PDE8B (phosphodiesterase 8B)

Gene

• Entrez ID: 8622
• Gene name: Phosphodiesterase 8B
• Gene symbol: PDE8B
• Synonyms (NCBI Gene): ADSD, PPNAD3
• Chromosome: 5
• Chromosome location: 5q13.3
• Summary: The protein encoded by this gene is a cyclic nucleotide phosphodiesterase (PDE) that catalyzes the hydrolysis of the second messenger cAMP. The encoded protein, which does not hydrolyze cGMP, is resistant to several PDE inhibitors. Defects in this gene ar

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs121918360	A>C	Pathogenic	Coding sequence variant, intron variant, missense variant
rs878853157	C>-	Pathogenic	Intron variant, genic upstream transcript variant, coding sequence variant, frameshift variant, 5 prime UTR variant
rs878853158	G>T	Pathogenic	Intron variant, genic upstream transcript variant, stop gained, coding sequence variant, 5 prime UTR variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT018136	hsa-miR-335-5p	Microarray	18185580
MIRT1221068	hsa-miR-135a	CLIP-seq
MIRT1221069	hsa-miR-135b	CLIP-seq
MIRT1221070	hsa-miR-203	CLIP-seq
MIRT1221071	hsa-miR-3646	CLIP-seq
MIRT1221072	hsa-miR-3662	CLIP-seq
MIRT1221073	hsa-miR-3671	CLIP-seq
MIRT1221074	hsa-miR-4252	CLIP-seq
MIRT1221075	hsa-miR-4761-3p	CLIP-seq
MIRT1221076	hsa-miR-548b-3p	CLIP-seq
MIRT1221077	hsa-miR-607	CLIP-seq
MIRT2063792	hsa-miR-128	CLIP-seq
MIRT2063793	hsa-miR-27a	CLIP-seq
MIRT2063794	hsa-miR-27b	CLIP-seq
MIRT2063795	hsa-miR-4679	CLIP-seq
MIRT2063796	hsa-miR-513a-5p	CLIP-seq
MIRT2292248	hsa-miR-1224-5p	CLIP-seq
MIRT2292249	hsa-miR-132	CLIP-seq
MIRT2292250	hsa-miR-212	CLIP-seq
MIRT2292251	hsa-miR-3915	CLIP-seq
MIRT2292252	hsa-miR-3928	CLIP-seq
MIRT2292253	hsa-miR-4659a-3p	CLIP-seq
MIRT2292254	hsa-miR-4659b-3p	CLIP-seq
MIRT2292255	hsa-miR-4689	CLIP-seq
MIRT2292256	hsa-miR-4803	CLIP-seq
MIRT2292257	hsa-miR-490-5p	CLIP-seq
MIRT2292258	hsa-miR-570	CLIP-seq
MIRT2465819	hsa-miR-1226	CLIP-seq
MIRT2465820	hsa-miR-3616-3p	CLIP-seq
MIRT2465821	hsa-miR-518d-5p	CLIP-seq
MIRT2465822	hsa-miR-519b-5p	CLIP-seq
MIRT2465823	hsa-miR-519c-5p	CLIP-seq
MIRT2465824	hsa-miR-520c-5p	CLIP-seq
MIRT2465825	hsa-miR-526a	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001662	Process	Behavioral fear response	IEA
GO:0004114	Function	3',5'-cyclic-nucleotide phosphodiesterase activity	IEA
GO:0004115	Function	3',5'-cyclic-AMP phosphodiesterase activity	IBA
GO:0004115	Function	3',5'-cyclic-AMP phosphodiesterase activity	IEA
GO:0004115	Function	3',5'-cyclic-AMP phosphodiesterase activity	IMP	9784418
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:0008542	Process	Visual learning	IEA
GO:0016787	Function	Hydrolase activity	IEA
GO:0035106	Process	Operant conditioning	IEA
GO:0046676	Process	Negative regulation of insulin secretion	IEA
GO:0046872	Function	Metal ion binding	IEA
GO:0047555	Function	3',5'-cyclic-GMP phosphodiesterase activity	IBA
GO:0050885	Process	Neuromuscular process controlling balance	IEA
GO:0061179	Process	Negative regulation of insulin secretion involved in cellular response to glucose stimulus	IEA
GO:0070374	Process	Positive regulation of ERK1 and ERK2 cascade	IBA
GO:0090032	Process	Negative regulation of steroid hormone biosynthetic process	IEA
GO:0141162	Process	Negative regulation of cAMP/PKA signal transduction	IBA

