PDE10A (phosphodiesterase 10A)

Gene

• Entrez ID: 10846
• Gene name: Phosphodiesterase 10A
• Gene symbol: PDE10A
• Synonyms (NCBI Gene): ADSD2, HSPDE10A, IOLOD, LINC00473, PDE10A19
• Chromosome: 6
• Chromosome location: 6q27
• Summary: The protein encoded by this gene belongs to the cyclic nucleotide phosphodiesterase family. It plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This protein can hydrolyze both cAMP and cGMP to the co

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs61733392	G>C	Conflicting-interpretations-of-pathogenicity	Non coding transcript variant, coding sequence variant, missense variant
rs778899140	T>C	Pathogenic, likely-pathogenic	Non coding transcript variant, missense variant, 5 prime UTR variant, coding sequence variant
rs875989839	C>G	Pathogenic	5 prime UTR variant, coding sequence variant, missense variant, non coding transcript variant
rs875989840	A>G	Pathogenic	Coding sequence variant, missense variant, non coding transcript variant
rs875989841	A>G	Pathogenic	5 prime UTR variant, coding sequence variant, missense variant, non coding transcript variant
rs1332740547	G>A,T	Likely-pathogenic	5 prime UTR variant, coding sequence variant, synonymous variant, missense variant, non coding transcript variant
rs1554258695	A>C	Likely-pathogenic, pathogenic	Missense variant, coding sequence variant, non coding transcript variant
rs1583275773	G>A	Likely-pathogenic	Stop gained, coding sequence variant, 5 prime UTR variant, non coding transcript variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT521992	hsa-miR-7151-5p	HITS-CLIP	21572407
MIRT509235	hsa-miR-6867-5p	HITS-CLIP	21572407
MIRT509234	hsa-miR-190a-3p	HITS-CLIP	21572407
MIRT509233	hsa-miR-1287-3p	HITS-CLIP	21572407
MIRT509238	hsa-miR-5011-5p	PAR-CLIP	20371350
MIRT509237	hsa-miR-511-3p	PAR-CLIP	20371350
MIRT509236	hsa-miR-223-5p	PAR-CLIP	20371350
MIRT509235	hsa-miR-6867-5p	PAR-CLIP	20371350
MIRT509234	hsa-miR-190a-3p	PAR-CLIP	20371350
MIRT521992	hsa-miR-7151-5p	PAR-CLIP	21572407
MIRT509237	hsa-miR-511-3p	PAR-CLIP	21572407
MIRT509236	hsa-miR-223-5p	PAR-CLIP	21572407
MIRT509235	hsa-miR-6867-5p	PAR-CLIP	21572407
MIRT509234	hsa-miR-190a-3p	PAR-CLIP	21572407
MIRT509233	hsa-miR-1287-3p	PAR-CLIP	21572407
MIRT509237	hsa-miR-511-3p	PAR-CLIP	21572407
MIRT509236	hsa-miR-223-5p	PAR-CLIP	21572407
MIRT509235	hsa-miR-6867-5p	PAR-CLIP	21572407
MIRT509234	hsa-miR-190a-3p	PAR-CLIP	21572407
MIRT509233	hsa-miR-1287-3p	PAR-CLIP	21572407
MIRT509238	hsa-miR-5011-5p	PAR-CLIP	21572407
MIRT509237	hsa-miR-511-3p	PAR-CLIP	21572407
MIRT509236	hsa-miR-223-5p	PAR-CLIP	21572407
MIRT509235	hsa-miR-6867-5p	PAR-CLIP	21572407
