Panel A shows histograms of extracellular and total OSMR expression in HEK293 cells transfected with wild-type OSMR, OSMR deficiency variants, and homozygous OSMR population variants. The x-axis represents OSMR expression levels, and the y-axis represents the frequency of cells. Panel B is a bar graph quantifying extracellular OSMR expression, with the x-axis listing different OSMR variants and the y-axis showing the mean fluorescence intensity (MFI) fold change relative to the empty vector. Panel C is a bar graph quantifying total OSMR expression, with the same x-axis and y-axis as Panel B. Panel D is a table listing minor allele frequencies, CADD scores, and AlphaMissense pathogenicity scores for various OSMR variants. The table includes columns for variant names, minor allele frequency, homozygotes reported in gnomAD, CADD scores, AlphaMissense pathogenicity scores, and pathogenicity class.
Homozygous missense OSMR population variants show normal cell surface expression of OSMRβ in HEK293 cells and are predicted to be benign. (A) Extracellular and total OSMRβ expression was quantified in HEK293 cells transfected with WT OSMRβ, OSMRβ disease-associated variants, (p.Ala349Asp and p.Val436Asp), or homozygous OSMRβ population variants reported in gnomAD with a MAF greater than the p.Val436Asp variant (p.Glu527Lys, p.His187Gln, p.Gly578Asp, p.Asp553Asn, p.Tyr364His, p.Pro959Arg, p.Pro936Ser, and p.Ala950Glu) using flow cytometry. OSMRβ expression was quantified in GFP+ cells; n = 3. (B) Quantification of A, extracellular OSMRβ expression; n = 3. (C) Quantification of A, total OSMRβ expression; n = 3. Statistical comparisons between OSMRβ WT and OSMRβ variants were performed using a Kruskal–Wallis test followed by Dunn’s multiple comparisons test. (D) MAFs, CADD scores, and AlphaMissense pathogenicity scores for OSMRβ population variants and OSMRβ disease-associated variants.