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Gene and Protein Information  |
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| Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | - | 609 | 3p14.3 | PDE12 | phosphodiesterase 12 | |
| Mouse | - | 608 | 14 A3 | Pde12 | phosphodiesterase 12 | |
| Rat | - | 608 | 16p16 | Pde12 | phosphodiesterase 12 | |
| Database Links |
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| Alphafold | Q6L8Q7 (Hs), Q3TIU4 (Mm), Q6AXQ5 (Rn) |
| BRENDA | 3.1.13.4 |
| ChEMBL Target | CHEMBL4523342 (Hs) |
| Ensembl Gene | ENSG00000174840 (Hs), ENSMUSG00000043702 (Mm), ENSRNOG00000059442 (Rn) |
| Entrez Gene | 201626 (Hs), 211948 (Mm), 306231 (Rn) |
| Human Protein Atlas | ENSG00000174840 (Hs) |
| KEGG Enzyme | 3.1.13.4 |
| KEGG Gene | hsa:201626 (Hs), mmu:211948 (Mm), rno:306231 (Rn) |
| OMIM | 616519 (Hs) |
| Pharos | Q6L8Q7 (Hs) |
| RefSeq Nucleotide | NM_177966 (Hs), NM_178668 (Mm), NM_001411708 (Rn) |
| RefSeq Protein | NP_808881 (Hs), NP_848783 (Mm), NP_001398637 (Rn) |
| UniProtKB | Q6L8Q7 (Hs), Q3TIU4 (Mm), Q6AXQ5 (Rn) |
| Wikipedia | PDE12 (Hs) |
| Selected 3D Structures |
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| Enzyme Reaction |
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Download all structure-activity data for this target as a CSV file 
| Inhibitors | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Immunopharmacology Comments |
| PDE12 acts as a negative regulator of a 2-5A (2′,5′-linked oligoadenylate) activated pathway of the innate interferon response to viral infection. Some RNA viruses, including coronaviruses, encode 2',5'-phosphodiesterases as a mechanism to combat their hosts' antiviral immunity [5-6]. Inhibitors of PDE12 function are proposed as novel antiviral agents [3-4]. |
| General Comments |
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RNase L which is part of the 2',5'-oligoadenylate synthetase (OAS)-Ribonuclease L (RNase L) innate immune pathway, is activated by 2',5'-oligoadenylates (2-5As; a signalling intermediate of OAS activity), with active RNase L going on to hydrolyse viral (and cellular) RNAs and suppress viral replication [1-2,4]. Phosphodiesterase 12 (PDE12) is a 2-5A degrading enzyme that counteracts RNase L activation during viral infections, to provide a braking mechanism on the innate interferon-mediated antiviral response [7]. PDE12 has potential as a pan-RNA virus antiviral drug target. Selective inhibitors are proposed as a method to maintain the presence of 2-5As and activation of RNaseL, to induce a clinically useful antiviral effect [3-4]. Two PDE12-selective inhibitors (CO-63 and CO-17; structures not disclosed) have demonstrated antiviral activity against a range of RNA viruses, including hepatitis C virus, dengue virus, West Nile virus and SARS-CoV-2 [3] Some RNA viruses, including coronaviruses, encode 2',5'-phosphodiesterases as an inbuilt capability to combat their hosts' antiviral immune response [4-6]. |
1. Dong B, Silverman RH. (1995) 2-5A-dependent RNase molecules dimerize during activation by 2-5A. J Biol Chem, 270 (8): 4133-7. [PMID:7876164]
2. Huang H, Zeqiraj E, Dong B, Jha BK, Duffy NM, Orlicky S, Thevakumaran N, Talukdar M, Pillon MC, Ceccarelli DF et al.. (2014) Dimeric structure of pseudokinase RNase L bound to 2-5A reveals a basis for interferon-induced antiviral activity. Mol Cell, 53 (2): 221-34. [PMID:24462203]
3. Thursz M, Sadiq F, Tree JA, Karayiannis P, Beasley DWC, Dejnirattisai W, Mongkolsapaya J, Screaton G, Wand M, Elmore MJ et al.. (2023) Inhibition of phosphodiesterase 12 results in antiviral activity against several RNA viruses including SARS-CoV-2. J Gen Virol, 104 (7). [PMID:37432877]
4. Wood ER, Bledsoe R, Chai J, Daka P, Deng H, Ding Y, Harris-Gurley S, Kryn LH, Nartey E, Nichols J et al.. (2015) The Role of Phosphodiesterase 12 (PDE12) as a Negative Regulator of the Innate Immune Response and the Discovery of Antiviral Inhibitors. J Biol Chem, 290 (32): 19681-96. [PMID:26055709]
5. Zhang R, Jha BK, Ogden KM, Dong B, Zhao L, Elliott R, Patton JT, Silverman RH, Weiss SR. (2013) Homologous 2',5'-phosphodiesterases from disparate RNA viruses antagonize antiviral innate immunity. Proc Natl Acad Sci U S A, 110 (32): 13114-9. [PMID:23878220]
6. Zhao L, Jha BK, Wu A, Elliott R, Ziebuhr J, Gorbalenya AE, Silverman RH, Weiss SR. (2012) Antagonism of the interferon-induced OAS-RNase L pathway by murine coronavirus ns2 protein is required for virus replication and liver pathology. Cell Host Microbe, 11 (6): 607-16. [PMID:22704621]
7. Zhou A, Hassel BA, Silverman RH. (1993) Expression cloning of 2-5A-dependent RNAase: a uniquely regulated mediator of interferon action. Cell, 72 (5): 753-65. [PMID:7680958]
Phosphodiesterases (other): phosphodiesterase 12. Last modified on 31/07/2023. Accessed on 17/01/2025. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=3207.
target has curated data in GtoImmuPdb