MIRT509234	hsa-miR-190a-3p	PAR-CLIP	21572407
MIRT509233	hsa-miR-1287-3p	PAR-CLIP	21572407
MIRT528903	hsa-miR-33a-3p	PAR-CLIP	22012620
MIRT528902	hsa-miR-5579-5p	PAR-CLIP	22012620
MIRT528901	hsa-miR-5681b	PAR-CLIP	22012620
MIRT509238	hsa-miR-5011-5p	PAR-CLIP	23446348
MIRT521992	hsa-miR-7151-5p	PAR-CLIP	23446348
MIRT509237	hsa-miR-511-3p	PAR-CLIP	23446348
MIRT509236	hsa-miR-223-5p	PAR-CLIP	23446348
MIRT509235	hsa-miR-6867-5p	PAR-CLIP	23446348
MIRT509234	hsa-miR-190a-3p	PAR-CLIP	23446348
MIRT509233	hsa-miR-1287-3p	PAR-CLIP	23446348
MIRT509238	hsa-miR-5011-5p	PAR-CLIP	23446348
MIRT509237	hsa-miR-511-3p	PAR-CLIP	23446348
MIRT509236	hsa-miR-223-5p	PAR-CLIP	23446348
MIRT509235	hsa-miR-6867-5p	PAR-CLIP	23446348
MIRT509234	hsa-miR-190a-3p	PAR-CLIP	23446348
MIRT509238	hsa-miR-5011-5p	PAR-CLIP	23446348
MIRT509237	hsa-miR-511-3p	PAR-CLIP	23446348
MIRT509236	hsa-miR-223-5p	PAR-CLIP	23446348
MIRT509235	hsa-miR-6867-5p	PAR-CLIP	23446348
MIRT509234	hsa-miR-190a-3p	PAR-CLIP	23446348
MIRT509233	hsa-miR-1287-3p	PAR-CLIP	23446348
MIRT738881	hsa-miR-3679-3p	HITS-CLIP	33718276
MIRT738883	hsa-miR-3665	HITS-CLIP	33718276
MIRT521992	hsa-miR-7151-5p	HITS-CLIP	21572407
MIRT509235	hsa-miR-6867-5p	HITS-CLIP	21572407
MIRT509234	hsa-miR-190a-3p	HITS-CLIP	21572407
MIRT509233	hsa-miR-1287-3p	HITS-CLIP	21572407
MIRT509238	hsa-miR-5011-5p	PAR-CLIP	20371350
MIRT509237	hsa-miR-511-3p	PAR-CLIP	20371350
MIRT509236	hsa-miR-223-5p	PAR-CLIP	20371350
MIRT509235	hsa-miR-6867-5p	PAR-CLIP	20371350
MIRT509234	hsa-miR-190a-3p	PAR-CLIP	20371350
MIRT521992	hsa-miR-7151-5p	PAR-CLIP	21572407
MIRT509237	hsa-miR-511-3p	PAR-CLIP	21572407
MIRT509236	hsa-miR-223-5p	PAR-CLIP	21572407
MIRT509235	hsa-miR-6867-5p	PAR-CLIP	21572407
MIRT509234	hsa-miR-190a-3p	PAR-CLIP	21572407
MIRT509233	hsa-miR-1287-3p	PAR-CLIP	21572407
MIRT509237	hsa-miR-511-3p	PAR-CLIP	21572407
MIRT509236	hsa-miR-223-5p	PAR-CLIP	21572407
MIRT509235	hsa-miR-6867-5p	PAR-CLIP	21572407
MIRT509234	hsa-miR-190a-3p	PAR-CLIP	21572407
MIRT509233	hsa-miR-1287-3p	PAR-CLIP	21572407
MIRT509238	hsa-miR-5011-5p	PAR-CLIP	21572407
MIRT509237	hsa-miR-511-3p	PAR-CLIP	21572407
MIRT509236	hsa-miR-223-5p	PAR-CLIP	21572407
MIRT509235	hsa-miR-6867-5p	PAR-CLIP	21572407
MIRT509234	hsa-miR-190a-3p	PAR-CLIP	21572407
MIRT509233	hsa-miR-1287-3p	PAR-CLIP	21572407
MIRT528903	hsa-miR-33a-3p	PAR-CLIP	22012620
MIRT528902	hsa-miR-5579-5p	PAR-CLIP	22012620
MIRT528901	hsa-miR-5681b	PAR-CLIP	22012620
MIRT509238	hsa-miR-5011-5p	PAR-CLIP	23446348
MIRT521992	hsa-miR-7151-5p	PAR-CLIP	23446348
MIRT509237	hsa-miR-511-3p	PAR-CLIP	23446348
MIRT509236	hsa-miR-223-5p	PAR-CLIP	23446348
MIRT509235	hsa-miR-6867-5p	PAR-CLIP	23446348
MIRT509234	hsa-miR-190a-3p	PAR-CLIP	23446348
