranebjaerg L, Fung VS. The phenotypic spectrum of dystonia in Mohr-Tranebjaergsyndrome. Mov Disord. 2012 Jul;27(8):1034-40. doi: 10.1002/mds.25033.
- Jyonouchi H, Geng L, Törüner GA, Vinekar K, Feng D, Fitzgerald-Bocarsly P.Monozygous twins with a microdeletion syndrome involving BTK, DDP1, and two othergenes; evidence of intact dendritic cell development and TLR responses. Eur JPediatr. 2008 Mar;167(3):317-21.
- Richter D, Conley ME, Rohrer J, Myers LA, Zahradka K, Kelecić J, Sertić J,Stavljenić-Rukavina A. A contiguous deletion syndrome of X-linkedagammaglobulinemia and sensorineural deafness. Pediatr Allergy Immunol. 2001Apr;12(2):107-11.
- Roesch K, Curran SP, Tranebjaerg L, Koehler CM. Human deafness dystoniasyndrome is caused by a defect in assembly of the DDP1/TIMM8a-TIMM13 complex. HumMol Genet. 2002 Mar 1;11(5):477-86.
- Roesch K, Hynds PJ, Varga R, Tranebjaerg L, Koehler CM. The calcium-bindingaspartate/glutamate carriers, citrin and aralar1, are new substrates for theDDP1/TIMM8a-TIMM13 complex. Hum Mol Genet. 2004 Sep 15;13(18):2101-11.
- Sedivá A, Smith CI, Asplund AC, Hadac J, Janda A, Zeman J, Hansíková H,Dvoráková L, Mrázová L, Velbri S, Koehler C, Roesch K, Sullivan KE, Futatani T,Ochs HD. Contiguous X-chromosome deletion syndrome encompassing the BTK, TIMM8A, TAF7L, and DRP2 genes. J Clin Immunol. 2007 Nov;27(6):640-6.
- Tranebjærg L. Deafness-Dystonia-Optic Neuronopathy Syndrome. 2003 Feb 6[updated 2019 Nov 21]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): Universityof Washington, Seattle; 1993-2020. Available fromhttp://www.ncbi.nlm.nih.gov/books/NBK1216/
