PDE10A

cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A is an enzyme that in humans is encoded by the PDE10A gene.^[5][6]

PDE10A
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2OUN, 2OUP, 2OUQ, 2OUR, 2OUS, 2OUU, 2OUV, 2OUY, 2WEY, 2Y0J, 2ZMF, 3SN7, 3SNI, 3SNL, 3UI7, 3UUO, 3WI2, 3WS8, 3WS9, 3WYK, 3WYL, 3WYM, 4AEL, 4AJD, 4AJF, 4AJG, 4AJM, 4BBX, 4DDL, 4DFF, 4FCB, 4FCD, 4HEU, 4HF4, 4LKQ, 4LLJ, 4LLK, 4LLP, 4LLX, 4LM0, 4LM1, 4LM2, 4LM3, 4LM4, 4MRW, 4MRZ, 4MS0, 4MSA, 4MSC, 4MSE, 4MSH, 4MSN, 4MUW, 4MVH, 4P0N, 4P1R, 4PHW, 4TPM, 4TPP, 4WN1, 4XY2, 4YQH, 4YS7, 4ZO5, 5C1W, 5C28, 5C29, 5C2A, 5C2H, 5DH5, 5AXQ, 5DH4, 5AXP, 5C2E, 5EDH, 5EDI, 5EDG, 5EDE, 5I2R, 5B4L, 5B4K
Identifiers
Aliases	PDE10A, HSPDE10A19, ADSD2, IOLOD, phosphodiesterase 10A, LINC00473
External IDs	OMIM: 610652; MGI: 1345143; HomoloGene: 4852; GeneCards: PDE10A; OMA:PDE10A - orthologs
Gene location (Human) Chr. Chromosome 6 (human)[1] Band 6q27 Start 165,327,287 bp[1] End 165,988,117 bp[1]
Gene location (Mouse) Chr. Chromosome 17 (mouse)[2] Band 17|17 A1 Start 8,744,204 bp[2] End 9,205,480 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in left uterine tube cartilage tissue left ovary external globus pallidus corpus epididymis putamen right ovary anterior pituitary stromal cell of endometrium caudate nucleus Top expressed in olfactory tubercle nucleus accumbens globus pallidus superior frontal gyrus temporal lobe amygdala lobe of cerebellum cerebellar vermis anterior amygdaloid area lateral septal nucleus More reference expression data BioGPS More reference expression data
Gene ontology Molecular function nucleotide binding 3',5'-cyclic-nucleotide phosphodiesterase activity cAMP binding cGMP binding metal ion binding cGMP-stimulated cyclic-nucleotide phosphodiesterase activity cyclic-nucleotide phosphodiesterase activity catalytic activity phosphoric diester hydrolase activity hydrolase activity 3',5'-cyclic-AMP phosphodiesterase activity 3',5'-cyclic-GMP phosphodiesterase activity Cellular component cytoplasm cytosol perikaryon membrane soma Biological process cAMP catabolic process regulation of protein kinase A signaling cGMP catabolic process regulation of cAMP-mediated signaling metabolism signal transduction G protein-coupled receptor signaling pathway negative regulation of cGMP-mediated signaling negative regulation of cAMP-mediated signaling Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 10846 23984 Ensembl ENSG00000112541 ENSMUSG00000023868 UniProt Q9Y233 Q8CA95 RefSeq (mRNA) NM_001130690 NM_006661 NM_001385079 NM_001290707 NM_011866 NM_001347321 RefSeq (protein) NP_001124162 NP_006652 NP_001277636 NP_001334250 NP_035996 Location (UCSC) Chr 6: 165.33 – 165.99 Mb Chr 17: 8.74 – 9.21 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Various cellular responses are regulated by the second messengers cAMP and cGMP. Phosphodiesterases, such as PDE10A, eliminate cAMP- and cGMP-mediated intracellular signaling by hydrolyzing the cyclic nucleotide to the corresponding nucleoside 5-prime monophosphate.^[6][7]

Inhibitors

3d model of compound #96 (Malamas, 2011)^[8]

• AMG-579^[9]
• Balipodect (TAK-063): IC₅₀ = 300 pM^[10]
• Compound 96: IC₅₀ = 700 pM, high selectivity against all other members of the PDE family^[8]
• CPL500036^[11]
• Mardepodect (PF-2545920)^[12]
• MK-8189
• Papaverine^[13]
• Tofisopam

Research

Preliminary evidence indicates a possible link between PDE10A expression and obesity in mice and humans.^[14] PDE10A is a regulatory protein involved in the signaling of the striatum, a region of the brain important for controlling movement and cognition. Dysfunction of the striatum has been linked to the development of schizophrenia. Inhibition of PDE10A has been identified as a potential treatment for the disorder, and an inhibitor compound (MK-8189) is as of February 2023 in Phase 2b clinical development for the treatment of schizophrenia.^[15]