Figure 3.

(A) SOCS1 protein domains and locations of the variants. The kinase inhibitory region (KIR) functions as a pseudo-substrate that can inhibit the tyrosine kinase activity of JAK proteins. The SRC-homology 2 (SH2) domain binds the activation loop of the JAK proteins’ catalytic domain. The SOCS box recruits the ubiquitin-transferase system and initiates the proteasomal degradation of JAK proteins. Mutations are described in the literature. Our patient's mutations are in red. (B) Pedigrees of the family with SOCS1 variants. Squares: males; circles: females; black: affected mutation carriers; gray: unaffected mutation carriers. WT, wild-type SOCS1 allele. (C) Sanger sequencing analysis. Sanger sequencing of the exon 1 of SOCS1 in the proband and his parents confirmed the maternal origin of: c.365G>A (p.G122E) and c.368C>A (p.P123H) in the same allele of SOCS1 gene. (D) STAT1 phosphorylation assay. Increased phosphorylation of monocytes (CD14⁺) after 15 min with IFN-γ stimulation in the patient and his mother compared with a healthy control (HD).