Professor & patients' paper on the solvable biological challenge of ME/CFS: reader-friendly version
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CLYBL

Discussion in 'Genetic Testing and SNPs' started by aquariusgirl, Mar 5, 2018.

  1. aquariusgirl

    aquariusgirl Senior Member

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    Anyone got any rare SNPs on this gene?
    Mitochondrial citramalyl-CoA lyase indirectly involved in the vitamin B12 metabolism (PubMed:29056341). Converts citramalyl-CoA into acetyl-CoA and pyruvate in the C5-dicarboxylate catabolism pathway (PubMed:29056341). The C5-dicarboxylate catabolism pathway is required to detoxify itaconate, a vitamin B12-poisoning metabolite (PubMed:29056341). Also acts as a malate synthase in vitro, converting glyoxylate and acetyl-CoA to malate (PubMed:24334609, PubMed:29056341). Also acts as a beta-methylmalate synthase in vitro, by mediating conversion of glyoxylate and propionyl-CoA to beta-methylmalate (PubMed:24334609, PubMed:29056341). Also has very weak citramalate synthase activity in vitro (PubMed:24334609, PubMed:29056341).2 Publications
    Catalytic activityi
    Acetyl-CoA + H2O + glyoxylate = (S)-malate + CoA.2 Publications
    Propionyl-CoA + H2O + glyoxylate = beta-methylmalate + CoA.2 Publications
    (3S)-citramalyl-CoA = acetyl-CoA + pyruvate.1 Publication
    Cofactori
    Mg2+2 PublicationsNote: Binds 1 Mg2+ ion per subunit.1 Publication
    Kineticsi
     
    Last edited: Mar 5, 2018
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  2. aquariusgirl

    aquariusgirl Senior Member

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    https://academic.oup.com/hmg/article/23/9/2313/632255

    CLYBL is a human mitochondrial enzyme of unknown function that is found in multiple eukaryotic taxa and conserved to bacteria. The protein is expressed in the mitochondria of all mammalian organs, with highest expression in brown fat and kidney. Approximately 5% of all humans harbor a premature stop polymorphism in CLYBL that has been associated with reduced levels of circulating vitamin B12. Using comparative genomics, we now show that CLYBL is strongly co-expressed with and co-evolved specifically with other components of the mitochondrial B12 pathway. We confirm that the premature stop polymorphism in CLYBL leads to a loss of protein expression.
     
  3. aquariusgirl

    aquariusgirl Senior Member

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    Vitamin B12 metabolism and utilization have been extensively studied, and with the exception of the mitochondrial transporter, the molecular identities of all proteins necessary for B12 maturation have been identified (1,2).

    Two recent human genetic association studies have begun to define the genetic loci that control B12 levels (3,4). Of the 12 non-intergenic loci collectively identified by these two studies, 11 lie near genes with established or purported roles in vitamin B12 biology, including B12 absorption (MS4A3, FUT2, FUT6, TCN1, TCN2, CUBN, CD320), B12 maturation (ABCD4, MMAA, MMACHC) and B12-dependent catalysis (MUT). The 12thlocus corresponds to a stop polymorphism within CLYBL, an uncharacterized protein. The B12-associated polymorphism (rs41281112) changes Arg259 to a stop codon, predicted to produce a truncated CLYBL protein. Notably, this polymorphism had the largest effect on B12 levels of all the SNPs reported:Chinese men homozygous for the premature stop had 3-fold reduced concentrations of circulating B12, with heterozygotes exhibiting an intermediate phenotype (3).
     
  4. aquariusgirl

    aquariusgirl Senior Member

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    How can I check if I have the defective rs4128112?
     
  5. nanonug

    nanonug Senior Member

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    Virginia, USA
    I have tons of mutations on that gene, most of them with high frequency alleles so that shouldn't in principle be a problem. Some are lowish frequency but all of them are of unknown clinical significance.

    Regarding rs4128112, I don't have it on my 23andMe data so I can't check. I'm very, very close to spending a grand on whole genome sequencing as 23andMe limitations are starting to bother me.
     
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  6. aquariusgirl

    aquariusgirl Senior Member

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    yes, I'm in the same boat
    post your low frequency alleles.... i'm talking to a researcher who thinks this one could be very interesting;.
     
  7. nanonug

    nanonug Senior Member

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    These are my variations with allele frequencies below 25%. Only one is homozygous (rs7317678).

    varType refSeq varSeq rsidList genesList geneComponentList globalAlleleFreq
    SNP (x1) A G rs2250311 CLYBL INTRON 6.55
    SNP (x1) A G rs2793749 CLYBL INTRON 7.03
    SNP (x1) T C rs4483710 CLYBL INTRON 6.95
    SNP (x1) G A rs9557284 CLYBL INTRON 24.58
    SNP (x1) A G rs9557286 CLYBL INTRON 22.08
    SNP (x1) A G rs4772237 CLYBL INTRON 10.6
    SNP (x1) A G rs9557290 CLYBL INTRON 20.85
    SNP (x1) C T rs9557298 CLYBL INTRON 22.14
    SNP (x1) A G rs12584570 CLYBL INTRON 22.38
    SNP (x1) C T rs9557308 CLYBL INTRON 24.06
    SNP (x1) T C rs9513667 CLYBL INTRON 18.37
    SNP (x1) G A rs7332098 CLYBL INTRON 19.29
    SNP (x1) G A rs4772247 CLYBL INTRON 7.47
    SNP (x1) G A rs1886030 CLYBL INTRON 11.76
    SNP (x1) C T rs17612087 CLYBL INTRON 6.69
    SNP (x1) C T rs7333886 CLYBL INTRON 17.53
    SNP (x2) G A rs7317678 CLYBL INTRON 0
     
  8. aquariusgirl

    aquariusgirl Senior Member

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    ok, you don't have the one she has been looking at.
     
  9. aquariusgirl

    aquariusgirl Senior Member

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  10. Dan_USAAZ

    Dan_USAAZ Senior Member

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    FYI... my 23andMe data does have rs41281112(C;C). I believe this variant is non-pathogenic, but please correct me if I am wrong.
    Thx.
     
  11. nanonug

    nanonug Senior Member

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    C/C is the major allele so you're good.
     
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  12. JaimeS

    JaimeS Senior Member

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    Shouldn't that be rs41281112? You should have it.

    [Edit: that is to say that one 1 was missing in the above content. It's (111) three in a row. So if you copied and searched, you might have missed it!]
     
  13. Critterina

    Critterina Senior Member

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    upload_2018-6-19_15-26-22.png
    23andMe has the last word.
     
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  14. JaimeS

    JaimeS Senior Member

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    Huh. When did you get yours done? That's interesting, my 23andme data definitely has this SNP.
     
  15. Critterina

    Critterina Senior Member

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    Good question... 2013, before the FDA prohibited the release of health information and then reversed the decision. But they continue to update the results, and I just captured that screenshot today.
     

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