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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
PDE10A
phosphodiesterase 10A
Chromosome 6 Β· 6q27
NCBI Gene: 10846Ensembl: ENSG00000112541.19HGNC: HGNC:8772UniProt: A0A1B1UZQ1
70PubMed Papers
22Diseases
6Drugs
11Pathogenic Variants
CLINICAL
FDA Approved TargetOMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
3',5'-cGMP-stimulated cyclic-nucleotide phosphodiesterase activitycAMP binding3',5'-cyclic-AMP phosphodiesterase activity3',5'-cyclic-GMP phosphodiesterase activityinfantile-onset generalized dyskinesia with orofacial involvementstriatal degeneration, autosomal dominant 2strokecoronary artery disease
✦AI Summary

PDE10A (phosphodiesterase 10A) is a cyclic nucleotide phosphodiesterase that regulates intracellular signaling by hydrolyzing both cAMP and cGMP, with preferential catalytic efficiency for cAMP 1234. PDE10A plays a critical role in regulating cyclic nucleotide levels within the striatum, a brain region controlling movement and cognition 4. The enzyme modulates signal transduction pathways including cAMP/PKA and cGMP/PKG signaling 5. Beyond neurological functions, PDE10A inhibition suppresses tumor cell growth and, notably, protects against doxorubicin-induced cardiotoxicity by antagonizing cardiomyocyte death through enhanced cGMP/PKG signaling and attenuating FoxO3-mediated atrophy 5. In humans, PDE10A variants are associated with complex hyperkinetic movement disorders presenting with chorea as a predominant feature in affected children 6. Additionally, PDE10A genetic variants show evidence of natural selection in the Bajau people (Sea Nomads), where they contribute to increased spleen size and enhanced hypoxia tolerance for breath-hold diving 7. PDE10A mutations are implicated in infantile-onset dyskinesia and autosomal dominant striatal degeneration, emphasizing its critical role in striatal motor control.

Sources cited
1
PDE10A hydrolyzes both cAMP and cGMP with higher affinity for cAMP
PMID: 10373451
2
PDE10A catalytic properties and substrate specificity for cyclic nucleotides
PMID: 10393245
3
PDE10A substrate preference and cyclic nucleotide hydrolysis efficiency
PMID: 17389385
4
PDE10A critical role in regulating cAMP/cGMP levels in striatum controlling movement and cognition
PMID: 27058447
5
PDE10A inhibition prevents doxorubicin cardiotoxicity via cGMP/PKG signaling and protects against tumor growth
PMID: 37232184
6
PDE10A mutations cause complex childhood-onset hyperkinetic movement disorders with chorea predominance
PMID: 36054588
7
PDE10A genetic variants show natural selection in Bajau people affecting spleen size and hypoxia tolerance
PMID: 29677510
Disease Associationsβ“˜22
infantile-onset generalized dyskinesia with orofacial involvementOpen Targets
0.76Strong
striatal degeneration, autosomal dominant 2Open Targets
0.72Strong
strokeOpen Targets
0.55Moderate
coronary artery diseaseOpen Targets
0.54Moderate
hypothyroidismOpen Targets
0.54Moderate
hypertensionOpen Targets
0.53Moderate
Autosomal dominant striatal neurodegenerationOpen Targets
0.52Moderate
thyroid diseaseOpen Targets
0.50Moderate
striatal degeneration, autosomal dominantOpen Targets
0.50Moderate
hyperthyroidismOpen Targets
0.49Moderate
cardiovascular diseaseOpen Targets
0.47Moderate
ThyrotoxicosisOpen Targets
0.41Moderate
myxedemaOpen Targets
0.41Moderate
Airway obstructionOpen Targets
0.37Weak
Castleman diseaseOpen Targets
0.37Weak
intermittent vascular claudicationOpen Targets
0.37Weak
Recurrent thrombophlebitisOpen Targets
0.37Weak
chronic kidney diseaseOpen Targets
0.35Weak
Hashimoto's thyroiditisOpen Targets
0.33Weak
Hepatitis, AlcoholicOpen Targets
0.33Weak
Dyskinesia, limb and orofacial, infantile-onsetUniProt
