| Full gene name: | phosphodiesterase 8B |
|---|---|
| Entrez Gene ID: | 8622 |
| Location: | 5q13.3 |
| Synonyms: | ADSD, PPNAD3 |
| Type: | protein-coding |
SNPs given by the user that are near or inside this gene:
| SNP | Distance (bp) | Direction |
|---|---|---|
| rs4457053 | 81757 | upstream |
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 are a cause of autosomal dominant striatal degeneration (ADSD). Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jul 2010]
| OMIM ID: | `OMIM ID 603390 `_ |
|---|
Allelic Variants (Selected Examples)
.0001 PIGMENTED NODULAR ADRENOCORTICAL DISEASE, PRIMARY, 3
In a young girl with micronodular adrenocortical hyperplasia who had presented with Cushing syndrome at age 2 years (614190), Horvath et al. (2008) identified a heterozygous 914A-C transversion in the PDE8B gene, resulting in a his305-to-pro (H305P) substitution. An adrenal computed tomographic scan showed enlargement of both left and right adrenal glands. Pigment granules were found in some cells of a biopsy specimen of the adrenocortical nodules. The patient inherited the mutation from her father, who was not known to have Cushing syndrome but was obese, had hypertension, and abnormal midnight cortisol levels. Furthermore, the father had mild hyperplasia, especially the left adrenal gland, shown on computed tomography. The mutation was not found in 1,030 unrelated control individuals. The H305P mutation affects an evolutionarily conserved residue. In vitro studies showed significantly higher cAMP levels after transfection with the mutant PDE8B than after transfection with the wildtype PDE8B, indicating an impaired ability of the mutant protein to degrade cAMP.
.0002 STRIATAL DEGENERATION, AUTOSOMAL DOMINANT
In affected members of a large German family with autosomal dominant striatal degeneration (ADSD; 609161), Appenzeller et al. (2010) identified a heterozygous complex mutation in exon 1 of the PDE8B gene: a 94G-C transversion and a 1-bp deletion (95delT) in residue 31, resulting in a premature stop codon after 63 amino acids. The mutation causes loss of all 3 functional domains of PDE8B isoforms 1 through 5, and in vitro functional expression studies in COS-7 cells showed that the mutation resulted in complete loss of enzymatic activity. Further studies in HEK293 and 3T3 cells showed no difference in subcellular localization between the wildtype and mutant protein. The mutant allele was not found in 500 controls. Appenzeller et al. (2010) speculated that the disorder could result from defective dopamine signaling.
Recent articles:
Top Pubmed articles linked to gene PDE8B matching any search term: