PDE8A

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

Basic information

Region (hg38): 15:84980440-85139145

Links

ENSG00000073417 ∙ NCBI:5151 ∙ OMIM:602972 ∙ HGNC:8793 ∙ Uniprot:O60658 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PDE8A gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PDE8A 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						0
missense			39	1		40
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	39	1	0

Variants in PDE8A

This is a list of pathogenic ClinVar variants found in the PDE8A region.

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

Position	Type	Phenotype	Significance	ClinVar
15-84982176-C-G		not specified	Uncertain significance (Nov 16, 2024)
15-84982185-A-G		not specified	Uncertain significance (Oct 17, 2024)
15-84982223-C-T		not specified	Uncertain significance (Jan 16, 2024)
15-84982224-C-T		not specified	Uncertain significance (Apr 04, 2023)
15-84982239-T-G		not specified	Uncertain significance (Oct 20, 2021)
15-84982302-G-A		not specified	Uncertain significance (Mar 25, 2024)
15-84982316-G-A		not specified	Uncertain significance (Apr 22, 2022)
15-85064410-A-G		not specified	Uncertain significance (Oct 12, 2024)
15-85067060-G-T		not specified	Uncertain significance (Mar 06, 2023)
15-85067096-T-C		not specified	Uncertain significance (Jun 17, 2024)
15-85076762-C-G		not specified	Uncertain significance (Aug 10, 2024)
15-85089358-C-G		not specified	Uncertain significance (Mar 24, 2023)
15-85089406-G-A		not specified	Likely benign (Jul 20, 2021)
15-85089406-G-T		not specified	Uncertain significance (Aug 08, 2022)
15-85091110-G-A		not specified	Uncertain significance (Dec 19, 2023)
15-85100029-A-G		not specified	Uncertain significance (Jul 19, 2023)
15-85100167-A-G		not specified	Uncertain significance (Feb 28, 2023)
15-85100169-C-T		not specified	Uncertain significance (Nov 14, 2024)
15-85100171-G-A		not specified	Uncertain significance (Apr 27, 2022)
15-85100193-A-G		not specified	Uncertain significance (Jun 11, 2024)
15-85109092-C-T		not specified	Uncertain significance (Nov 15, 2021)
15-85109100-G-A		not specified	Uncertain significance (Jun 08, 2022)
15-85109113-C-T		not specified	Uncertain significance (May 22, 2023)
15-85109118-C-T		not specified	Uncertain significance (Mar 13, 2023)
15-85109119-G-A		not specified	Uncertain significance (Feb 23, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PDE8A	protein_coding	protein_coding	ENST00000310298	22	158706

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000115	1.00	125718	0	30	125748	0.000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.10	377	442	0.853	0.0000231	5447
Missense in Polyphen		129	178.25	0.72372		2275
Synonymous	1.60	132	158	0.838	0.00000829	1544
Loss of Function	4.00	15	43.4	0.345	0.00000228	532

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000396	0.000395
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000151	0.000149
Middle Eastern	0.0000544	0.0000544
South Asian	0.000135	0.000131
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 (PubMed:18983167). May be involved in maintaining basal levels of the cyclic nucleotide and/or in the cAMP regulation of germ cell development (PubMed:18983167). Binding to RAF1 reduces RAF1 'Ser- 259' inhibitory-phosphorylation and stimulates RAF1-dependent EGF- activated ERK-signaling (PubMed:23509299). Protects against cell death induced by hydrogen peroxide and staurosporine (PubMed:23509299). {ECO:0000269|PubMed:18983167, ECO:0000269|PubMed:23509299}.
• 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)

Recessive Scores

• pRec: 0.132

Intolerance Scores

• loftool: 0.329
• rvis_EVS: -0.2
• rvis_percentile_EVS: 39.11

Haploinsufficiency Scores

• pHI: 0.440
• hipred: Y
• hipred_score: 0.651
• ghis: 0.619

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.748

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pde8a
• Phenotype: adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); homeostasis/metabolism phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); skeleton phenotype

Gene ontology

• Biological process: positive regulation of protein phosphorylation;cAMP catabolic process;regulation of transcription, DNA-templated;G protein-coupled receptor signaling pathway;negative regulation of cell death;positive regulation of ERK1 and ERK2 cascade;cellular response to epidermal growth factor stimulus;negative regulation of hydrogen peroxide-induced cell death
• Cellular component: cytosol;extracellular exosome
• Molecular function: 3',5'-cyclic-AMP phosphodiesterase activity;kinase binding;metal ion binding;3',5'-cyclic-GMP phosphodiesterase activity