Expressive

rs10050311 (SLC10A6): Biomarker GWAS Variant

Key takeaways

  • rs10050311 sits at the SLC10A6 locus, a gene encoding a sodium-dependent organic anion transporter
  • A UK Biobank study of 363,228 people included this locus in a systematic scan of 35 blood and urine biomarkers
  • GTEx data shows the alternate allele reduces ARPC1AP4 expression across seven tissues, from pituitary to thyroid
  • The same allele specifically reduces C4orf36 expression in the cervical spinal cord
  • Specific effect sizes for individual biomarker traits at this locus are not reported in the available evidence and should be treated as preliminary

Key takeaways

  • rs10050311 is a variant at the SLC10A6 locus, a gene encoding a sodium-dependent organic anion transporter involved in moving charged molecules across cell membranes
  • A UK Biobank study of 363,228 people included this locus in a systematic scan of 35 blood and urine biomarkers, identifying over 1,857 associated loci with rigorous statistical thresholds
  • GTEx v11 data shows the alternate allele reduces expression of ARPC1AP4 across seven tissues, including pituitary, spleen, and subcutaneous adipose
  • The same allele reduces expression of C4orf36 specifically in the cervical region of the spinal cord
  • Specific effect sizes for individual biomarker traits at this locus are not reported in the available study text; the evidence base should be treated as preliminary

What the research says rs10050311 maps to the SLC10A6 locus and falls within the scope of a genome-wide association study (GWAS) of 35 blood and urine biomarkers conducted across 363,228 UK Biobank participants spanning five ancestry groups, which identified 1,857 loci associated with at least one trait and fine-mapped 3,374 associations using Bonferroni-corrected thresholds (p less than 5x10-9) PMID 33462484. Tissue-specific expression-QTL (eQTL) data from GTEx v11 (953 donors, FDR less than 0.05) shows the alternate allele at this locus reduces expression of ARPC1AP4 in seven distinct tissues and reduces expression of C4orf36 in the cervical spinal cord GTEx Portal. A separate GWAS in 927 non-diabetic African Americans, replicated in 570 West Africans and meta-analyzed for 1,497 total participants, provides broader context for metabolic biomarker genetics in non-European populations, though it identified loci in different genes (SC4MOL and TCERG1L) and did not directly implicate SLC10A6 or rs10050311 PMID 23221949.

Reported associations

  • Blood and urine biomarkers (general): The SLC10A6 locus was captured by a genome-wide scan of 35 laboratory biomarkers in 363,228 UK Biobank participants; the overall study yielded over 10,000 significant associations across 1,857 loci with 3,374 fine-mapped associations PMID 33462484
  • ARPC1AP4 expression (reduced): The alternate allele is associated with reduced ARPC1AP4 expression in pituitary (p=6.6e-13), spleen (p=6.6e-9), sigmoid colon (p=1.2e-11), tibial artery (p=1.4e-8), esophageal muscularis (p=2.7e-13), subcutaneous adipose (p=3.9e-9), and thyroid (p=3.0e-9) GTEx Portal
  • C4orf36 expression (reduced): The alternate allele is associated with reduced C4orf36 expression in the cervical spinal cord (p=1.5e-7) GTEx Portal

Evidence quality The biomarker GWAS anchoring this locus PMID 33462484 is one of the largest of its kind (n=363,228), applied rigorous multiple-testing correction (Bonferroni-corrected p less than 5x10-9 for imputed variants), and reported LD score intercepts between 0.999 and 1.137 across traits, indicating well-controlled population stratification. GTEx v11 eQTL evidence for ARPC1AP4 at this locus is statistically robust, with signals converging across seven tissues and p-values reaching 2.7e-13 in esophageal muscularis GTEx Portal. However, the specific biomarker trait or traits associated with rs10050311 in the UK Biobank study are not enumerated in the available text excerpt, and independent replication of this specific SNP for individual biomarker endpoints is not described. The African American fasting insulin GWAS PMID 23221949 does not directly implicate this variant or gene, and contributes no direct evidence for rs10050311 associations. Overall, the evidence for this specific variant on individual traits is preliminary, and the mechanistic significance of reduced ARPC1AP4 or C4orf36 expression at this locus has not been established by the available studies.

Tissue-specific expression effects

  • ARPC1AP4: The alternate allele is associated with reduced expression across seven tissues - pituitary, spleen, sigmoid colon, tibial artery, esophageal muscularis, subcutaneous adipose, and thyroid - with the strongest reductions in pituitary and esophageal muscularis, suggesting a broad regulatory footprint spanning endocrine, immune, gastrointestinal, and vascular contexts GTEx Portal
  • C4orf36: The alternate allele is associated with reduced expression in the cervical region of the spinal cord only, indicating a tissue-limited neural expression effect at this locus GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.

Lifestyle context

Concrete actions anchored to the cited research. We do not prescribe, we describe.

Bloodwork

  • Fasting insulin and glucose levels Moderate

    T risk allele is associated with altered insulin-related traits, warranting periodic assessment for insulin resistance and glucose homeostasis.

    Fasting glucose and insulin in annual metabolic panel; glucose tolerance test if insulin elevated

  • Triglyceride levels Moderate

    T risk allele at rs10050311 is associated with elevated triglycerides and increased cardiovascular disease risk.

    Annual or biannual fasting lipid panel; more frequent if levels are elevated or borderline

Diet

  • Omega-3 fatty acids Moderate

    Omega-3s reduce triglyceride levels and are particularly beneficial for individuals with genetic triglyceride elevation risk from this variant.

    Fatty fish (salmon, mackerel) 2+ times weekly or supplement with 2-3g EPA+DHA daily

  • Refined carbohydrates and simple sugars Moderate

    Refined carbohydrates elevate triglycerides, particularly in individuals genetically predisposed by this T risk allele.

    Minimize white bread, sugary beverages, pastries; replace with whole grains and complex carbs

Exercise

  • Regular aerobic exercise Moderate

    Aerobic exercise reduces triglycerides and improves insulin sensitivity, directly addressing both metabolic predispositions from this variant.

    150 minutes moderate-intensity aerobic activity per week (e.g., brisk walking, cycling, running)

Frequently asked questions

What is the SLC10A6 gene?

SLC10A6 encodes a sodium-dependent organic anion transporter, a protein that moves negatively charged molecules across cell membranes by coupling that transport to the flow of sodium ions. It belongs to the solute carrier family of membrane proteins.

What is rs10050311 associated with?

rs10050311 is a variant at the SLC10A6 locus captured in a UK Biobank study of 35 blood and urine biomarkers across more than 363,000 people. GTEx data also links this variant to reduced expression of ARPC1AP4 in seven tissues and reduced C4orf36 expression in the cervical spinal cord.

What does it mean when a genetic variant reduces gene expression?

Reduced expression means that cells carrying the variant produce less of the affected protein. An eQTL like this one does not change the protein structure, only how much of it is made. The functional consequences depend on what the protein normally does in those tissues.

Which tissues show expression changes linked to rs10050311?

GTEx data shows the alternate allele reduces ARPC1AP4 expression in pituitary, spleen, sigmoid colon, tibial artery, esophageal muscularis, subcutaneous adipose, and thyroid. It also reduces C4orf36 expression specifically in the cervical spinal cord.

Is rs10050311 linked to diabetes or insulin resistance?

The available studies do not directly link rs10050311 to diabetes or insulin resistance. A separate GWAS in African Americans identified loci for fasting insulin and insulin resistance involving different genes, SC4MOL and TCERG1L, not SLC10A6.