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Gene Review

PDE11A  -  phosphodiesterase 11A

Homo sapiens

Synonyms: Dual 3',5'-cyclic-AMP and-GMP phosphodiesterase 11A, cAMP and cGMP phosphodiesterase 11A
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Disease relevance of PDE11A

  • A genome-wide scan identifies mutations in the gene encoding phosphodiesterase 11A4 (PDE11A) in individuals with adrenocortical hyperplasia [1].
  • Furthermore, PDE11A expression was also detected in several human carcinomas [2].
  • The present investigation of a large cohort of adrenocortical tumors suggests that PDE11A sequence defects predispose to a variety of lesions (beyond micronodular adrenocortical hyperplasia) and may contribute to the development of these tumors in the general population [3].

High impact information on PDE11A

  • PDE11A codes for a dual-specificity PDE that is expressed in adrenal cortex and is partially inhibited by tadalafil and other PDE inhibitors; its germline inactivation is associated with adrenocortical hyperplasia, suggesting another means by which dysregulation of cAMP signaling causes endocrine tumors [1].
  • Remission on antidepressants was significantly associated with polymorphisms in PDE1A and PDE11A [4].
  • Polymorphisms in PDE9A and PDE11A were found to be associated with the diagnosis of MDD [4].
  • Thus, we found significant associations with both the diagnosis of MDD and remission in response to antidepressants with SNPs in the PDE11A gene [4].
  • We show here that PDE11A haplotype GAACC is significantly associated with MDD [4].

Biological context of PDE11A


Anatomical context of PDE11A


Associations of PDE11A with chemical compounds

  • PDE11A is sensitive to the nonselective PDE inhibitor 3-isobutyl-1-methylxanthine (IBMX) as well as zaprinast and dipyridamole, inhibitors that are generally considered relatively specific for the cGMP-selective PDEs, with IC(50) values of 49.8 microM, 12.0 microM, and 0.37 microM, respectively [6].

Other interactions of PDE11A

  • Interestingly, both PRKAR1A and PDE11A gene products control the cAMP signaling pathway, which can be altered at various levels in endocrine tumors [9].

Analytical, diagnostic and therapeutic context of PDE11A

  • This possibility is further supported by the detection of three distinct proteins of approximately 78, approximately 65, and approximately 56 kDa by Western blotting of human tissues for PDE11A isoforms [6].
  • Molecular cloning and characterization of a distinct human phosphodiesterase gene family: PDE11A [6].
  • cDNAs encoding a novel phosphodiesterase, phosphodiesterase 11A (PDE11A), were isolated by a combination of reverse transcriptase-polymerase chain reaction using degenerate oligonucleotide primers and rapid amplification of cDNA ends [7].
  • We now studied the frequency of two missense substitutions, R804H and R867G, in conserved regions of the enzyme in several sets of normal controls, including 745 individuals enrolled in a longitudinal cohort study, the New York Cancer Project. In the latter, we also screened for the presence of the previously identified PDE11A nonsense mutations [10].


  1. A genome-wide scan identifies mutations in the gene encoding phosphodiesterase 11A4 (PDE11A) in individuals with adrenocortical hyperplasia. Horvath, A., Boikos, S., Giatzakis, C., Robinson-White, A., Groussin, L., Griffin, K.J., Stein, E., Levine, E., Delimpasi, G., Hsiao, H.P., Keil, M., Heyerdahl, S., Matyakhina, L., Libè, R., Fratticci, A., Kirschner, L.S., Cramer, K., Gaillard, R.C., Bertagna, X., Carney, J.A., Bertherat, J., Bossis, I., Stratakis, C.A. Nat. Genet. (2006) [Pubmed]
  2. Expression of PDE11A in normal and malignant human tissues. D'Andrea, M.R., Qiu, Y., Haynes-Johnson, D., Bhattacharjee, S., Kraft, P., Lundeen, S. J. Histochem. Cytochem. (2005) [Pubmed]
  3. Phosphodiesterase 11A (PDE11A) and genetic predisposition to adrenocortical tumors. Libé, R., Fratticci, A., Coste, J., Tissier, F., Horvath, A., Ragazzon, B., Rene-Corail, F., Groussin, L., Bertagna, X., Raffin-Sanson, M.L., Stratakis, C.A., Bertherat, J. Clin. Cancer Res. (2008) [Pubmed]
  4. Phosphodiesterase genes are associated with susceptibility to major depression and antidepressant treatment response. Wong, M.L., Whelan, F., Deloukas, P., Whittaker, P., Delgado, M., Cantor, R.M., McCann, S.M., Licinio, J. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  5. Genomic organization of the human phosphodiesterase PDE11A gene. Evolutionary relatedness with other PDEs containing GAF domains. Yuasa, K., Kanoh, Y., Okumura, K., Omori, K. Eur. J. Biochem. (2001) [Pubmed]
  6. Molecular cloning and characterization of a distinct human phosphodiesterase gene family: PDE11A. Fawcett, L., Baxendale, R., Stacey, P., McGrouther, C., Harrow, I., Soderling, S., Hetman, J., Beavo, J.A., Phillips, S.C. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  7. Isolation and characterization of two novel phosphodiesterase PDE11A variants showing unique structure and tissue-specific expression. Yuasa, K., Kotera, J., Fujishige, K., Michibata, H., Sasaki, T., Omori, K. J. Biol. Chem. (2000) [Pubmed]
  8. 3',5'-cyclic nucleotide phosphodiesterase 11A: localization in human tissues. Loughney, K., Taylor, J., Florio, V.A. Int. J. Impot. Res. (2005) [Pubmed]
  9. PRKAR1A mutations in primary pigmented nodular adrenocortical disease. Cazabat, L., Ragazzon, B., Groussin, L., Bertherat, J. Pituitary (2006) [Pubmed]
  10. Adrenal hyperplasia and adenomas are associated with inhibition of phosphodiesterase 11A in carriers of PDE11A sequence variants that are frequent in the population. Horvath, A., Giatzakis, C., Robinson-White, A., Boikos, S., Levine, E., Griffin, K., Stein, E., Kamvissi, V., Soni, P., Bossis, I., de Herder, W., Carney, J.A., Bertherat, J., Gregersen, P.K., Remmers, E.F., Stratakis, C.A. Cancer Res. (2006) [Pubmed]
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