Other IDs

• MIM: 603390
• HGNC: 8794
• e!Ensembl: ENSG00000113231

Protein

• UniProt ID: O95263
• Protein name: High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8B (HsPDE8B) (EC 3.1.4.53) (Cell proliferation-inducing gene 22 protein)
• Protein function: Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. May be involved in specific signaling in the thyroid gland.
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF08629	PDE8	1 → 47	PDE8 phosphodiesterase	Family
  PF13426	PAS_9	279 → 385	PAS domain	Domain
  PF00233	PDEase_I	614 → 862		Domain

• Tissue specificity: TISSUE SPECIFICITY: Abundantly expressed in the thyroid. Also very weakly expressed in brain, spinal cord and placenta. In the thyroid isoform 1 predominates, and isoforms 2 and 6 are also highly expressed. In the placenta isoforms 1 and 2 are expressed e
• Sequence:

  MGCAPSIHVSQSGVIYCRDSDESSSPRQTTSVSQGPAAPLPGLFVQTDAADAIPPSRASG
  PPSVARVRRARTELGSGSSAGSAAPAATTSRGRRRHCCSSAEAETQTCYTSVKQVSSAEV
  RIGPMRLTQDPIQVLLIFAKEDSQSDGFWWACDRAGYRCNIARTPESALECFLDKHHEII
  VIDHRQTQNFDAEAVCRSIRATNPSEHTVILAVVSRVSDDHEEASVLPLLHAGFNRRFME
  NSSIIACYNELIQIEHGEVRSQFKLRACNSVFTALDHCHEAIEITSDDHVIQYVNPAFER
  MMGYHKGELLGKELADLPKSDKNRADLLDTINTCIKKGKEWQGVYYARRKSGDSIQQHVK
  ITPVIGQGGKIRHFVSLKKLCCTTDNNKQIHKIHRDSGDNSQTEPHSFRYKNRRKESIDV
  KSISSRGSDAPSLQNRRYPSMARIHSMTIEAPITKVINIINAAQENSPVTVAEALDRVLE
  ILRTTELYSPQLGTKDEDPHTSDLVGGLMTDGLRRLSGNEYVFTKNVHQSHSHLAMPITI
  NDVPPCISQLLDNEESWDFNIFELEAITHKRPLVYLGLKVFSRFGVCEFLNCSETTLRAW
  FQVIEANYHSSNAYHNSTHAADVLHATAFFLGKERVKGSLDQLDEVAALIAATVHDVDHP
  GRTNSFLCNAGSELAVLYNDTAVLESHHTALAFQLTVKDTKCNIFKNIDRNHYRTLRQAI
  IDMVLATEMTKHFEHVNKFVNSINKPMAAEIEGSDCECNPAGKNFPENQILIKRMMIKCA
  DVANPCRPLDLCIEWAGRISEEYFAQTDEEKRQGLPVVMPVFDRNTCSIPKSQISFIDYF
  ITDMFDAWDAFAHLPALMQHLADNYKHWKTLDDLKCKSLRLPSDS

• Sequence length: 885

Pathways

KEGG:

Purine metabolism
Metabolic pathways
Cortisol synthesis and secretion
Cushing syndrome
Morphine addiction

Reactome:

