TOMM40 explained

Mitochondrial import receptor subunit TOM40 homolog is a protein which in humans is encoded by the TOMM40 gene.^{[1] [2]}

Function

TOMM40 codes for a protein that is embedded into outer membranes of mitochondria and is required for the movement of proteins into mitochondria. More precisely, TOMM40 is the channel-forming subunit of the translocase of the outer membrane (TOM) complex, a translocase of the outer mitochondrial membrane that is essential for protein transport into the mitochondrion.^[3]

Clinical significance

Certain alleles of this gene have been statistically associated with an increased risk of developing late-onset Alzheimer's disease.^{[4] [5]} One study has found that TOMM40 risk alleles appear twice as often in people with Alzheimer's disease than those without it.^[6] Because TOMM40 is located on chromosome 19, and is closely adjacent to APOE,^[2] another gene known to be associated with Alzheimer's, another study has suggested that the statistically significant correlation of TOMM40 with Alzheimer's is due to linkage disequilibrium.^{[7] [8]}

See also

• TOMM20
• TOMM22
• TOMM70A

Further reading

• Walker LC, Waddell N, Ten Haaf A, etal . Use of expression data and the CGEMS genome-wide breast cancer association study to identify genes that may modify risk in BRCA1/2 mutation carriers . Breast Cancer Research and Treatment. 112. 2. 229–36. 2008. 18095154 . 10.1007/s10549-007-9848-5 . 795870 .
• Szafranski K, Schindler S, Taudien S, etal . Violating the splicing rules: TG dinucleotides function as alternative 3' splice sites in U2-dependent introns . Genome Biol. . 8 . 8 . R154 . 2008 . 17672918 . 10.1186/gb-2007-8-8-r154 . 2374985 . free .
• Borowsky ME, Das B, Axiotis CA, etal . Haymaker gene expression in malignant and normal gynecologic tissues . J. Histochem. Cytochem. . 54 . 7 . 753–61 . 2006 . 16495475 . 10.1369/jhc.5A6765.2006 . free .
• Gerhard DS, Wagner L, Feingold EA, etal . The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC) . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 .
• Strausberg RL, Feingold EA, Grouse LH, etal . 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 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .
• Johnston AJ, Hoogenraad J, Dougan DA, etal . Insertion and assembly of human tom7 into the preprotein translocase complex of the outer mitochondrial membrane . J. Biol. Chem. . 277 . 44 . 42197–204 . 2003 . 12198123 . 10.1074/jbc.M205613200 . free .
• Das B, Tao SZ, Mushnitsky R, Norin AJ . Genetic identity and differential expression of p38.5 (Haymaker) in human malignant and nonmalignant cells . Int. J. Cancer . 94 . 6 . 800–6 . 2002 . 11745481 . 10.1002/ijc.1555 . 20287267 .
• Suzuki H, Okazawa Y, Komiya T, etal . Characterization of rat TOM40, a central component of the preprotein translocase of the mitochondrial outer membrane . J. Biol. Chem. . 275 . 48 . 37930–6 . 2001 . 10980201 . 10.1074/jbc.M006558200 . free .

Notes and References

1. Web site: Entrez Gene: TOMM40 translocase of outer mitochondrial membrane 40 homolog (yeast).
2. Freitas EM, Zhang WJ, Lalonde JP, Tay GK, Gaudieri S, Ashworth LK, Van Bockxmeer FM, Dawkins RL . Sequencing of 42kb of the APO E-C2 gene cluster reveals a new gene: PEREC1 . DNA Seq. . 9 . 2 . 89–100 . 1998 . 10520737 . 10.3109/10425179809086433.
3. Humphries AD, Streimann IC, Stojanovski D, Johnston AJ, Yano M, Hoogenraad NJ, Ryan MT . Dissection of the mitochondrial import and assembly pathway for human Tom40 . J. Biol. Chem. . 280 . 12 . 11535–43 . March 2005 . 15644312 . 10.1074/jbc.M413816200 . free .
4. Devi L, Prabhu BM, Galati DF, Avadhani NG, Anandatheerthavarada HK . Accumulation of amyloid precursor protein in the mitochondrial import channels of human Alzheimer's disease brain is associated with mitochondrial dysfunction . J. Neurosci. . 26 . 35 . 9057–68 . August 2006 . 16943564 . 10.1523/JNEUROSCI.1469-06.2006 . 6675337 . free .
5. Web site: Apoe-3 And Tomm-40 Haplotypes Determine Inheritance Of Alzheimer's Disease Independently Of Apoe-4 Risk . Roses AD, Lutz MW, Huentelman MJ, Chiba-Falek O, Welsh-Bohmer KA, Reiman EM . 2009-07-12 . Alzheimer's Association 2009 International Conference on Alzheimer's Disease . Alzheimer's Association . 2009-07-14.

   Web site: Alzheimer's Gene Discovery May Help Predict Age Disease Hits . Cortez MF . 2009-07-12 . Bloomberg.com . 2009-07-14 .

6. Potkin SG, Guffanti G, Lakatos A, etal . Hippocampal Atrophy as a Quantitative Trait in a Genome-Wide Association Study Identifying Novel Susceptibility Genes for Alzheimer's Disease . PLOS ONE . 4 . 8 . e6501 . 2009 . 19668339 . 10.1371/journal.pone.0006501 . 2719581 . 2009PLoSO...4.6501P . Domschke . Katharina. free .
7. Yu CE, Seltman H, Peskind ER, Galloway N, Zhou PX, Rosenthal E, Wijsman EM, Tsuang DW, Devlin B, Schellenberg GD . Comprehensive Analysis of APOE and Selected Proximate Markers for Late-onset Alzheimer Disease: Pattern of Linkage Disequilibrium and Disease/Marker Association . Genomics . 89 . 6 . 655–65 . June 2007 . 17434289 . 1978251 . 10.1016/j.ygeno.2007.02.002 .
8. Bu G . Apolipoprotein E and its receptors in Alzheimer's disease: pathways, pathogenesis and therapy . Nat. Rev. Neurosci. . 10 . 5 . 333–44 . May 2009 . 19339974 . 2908393 . 10.1038/nrn2620 .