rs11003118 (MBL2): Plasma Protein and Nerve Expression
Key takeaways
- rs11003118 sits in the LNCAROD-MBL2 genomic region and is linked to levels of mannose-binding lectin 2 (MBL2), an immune protein that circulates in blood plasma
- A large proteomics study of 3,301 healthy blood donors identified thousands of genetic associations with plasma protein levels, placing this locus among those tied to circulating MBL2
- GTEx data from 953 donors shows the ALT allele reduces expression of MBL2 and two other nearby genes specifically in tibial nerve tissue
- All three genes at this locus show reduced expression in tibial nerve tissue with the ALT allele, suggesting a consistent local regulatory effect
Key takeaways
- rs11003118 sits in the LNCAROD-MBL2 genomic region and is linked to levels of mannose-binding lectin 2 (MBL2), an immune protein that circulates in blood plasma
- A large proteomics study of 3,301 healthy blood donors identified thousands of genetic associations with plasma protein levels, placing this locus among those tied to circulating MBL2
- GTEx data from 953 donors shows the ALT allele reduces expression of MBL2 and two other nearby genes specifically in tibial nerve tissue
- All three genes at this locus show reduced expression in tibial nerve tissue with the ALT allele, suggesting a consistent local regulatory effect
What the research says A genome-wide plasma proteomics study tested 10.6 million genetic variants against levels of 2,994 proteins in 3,301 healthy blood donors from the INTERVAL study, identifying 1,927 significant pQTLs (protein quantitative trait loci, meaning genetic variants that influence how much of a given protein circulates in the blood) across 1,478 proteins, with 89% being previously unreported; replication was conducted in 4,998 individuals using a second protein measurement platform. The rs11003118 variant sits in the LNCAROD-MBL2 region, encompassing MBL2, which encodes mannose-binding lectin 2, a plasma protein that forms part of the complement system of innate immune defence (the complement system is a cascade of blood proteins that help fight infection). Separately, GTEx eQTL (expression quantitative trait locus, meaning a genetic variant associated with differences in how much of a given gene is expressed) data from 953 donors shows the ALT (alternative) allele at rs11003118 is associated with reduced expression of MBL2 and two additional genes at this locus in tibial nerve tissue GTEx Portal.
Reported associations
- MBL2 plasma protein levels: rs11003118 was identified at the LNCAROD-MBL2 locus in a genome-wide proteomics atlas that found 1,927 pQTLs across 3,301 healthy donors from the INTERVAL bioresource, with cis-acting (local, within a few hundred kilobases of the gene) pQTLs replicating at 81% in an independent cohort of 4,998 individuals
- MBL2 expression in tibial nerve: the ALT allele is associated with reduced MBL2 expression in tibial nerve tissue (slope -0.27, p=2.3e-9, n=953) GTEx Portal
- ENSG00000306279 expression in tibial nerve: the ALT allele is associated with reduced expression of this locus gene in tibial nerve tissue (slope -0.52, p=1.6e-28, n=953), the strongest effect among the three genes reported at this locus GTEx Portal
- ENSG00000306325 expression in tibial nerve: the ALT allele is associated with reduced expression of this locus gene in tibial nerve tissue (slope -0.38, p=4.3e-16, n=953) GTEx Portal
Evidence quality The plasma proteomics association derives from a single large study of 3,301 participants (no PMID is available in the provided study metadata for direct inline citation), using the SOMAscan aptamer-based assay; effect-size estimates replicated at r=0.83 correlation between this and the Olink platform used in the 4,998-person replication cohort. Overall, 65% of pQTLs replicated (81% cis-acting, 52% trans-acting). The GTEx eQTL associations are based on 953 donors, with all three genes at this locus passing an FDR (false discovery rate, a statistical threshold limiting false positives) below 0.05 and highly significant p-values ranging from 2.3e-9 to 1.6e-28. The consistent direction of effect across all three genes in the same tissue strengthens confidence in the eQTL signal. No conflicting findings were identified across the two evidence sources. The functional or clinical significance of reduced gene expression in tibial nerve tissue is not established by the available evidence.
Tissue-specific expression effects
- ENSG00000306279: the ALT allele is associated with reduced expression in tibial nerve tissue, with the largest effect size of the three genes at this locus GTEx Portal
- ENSG00000306325: the ALT allele is associated with reduced expression in tibial nerve tissue GTEx Portal
- MBL2: the ALT allele is associated with reduced expression in tibial nerve tissue GTEx Portal
Lifestyle considerations No lifestyle considerations on file for this variant.
Frequently asked questions
What is the MBL2 gene?
MBL2 encodes mannose-binding lectin 2, a protein secreted into the bloodstream that plays a role in the innate immune system by helping recognize and respond to pathogens. It is part of the complement system, a group of blood proteins involved in fighting infection.
What does rs11003118 affect?
rs11003118 is located in a genomic region spanning LNCAROD and MBL2 and has been linked to plasma levels of MBL2 protein in a large proteomics study. GTEx data also shows the variant is associated with reduced expression of MBL2 and two other nearby genes in tibial nerve tissue.
What is a protein quantitative trait locus (pQTL)?
A pQTL is a genetic variant that influences how much of a specific protein circulates in the bloodstream. Large proteomics studies test millions of genetic variants against hundreds of proteins simultaneously to identify these associations.
What is LNCAROD?
LNCAROD is a long non-coding RNA gene, meaning it is transcribed from DNA but does not encode a protein. It sits near MBL2 in the genome, and rs11003118 lies within this region.
Is rs11003118 linked to immune function?
The variant is located near MBL2, which encodes a circulating immune protein, and a large plasma proteomics study identified this locus in connection with circulating protein levels. The clinical significance of any effect on immune function is not established by the evidence available for this specific variant.