Expressive

rs11067376 (MVK): Mevalonate Kinase Expression Variant

Key takeaways

  • rs11067376 sits near the MVK gene and is linked to reduced mevalonate kinase expression in whole blood - MVK is an enzyme in the same cholesterol-making pathway that statins target
  • The same variant shifts expression of five other genes across lung, skin, lymphocytes, tibial nerve, and colon, showing broad regulatory reach
  • In lung tissue, it increases MYO1H (myosin motor protein) expression with one of the strongest signals at this locus (p=6.3e-34 in GTEx v11, 953 donors)
  • It reduces expression of MMAB, a gene involved in vitamin B12 metabolism, in nerve tissue and immune cells
  • Large-scale genetic studies in lipid metabolism and neuropsychology have examined this genomic region

Key takeaways

  • rs11067376 sits near the MVK gene and is linked to reduced mevalonate kinase expression in whole blood - MVK is an enzyme in the same cholesterol-making pathway that statins target
  • The same variant shifts expression of five other genes across lung, skin, lymphocytes, tibial nerve, and colon, showing broad regulatory reach
  • In lung tissue, it increases MYO1H (myosin motor protein) expression with one of the strongest signals at this locus (p=6.3e-34 in GTEx v11, 953 donors)
  • It reduces expression of MMAB, a gene involved in vitamin B12 metabolism, in nerve tissue and immune cells
  • Large-scale genetic studies in lipid metabolism and neuropsychology have examined this genomic region

What the research says rs11067376 is a common genetic variant located near MVK (mevalonate kinase), a gene encoding an enzyme in the isoprenoid and cholesterol synthesis pathway. Tissue expression data from GTEx v11 (953 donors) show that the alternate allele reduces MVK mRNA levels in whole blood and shifts expression of five additional genes across lung, skin, lymphocytes, tibial nerve, and colon GTEx Portal. The locus has been examined in large-scale genetic studies of lipid metabolism and neuropsychological traits, with upstream pathway members such as HMGCR (the enzyme that statin drugs inhibit) studied in UK Biobank samples of up to 115,082 participants.

Reported associations

  • MVK expression (whole blood): The alternate allele is associated with reduced mevalonate kinase mRNA levels in whole blood GTEx Portal
  • MYO1H expression (lung): The alternate allele is associated with increased expression of MYO1H (a myosin motor protein gene) in lung tissue GTEx Portal
  • FOXN4 expression (skin): The alternate allele is associated with reduced expression of FOXN4 (a transcription factor gene) in both non-sun-exposed (suprapubic) and sun-exposed (lower leg) skin GTEx Portal
  • MMAB expression (lymphocytes and tibial nerve): The alternate allele is associated with reduced expression of MMAB (a gene involved in adenosylcobalamin synthesis, an active form of vitamin B12) in EBV-transformed lymphocytes and tibial nerve GTEx Portal
  • UBE3B expression (transverse colon): The alternate allele is associated with reduced expression of UBE3B (a ubiquitin ligase gene involved in protein degradation signaling) in transverse colon GTEx Portal
  • UNG expression (sun-exposed skin): The alternate allele is associated with reduced expression of UNG (uracil-DNA glycosylase, a base excision repair enzyme) in sun-exposed lower leg skin GTEx Portal
  • Lipid metabolism pathway context: A Mendelian randomization study of lipid-modifying drug targets in up to 115,082 UK Biobank participants found that genetic perturbation of cholesterol synthesis pathway members including HMGCR had broad effects on 249 metabolic traits and coronary artery disease risk; that study focused on upstream pathway genes and did not directly examine rs11067376 or MVK
  • Liver protein expression context: A genome-wide pQTL study in 287 normal human liver samples identified over 4,900 pQTL variants, including more than 2,000 not previously reported in mRNA-level eQTL studies, suggesting extensive post-transcriptional regulation at loci in this genomic region
  • Neuropsychological trait context: A GWAS of 12 individual neuroticism items in up to 266,896 UK Biobank participants identified 255 genome-wide significant independent genomic regions, including 138 item-specific loci, with genetic correlations between items ranging from 0.38 to 0.91

Evidence quality The tissue expression associations come from GTEx v11 (953 donors, cis-window, FDR<0.05), providing robust and well-powered evidence for the eQTL effects at this locus GTEx Portal. Individual p-values range from p=6.3e-34 for MYO1H in lung down to p=2.6e-11 for UBE3B in transverse colon, all well below genome-wide significance thresholds. The lipid pathway Mendelian randomization study was powered by up to 115,082 UK Biobank participants; the liver pQTL study covered 287 liver samples; and the neuroticism GWAS covered up to 266,896 UK Biobank participants. However, the specific involvement of rs11067376 in the pQTL and neuroticism findings is not detailed in the available excerpts, so those associations should be treated as contextual background rather than confirmed trait associations for this variant. No conflicting findings were identified among the provided sources.

Tissue-specific expression effects

  • MYO1H: Increased expression in lung tissue GTEx Portal
  • FOXN4: Reduced expression in both non-sun-exposed (suprapubic) and sun-exposed (lower leg) skin GTEx Portal
  • MVK: Reduced expression in whole blood GTEx Portal
  • MMAB: Reduced expression in EBV-transformed lymphocytes and tibial nerve GTEx Portal
  • UBE3B: Reduced expression in transverse colon GTEx Portal
  • UNG: Reduced expression in sun-exposed lower leg skin 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.

Discuss with your doctor

  • Genetic predisposition to neuroticism and mood traits Moderate

    rs11067376-A allele shows strong GWAS association with neuroticism and irritable mood, warranting discussion of mood monitoring benefits.

    Discuss with healthcare provider; consider mood assessment if experiencing neuroticism or irritability symptoms

Frequently asked questions

What does the MVK gene do?

MVK encodes mevalonate kinase, an enzyme in the mevalonate pathway - the biochemical chain cells use to produce cholesterol and other isoprenoids. Statin drugs work by blocking a different enzyme (HMGCR) in the same pathway.

What is an eQTL and why does it matter for rs11067376?

An eQTL (expression quantitative trait locus) is a DNA variant associated with how much mRNA a gene produces in a given tissue. rs11067376 is an eQTL for at least six genes, meaning carriers of its alternate allele tend to show different expression levels of those genes in specific tissues.

Which tissues does rs11067376 affect?

Based on GTEx v11 data from 953 donors, this variant shows expression effects in lung (increased MYO1H), sun-exposed and non-sun-exposed skin (reduced FOXN4 and UNG), whole blood (reduced MVK), EBV-transformed lymphocytes and tibial nerve (reduced MMAB), and transverse colon (reduced UBE3B).

Is rs11067376 linked to cholesterol or heart disease?

The variant reduces expression of MVK, an enzyme in the cholesterol biosynthesis pathway. Research on upstream members of the same pathway found broad effects on blood metabolome traits and coronary artery disease risk in large UK Biobank samples. A direct link from rs11067376 specifically to cardiovascular outcomes is not established in the available evidence.

What is the MMAB gene and why is its expression affected here?

MMAB encodes a protein involved in the synthesis of adenosylcobalamin, an active form of vitamin B12. rs11067376 is associated with reduced MMAB expression in immune cells and tibial nerve. The downstream effects of this expression change on B12 metabolism or nerve function are not described in the available evidence.