MIRT509233	hsa-miR-1287-3p	PAR-CLIP	23446348
MIRT509238	hsa-miR-5011-5p	PAR-CLIP	23446348
MIRT509237	hsa-miR-511-3p	PAR-CLIP	23446348
MIRT509236	hsa-miR-223-5p	PAR-CLIP	23446348
MIRT509235	hsa-miR-6867-5p	PAR-CLIP	23446348
MIRT509234	hsa-miR-190a-3p	PAR-CLIP	23446348
MIRT509238	hsa-miR-5011-5p	PAR-CLIP	23446348
MIRT509237	hsa-miR-511-3p	PAR-CLIP	23446348
MIRT509236	hsa-miR-223-5p	PAR-CLIP	23446348
MIRT509235	hsa-miR-6867-5p	PAR-CLIP	23446348
MIRT509234	hsa-miR-190a-3p	PAR-CLIP	23446348
MIRT509233	hsa-miR-1287-3p	PAR-CLIP	23446348
MIRT1219885	hsa-miR-142-5p	CLIP-seq
MIRT1219886	hsa-miR-181a	CLIP-seq
MIRT1219887	hsa-miR-181b	CLIP-seq
MIRT1219888	hsa-miR-181c	CLIP-seq
MIRT1219889	hsa-miR-181d	CLIP-seq
MIRT739842	hsa-miR-2116	CLIP-seq
MIRT1219890	hsa-miR-217	CLIP-seq
MIRT1219891	hsa-miR-23a	CLIP-seq
MIRT1219892	hsa-miR-23b	CLIP-seq
MIRT1219893	hsa-miR-23c	CLIP-seq
MIRT1219894	hsa-miR-2467-3p	CLIP-seq
MIRT1219895	hsa-miR-297	CLIP-seq
MIRT1219896	hsa-miR-3121-5p	CLIP-seq
MIRT1219897	hsa-miR-3122	CLIP-seq
MIRT1219898	hsa-miR-3153	CLIP-seq
MIRT1219899	hsa-miR-3179	CLIP-seq
MIRT1219900	hsa-miR-3202	CLIP-seq
MIRT1219901	hsa-miR-342-5p	CLIP-seq
MIRT1219902	hsa-miR-3615	CLIP-seq
MIRT1219903	hsa-miR-3671	CLIP-seq
MIRT1219904	hsa-miR-3678-3p	CLIP-seq
MIRT1219905	hsa-miR-3913-5p	CLIP-seq
MIRT1219906	hsa-miR-3936	CLIP-seq
MIRT1219907	hsa-miR-4262	CLIP-seq
MIRT739844	hsa-miR-4273	CLIP-seq
MIRT739845	hsa-miR-4289	CLIP-seq
MIRT1219908	hsa-miR-4307	CLIP-seq
MIRT1219909	hsa-miR-4476	CLIP-seq
MIRT1219910	hsa-miR-452	CLIP-seq
MIRT1219911	hsa-miR-4664-5p	CLIP-seq
MIRT1219912	hsa-miR-4668-5p	CLIP-seq
MIRT1219913	hsa-miR-4676-3p	CLIP-seq
MIRT739843	hsa-miR-4677-5p	CLIP-seq
MIRT1219914	hsa-miR-4705	CLIP-seq
MIRT1219915	hsa-miR-4719	CLIP-seq
MIRT1219916	hsa-miR-4731-3p	CLIP-seq
MIRT1219917	hsa-miR-4738-3p	CLIP-seq
MIRT1219918	hsa-miR-4801	CLIP-seq
MIRT1219919	hsa-miR-485-3p	CLIP-seq
MIRT1219920	hsa-miR-496	CLIP-seq
MIRT1219921	hsa-miR-520d-5p	CLIP-seq
MIRT1219922	hsa-miR-524-5p	CLIP-seq
MIRT1219923	hsa-miR-543	CLIP-seq
MIRT739846	hsa-miR-548c-3p	CLIP-seq
MIRT1219924	hsa-miR-548g	CLIP-seq
MIRT1219925	hsa-miR-561	CLIP-seq
MIRT1219926	hsa-miR-567	CLIP-seq
MIRT738882	hsa-miR-657	CLIP-seq
MIRT738884	hsa-miR-764	CLIP-seq
MIRT738882	hsa-miR-657	CLIP-seq
MIRT738884	hsa-miR-764	CLIP-seq
MIRT2063578	hsa-miR-3646	CLIP-seq
MIRT2292063	hsa-miR-545	CLIP-seq
MIRT2292064	hsa-miR-2276	CLIP-seq
MIRT2292065	hsa-miR-3609	CLIP-seq
MIRT2292066	hsa-miR-3647-3p	CLIP-seq
MIRT2292067	hsa-miR-425	CLIP-seq
MIRT2292068	hsa-miR-4772-3p	CLIP-seq
MIRT2292069	hsa-miR-520g	CLIP-seq
MIRT2292070	hsa-miR-520h	CLIP-seq
MIRT2292071	hsa-miR-544	CLIP-seq
