PDE10A
Basic information
Region (hg38): 6:165327287-165988117
Links
Phenotypes
GenCC
Source:
- striatal degeneration, autosomal dominant 2 (Strong), mode of inheritance: AD
- dyskinesia, limb and orofacial, infantile-onset (Strong), mode of inheritance: AR
- striatal degeneration, autosomal dominant 2 (Moderate), mode of inheritance: AD
- dyskinesia, limb and orofacial, infantile-onset (Moderate), mode of inheritance: AR
- childhood-onset benign chorea with striatal involvement (Supportive), mode of inheritance: AD
- infantile-onset generalized dyskinesia with orofacial involvement (Strong), mode of inheritance: AR
- striatal degeneration, autosomal dominant 2 (Strong), mode of inheritance: AD
Clinical Genomic Database
Source:
Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
---|---|---|---|---|---|
Striatal degeneration, autosomal dominant 2 | AD/AR | Neurologic | In Striatal degeneration, autosomal dominant 2, treatment with levodopa has been described as beneficial in some individuals who developed Parkinsonism | Neurologic | 27058446; 27058447 |
ClinVar
This is a list of variants' phenotypes submitted to
- not provided (3 variants)
- Striatal degeneration, autosomal dominant 2 (2 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the PDE10A gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
---|---|---|---|---|---|---|
synonymous | 46 | 12 | 59 | |||
missense | 69 | 78 | ||||
nonsense | 5 | |||||
start loss | 0 | |||||
frameshift | 1 | |||||
inframe indel | 0 | |||||
splice donor/acceptor (+/-2bp) | 1 | |||||
splice region | 6 | 7 | 1 | 14 | ||
non coding | 30 | 11 | 44 | |||
Total | 3 | 3 | 79 | 80 | 23 |
Variants in PDE10A
This is a list of pathogenic ClinVar variants found in the PDE10A region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
Position | Type | Phenotype | Significance | ClinVar |
---|---|---|---|---|
6-165333039-C-A | Inborn genetic diseases | Uncertain significance (Aug 08, 2023) | ||
6-165333053-G-A | Uncertain significance (Feb 04, 2022) | |||
6-165333058-G-A | Likely benign (Aug 23, 2021) | |||
6-165333065-G-T | Infantile-onset generalized dyskinesia with orofacial involvement | Uncertain significance (Oct 30, 2020) | ||
6-165333086-T-C | Uncertain significance (Nov 01, 2023) | |||
6-165333095-C-T | Uncertain significance (Jun 13, 2022) | |||
6-165333102-C-T | Uncertain significance (Nov 27, 2023) | |||
6-165333142-T-C | Likely benign (Mar 01, 2022) | |||
6-165333143-G-A | Likely benign (Dec 02, 2021) | |||
6-165336146-C-T | Uncertain significance (Jul 19, 2023) | |||
6-165336147-G-A | Inborn genetic diseases | Uncertain significance (Aug 10, 2021) | ||
6-165336155-G-C | PDE10A-related disorder | Benign (Jan 15, 2024) | ||
6-165336176-A-G | PDE10A-related disorder | Likely benign (Dec 21, 2023) | ||
6-165336177-T-G | Inborn genetic diseases | Uncertain significance (Jan 25, 2022) | ||
6-165336186-A-C | Uncertain significance (Feb 05, 2024) | |||
6-165336193-C-T | Uncertain significance (Aug 14, 2023) | |||
6-165336194-G-A | Likely benign (Aug 09, 2022) | |||
6-165336194-G-C | not specified | Likely benign (Jun 25, 2024) | ||
6-165336206-C-T | Benign (Oct 13, 2023) | |||
6-165336221-T-C | Likely benign (Aug 23, 2021) | |||
6-165336230-C-G | Likely benign (Oct 13, 2023) | |||
6-165339266-A-G | Likely benign (Jun 22, 2023) | |||
6-165339268-T-C | Benign (Nov 23, 2023) | |||
6-165339299-C-T | Likely benign (Dec 31, 2022) | |||
6-165339323-A-C | Inborn genetic diseases | Uncertain significance (Dec 18, 2023) |
GnomAD
Source:
Gene | Type | Bio Type | Transcript | Coding Exons | Length |
---|---|---|---|---|---|
PDE10A | protein_coding | protein_coding | ENST00000539869 | 22 | 659316 |
pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
---|---|---|---|---|---|---|
1.00 | 0.000137 | 125739 | 0 | 9 | 125748 | 0.0000358 |
Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