G alpha (s) signalling events

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)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Autosomal dominant striatal neurodegeneration type 1	Pathogenic; Likely pathogenic	rs2149371451, rs878853157, rs878853158, rs1793090227	RCV000006763 RCV000224988 RCV000224977 RCV003234861	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
PDE8B-Related Disorders	Pathogenic	rs1389677367	RCV004579632	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Pigmented nodular adrenocortical disease, primary, 3	Pathogenic	rs121918360	RCV000006762	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATRIAL FIBRILLATION	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTISM	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTOIMMUNE THYROID DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTOSOMAL DOMINANT STRIATAL NEURODEGENERATION	—	Disgenet, Orphanet Disgenet, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BASAL GANGLIA DISEASES	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEGENERATIVE DISORDER	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DENTAL CARIES	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DIABETES MELLITUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DIABETIC NEUROPATHY	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DYSARTHRIA	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HASHIMOTO'S THYROIDITIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPERTHYROIDISM	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPOTHYROIDISM	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Melanoma	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
METABOLIC SYNDROME	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NEURODEGENERATIVE DISEASES	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NEURODEGENERATIVE DISORDERS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Nonpapillary renal cell carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OLIGODENDROGLIOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PDE8B-related disorder	Likely benign; Benign; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCHIZOPHRENIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SJOGREN SYNDROME	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Striatal Degeneration	Uncertain significance; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
THYROID DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TREATMENT-RESISTANT HYPERTENSION	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TYPE 2 DIABETES MELLITUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Adenoma	Adenoma	BEFREE	11502813		★☆☆☆☆ Found in Text Mining only
Adrenal Cortical Adenoma	Adrenocortical adenoma	BEFREE	19522821		★☆☆☆☆ Found in Text Mining only
Adrenal Gland Neoplasms	Adrenal neoplasia	BEFREE	22335482		★☆☆☆☆ Found in Text Mining only
Adrenal Gland Pheochromocytoma	Adrenal Gland Pheochromocytoma	BEFREE	19522821		★☆☆☆☆ Found in Text Mining only
Adrenal hyperplasia	Adrenal hyperplasia	BEFREE	19063937, 21115159		★☆☆☆☆ Found in Text Mining only
Adrenal hyperplasia	Adrenal hyperplasia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Atrial Fibrillation	Atrial fibrillation	Pubtator	36810794	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Autoimmune Diseases	Autoimmune Diseases	BEFREE	22493691		★☆☆☆☆ Found in Text Mining only
Autoimmune Diseases	Autoimmune disease	Pubtator	22493691	Associate	★☆☆☆☆ Found in Text Mining only
Autosomal dominant striatal neurodegeneration	Striatal Neurodegeneration	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Basal Ganglia Diseases	Basal Ganglia Diseases	CTD_human_DG	20085714		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Carney Complex	Carney complex	Pubtator	19522821	Associate	★☆☆☆☆ Found in Text Mining only
Carney Triad	Carney Triad	BEFREE	19522821		★☆☆☆☆ Found in Text Mining only
Congenital adrenal hyperplasia	Congenital adrenal hyperplasia	CTD_human_DG	18272904		★☆☆☆☆ Found in Text Mining only
Congenital adrenal hyperplasia	Congenital adrenal hyperplasia	BEFREE	19063937, 21115159		★☆☆☆☆ Found in Text Mining only
Congenital adrenal hyperplasia	Congenital adrenal hyperplasia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cushing Syndrome	Cushing`s Syndrome	BEFREE	19063937, 20829611, 21115159		★☆☆☆☆ Found in Text Mining only
Degeneration of the striatum	Degeneration of the striatum	HPO_DG			★☆☆☆☆ Found in Text Mining only
Degenerative Diseases, Central Nervous System	Degenerative Diseases, Central Nervous System	CTD_human_DG	20085714		★☆☆☆☆ Found in Text Mining only
Degenerative Diseases, Spinal Cord	Degenerative Diseases, Central Nervous System	CTD_human_DG	20085714		★☆☆☆☆ Found in Text Mining only
