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URL of this page: https://medlineplus.gov/genetics/gene/timm8a/

TIMM8A gene

translocase of inner mitochondrial membrane 8A

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.

Health Conditions Related to Genetic Changes

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.

More About This Health Condition

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)

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Gene and Variant Databases

References

  • Arai T, Zhao M, Kanegane H, van Zelm MC, Futatani T, Yamada M, Ariga T, Ochs HD, Miyawaki T, Oh-ishi T. Genetic analysis of contiguous X-chromosome deletion syndrome encompassing the BTK and TIMM8A genes. J Hum Genet. 2011 Aug;56(8):577-82. doi: 10.1038/jhg.2011.61. Epub 2011 Jul 14. Citation on PubMed
  • Binder J, Hofmann S, Kreisel S, Wohrle JC, Bazner H, Krauss JK, Hennerici MG, Bauer MF. Clinical and molecular findings in a patient with a novel mutation in the deafness-dystonia peptide (DDP1) gene. Brain. 2003 Aug;126(Pt 8):1814-20. doi: 10.1093/brain/awg174. Epub 2003 Jun 4. Citation on PubMed
  • Engl G, Florian S, Tranebjaerg 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. Epub 2011 Oct 7. Citation on PubMed
  • 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-Tranebjaerg syndrome. Mov Disord. 2012 Jul;27(8):1034-40. doi: 10.1002/mds.25033. Epub 2012 Jun 26. Citation on PubMed
  • Jyonouchi H, Geng L, Toruner GA, Vinekar K, Feng D, Fitzgerald-Bocarsly P. Monozygous twins with a microdeletion syndrome involving BTK, DDP1, and two other genes; evidence of intact dendritic cell development and TLR responses. Eur J Pediatr. 2008 Mar;167(3):317-21. doi: 10.1007/s00431-007-0493-0. Epub 2007 May 23. Citation on PubMed
  • Richter D, Conley ME, Rohrer J, Myers LA, Zahradka K, Kelecic J, Sertic J, Stavljenic-Rukavina A. A contiguous deletion syndrome of X-linked agammaglobulinemia and sensorineural deafness. Pediatr Allergy Immunol. 2001 Apr;12(2):107-11. doi: 10.1034/j.1399-3038.2001.0129999107.x. Citation on PubMed
  • Roesch K, Curran SP, Tranebjaerg L, Koehler CM. Human deafness dystonia syndrome is caused by a defect in assembly of the DDP1/TIMM8a-TIMM13 complex. Hum Mol Genet. 2002 Mar 1;11(5):477-86. doi: 10.1093/hmg/11.5.477. Citation on PubMed
  • Roesch K, Hynds PJ, Varga R, Tranebjaerg L, Koehler CM. The calcium-binding aspartate/glutamate carriers, citrin and aralar1, are new substrates for the DDP1/TIMM8a-TIMM13 complex. Hum Mol Genet. 2004 Sep 15;13(18):2101-11. doi: 10.1093/hmg/ddh217. Epub 2004 Jul 14. Citation on PubMed
  • Sediva A, Smith CI, Asplund AC, Hadac J, Janda A, Zeman J, Hansikova H, Dvorakova L, Mrazova 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. doi: 10.1007/s10875-007-9123-x. Epub 2007 Sep 12. Citation on PubMed
  • Tranebjaerg L. Deafness-Dystonia-Optic Neuronopathy Syndrome. 2003 Feb 6 [updated 2019 Nov 21]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from http://www.ncbi.nlm.nih.gov/books/NBK1216/ Citation on PubMed

The information on this site should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.