Striatal degeneration, autosomal dominant 2UniProt
Pathogenic Variants11
NM_001385079.1(PDE10A):c.1698C>G (p.Phe566Leu)Likely pathogenic
not provided|Infantile-onset generalized dyskinesia with orofacial involvement
β˜…β˜…β˜†β˜†2026β†’ Residue 566
NM_001385079.1(PDE10A):c.1798T>C (p.Phe600Leu)Pathogenic
Striatal degeneration, autosomal dominant 2|not provided
β˜…β˜…β˜†β˜†2023β†’ Residue 600
NM_001385079.1(PDE10A):c.1696T>C (p.Phe566Leu)Pathogenic
Striatal degeneration, autosomal dominant 2|not provided
β˜…β˜…β˜†β˜†2022β†’ Residue 566
NM_001385079.1(PDE10A):c.1799T>G (p.Phe600Cys)Pathogenic
Infantile-onset generalized dyskinesia with orofacial involvement|Striatal degeneration, autosomal dominant 2
β˜…β˜…β˜†β˜†2018β†’ Residue 600
NM_001385079.1(PDE10A):c.2375dup (p.Asn792fs)Likely pathogenic
Infantile-onset generalized dyskinesia with orofacial involvement
β˜…β˜†β˜†β˜†2022β†’ Residue 792
NM_001385079.1(PDE10A):c.1450C>T (p.Arg484Trp)Likely pathogenic
Infantile-onset generalized dyskinesia with orofacial involvement
β˜…β˜†β˜†β˜†2019β†’ Residue 484
NM_001385079.1(PDE10A):c.2575C>T (p.Gln859Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2018β†’ Residue 859
NM_001385079.1(PDE10A):c.1144G>C (p.Ala382Pro)Pathogenic
Infantile-onset generalized dyskinesia with orofacial involvement
β˜†β˜†β˜†β˜†2016β†’ Residue 382
NM_001385079.1(PDE10A):c.1118A>G (p.Tyr373Cys)Pathogenic
Infantile-onset generalized dyskinesia with orofacial involvement|Global developmental delay;Generalized hypotonia
β˜†β˜†β˜†β˜†2016β†’ Residue 373
NM_001385079.1(PDE10A):c.2133_2142del (p.Ser712fs)Likely pathogenic
Infantile-onset generalized dyskinesia with orofacial involvement
β˜†β˜†β˜†β˜†β†’ Residue 712
NM_001385079.1(PDE10A):c.2795T>G (p.Ile932Ser)Likely pathogenic
Infantile-onset generalized dyskinesia with orofacial involvement
β˜†β˜†β˜†β˜†β†’ Residue 932
View on ClinVar β†—
Drug Targets6
BALIPODECTPhase II
Phosphodiesterase 10A inhibitor
schizophrenia
DIPYRIDAMOLEApproved
3',5'-cyclic phosphodiesterase inhibitor
coronary artery disease
IBUDILASTApproved
Phosphodiesterase 10A inhibitor
Castleman disease
MARDEPODECTPhase II
Phosphodiesterase 10A inhibitor
Huntington disease
PBF-999Phase I
Phosphodiesterase 10A inhibitor
Huntington disease
PENTOXIFYLLINEApproved
Adenosine A2 receptor antagonist
cardiovascular disease
Related Genes
PRKACGProtein interaction98%PRKACAProtein interaction97%PRKACBProtein interaction96%ADCY4Protein interaction95%GMPSProtein interaction93%CAMK2AProtein interaction92%
Tissue Expression6 tissues
Heart
100%
Ovary
47%
Brain
21%
Lung
8%
Liver
7%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
PDE10APRKACGPRKACAPRKACBADCY4GMPSCAMK2A
PROTEIN STRUCTURE
Preparing viewer…
PDB2OUR Β· 1.45 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.43Moderately Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.26 [0.17–0.43]
RankingsWhere PDE10A stands among ~20K protein-coding genes
  • #6,743of 20,598
    Most Researched70
  • #479of 1,025
    FDA-Approved Drug Targets3
  • #2,767of 5,498
    Most Pathogenic Variants11
  • #2,284of 17,882
    Most Constrained (LOEUF)0.43 Β· top quartile
Genes detectedPDE10A
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Diagnosis of myelin oligodendrocyte glycoprotein antibody-associated disease: International MOGAD Panel proposed criteria.
PMID: 36706773
Lancet Neurol Β· 2023
1.00
2
Myelin-oligodendrocyte glycoprotein antibody-associated disease.
PMID: 34418402
Lancet Neurol Β· 2021
0.90
3
Autoimmune Encephalitis Misdiagnosis in Adults.
PMID: 36441519
JAMA Neurol Β· 2023
0.80
4
Paraneoplastic Neurologic Disorders.
PMID: 36781586
Curr Neurol Neurosci Rep Β· 2023
0.70
5
PDE10A Inactivation Prevents Doxorubicin-Induced Cardiotoxicity and Tumor Growth.
PMID: 37232184
Circ Res Β· 2023
0.60