Disease relevance of PDE6A

• In vivo DNase I hypersensitivity assays revealed two sites immediately upstream of the PDE6A core promoter region [1].

High impact information on PDE6A

• We found three point mutations in PDEA in affected members of two pedigrees with recessive RP [2].
• PDEA is the seventh RP gene identified, highlighting the extensive genetic heterogeneity of the disorder and encouraging further investigation into the role of other members of the phototransduction cascade in RP [2].
• PURPOSE: To determine the mutation spectrum of the PDE6A gene encoding the alpha subunit of rod cyclic guanosine monophosphate (cGMP)phosphodiesterase and the proportion of patients with recessive retinitis pigmentosa (RP) due to mutations in this gene [3].
• Alternatively, commercial Cy5 succinimidyl ester was reacted with a primary amine (MTSEA, methanethiosulfonylethylamine, or PDEA, pyridyldithioethylamine) or a secondary amine (PEM, piperazinylethylmaleimide) to give the corresponding thiol-reactive derivatives in a single step [4].
• Sequencing of PDE6A showed a homozygous single base pair change; c.889C->T, single base pair insertion; c.2218-2219insT, and single base pair substitution in the splice acceptor site; IVS10-2A->G in each of three families [5].

Biological context of PDE6A

• RESULTS: By haplotype analysis, 6/14, 11/14, and 4/13 families were ruled out for PDE6A, PDE6B, and RPE65, respectively [6].
• The human PDE6A gene consists of 22 exons spanning about 60 kb with the intron/exon junctions highly conserved in comparison to the mouse and human PDE6B genes [7].
• In addition, the kinetics of swelling for the PDPA microgels was somewhat slower than that observed for PDEA microgels; presumably this is related to the greater hydrophobic character of the former particles [8].

Anatomical context of PDE6A

• Here, we show that adenofection can be used to analyze activity of the rod photoreceptor PDE6A gene promoter [9].

Associations of PDE6A with chemical compounds

• The critical pH for this latex-to-microgel transition was around pH 6.5-7.0, which corresponds approximately to the known pKa of 7.0-7.3 for linear PDEA homopolymer [8].
• The levels of the cyclic adenosine 3',5'-monophosphate (cyclic AMP)-phosphodiesterase (PDE) and the biochemical properties of its endogenous protein activator (PDEA) obtained from the human brain cortex and from different types of human cerebral tumours have been evaluated [10].
• The PDEA, obtained from normal and pathological tissues, did not change the affinity of the purified PDE for cyclic AMP, while it increased the Vmax of the enzyme [10].

Other interactions of PDE6A

• Candidate disease genes or loci include PDE6A, WGN1, and USH2C [11].
• These genes include rhodopsin, beta-subunit of rod cGMP phosphodiesterase (PDEB), alpha-subunit of rod cGMP phosphodiesterase (PDEA), and alpha-subunit of rod cGMP-gated channel [12].

References