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 a translocase of the mitochondrial outer membrane (TOM) that is essential for protein transport into mitochondria.
In humans, certain alleles of this gene have been statistically associated with an increased risk of developing late-onset Alzheimer's Disease. One study has found that TOMM40 risk alleles appears twice as often in people with Alzheimer's disease than those without it. Because TOMM40 is located on chromosome 19, and is closely adjacent to APOE, 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.
^ abFreitas EM, Zhang WJ, Lalonde JP, Tay GK, Gaudieri S, Ashworth LK, Van Bockxmeer FM, Dawkins RL (1998). "Sequencing of 42kb of the APO E-C2 gene cluster reveals a new gene: PEREC1". DNA Seq. 9 (2): 89–100. doi:10.3109/10425179809086433. PMID10520737.
^Humphries AD, Streimann IC, Stojanovski D, Johnston AJ, Yano M, Hoogenraad NJ, Ryan MT (March 2005). "Dissection of the mitochondrial import and assembly pathway for human Tom40". J. Biol. Chem. 280 (12): 11535–43. doi:10.1074/jbc.M413816200. PMID15644312.
^Devi L, Prabhu BM, Galati DF, Avadhani NG, Anandatheerthavarada HK (August 2006). "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. doi:10.1523/JNEUROSCI.1469-06.2006. PMID16943564.
Walker LC, Waddell N, Ten Haaf A, et al. (2008). "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. doi:10.1007/s10549-007-9848-5. PMID18095154.
Borowsky ME, Das B, Axiotis CA, et al. (2006). "Haymaker gene expression in malignant and normal gynecologic tissues". J. Histochem. Cytochem. 54 (7): 753–61. doi:10.1369/jhc.5A6765.2006. PMID16495475.
Johnston AJ, Hoogenraad J, Dougan DA, et al. (2003). "Insertion and assembly of human tom7 into the preprotein translocase complex of the outer mitochondrial membrane". J. Biol. Chem. 277 (44): 42197–204. doi:10.1074/jbc.M205613200. PMID12198123.
Das B, Tao SZ, Mushnitsky R, Norin AJ (2002). "Genetic identity and differential expression of p38.5 (Haymaker) in human malignant and nonmalignant cells". Int. J. Cancer. 94 (6): 800–6. doi:10.1002/ijc.1555. PMID11745481.
Suzuki H, Okazawa Y, Komiya T, et al. (2001). "Characterization of rat TOM40, a central component of the preprotein translocase of the mitochondrial outer membrane". J. Biol. Chem. 275 (48): 37930–6. doi:10.1074/jbc.M006558200. PMID10980201.