MIRT2292072	hsa-miR-548ah	CLIP-seq
MIRT2292073	hsa-miR-548v	CLIP-seq
MIRT2292074	hsa-miR-642b	CLIP-seq
MIRT2456057	hsa-miR-186	CLIP-seq
MIRT2456058	hsa-miR-3133	CLIP-seq
MIRT2456059	hsa-miR-4694-3p	CLIP-seq
MIRT2456060	hsa-miR-522	CLIP-seq
MIRT2589668	hsa-miR-1178	CLIP-seq
MIRT2589669	hsa-miR-1293	CLIP-seq
MIRT2589670	hsa-miR-3125	CLIP-seq
MIRT2589671	hsa-miR-323-5p	CLIP-seq
MIRT2589672	hsa-miR-3916	CLIP-seq
MIRT2589673	hsa-miR-4257	CLIP-seq
MIRT2589674	hsa-miR-4302	CLIP-seq
MIRT2589675	hsa-miR-4483	CLIP-seq
MIRT2589676	hsa-miR-4796-5p	CLIP-seq
MIRT2589677	hsa-miR-548a-3p	CLIP-seq
MIRT2589678	hsa-miR-548e	CLIP-seq
MIRT2589679	hsa-miR-548f	CLIP-seq
MIRT2589668	hsa-miR-1178	CLIP-seq
MIRT2589669	hsa-miR-1293	CLIP-seq
MIRT2589671	hsa-miR-323-5p	CLIP-seq
MIRT2589674	hsa-miR-4302	CLIP-seq
MIRT2589675	hsa-miR-4483	CLIP-seq
MIRT2589676	hsa-miR-4796-5p	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000166	Function	Nucleotide binding	IEA
GO:0003824	Function	Catalytic activity	IEA
GO:0004112	Function	Cyclic-nucleotide phosphodiesterase activity	IEA
GO:0004114	Function	3',5'-cyclic-nucleotide phosphodiesterase activity	IEA
GO:0004114	Function	3',5'-cyclic-nucleotide phosphodiesterase activity	TAS	10373451
GO:0004115	Function	3',5'-cyclic-AMP phosphodiesterase activity	IBA
GO:0004115	Function	3',5'-cyclic-AMP phosphodiesterase activity	IEA
GO:0004118	Function	3',5'-cGMP-stimulated cyclic-nucleotide phosphodiesterase activity	IBA
GO:0004118	Function	3',5'-cGMP-stimulated cyclic-nucleotide phosphodiesterase activity	IDA	19689430
GO:0005737	Component	Cytoplasm	IEA
GO:0005829	Component	Cytosol	IEA
GO:0005829	Component	Cytosol	TAS
GO:0006198	Process	CAMP catabolic process	IEA
GO:0007165	Process	Signal transduction	IEA
GO:0008081	Function	Phosphoric diester hydrolase activity	IEA
GO:0010754	Process	Negative regulation of cGMP-mediated signaling	IBA
GO:0016787	Function	Hydrolase activity	IEA
GO:0030552	Function	CAMP binding	IDA	19689430
GO:0030552	Function	CAMP binding	IEA
GO:0030552	Function	CAMP binding	NAS	15938621
GO:0030553	Function	CGMP binding	IEA
GO:0030553	Function	CGMP binding	NAS	15938621
GO:0045202	Component	Synapse	IEA
GO:0046069	Process	CGMP catabolic process	IEA
GO:0046872	Function	Metal ion binding	IEA
GO:0047555	Function	3',5'-cyclic-GMP phosphodiesterase activity	IBA
GO:0047555	Function	3',5'-cyclic-GMP phosphodiesterase activity	IEA
GO:0098978	Component	Glutamatergic synapse	IEA
GO:0106070	Process	Regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway	IEA
GO:0141161	Process	Regulation of cAMP/PKA signal transduction	IEA
GO:0141162	Process	Negative regulation of cAMP/PKA signal transduction	IBA

