ArticleFrontiers in pharmacology2026
Sigma-1 and Sigma-2 receptors exhibit divergent genome-wide Co-expression architectures in human brain despite shared subcellular localization.
Article in Frontiers in pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
The sigma-1 receptor (SIGMAR1) and sigma-2 receptor (TMEM97) are both enriched at the mitochondria-associated membrane (MAM) and have been pharmacologically co-classified for decades, yet their functional relationship at the transcriptomic level remains uncharacterized. We performed genome-wide co-expression analysis for both receptors across five brain regions from the GTEx v8 dataset (n = 209 in the primary region, 16,225 expressed genes) using Spearman correlations. Three Weighted Jaccard (WJ) formulations on continuous correlation vectors - (r+1)/2 shifted, unsigned |r|, and signed-all revealed that SIGMAR1 and TMEM97 share the majority of their global transcriptional architecture (WJ shifted = 0.964, unsigned = 0.907, signed = 0.906; all three rank-identical across 21 pairwise comparisons, ρ = 1.000), yet their top 5% co-expression networks overlap by only 10.0% (binary Jaccard = 0.100). Cosine similarity on raw vectors confirmed metric robustness (ρ = 0.856 with WJ, p = 7.5 × 10
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