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Gene Review

ALDH1A2  -  aldehyde dehydrogenase 1 family, member A2

Homo sapiens

Synonyms: Aldehyde dehydrogenase family 1 member A2, RALDH 2, RALDH(II), RALDH2, RALDH2-T, ...
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Disease relevance of ALDH1A2

  • RESULTS: An association analysis using both allelic and genotypic single-locus tests revealed a significant association between the risk for spina bifida and 3 polymorphisms in the gene ALDH1A2; however, we found no evidence of a significant multilocus association [1].
  • CONCLUSIONS: These results may suggest that polymorphisms in ALDH1A2 may influence the risk for lumbosacral myelomeningocele in humans [1].
  • The RALDH2 transcripts in T-ALL were, however, mostly initiated within the second intron [2].
  • RALDH2 was dramatically upregulated in podocytes of puromycin aminonucleoside-induced nephrosis (PAN nephrosis) rats [3].
  • The first aim of the study was to determine the tissue-specific distribution of two molecules that are thought to play a crucial function in the interaction between EPDCs and other cardiac tissues, namely the Wilms' Tumor transcription factor (WT1) and retinaldehyde-dehydrogenase2 (RALDH2) [4].

High impact information on ALDH1A2


Biological context of ALDH1A2

  • Endogenous patterns of retinoic acid (RA) signaling in avian cardiac morphogenesis were characterized by localized expression of a key RA-synthetic enzyme, RALDH2, which displayed a biphasic pattern during heart development [8].
  • At sites of bone formation, differentiated osteoblasts which express the bone-specific protein osteocalcin express high levels of RALDH2 [9].
  • Analysis of the expression of Raldh2 and local treatments with retinoic acid indicate that this signaling pathway mediates apoptosis in myogenic cells, appearing also involved in tendon maturation [10].

Anatomical context of ALDH1A2

  • Thus, RALDH2 plays a crucial role in producing RA required for pharyngeal development, and RA is one of the diffusible mesodermal signals that pattern the pharyngeal endoderm [7].
  • In conclusion, active metabolites of vitamin A, especially ATRA produced by RALDH2 play relevant roles during the repairing process of injured podocytes [3].
  • Initial RALDH2 synthesis in the posterior myocardium coincided with activation of the AMHC1 gene, a RA-responsive marker of inflow heart segments [8].
  • RALDH2 immunoreactivity was initially apparent posterior to Hensen's node of stage 5-6 embryos and subsequently in somites and unsegmented paraxial and lateral plate mesoderm overlapping atrial precursors in the cardiogenic plate of stage 9- embryos [8].
  • Experimental delay of epicardial growth distorted normal epicardial development, reduced the number of invasive WT1/RALDH2-positive EPDCs, and provoked anomalies in the coronary vessels, the ventricular myocardium, and the AV cushions [4].

Associations of ALDH1A2 with chemical compounds

  • Here, we show that the genes for retinaldehyde dehydrogenase (RALDH2) and a retinoic acid hydroxylase (CYP26A1) are expressed in complementary patterns in the Xenopus gut during looping [11].
  • It is presumed that these cells release RA in a paracrine fashion in the region of the wound; however, the RALDH2/NG2-immunoreactive cells expressed the retinoid receptors RARalpha, RARbeta, RXRalpha and RXRbeta, suggesting that RA also serves an autocrine function [12].
  • ALDH12, however, has approximately 40-fold higher activity with 9-cis- retinal than with all-trans-retinal, whereas RALDH1 and RALDH2 have equivalent and approximately 4-fold less efficiencies for 9-cis-retinal versus all-trans-retinal, respectively [13].
  • In summary, this study has shown that antler tissues contain endogenous retinoids, including 9-cis RA, and the enzyme RALDH2 that generates RA [9].
  • The developmental expression patterns of two ALDHs that function as retinaldehyde dehydrogenases, RALDH1 and RALDH2, have been described [14].

Other interactions of ALDH1A2

  • So, this gene was designated as hRDH-E2 (human epidermal retinal dehydrogenase 2) [15].
  • As for the second step of RA synthesis, a null mutation of RALDH2 is embryonic lethal, eliminating most mesodermal RA synthesis, whereas loss of RALDH1 eliminates RA synthesis only in the embryonic dorsal retina with no obvious effect on development [16].