Deglutition Disorders	Dysphagia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus	Diabetes Mellitus	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Dwarfism	Dwarfism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dysarthria	Dysarthria	CTD_human_DG	20085714		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Dysarthria	Dysarthria	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Extrapyramidal Disorders	Extrapyramidal disease	CTD_human_DG	20085714		★☆☆☆☆ Found in Text Mining only
Gastrointestinal Stromal Tumors	Gastrointestinal stromal tumor	BEFREE	19522821		★☆☆☆☆ Found in Text Mining only
Hypertensive disease	Hypertension	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hyperthyroidism	Hyperthyroidism	GWASCAT_DG	30367059		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hypogonadism	Hypogonadism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypothyroidism	Hypothyroidism	BEFREE	22493691		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hypothyroidism	Hypothyroidism	Pubtator	22493691, 23237535	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hypothyroidism	Hypothyroidism	GWASCAT_DG	27182965, 30367059, 30595370		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lenticulostriate Disorders	Lenticulostriate Disorders	CTD_human_DG	20085714		★☆☆☆☆ Found in Text Mining only
Leukemia, Myelocytic, Acute	Leukemia	GWASCAT_DG	27903959		★☆☆☆☆ Found in Text Mining only
Linear atrophy	Atrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Miscarriage	Miscarriage	BEFREE	23237535		★☆☆☆☆ Found in Text Mining only
Movement Disorders	Movement Disorders	BEFREE	20085714, 31726290		★☆☆☆☆ Found in Text Mining only
Multiple Endocrine Neoplasia	Multiple Endocrine Neoplasia	BEFREE	19522821		★☆☆☆☆ Found in Text Mining only
Multiple Endocrine Neoplasia Type 1	Multiple Endocrine Neoplasia	BEFREE	19522821		★☆☆☆☆ Found in Text Mining only
Myocardial Infarction	Myocardial Infarction	BEFREE	23941514		★☆☆☆☆ Found in Text Mining only
Myopathy	Myopathy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	18431404		★☆☆☆☆ Found in Text Mining only
Neurodegenerative Disorders	Neurodegenerative Disorders	CTD_human_DG	20085714		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Osteoporosis	Osteoporosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Paraganglioma	Paraganglioma	BEFREE	19522821		★☆☆☆☆ Found in Text Mining only
PARAGANGLIOMA AND GASTRIC STROMAL SARCOMA	Paraganglioma and gastric stromal sarcoma	BEFREE	19522821		★☆☆☆☆ Found in Text Mining only
Parkinson Disease	Parkinson disease	BEFREE	29909144, 31726290		★☆☆☆☆ Found in Text Mining only
Parkinsonian Disorders	Parkinson Disease	BEFREE	29909144, 31726290		★☆☆☆☆ Found in Text Mining only
Pediatric Obesity	Childhood obesity	BEFREE	22084153		★☆☆☆☆ Found in Text Mining only
Pheochromocytoma	Pheochromocytoma	BEFREE	19522821		★☆☆☆☆ Found in Text Mining only
PIGMENTED NODULAR ADRENOCORTICAL DISEASE, PRIMARY, 3	Pigmented Nodular Adrenocortical Disease	GENOMICS_ENGLAND_DG	18272904		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
PIGMENTED NODULAR ADRENOCORTICAL DISEASE, PRIMARY, 3	Pigmented Nodular Adrenocortical Disease	UNIPROT_DG	18431404		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
PIGMENTED NODULAR ADRENOCORTICAL DISEASE, PRIMARY, 3	Pigmented Nodular Adrenocortical Disease	CLINVAR_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
PIGMENTED NODULAR ADRENOCORTICAL DISEASE, PRIMARY, 3	Pigmented Nodular Adrenocortical Disease	CTD_human_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Primary pigmented nodular adrenocortical disease	Pigmented Nodular Adrenocortical Disease	ORPHANET_DG	18431404		★☆☆☆☆ Found in Text Mining only
Primary pigmented nodular adrenocortical disease	Pigmented Nodular Adrenocortical Disease	Orphanet			★☆☆☆☆ Found in Text Mining only
Retinoblastoma	Retinoblastoma	Pubtator	37179305	Associate	★☆☆☆☆ Found in Text Mining only
Striatal Degeneration, Autosomal Dominant	Striatal Degeneration	BEFREE	20085714, 26769607, 29909144, 31726290		★☆☆☆☆ Found in Text Mining only
Striatal Degeneration, Autosomal Dominant	Striatal Degeneration	ORPHANET_DG	20085714		★☆☆☆☆ Found in Text Mining only
Striatal Degeneration, Autosomal Dominant	Striatal Degeneration	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
STRIATAL DEGENERATION, AUTOSOMAL DOMINANT 1	Striatal Degeneration	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Subclinical hypothyroidism	Subclinical Hypothyroidism	BEFREE	19820008, 24497218, 25822812		★☆☆☆☆ Found in Text Mining only
Symmetric lesions of the basal ganglia	Symmetric lesions of the basal ganglia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Thyroid Carcinoma Anaplastic	Thyroid cancer	Pubtator	27796151	Associate	★☆☆☆☆ Found in Text Mining only
Thyroid Diseases	Thyroid disease	Pubtator	23344678	Associate	★☆☆☆☆ Found in Text Mining only
Thyroid Diseases	Thyroid Diseases	BEFREE	28382505		★☆☆☆☆ Found in Text Mining only
Thyroid Neoplasms	Thyroid cancer	Pubtator	34966441	Associate	★☆☆☆☆ Found in Text Mining only
Thyroiditis Autoimmune	Thyroiditis	Pubtator	37197658	Associate	★☆☆☆☆ Found in Text Mining only