---|---|---|---|---|---|---|
Missense | 3.76 | 222 | 445 | 0.499 | 0.0000241 | 5200 |
Missense in Polyphen | 54 | 166.1 | 0.32511 | 1936 | ||
Synonymous | 0.258 | 156 | 160 | 0.974 | 0.00000901 | 1462 |
Loss of Function | 5.51 | 4 | 43.0 | 0.0931 | 0.00000200 | 547 |
LoF frequencies by population
Ethnicity | Sum of pLOFs | p |
---|---|---|
African & African-American | 0.0000905 | 0.0000905 |
Ashkenazi Jewish | 0.00 | 0.00 |
East Asian | 0.0000544 | 0.0000544 |
Finnish | 0.0000926 | 0.0000924 |
European (Non-Finnish) | 0.0000176 | 0.0000176 |
Middle Eastern | 0.0000544 | 0.0000544 |
South Asian | 0.00 | 0.00 |
Other | 0.000336 | 0.000326 |
dbNSFP
Source:
- Function
- FUNCTION: Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. Can hydrolyze both cAMP and cGMP, but has higher affinity for cAMP and is more efficient with cAMP as substrate. May play a critical role in regulating cAMP and cGMP levels in the striatum, a region of the brain that contributes to the control of movement and cognition. {ECO:0000250|UniProtKB:Q8CA95, ECO:0000269|PubMed:17389385}.;
- Disease
- DISEASE: Dyskinesia, limb and orofacial, infantile-onset (IOLOD) [MIM:616921]: An autosomal recessive, early-onset hyperkinetic movement disorder characterized by axial hypotonia, dyskinesia of the limbs and trunk, orofacial dyskinesia, drooling, and dysarthria. The severity of the hyperkinesis is variable. {ECO:0000269|PubMed:27058446}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Striatal degeneration, autosomal dominant 2 (ADSD2) [MIM:616922]: An autosomal dominant disorder characterized by striatal degeneration and dysfunction of basal ganglia, resulting in hyperkinesis. {ECO:0000269|PubMed:27058447}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Purine metabolism - Homo sapiens (human);Morphine addiction - Homo sapiens (human);Purine Nucleoside Phosphorylase Deficiency;Mercaptopurine Action Pathway;Azathioprine Action Pathway;Xanthine Dehydrogenase Deficiency (Xanthinuria);Adenylosuccinate Lyase Deficiency;AICA-Ribosiduria;Thioguanine Action Pathway;Adenine phosphoribosyltransferase deficiency (APRT);Mitochondrial DNA depletion syndrome;Myoadenylate deaminase deficiency;Purine Metabolism;Molybdenum Cofactor Deficiency;Adenosine Deaminase Deficiency;Gout or Kelley-Seegmiller Syndrome;Lesch-Nyhan Syndrome (LNS);Xanthinuria type I;Xanthinuria type II;Phosphodiesterases in neuronal function;Signaling by GPCR;Signal Transduction;G alpha (s) signalling events;Purine nucleotides nucleosides metabolism;Hemostasis;cGMP effects;Nitric oxide stimulates guanylate cyclase;Platelet homeostasis;GPCR downstream signalling
(Consensus)
Recessive Scores
- pRec
- 0.149
Intolerance Scores
- loftool
- 0.378
- rvis_EVS
- -0.98
- rvis_percentile_EVS
- 8.8
Haploinsufficiency Scores
- pHI
- 0.330
- hipred
- Y
- hipred_score
- 0.809
- ghis
- 0.511
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.733
Gene Damage Prediction
All | Recessive | Dominant | |
---|---|---|---|
Mendelian | Medium | Medium | Medium |
Primary Immunodeficiency | Medium | Medium | Medium |
Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Pde10a
- Phenotype
- growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); homeostasis/metabolism phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan);
Gene ontology
- Biological process
- cAMP catabolic process;G protein-coupled receptor signaling pathway;regulation of protein kinase A signaling;negative regulation of cGMP-mediated signaling;negative regulation of cAMP-mediated signaling;cGMP catabolic process
- Cellular component
- cytosol;membrane;perikaryon
- Molecular function
- 3',5'-cyclic-nucleotide phosphodiesterase activity;3',5'-cyclic-AMP phosphodiesterase activity;cGMP-stimulated cyclic-nucleotide phosphodiesterase activity;cAMP binding;cGMP binding;metal ion binding;3',5'-cyclic-GMP phosphodiesterase activity