Expressive

rs11576830 (KLHDC9): B4GALT3 and ADAMTS4 eQTL

Key takeaways

  • rs11576830 near KLHDC9 was identified as a proteogenomic signal in a UK Biobank study covering over 54,000 participants.
  • The variant reduces B4GALT3 expression - a glycan-synthesis gene - in fibroblasts, brain, fat, and skin.
  • The same variant reduces ADAMTS4 expression in fibroblasts; ADAMTS4 breaks down cartilage structural proteins.
  • The variant increases TSTD1 expression in esophagus and colon tissue.
  • All reported effects are expression-level changes; no disease diagnoses are documented in the sources provided.

Key takeaways

  • rs11576830 near the KLHDC9 (Kelch domain-containing protein 9) gene was identified as a proteogenomic signal in a UK Biobank study of over 54,000 participants.
  • The variant is linked to reduced B4GALT3 expression - a gene involved in sugar-chain (glycan) synthesis - in fibroblasts, brain, fat, and skin.
  • The same variant is linked to reduced ADAMTS4 expression in fibroblasts; ADAMTS4 is an enzyme that breaks down proteoglycans (structural proteins) in cartilage and connective tissue matrix.
  • The variant is linked to increased TSTD1 expression in esophagus and colon tissue.
  • All reported effects are gene-expression changes from GTEx eQTL data; no established disease diagnoses are documented in the sources provided.

What the research says A 2024 UK Biobank proteomics study measured 1,463 circulating blood proteins across more than 54,000 participants and identified protein quantitative trait loci (pQTLs) - genetic variants that influence protein levels in blood. The study's ratio-based approach, which tests genetic associations with the ratio between pairs of proteins rather than single protein levels, increased the number of discovered genetic signals by 24.7% and found that those ratio QTLs (rQTLs) were 7.6-fold enriched in known protein-protein interactions, providing broad proteomics context for loci in this genomic region. Independently, GTEx v11 eQTL data from 953 donors show that rs11576830 influences expression of at least four nearby genes across fibroblast, brain, adipose, skin, and digestive tissues GTEx Portal.

Reported associations

  • B4GALT3 expression, reduced: The alternate allele is associated with lower B4GALT3 (beta-1,4-galactosyltransferase 3, a glycan-synthesis enzyme) expression across four tissues; effect slopes range from -0.12 in sun-exposed skin (p=2.7e-9) to -0.27 in cultured fibroblasts (p=3.1e-10) GTEx Portal
  • TSTD1 expression, increased: The alternate allele is associated with higher TSTD1 (thiosulfate sulfurtransferase-like domain-containing protein 1) expression in esophagus muscularis (slope +0.26, p=1.8e-6) and colon sigmoid (slope +0.23, p=7.1e-5) GTEx Portal
  • ENSG00000297567 expression, reduced: The alternate allele is associated with lower expression of this annotated locus in esophagus mucosa (slope -0.24, p=7.8e-6) GTEx Portal
  • ADAMTS4 expression, reduced: The alternate allele is associated with lower ADAMTS4 expression in cultured fibroblasts (slope -0.17, p=5.5e-6); ADAMTS4 is a metalloprotease that cleaves aggrecan and other proteoglycans in extracellular matrix GTEx Portal
  • Blood proteomics signal (pQTL): Identified as a proteogenomic locus in a UK Biobank analysis of 1,463 proteins in more than 54,000 participants using ratio-based GWAS methodology; specific protein-level associations for rs11576830 are not detailed in the provided study text.

Evidence quality GTEx v11 eQTL data are derived from 953 donors and all entries reported here pass a 5% false discovery rate threshold within a cis-window around each gene. The B4GALT3 associations in cultured fibroblasts (p=3.1e-10), subcutaneous adipose (p=2.3e-8), and sun-exposed skin (p=2.7e-9) are among the most statistically robust signals in this dataset GTEx Portal. The brain cerebellar hemisphere association (p=1.9e-5) is nominally significant but less robust than the other three B4GALT3 tissues. The TSTD1, ENSG00000297567, and ADAMTS4 associations (p values ranging from 5.5e-6 to 1.8e-6) pass FDR thresholds within their respective tissue datasets GTEx Portal. The UK Biobank proteomics study provides large-sample context (more than 54,000 participants) for a pQTL signal in this genomic region, but the specific protein-level associations for rs11576830 are not detailed in the provided study text and should be treated as preliminary context only. Overall, evidence for this locus is primarily mechanistic (gene-expression level) rather than disease-outcome level.

Tissue-specific expression effects

  • B4GALT3 (beta-1,4-galactosyltransferase 3, involved in building sugar chains on glycoproteins and cell-surface molecules): Reduced expression in cultured fibroblasts, brain cerebellar hemisphere, subcutaneous adipose tissue, and sun-exposed skin GTEx Portal
  • TSTD1 (thiosulfate sulfurtransferase-like domain-containing protein 1): Increased expression in esophagus muscularis and colon sigmoid tissue GTEx Portal
  • ENSG00000297567: Reduced expression in esophagus mucosa GTEx Portal
  • ADAMTS4 (a metalloprotease that cleaves aggrecan and other structural proteins in cartilage and connective tissue extracellular matrix): Reduced expression in cultured fibroblasts GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is rs11576830?

rs11576830 is a genetic variant located near the KLHDC9 gene (Kelch domain-containing protein 9). It has been studied for its effects on nearby gene expression across multiple tissues and appeared as a signal in a large UK Biobank blood proteomics study of over 54,000 participants.

What does KLHDC9 do?

KLHDC9 encodes a Kelch domain-containing protein, a family broadly involved in protein-protein interactions and cellular regulation. The specific biological role of this gene in relation to rs11576830 is not detailed in the sources provided.

Which genes does rs11576830 affect?

GTEx data show the alternate allele reduces B4GALT3 expression (a glycan-synthesis enzyme) in brain, skin, fat, and fibroblasts; reduces ADAMTS4 (a cartilage-matrix protease) in fibroblasts; and increases TSTD1 expression in esophagus and colon tissue.

Is rs11576830 linked to any disease?

No direct disease associations are documented in the provided sources. Current evidence describes gene-expression effects and a protein-level signal in blood; these reflect biological mechanisms rather than clinical diagnoses.

What is an eQTL and why does it matter for rs11576830?

An eQTL (expression quantitative trait locus) is a genetic variant that influences how much a nearby gene is expressed in a given tissue. For rs11576830, GTEx eQTL data show tissue-specific changes in at least four genes, which may help researchers trace how this variant influences biological processes.