  1. Analysis of ALDH1A2, CYP26A1, CYP26B1, CRABP1, and CRABP2 in human neural tube defects suggests a possible association with alleles in ALDH1A2. Deak, K.L., Dickerson, M.E., Linney, E., Enterline, D.S., George, T.M., Melvin, E.C., Graham, F.L., Siegel, D.G., Hammock, P., Mehltretter, L., Bassuk, A.G., Kessler, J.A., Gilbert, J.R., Speer, M.C. Birth Defects Res. Part A Clin. Mol. Teratol. (2005) [Pubmed]
  2. TAL1 and LIM-only proteins synergistically induce retinaldehyde dehydrogenase 2 expression in T-cell acute lymphoblastic leukemia by acting as cofactors for GATA3. Ono, Y., Fukuhara, N., Yoshie, O. Mol. Cell. Biol. (1998) [Pubmed]
  3. Retinoids regulate the repairing process of the podocytes in puromycin aminonucleoside-induced nephrotic rats. Suzuki, A., Ito, T., Imai, E., Yamato, M., Iwatani, H., Kawachi, H., Hori, M. J. Am. Soc. Nephrol. (2003) [Pubmed]
  4. Experimental studies on the spatiotemporal expression of WT1 and RALDH2 in the embryonic avian heart: a model for the regulation of myocardial and valvuloseptal development by epicardially derived cells (EPDCs). Pérez-Pomares, J.M., Phelps, A., Sedmerova, M., Carmona, R., González-Iriarte, M., Muñoz-Chápuli, R., Wessels, A. Dev. Biol. (2002) [Pubmed]
  5. Genetic evidence that oxidative derivatives of retinoic acid are not involved in retinoid signaling during mouse development. Niederreither, K., Abu-Abed, S., Schuhbaur, B., Petkovich, M., Chambon, P., Dollé, P. Nat. Genet. (2002) [Pubmed]
  6. PPAR{gamma} controls CD1d expression by turning on retinoic acid synthesis in developing human dendritic cells. Szatmari, I., Pap, A., R??hl, R., Ma, J.X., Illarionov, P.A., Besra, G.S., Rajnavolgyi, E., Dezso, B., Nagy, L. J. Exp. Med. (2006) [Pubmed]
  7. The regional pattern of retinoic acid synthesis by RALDH2 is essential for the development of posterior pharyngeal arches and the enteric nervous system. Niederreither, K., Vermot, J., Le Roux, I., Schuhbaur, B., Chambon, P., Dollé, P. Development (2003) [Pubmed]
  8. Sequential programs of retinoic acid synthesis in the myocardial and epicardial layers of the developing avian heart. Xavier-Neto, J., Shapiro, M.D., Houghton, L., Rosenthal, N. Dev. Biol. (2000) [Pubmed]
  9. A role for retinoic acid in regulating the regeneration of deer antlers. Allen, S.P., Maden, M., Price, J.S. Dev. Biol. (2002) [Pubmed]
  10. Tendon-muscle crosstalk controls muscle bellies morphogenesis, which is mediated by cell death and retinoic acid signaling. Rodriguez-Guzman, M., Montero, J.A., Santesteban, E., Gañan, Y., Macias, D., Hurle, J.M. Dev. Biol. (2007) [Pubmed]
  11. Role for retinoid signaling in left-right asymmetric digestive organ morphogenesis. Lipscomb, K., Schmitt, C., Sablyak, A., Yoder, J.A., Nascone-Yoder, N. Dev. Dyn. (2006) [Pubmed]
  12. Characterization of retinaldehyde dehydrogenase-2 induction in NG2-positive glia after spinal cord contusion injury. Kern, J., Schrage, K., Koopmans, G.C., Joosten, E.A., McCaffery, P., Mey, J. Int. J. Dev. Neurosci. (2007) [Pubmed]
  13. cDNA cloning and expression of a human aldehyde dehydrogenase (ALDH) active with 9-cis-retinal and identification of a rat ortholog, ALDH12. Lin, M., Napoli, J.L. J. Biol. Chem. (2000) [Pubmed]
  14. RALDH3, a retinaldehyde dehydrogenase that generates retinoic acid, is expressed in the ventral retina, otic vesicle and olfactory pit during mouse development. Mic, F.A., Molotkov, A., Fan, X., Cuenca, A.E., Duester, G. Mech. Dev. (2000) [Pubmed]
  15. Identification of the hRDH-E2 gene, a novel member of the SDR family, and its increased expression in psoriatic lesion. Matsuzaka, Y., Okamoto, K., Tsuji, H., Mabuchi, T., Ozawa, A., Tamiya, G., Inoko, H. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  16. Cytosolic retinoid dehydrogenases govern ubiquitous metabolism of retinol to retinaldehyde followed by tissue-specific metabolism to retinoic acid. Duester, G., Mic, F.A., Molotkov, A. Chem. Biol. Interact. (2003) [Pubmed]
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