Expressive

rs11248850 (NPRL3): Red Blood Cell Trait Variant

Key takeaways

  • rs11248850 near NPRL3 was identified in a GWAS of over 135,000 people as one of 75 loci shaping red blood cell traits.
  • The variant meets the highest genetic confidence threshold, with p-values below 1 in 100 million.
  • All 75 red blood cell loci found in the study together explain 4 to 9 percent of trait variance.
  • GTEx data shows the ALT allele increases NPRL3 expression in arteries, heart, nerves, and other non-blood tissues.

Key takeaways

  • rs11248850 falls near the NPRL3 gene and was identified among 75 loci associated with red blood cell traits in a study of up to 135,367 individuals.
  • The variant meets the highest threshold of genetic confidence, with association p-values below 1 in 100 million.
  • All 75 red blood cell loci from the discovery study together explain 4 to 9 percent of variance per trait.
  • GTEx data shows the ALT allele of this variant is linked to increased NPRL3 expression across multiple tissues including arteries, heart, and tibial nerve.

What the research says rs11248850 maps to the NPRL3 (Nitrogen Permease Regulator-Like 3) locus and was identified as one of 75 independent genetic loci associated with red blood cell phenotypes in a meta-analysis of genome-wide association studies involving up to 135,367 individuals of European or South Asian ancestry PMID 23222517. The study examined six phenotypes: hemoglobin concentration, mean cell hemoglobin (MCH), mean cell hemoglobin concentration (MCHC), mean cell volume (MCV), packed cell volume (PCV), and red blood cell count (RBC), with replication testing of suggestive loci performed in a further 63,506 individuals PMID 23222517. Collectively, all 75 identified loci explain 4 to 9 percent of phenotypic variance per trait, and 43 of the 75 were novel at the time of publication PMID 23222517.

Reported associations

  • Red blood cell phenotypes: The locus reached genome-wide significance (P < 10^-8) for association with one or more of six red blood cell traits in a multi-ancestry discovery sample of up to 135,367 individuals; NPRL3 was identified as a candidate gene using expression quantitative trait loci (eQTL) and bioinformatic prioritization strategies PMID 23222517.

Evidence quality The association evidence derives from a single large GWAS meta-analysis involving up to 135,367 discovery-stage participants, reaching genome-wide significance at P < 10^-8 PMID 23222517. The 75 loci together account for 4 to 9 percent of phenotypic variance per trait, and the candidate gene list was enriched for haematological functions at P = 10^-63, indicating strong biological plausibility PMID 23222517. No conflicting findings are reported in the provided materials, though the variant-level evidence for this specific locus rests on a single published source and independent external replication of this locus beyond the study's internal replication stage is not documented in the available data.

Tissue-specific expression effects

  • NPRL3: The ALT allele is associated with increased NPRL3 expression in eight tissues, with the largest effect sizes observed in aortic artery, esophageal-gastric junction, and esophageal muscularis, and the most statistically significant effects in tibial nerve and esophageal muscularis; increased expression is also seen in heart atrial appendage, subcutaneous adipose tissue, thyroid, and non-sun-exposed skin. These are eQTL associations describing a molecular mechanism, not a direct health outcome GTEx Portal.

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is the NPRL3 gene?

NPRL3, or Nitrogen Permease Regulator-Like 3, is a gene identified as a candidate in studies of red blood cell traits. GTEx data indicates it is expressed across many tissues including arteries, heart muscle, tibial nerve, and skin, and its expression is influenced by nearby genetic variants including rs11248850.

What red blood cell traits is rs11248850 linked to?

The variant near NPRL3 was associated with one or more of six red blood cell measurements: hemoglobin concentration, mean cell hemoglobin, mean cell hemoglobin concentration, mean cell volume, packed cell volume, and red blood cell count.

How strong is the evidence for rs11248850?

The association was found in a large study of over 135,000 individuals reaching genome-wide significance, which is the highest standard in genetic epidemiology. The variant-level evidence currently rests on a single published source, and independent external replication of this specific locus is not documented in the available data.

Does rs11248850 affect gene expression in tissues beyond blood?

Yes. GTEx data shows the variant is associated with increased NPRL3 expression in eight tissues including aortic artery, heart atrial appendage, tibial nerve, subcutaneous adipose tissue, thyroid, and skin. These are expression quantitative trait loci effects describing a molecular mechanism, not a direct health outcome.

Is rs11248850 associated with any disease?

The available evidence links this variant to variation in normal red blood cell traits such as hemoglobin concentration and cell volume in the general population. No disease-specific association or clinical annotation is documented in the provided data.