PDE9A (phosphodiesterase 9A)

Gene

• Entrez ID: 5152
• Gene name: Phosphodiesterase 9A
• Gene symbol: PDE9A
• Synonyms (NCBI Gene): HSPDE9A2
• Chromosome: 21
• Chromosome location: 21q22.3
• Summary: The protein encoded by this gene catalyzes the hydrolysis of cAMP and cGMP to their corresponding monophosphates. The encoded protein plays a role in signal transduction by regulating the intracellular concentration of these cyclic nucleotides. Multiple t

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT1221078	hsa-miR-1915	CLIP-seq
MIRT1221079	hsa-miR-4436b-3p	CLIP-seq
MIRT1221080	hsa-miR-4660	CLIP-seq
MIRT1221081	hsa-miR-4685-5p	CLIP-seq
MIRT1221082	hsa-miR-4755-3p	CLIP-seq
MIRT1221083	hsa-miR-764	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004114	Function	3',5'-cyclic-nucleotide phosphodiesterase activity	IEA
GO:0004114	Function	3',5'-cyclic-nucleotide phosphodiesterase activity	TAS	9856478
GO:0004115	Function	3',5'-cyclic-AMP phosphodiesterase activity	IBA
GO:0005515	Function	Protein binding	IPI	16189514, 19060904, 25416956, 25910212, 26871637, 29892012, 31515488, 32296183
GO:0005654	Component	Nucleoplasm	IDA
GO:0005737	Component	Cytoplasm	IEA
GO:0005783	Component	Endoplasmic reticulum	IEA
GO:0005794	Component	Golgi apparatus	IEA
GO:0005829	Component	Cytosol	HDA	16780588
GO:0005829	Component	Cytosol	IDA
GO:0005829	Component	Cytosol	TAS
GO:0005886	Component	Plasma membrane	IDA
GO:0005886	Component	Plasma membrane	IEA
GO:0007165	Process	Signal transduction	IEA
GO:0007165	Process	Signal transduction	TAS	9856478
GO:0008081	Function	Phosphoric diester hydrolase activity	IEA
GO:0010613	Process	Positive regulation of cardiac muscle hypertrophy	IEA
GO:0010613	Process	Positive regulation of cardiac muscle hypertrophy	ISS
GO:0016020	Component	Membrane	IEA
GO:0016787	Function	Hydrolase activity	IEA
GO:0032587	Component	Ruffle membrane	IEA
GO:0042383	Component	Sarcolemma	IDA	25799991
GO:0042383	Component	Sarcolemma	IEA
GO:0042802	Function	Identical protein binding	IPI	26871637
GO:0042995	Component	Cell projection	IEA
GO:0043204	Component	Perikaryon	IEA
GO:0046068	Process	CGMP metabolic process	IDA	9624146
GO:0046069	Process	CGMP catabolic process	IBA
GO:0046069	Process	CGMP catabolic process	IDA	25799991
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	IDA	9624146, 25799991
GO:0047555	Function	3',5'-cyclic-GMP phosphodiesterase activity	IEA
GO:0048471	Component	Perinuclear region of cytoplasm	IEA
GO:0141162	Process	Negative regulation of cAMP/PKA signal transduction	IBA
GO:1900273	Process	Positive regulation of long-term synaptic potentiation	IEA
GO:2000178	Process	Negative regulation of neural precursor cell proliferation	IEA

Other IDs

• MIM: 602973
• HGNC: 8795
• e!Ensembl: ENSG00000160191

Protein

• UniProt ID: O76083
• Protein name: High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A (EC 3.1.4.35)
• Protein function: Specifically hydrolyzes the second messenger cGMP, which is a key regulator of many important physiological processes. Highly specific: compared to other members of the cyclic nucleotide phosphodiesterase family, has the highest affinity and sel
• PDB: 2HD1, 2YY2, 3DY8, 3DYL, 3DYN, 3DYQ, 3DYS, 3JSI, 3JSW, 3K3E, 3K3H, 3N3Z, 3QI3, 3QI4, 4E90, 4G2J, 4G2L, 4GH6, 4Y86, 4Y87, 4Y8C, 6A3N, 6LZZ, 7F0I, 8BPY
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00233	PDEase_I	311 → 542		Domain

