PDE8B

phosphodiesterase 8B, the group of PAS domain containing|Phosphodiesterases

Basic information

Region (hg38): 5:77210449-77428256

Links

ENSG00000113231

∙ NCBI:8622 ∙ OMIM:603390 ∙ HGNC:8794 ∙ Uniprot:O95263 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

schizophrenia (No Known Disease Relationship), mode of inheritance: Unknown
pigmented nodular adrenocortical disease, primary, 3 (Strong), mode of inheritance: AD
primary pigmented nodular adrenocortical disease (Supportive), mode of inheritance: AD
striatal degeneration, autosomal dominant (Supportive), mode of inheritance: AD
pigmented nodular adrenocortical disease, primary, 3 (Limited), mode of inheritance: AD
autosomal dominant striatal neurodegeneration type 1 (Strong), mode of inheritance: AD
autosomal dominant striatal neurodegeneration type 1 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pigmented nodular adrenocortical disease, primary, 3	AD	Endocrine	Treatment of adrenal disease (eg, potentially including surgical intervention) may be beneficial	Endocrine; Neurologic	15210883; 18272904; 21115159; 20085714; 20373981

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PDE8B gene.

not_provided (187 variants)
Inborn_genetic_diseases (69 variants)
Autosomal_dominant_striatal_neurodegeneration_type_1 (55 variants)
PDE8B-related_disorder (11 variants)
not_specified (9 variants)
PDE8B-Related_Disorders (1 variants)
Pigmented_nodular_adrenocortical_disease,_primary,_3 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PDE8B gene is commonly pathogenic or not. These statistics are base on transcript: NM_000003719.5. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			5 clinvar	60 clinvar	9 clinvar	74
missense	3 clinvar		115 clinvar	7 clinvar	4 clinvar	129
nonsense	1 clinvar	3 clinvar	1 clinvar			5
start loss						0
frameshift	5 clinvar	1 clinvar	2 clinvar			8
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	9	4	125	67	13

Highest pathogenic variant AF is 0.00000277741

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PDE8B	protein_coding	protein_coding	ENST00000264917	22	219359

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.000953	125734	0	14	125748	0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.00	305	492	0.620	0.0000289	5870
Missense in Polyphen		96	226.81	0.42326		2732
Synonymous	-0.690	203	191	1.06	0.0000126	1657
Loss of Function	5.31	5	42.2	0.118	0.00000197	523

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000148	0.000148
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000528	0.0000527
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: 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.;
Disease: DISEASE: Striatal degeneration, autosomal dominant 1 (ADSD1) [MIM:609161]: A movement disorder affecting the striatal part of the basal ganglia and characterized by bradykinesia, dysarthria and muscle rigidity. These symptoms resemble idiopathic Parkinson disease, but tremor is not present. {ECO:0000269|PubMed:20085714}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Primary pigmented nodular adrenocortical disease 3 (PPNAD3) [MIM:614190]: A rare bilateral adrenal defect causing ACTH-independent Cushing syndrome. Macroscopic appearance of the adrenals is characteristic with small pigmented micronodules observed in the cortex. Adrenal glands show overall normal size and weight, and multiple small yellow-to-dark brown nodules surrounded by a cortex with a uniform appearance. Microscopically, there are moderate diffuse cortical hyperplasia with mostly nonpigmented nodules, multiple capsular deficits and massive circumscribed and infiltrating extra-adrenal cortical excrescences with micronodules. Clinical manifestations of Cushing syndrome include facial and truncal obesity, abdominal striae, muscular weakness, osteoporosis, arterial hypertension, diabetes. {ECO:0000269|PubMed:18431404}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Cortisol synthesis and secretion - Homo sapiens (human);Cushing,s syndrome - Homo sapiens (human);Purine metabolism - Homo sapiens (human);Morphine addiction - Homo sapiens (human);G Protein Signaling Pathways;Phosphodiesterases in neuronal function;Signaling by GPCR;Signal Transduction;G alpha (s) signalling events;Purine nucleotides nucleosides metabolism;GPCR downstream signalling (Consensus)

Intolerance Scores

loftool: 0.237
rvis_EVS: -0.69
rvis_percentile_EVS: 15.2

Haploinsufficiency Scores

pHI: 0.475
hipred: Y
hipred_score: 0.749
ghis: 0.552

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.752

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Pde8b
Phenotype: homeostasis/metabolism phenotype; renal/urinary system phenotype;

Gene ontology

Biological process: cAMP catabolic process;signal transduction;G protein-coupled receptor signaling pathway
Cellular component: cellular_component;cytosol
Molecular function: 3',5'-cyclic-nucleotide phosphodiesterase activity;3',5'-cyclic-AMP phosphodiesterase activity;metal ion binding