PDE8B

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

Basic information

Region (hg38): 5:77210448-77428256

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 (137 variants)
• Autosomal dominant striatal neurodegeneration type 1 (94 variants)
• Inborn genetic diseases (19 variants)
• Striatal Degeneration (12 variants)
• not specified (3 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.

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			7	39	10	56
missense	1		59	6	4	70
nonsense		2	1			3
start loss						0
frameshift	2		1			3
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			6	9	4	19
non coding			29	23	23	75
Total	3	2	97	68	37

Variants in PDE8B

This is a list of pathogenic ClinVar variants found in the PDE8B region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
5-77210882-C-T		Autosomal dominant striatal neurodegeneration type 1	Uncertain significance (Jan 12, 2018)
5-77210902-C-T		Autosomal dominant striatal neurodegeneration type 1	Uncertain significance (Jan 12, 2018)
5-77210903-G-T		Autosomal dominant striatal neurodegeneration type 1	Benign (Jan 13, 2018)
5-77210907-G-T		Autosomal dominant striatal neurodegeneration type 1	Uncertain significance (Jan 15, 2018)
5-77210929-G-A			Uncertain significance (Jun 11, 2019)
5-77210936-C-T		Inborn genetic diseases	Uncertain significance (Feb 28, 2024)
5-77210944-A-T			Uncertain significance (Oct 18, 2021)
5-77210946-C-A			Likely benign (Jan 13, 2024)
5-77210977-C-A		Autosomal dominant striatal neurodegeneration type 1	Uncertain significance (Jan 13, 2018)
5-77210988-C-A			Uncertain significance (Mar 06, 2023)
5-77210988-C-T		Autosomal dominant striatal neurodegeneration type 1	Benign (Dec 01, 2023)
5-77210995-A-G			Uncertain significance (Aug 10, 2022)
5-77210998-T-G		Inborn genetic diseases	Uncertain significance (Dec 07, 2021)
5-77211000-GC-G		Autosomal dominant striatal neurodegeneration type 1	Pathogenic (Feb 29, 2024)
5-77211003-C-A			Likely benign (Jun 05, 2023)
5-77211009-G-A			Likely benign (Jun 05, 2023)
5-77211012-C-T			Likely benign (Sep 09, 2021)
5-77211018-CG-C			Pathogenic (Jun 17, 2021)
5-77211019-G-A			Uncertain significance (Dec 24, 2023)
5-77211019-GT-C		Autosomal dominant striatal neurodegeneration type 1	Pathogenic (Jan 01, 2010)
5-77211020-T-C			Pathogenic (Jun 17, 2021)
5-77211032-C-G			Uncertain significance (Oct 03, 2021)
5-77211050-G-C		Autosomal dominant striatal neurodegeneration type 1 • not specified	Uncertain significance (Jan 22, 2024)
5-77211054-C-T		not specified	Likely benign (Jan 19, 2024)
5-77211068-A-T			Uncertain significance (Dec 06, 2021)

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