Other IDs

• MIM: 610652
• HGNC: 8772
• e!Ensembl: ENSG00000112541

Protein

• UniProt ID: Q9Y233
• Protein name: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (EC 3.1.4.17)
• Protein function: Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides (PubMed:10373451, PubMed:10393245, PubMed:16330539, PubMed:17389385, PubMed:27058447). Can hydrolyze both cAMP and cGMP, but has higher affin
• PDB: 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
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF01590	GAF	91 → 235	GAF domain	Domain
  PF01590	GAF	266 → 412	GAF domain	Domain
  PF00233	PDEase_I	514 → 746		Domain

• Tissue specificity: TISSUE SPECIFICITY: Abundant in the putamen and caudate nucleus regions of brain and testis, moderately expressed in the thyroid gland, pituitary gland, thalamus and cerebellum. {ECO:0000269|PubMed:10373451, ECO:0000269|PubMed:27058447}.
• Sequence:

  MRIEERKSQHLTGLTDEKVKAYLSLHPQVLDEFVSESVSAETVEKWLKRKNNKSEDESAP
  KEVSRYQDTNMQGVVYELNSYIEQRLDTGGDNQLLLYELSSIIKIATKADGFALYFLGEC
  NNSLCIFTPPGIKEGKPRLIPAGPITQGTTVSAYVAKSRKTLLVEDILGDERFPRGTGLE
  SGTRIQSVLCLPIVTAIGDLIGILELYRHWGKEAFCLSHQEVATANLAWASVAIHQVQVC
  RGLAKQTELNDFLLDVSKTYFDNIVAIDSLLEHIMIYAKNLVNADRCALFQVDHKNKELY
  SDLFDIGEEKEGKPVFKKTKEIRFSIEKGIAGQVARTGEVLNIPDAYADPRFNREVDLYT
  GYTTRNILCMPIVSRGSVIGVVQMVNKISGSAFSKTDENNFKMFAVFCALALHCANMYHR
  IRHSECIYRVTMEKLSYHSICTSEEWQGLMQFTLPVRLCKEIELFHFDIGPFENMWPGIF
  VYMVHRSCGTSCFELEKLCRFIMSVKKNYRRVPYHNWKHAVTVAHCMYAILQNNHTLFTD
  LERKGLLIACLCHDLDHRGFSNSYLQKFDHPLAALYSTSTMEQHHFSQTVSILQLEGHNI
  FSTLSSSEYEQVLEIIRKAIIATDLALYFGNRKQLEEMYQTGSLNLNNQSHRDRVIGLMM
  TACDLCSVTKLWPVTKLTANDIYAEFWAEGDEMKKLGIQPIPMMDRDKKDEVPQGQLGFY
  NAVAIPCYTTLTQILPPTEPLLKACRDNLSQWEKVIRGEETATWISSPSVAQKAAASED