• Tissue specificity: TISSUE SPECIFICITY: Expressed in all tissues examined (testis, brain, small intestine, skeletal muscle, heart, lung, thymus, spleen, placenta, kidney, liver, pancreas, ovary and prostate) except blood (PubMed:9624146). Highest levels in brain, heart, kidn
• Sequence:

  MGSGSSSYRPKAIYLDIDGRIQKVIFSKYCNSSDIMDLFCIATGLPRNTTISLLTTDDAM
  VSIDPTMPANSERTPYKVRPVAIKQLSAGVEDKRTTSRGQSAERPLRDRRVVGLEQPRRE
  GAFESGQVEPRPREPQGCYQEGQRIPPEREELIQSVLAQVAEQFSRAFKINELKAEVANH
  LAVLEKRVELEGLKVVEIEKCKSDIKKMREELAARSSRTNCPCKYSFLDNHKKLTPRRDV
  PTYPKYLLSPETIEALRKPTFDVWLWEPNEMLSCLEHMYHDLGLVRDFSINPVTLRRWLF
  CVHDNYRNNPFHNFRHCFCVAQMMYSMVWLCSLQEKFSQTDILILMTAAICHDLDHPGYN
  NTYQINARTELAVRYNDISPLENHHCAVAFQILAEPECNIFSNIPPDGFKQIRQGMITLI
  LATDMARHAEIMDSFKEKMENFDYSNEEHMTLLKMILIKCCDISNEVRPMEVAEPWVDCL
  LEEYFMQSDREKSEGLPVAPFMDRDKVTKATAQIGFIKFVLIPMFETVTKLFPMVEEIML
  QPLWESRDRYEELKRIDDAMKELQKKTDSLTSGATEKSRERSRDVKNSEGDCA

• Sequence length: 593

Pathways

KEGG:

Purine metabolism
Metabolic pathways

Reactome:

cGMP effects

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ALZHEIMER DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BIPOLAR DISORDER	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CORONARY ARTERY DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEMENTIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OROFACIAL CLEFT	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
RESTLESS LEGS SYNDROME	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SAPHO SYNDROME	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Anemia Sickle Cell	Sickle cell anemia	Pubtator	18564357	Associate	★☆☆☆☆ Found in Text Mining only
Atherosclerosis	Atherosclerosis	BEFREE	30249014		★☆☆☆☆ Found in Text Mining only
Bipolar Disorder	Bipolar Disorder	PSYGENET_DG	10950928		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cognition Disorders	Cognitive disorder	BEFREE	22780914		★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	37446311	Associate	★☆☆☆☆ Found in Text Mining only
Congestive heart failure	Congestive Heart Failure	BEFREE	25799991, 28649129		★☆☆☆☆ Found in Text Mining only
Dementia	Dementia	BEFREE	29505961		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Dementia, Vascular	Dementia	BEFREE	30916555		★☆☆☆☆ Found in Text Mining only
Down Syndrome	Down Syndrome	BEFREE	22132128		★☆☆☆☆ Found in Text Mining only
Down Syndrome	Down syndrome	Pubtator	22132128	Associate	★☆☆☆☆ Found in Text Mining only
Heart Diseases	Heart Diseases	BEFREE	25799991, 28649129		★☆☆☆☆ Found in Text Mining only
Heart failure	Heart Failure	BEFREE	25799991, 28649129		★☆☆☆☆ Found in Text Mining only
Impaired cognition	Impaired Cognition	BEFREE	28783948		★☆☆☆☆ Found in Text Mining only
Major Depressive Disorder	Mental Depression	BEFREE	17008408, 23319000		★☆☆☆☆ Found in Text Mining only
Neurodegenerative Disorders	Neurodegenerative Disorders	BEFREE	22328573		★☆☆☆☆ Found in Text Mining only
Parkinson Disease	Parkinson disease	Pubtator	40240887	Associate	★☆☆☆☆ Found in Text Mining only
Presenile dementia	Senile Dementia	BEFREE	29505961		★☆☆☆☆ Found in Text Mining only
Pulmonary Disease Chronic Obstructive	Chronic obstructive pulmonary disease	Pubtator	33658578	Associate	★☆☆☆☆ Found in Text Mining only
Schizophrenia	Schizophrenia	BEFREE	31507355		★☆☆☆☆ Found in Text Mining only
Unipolar Depression	Mental Depression	BEFREE	23319000		★☆☆☆☆ Found in Text Mining only