Know anything about this rare missense mutation?

[SOC]

I'm homozygous for this rare (0.01%) missense mutation -- SNP: rs3730071, gene: ADCY6

According to @Valentijn 's amazing rare allele program it's related to formation of cyclic adenosine monophosphate (whatever that is when it's at home ). As far as I can figure out at the moment (which is not far at all, I'm afraid), it's somehow related to ATP.

According to Wikipedia:

cAMP is a second messenger, used for intracellular signal transduction, such as transferring into cells the effects of hormones like glucagon and adrenaline, which cannot pass through the cell membrane. It is involved in the activation of protein kinases and regulates the effects of adrenaline and glucagon. cAMP also binds to and regulates the function ofion channels such as the HCN channels and a few other cyclic nucleotide-binding proteins such as Epac1 and RAPGEF2.

Translation?

 

[alex3619]

cAMP is something I have blogged about. Its best not to think of it as ATP, but as a high energy messenger molecule, one of two super hormones. If there is insufficient it will lead to a dominance of Ca++ as an intracellular messenger. Raising cAMP is in part why I take resveratrol. In several of my models restoring cAMP should lead to an improvement in symptoms. That is not proven however, and messing about with cAMP does have risks ... it is a hormone (technically an intracellular messenger) after all.

Poor cAMP might lead to both sleep and breathing issues, as well as a tendency to insulin resistance.

I will have another look into this later today.

On rare occasions though a mutation is actually about increasing the impact of a protein, not decreasing it, in which case there might be too much cAMP.

 

[SOC]

cAMP is something I have blogged about. Its best not to think of it as ATP, but as a high energy messenger molecule, one of two super hormones. If there is insufficient it will lead to a dominance of Ca++ as an intracellular messenger. Raising cAMP is in part why I take resveratrol. In several of my models restoring cAMP should lead to an improvement in symptoms. That is not proven however, and messing about with cAMP does have risks ... it is a hormone (technically an intracellular messenger) after all.

Poor cAMP might lead to both sleep and breathing issues, as well as a tendency to insulin resistance.

I will have another look into this later today.

On rare occasions though a mutation is actually about increasing the impact of a protein, not decreasing it, in which case there might be too much cAMP.

Thanks, Alex. I do have sleep problems and a tendency to insulin resistance.

I agree that I don't know the "direction" of the mutation -- whether it is increasing or decreasing the impact of the protein -- so I am very hesitant to do anything to try to alter the effect until I'm far more confident about what's going on.

 

[alex3619]

Just speaking generally, but in many cases if a mutation causes a slight problem other feedback loops kick in and regulate everything properly anyway. Its only major mutations, or situations in which other regulatory pathways are fubar, that a minor mutation (in terms of functional impact) might cause a problem. That is the impact of the mutation is only revealed with another problem stresses the system.

 

[Valentijn]

@SOC - I've got charts of rare ADCY mutations (ADCY1 - ADCY10) at http://forums.phoenixrising.me/inde...with-adenosine-antagonists.27411/#post-418026 . Other adenosine-related genes are elsewhere in that thread.

One other ME patient has the rs3730071 missense mutation, but is heterozygous instead of homozygous.