Alternative titles; symbols
HGNC Approved Gene Symbol: ALDH3A1
Cytogenetic location: 17p11.2 Genomic coordinates (GRCh38): 17:19,737,984-19,748,298 (from NCBI)
See 100640. Teng (1981) described an isozymic form of aldehyde dehydrogenase (ALDH) in stomach tissue. It did not use formaldehyde, acetaldehyde, or pyruvic aldehyde. Furfuraldehyde and, to a lesser extent, propionaldehyde were readily oxidized. Teng (1981) found 1 genetic variant among 71 Chinese stomach specimens and a second different variant among 33 Asiatic Indian specimens. Unlike liver ALDH, which appears to be a tetramer, the electrophoretic pattern in the heterozygotes suggested that stomach ALDH is a monomer. ALDH3 is also present in lung.
Using PCR with primers based on conserved regions of aldehyde dehydrogenases, Hsu et al. (1992) isolated ALDH3 clones from a human stomach cDNA library. The ALDH3 open reading frame encodes a protein of 453 amino acids. Human ALDH3 protein is 81% identical to that of ALDH3 from rat hepatocarcinoma cells. By analysis of Northern blots and PCR products, Hsu et al. (1992) found that ALDH3 is transcribed at high levels in human stomach and in hepatoma cells, but at very low levels in normal liver. ALDH3 protein expressed in E. coli exhibited kinetic properties similar to that of ALDH3 purified from human stomach and liver.
Reviews
Vasiliou et al. (1999) reviewed eukaryotic aldehyde dehydrogenase genes, tabulated allelic variants in the human, and recommended nomenclature based on divergent evolution and chromosomal mapping. They considered ALDH3 a 'trivial' designation and suggested ALDH3A1 as the official symbol.
Hsu et al. (1992) found that the ALDH3 gene contains 10 exons spanning approximately 8 kb.
By study of somatic cell hybrids, Santisteban et al. (1985) assigned the ALDH3 gene to chromosome 17.
By in situ hybridization, Hiraoka et al. (1995) mapped the ALDH3 gene to 17p11.2. Rogers et al. (1997) found that ALDH3 is 50 to 85 kb from a closely related gene, ALDH10 (270200), and stated that the close linkage, sequence similarity (66% identity between the coding sequences, excluding the final 35 codons unique to ALDH10), and structural conservation indicate that the 2 genes share a common origin.
ALDH3 constitutes 20 to 40% of the total water-soluble proteins in mammalian cornea. Kays and Piatigorsky (1997) showed by Northern blot analysis that ALDH3 expression in the mouse is at least 500-fold higher in the cornea than in any other tissue examined, with very low levels of expression detected in stomach, urinary bladder, ocular lens, and lung. Histochemical localization showed that this exceptional level of expression in the mouse cornea occurs in the anterior epithelial cells, and that little ALDH3 is present in the keratocytes or corneal endothelial cells. As the anterior-most layer of the cornea, the epithelium is faced with continual impingement by environmental stressors, such as UV radiation, that can have deleterious effects on cellular function. The abundant expression of ALDH3 in the corneal epithelium is believed to play a role in protecting this vital tissue, as well as the rest of the eye, from damage generated by UV exposure. With a demonstrated substrate preference for the medium-length aliphatic aldehyde products of UV-induced lipid peroxidation, ALDH3 is thought to be responsible for preventing the accumulation of these toxic products in the cornea. In addition to its detoxification function, ALDH3 may protect the eye by the direct absorption of UV radiation. The high UV-absorbing capacity of ALDH3, which is attributed both to its high tryptophan content and to its ability to bind NAD, led some investigators to term this major corneal protein 'absorbin.'
Kays and Piatigorsky (1997) showed that a promoter fragment derived from the mouse ALDH3 gene is capable of targeting expression of the chloramphenicol acetyltransferease (cat) reporter gene specifically to the epithelial layer of the cornea in transgenic mice, mimicking the expression pattern of the endogenous ALDH3 gene. Together with other results, the experiments indicated that tissue-specific expression of ALDH3 is determined by positive and negative elements in the 5-prime flanking region of the gene and suggested putative silencers located in intron 1.
Data on gene frequencies of allelic variants were tabulated by Roychoudhury and Nei (1988).
Hiraoka, L. R., Hsu, L., Hsieh, C.-L. Assignment of ALDH3 to human chromosome 17p11.2 and ALDH5 to human chromosome 9p13. Genomics 25: 323-325, 1995. [PubMed: 7774944] [Full Text: https://doi.org/10.1016/0888-7543(95)80150-k]
Hsu, L. C., Chang, W.-C., Shibuya, A., Yoshida, A. Human stomach aldehyde dehydrogenase cDNA and genomic cloning, primary structure, and expression in Escherichia coli. J. Biol. Chem. 267: 3030-3037, 1992. [PubMed: 1737758]
Kays, W. T., Piatigorsky, J. Aldehyde dehydrogenase class 3 expression: identification of a cornea-preferred gene promoter in transgenic mice. Proc. Nat. Acad. Sci. 94: 13594-13599, 1997. [PubMed: 9391071] [Full Text: https://doi.org/10.1073/pnas.94.25.13594]
Rogers, G. R., Markova, N. G., De Laurenzi, V., Rizzo, W. B., Compton, J. G. Genomic organization and expression of the human fatty aldehyde dehydrogenase gene (FALDH). Genomics 39: 127-135, 1997. [PubMed: 9027499] [Full Text: https://doi.org/10.1006/geno.1996.4501]
Roychoudhury, A. K., Nei, M. Human Polymorphic Genes: World Distribution. New York: Oxford Univ. Press (pub.) 1988.
Santisteban, I., Povey, S., West, L. F., Parrington, J. M., Hopkinson, D. A. Chromosome assignment, biochemical and immunological studies on a human aldehyde dehydrogenase, ALDH3. Ann. Hum. Genet. 49: 87-100, 1985. [PubMed: 4073832] [Full Text: https://doi.org/10.1111/j.1469-1809.1985.tb01680.x]
Teng, Y.-S. Stomach aldehyde dehydrogenase: report of a new locus. Hum. Hered. 31: 74-77, 1981. [PubMed: 7228061] [Full Text: https://doi.org/10.1159/000153181]
Vasiliou, V., Bairoch, A., Tipton, K. F., Nebert, D. W. Eukaryotic aldehyde dehydrogenase (ALDH) genes: human polymorphisms, and recommended nomenclature based on divergent evolution and chromosomal mapping. Pharmacogenetics 9: 421-434, 1999. [PubMed: 10780262]