• Sequence length: 779

Pathways

KEGG:

Purine metabolism
Metabolic pathways
cAMP signaling pathway
Morphine addiction

Reactome:

cGMP effects
G alpha (s) signalling events

Associated diseases

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Generalized hypotonia	Likely pathogenic; Pathogenic	rs778899140	RCV001003963
Global developmental delay	Likely pathogenic; Pathogenic	rs778899140	RCV001003963
Infantile-onset generalized dyskinesia with orofacial involvement	Likely pathogenic; Pathogenic	rs2483700484, rs2533716846, rs778899140, rs875989839, rs1554258695, rs1332740547	RCV003156373 RCV003156374 RCV000210940 RCV000210942 RCV000625744 RCV000995600
Striatal degeneration, autosomal dominant 2	Pathogenic; Likely pathogenic	rs875989840, rs875989841, rs1554258695	RCV000210938 RCV000210939 RCV000995599

Unknown
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Clear cell carcinoma of kidney	Benign	rs61733391	RCV005911662
Familial cancer of breast	Likely benign	rs556354100	RCV005869855
Gastric cancer	Benign; Likely benign	rs61733392	RCV005899705
Malignant lymphoma, large B-cell, diffuse	Likely benign	rs556354100	RCV005869857
PDE10A-related disorder	Likely benign; Benign; Uncertain significance; Conflicting classifications of pathogenicity	rs1173003721, rs77122094, rs199680048, rs140098147, rs2483700133, rs2533689494, rs79199585, rs61733392, rs143718875, rs148845227, rs6924943, rs111737394, rs761017460, rs141863025, rs754387675	RCV003965893 RCV003931076 RCV003943585 RCV003961242 RCV003412453 RCV003944188 RCV003919529 RCV003915343 RCV003936068 RCV003936143 RCV003918444 RCV003958073 RCV003902892 RCV003953389 RCV003953414
Sarcoma	Benign; Likely benign	rs61733392	RCV005899704
Thyroid cancer, nonmedullary, 1	Benign; Likely benign	rs61733392	RCV005899706
Uveal melanoma	Likely benign; Benign	rs556354100, rs61733392	RCV005869856 RCV005899703

Associations from Text Mining
Disease Name	Relationship Type	References
Aging Premature	Associate	22773346
Autism Spectrum Disorder	Associate	27404287
Bipolar Disorder	Associate	22205951, 23032945, 26905414
Carcinogenesis	Associate	27939638
Carcinoma	Associate	34120511
Carcinoma Non Small Cell Lung	Associate	27939638
Carcinoma Ovarian Epithelial	Associate	36324187
Chorea	Associate	36054588
Colonic Neoplasms	Associate	24704829
Colorectal Neoplasms	Associate	26713600
Dyskinesia Drug Induced	Associate	26210536
Fibrosarcoma	Associate	34120511
Heredodegenerative Disorders Nervous System	Associate	23691025
Huntington Disease	Associate	26198591
Inflammation	Stimulate	36324187
Kidney Neoplasms	Associate	37433798
Lesch Nyhan Syndrome	Stimulate	23691025
Mental Disorders	Associate	22521361
Myopia	Associate	35021948
Neoplasm Metastasis	Associate	27270314
Neoplasms	Associate	25979379, 27939638, 36324187, 37433798
Ovarian Neoplasms	Associate	36324187
Parkinson Disease	Inhibit	26210536
Pediatric acute onset neuropsychiatric syndrome	Associate	26905414
Personality Disorders	Associate	33450964
Prostatic Neoplasms	Associate	25979379, 33450964
Psychotic Disorders	Associate	22205951
Pulmonary Disease Chronic Obstructive	Associate	37466093
Sarcoma	Associate	34120511
Stomach Neoplasms	Associate	27270314
Substance Related Disorders	Associate	22205951