Genetics: locus 1:69,696,474 - gene LRRC7

[ME/CFS Science Blog]

This locus was just below the significance threshold in DecodeME. The credible set includes 189 SNPs and all lie in LRRC7, which is the most likely causal gene.



The eQTL showed that LRRC7 colocalized with several different tissues but with PP.H4 around 0.6-0.8, so it wasn't a perfect match. The ME/CFS alleles are most often associated with increased LLRC7.



The phewas found not matching signals. The best match was for brain connectivity and cortical surface.

 

[ME/CFS Science Blog]

Here's the genecard info on LRRC7.

LRRC7 encodes leucine-rich repeat-containing protein 7, an adaptor and PDZ domain-containing protein that participates in receptor clustering, neurotransmitter receptor transport, and positive regulation of neuron projection development. It is also involved in cell-cell adhesion and establishment or maintenance of epithelial cell apical/basal polarity, placing it at the interface of neuronal organization and epithelial polarity control.

LRRC7 is linked to molecular adaptor activity and protein kinase binding, and it localizes to the postsynaptic density, cytoplasm, cytosol, and centrosome. Its biological context includes endosome-to-postsynaptic membrane transport, clustering of voltage-gated calcium channels, and regulation of long-term synaptic depression. Expression measurements show prominent signal in brain, with RNA expression also detected in the peripheral nervous system.

Pathogenic variants in LRRC7 are reported in intellectual developmental disorder, autosomal dominant 77 and alacrima, achalasia, and impaired intellectual development syndrome. These findings connect LRRC7 to neurodevelopmental and multisystem phenotypes, including broad nervous system, digestive system, endocrine, eye, and musculoskeletal involvement. It has also been implicated in cocaine dependence.

LRRC7 Gene - GeneCards