Enhanced CD4 ⁺ T cell activation and CD8 ⁺ T cell dysfunction in the ORAI1 mutant patient. scRNA-seq analysis of PBMC from the ORAI1 mutant patient and three HD controls combined. (A) Aggregate UMAP plot of T-NK cell subsets identified in PBMC of the patient and HD controls. (B) UMAP plot of PBMC colored by the expression of the GEP associated with CD4⁺T_emcells identified by NMF. (C) Boxplot showing usage scores for this GEP in CD4⁺ and CD8⁺ T cells, and NK cells. P < 0.001. (D) Top 10 dysregulated National Cancer Institute (NCI)-Nature pathways in the CD4⁺T_emcell GEP. (E) Heatmap of DEGs contained in the CD4⁺T_emcell GEP in all CD4⁺ T cells of the patient compared with HD controls. Colors depict log₂FC in expression. (F) UMAP plot of PBMC colored by the expression of the GEP associated with CD8⁺T_emcells identified by NMF. (G) Boxplot showing usage scores for this GEP in naive and T_em CD8⁺ T cells. P < 0.01. (H) Top 10 dysregulated NCI-Nature pathways in the CD8⁺T_emcell GEP. (I) Heatmap of DEGs contained in the CD8⁺T_emcell GEP in all CD8⁺ T cells of the patient compared with HD controls. Colors depict log₂FC in expression. (J) Heatmap of exhaustion markers in CD8⁺ T cells from three HD controls and the patient. Statistical analyses in D and H were conducted using a right-tailed Fisher’s exact test. Statistical analyses in C and G were performed using a Wilcoxon rank sum test. Z scores in J were calculated using the normalized average expression per sample in all CD8⁺ T cells. Significance in C, D, G, and H was adjusted using the Benjamini–Hochberg method. **P < 0.01, ***P < 0.001. FC, fold change.