ABCC6 and pathogenic SNPs

[mariovitali]

Dear All,


I am preparing an email to a number of researchers for the gene called ABCC6. Looking for further information regarding its function, one can find that it is a gene responsible for Pseudoxanthoma Elasticum (PXE) but the techniques i use suggest otherwise, meaning it should be further investigated.

Interestingly, a website discussing about PXE shows the following information in its FAQ :





Please report on any of the SNPs shown below, despite the mention that an epidemiological study has been made between 1997 and 2001.


Here is the list of the SNPs. :

https://www.ncbi.nlm.nih.gov/snp/?term=rs2238472
Pathogenic

rs59513011 - Risk T
rs2606921 - Risk A
rs55778939 : Risk T
(New addition) rs58668703 - Risk T
(New addition) rs41278172 - Risk A
Likely benign :

rs72657698 : Risk C



Thank you for your help.

 

[Kitty]

I only have one showing up on this gene, rs58668703, which is assessed as rare, clinically significant, and pathogenic. However, PXE is a recessive disease and my type's heterozygous, so whilst I might be a carrier, I don't have symptoms.

 

[mariovitali]

For the record :


Here are the results from 5 out 7 patients for whom i have full gemome data


rs2238472 : p1,p2,p3
rs59513011 : p1
rs2606921 : p1
rs72657698 : p3,p4,p5
rs55778939 : p4

 

[mariovitali]

I only have one showing up on this gene, rs58668703, which is assessed as rare, clinically significant, and pathogenic. However, PXE is a recessive disease and my type's heterozygous, so whilst I might be a carrier, I don't have symptoms.

Thank you so much for this. Pathogenic + rare. I added it to the original post

As disucssed in my initial post, this gene may be much more important than what it seems.

 

[ScottTriGuy]

I didn't find any of the 6 you listed.

 

[mariovitali]

I didn't find any of the 6 you listed.

Did you look for this information at full genome data (e.g DanteLabs) or you looked it up on 23andme data?

 

[ScottTriGuy]

Did you look for this information at full genome data (e.g DanteLabs) or you looked it up on 23andme data?

On my 23andme / Genetic Genie.

 

[wigglethemouse]

Some info from NIH site about this gene.
https://ghr.nlm.nih.gov/gene/ABCC6#

The ABCC6 gene provides instructions for making a protein called multidrug resistance-associated protein 6 (MRP6, also known as the ABCC6 protein). This protein is found primarily in the liver and kidneys, with small amounts in other tissues such as the skin, stomach, blood vessels, and eyes. The MRP6 protein belongs to a group of proteins that transport molecules across cell membranes; however, little is known about the substances transported by MRP6.

Some studies suggest that MRP6 stimulates the release of a molecule called adenosine triphosphate (ATP) from cells through an unknown mechanism. This ATP is quickly broken down into other molecules called adenosine monophosphate (AMP) and pyrophosphate. Pyrophosphate helps control deposition of calcium (calcification) and other minerals (mineralization) in the body.

Other studies suggest that MRP6 transports a substance that is involved in the breakdown of ATP. This unidentified substance is thought to help prevent mineralization of tissues.

 

[wigglethemouse]

rs2238472 : p1,p2,p3

Please, please, please check OpenSNP and dBSNP for allele and genotype frequency. Cross reference with kaviar frequency and CADD score. Provide links to ClinVar. rs2238472 for example has an allele frequency of 25% (dnSNP) and a genotype frequency of 46%=CT+TT (OpenSNP). This is in line with the 3 out of 7 that you quote in your small sample.

If you do not get your facts and analysis 200% validated researchers may tune out your future emails and ignore you.

 

[mariovitali]

Please, please, please check OpenSNP and dBSNP for allele and genotype frequency. Cross reference with kaviar frequency and CADD score. Provide links to ClinVar. rs2238472 for example has an allele frequency of 25% (dnSNP) and a genotype frequency of 46%=CT+TT (OpenSNP). This is in line with the 3 out of 7 that you quote in your small sample.

If you do not get your facts and analysis 200% validated researchers may tune out your future emails and ignore you.

Right, the likely benign one. Thank you @wigglethemouse i will remove it.

 

[mariovitali]

@wigglethemouse

I forgot to write that a prominent ME researcher has previously identified ABCC6 SNPs to ME patients.

 

[mariovitali]

On my 23andme / Genetic Genie.

It's possible that these SNPs are not analysed from 23andme. Perhaps someone can confirm.

 

[Kitty]

rs59513011 - Risk T
rs2606921 - Risk A
rs55778939 : Risk T
(Newly added) rs58668703 : Risk T

None of these (including the newly-added one that came from my WGS) appear in my 23andMe data from 2017.

ETA: the 'likely benign' rs72657698 does appear, but in my case is not genotyped.

 

[Ravn]

I don't have the snps on your list (Dante) but I do have some others on the ABCC6 gene.
Have attached screenshot of list, in case it's of any use (note that 1 snp is listed twice, once as pathogenic, once as benign ).

 

[mariovitali]

I don't have the snps on your list (Dante) but I do have some others on the ABCC6 gene.
Have attached screenshot of list, in case it's of any use (note that 1 snp is listed twice, once as pathogenic, once as benign ).

View attachment 10253

rs41278172 is actually pathogenic according to the DBSNP and should be added to the list on the first post.

Thank you!