PDE10A

phosphodiesterase 10A, the group of Phosphodiesterases

Basic information

Region (hg38): 6:165327286-165988117

Links

ENSG00000112541 ∙ NCBI:10846 ∙ OMIM:610652 ∙ HGNC:8772 ∙ Uniprot:Q9Y233 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 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: CGD

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 ClinVar and linked to the PDE10A gene.

• not provided (153 variants)
• Inborn genetic diseases (18 variants)
• Striatal degeneration, autosomal dominant 2 (6 variants)
• Infantile-onset generalized dyskinesia with orofacial involvement (5 variants)
• not specified (2 variants)
• Infantile-onset generalized dyskinesia with orofacial involvement;Striatal degeneration, autosomal dominant 2 (1 variants)
• PDE10A-related condition (1 variants)
• Striatal degeneration, autosomal dominant 2;Infantile-onset generalized dyskinesia with orofacial involvement (1 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			1	34	12	47
missense	2	3	53	4		62
nonsense	1		4			5
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region			5	7	1	13
non coding			2	25	11	38
Total	3	3	62	63	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	Benign/Likely benign (Dec 21, 2023)
6-165336177-T-G		Inborn genetic diseases	Uncertain significance (Jan 25, 2022)
6-165336193-C-T			Uncertain significance (Aug 14, 2023)
6-165336194-G-A			Likely benign (Aug 09, 2022)
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)
6-165339338-C-T			Likely benign (Nov 29, 2021)
6-165339366-G-T		PDE10A-related disorder	Conflicting classifications of pathogenicity (Jan 16, 2024)

GnomAD

Source: gnomAD

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: dbNSFP

• 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