Expressive

rs10465799 (NDUFS5-MACF1): Athlete Metabolomics Variant

Key takeaways

  • rs10465799 sits near NDUFS5 (a mitochondrial complex I subunit) and MACF1 and was flagged in a metabolomics scan of 490 elite athletes.
  • GTEx data show the alternate allele reduces NDUFS5 expression in testis and cultured fibroblasts.
  • The same allele reduces AKIRIN1 expression in several brain regions and the tibial nerve, but increases it in lymphocytes and testis.
  • Evidence is preliminary: the finding comes from a single small study with no published replication and no specific metabolite association available.

Key takeaways

  • rs10465799 sits near the NDUFS5 (a mitochondrial complex I subunit) and MACF1 genes and was identified in a metabolomics genome-wide scan of 490 elite athletes.
  • GTEx data show the alternate allele is linked to reduced NDUFS5 expression in testis and cultured fibroblasts.
  • The same allele is associated with reduced AKIRIN1 expression in several brain regions and the tibial nerve, but increased AKIRIN1 expression in lymphocytes and testis.
  • Evidence is preliminary: a single small study with no published replication, and the specific metabolite linked to this variant is not reported in the available study text.

What the research says A metabolomics genome-wide association study (mGWAS) in 490 elite athletes genotyped 275,016 variants alongside 751 serum metabolites to identify metabolic quantitative trait loci (mQTLs, genomic regions that influence circulating metabolite levels); findings were compared to mQTLs previously published in non-elite populations, with emphasis on metabolites associated with endurance sports. Rs10465799 was examined in this context; however, the specific metabolite association and effect size for this locus are not reported in the available study text.

GTEx v11 eQTL data from 953 donors independently link rs10465799 to reduced expression of NDUFS5 in testis and cultured fibroblasts, and to tissue-dependent changes in AKIRIN1 expression across brain and peripheral nerve tissues GTEx Portal.

Reported associations

  • mGWAS in elite athletes: This variant was examined in a metabolomics-based GWAS of 490 elite athletes profiling 751 serum metabolites; the specific metabolite linked to rs10465799 is not named in the available study excerpt, so no effect size can be reported.
  • NDUFS5 expression in testis: The alternate allele is associated with reduced NDUFS5 expression in testis tissue GTEx Portal.
  • NDUFS5 expression in cultured fibroblasts: The alternate allele is associated with reduced NDUFS5 expression in cultured fibroblasts GTEx Portal.
  • AKIRIN1 expression in brain and peripheral nerve (reduced): The alternate allele is associated with reduced AKIRIN1 expression in the cervical spinal cord, substantia nigra, hippocampus, and tibial nerve GTEx Portal.
  • AKIRIN1 expression in lymphocytes and testis (increased): The alternate allele is associated with increased AKIRIN1 expression in EBV-transformed lymphocytes and testis GTEx Portal.

Evidence quality The primary association study used 490 elite athletes, a sample size small for a GWAS, and the available study text does not report a p-value or effect size specific to rs10465799. No independent replication, ClinVar annotation, or PharmGKB clinical annotation was provided for this variant. The GTEx eQTL associations are drawn from 953 donors across many tissue types and represent a more thoroughly powered reference dataset, though eQTL effects describe gene-expression mechanisms rather than clinical outcomes. Overall, evidence for this variant should be considered preliminary until independently replicated with a defined metabolite endpoint.

Tissue-specific expression effects

  • NDUFS5: The alternate allele is associated with reduced expression of this mitochondrial complex I subunit in testis and cultured fibroblasts GTEx Portal.
  • AKIRIN1: The alternate allele shows tissue-dependent directionality: reduced expression in the cervical spinal cord, substantia nigra, hippocampus, and tibial nerve, but increased expression in EBV-transformed lymphocytes and testis GTEx Portal.

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is rs10465799?

rs10465799 is a single-nucleotide variant located near the NDUFS5 and MACF1 genes. It was examined in a metabolomics genome-wide association study of elite athletes and is linked through GTEx data to changes in gene expression in testis, fibroblasts, and brain tissues.

What does the NDUFS5 gene do?

NDUFS5 encodes a subunit of mitochondrial complex I, the first enzyme in the electron transport chain that cells use to generate energy. GTEx data indicate the alternate allele of rs10465799 is associated with reduced NDUFS5 expression in testis and cultured fibroblasts.

Is rs10465799 linked to athletic performance?

This variant was examined in a metabolomics genome-wide study of 490 elite athletes, but the specific metabolite it influences is not reported in the available study excerpt. Any link to athletic performance should be treated as preliminary until independently replicated.

Which brain regions are affected by rs10465799?

GTEx eQTL data show the alternate allele is associated with reduced AKIRIN1 expression in the cervical spinal cord, substantia nigra, hippocampus, and tibial nerve. In EBV-transformed lymphocytes and testis the direction reverses, with increased AKIRIN1 expression.

Is rs10465799 near MACF1?

Yes. The variant is catalogued under the NDUFS5-MACF1 locus designation, indicating it falls in a genomic region containing or flanking both NDUFS5 and MACF1.