PDE8A
phosphodiesterase 8A, the group of Phosphodiesterases|PAS domain containing
Basic information
Region (hg38): 15:84980440-85139145
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- not_specified (95 variants)
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. These statistics are base on transcript: NM_000002605.3. 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 | 0 | |||||
| missense | 92 | 95 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 92 | 3 | 0 |
Loading clinvar variants...
GnomAD
Source:
| 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:
- 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