SOCS1

Overview

First described 1997. Earliest sequence paper UniProt cites for the protein: Minamoto et al, Biochem. Biophys. Res. Commun, 1997, "Cloning and functional analysis of new members of STAT induced STAT inhibitor (SSI) family: SSI-2 and SSI-3". Source.

Sources: HGNC HGNC:19383 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt O15524 (protein name, function text, keywords and locations (REST API)); CIViC gene SOCS1 (1 evidence items, 0 assertions, 1 variants; diseases: Diffuse Large B-cell Lymphoma (GraphQL API, CC0)); Open Targets ENSG00000185338 (association with cancer (MONDO_0004992) 0.49; per-cancer scores at or above 0.5: diffuse large B-cell lymphoma 0.63, non-Hodgkin lymphoma 0.68 (GraphQL API, CC0)); IntOGen SOCS1 (driver in 5 cohorts (Act 3, LoF 2); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)

• Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: IntOGen calls it an activating (Act) driver in 3 cohorts; IntOGen calls it a loss-of-function (LoF) driver in 2 cohorts; CIViC holds 1 clinical evidence items on its variants. Evidence tier "clinical-evidence" is the strongest of those signals.
• Prevalence not recorded: none of the sources gives a positivity rate.
• Lymphoma, JAK-STAT, in NK/T-cell lymphoma and in Hodgkin lymphoma: STAT3 and STAT5B mutations lock the transcription factor in its phosphorylated form. The STAT5B N642H substitution increases the binding affinity of the phosphotyrosine for the mutant histidine, so the phosphorylated protein persists and binds its target sites far more, and the growth advantage it gives can be partly reversed by a JAK1/2 inhibitor in the laboratory (Kucuk 2015). In Hodgkin lymphoma and primary mediastinal B-cell lymphoma the pathway is switched on from the other end, by amplification of JAK2 inside the 9p24.1 amplicon and by loss of the brakes SOCS1 and PTPN1. Frequency: Activating STAT3 and STAT5B mutations across 51 NK/T-cell lymphomas and 43 gamma-delta T-cell lymphomas, with STAT5B N642H particularly frequent in the gamma-delta group (Kucuk 2015). JAK2 sits in the 9p24.1 amplicon in Hodgkin lymphoma and mediastinal large B-cell lymphoma, and its amplification raises both protein and activity and specifically induces PD-1 ligand transcription (Green 2010). What it changes about treatment: Not through an approved drug. JAK inhibitors have been tested in both settings without becoming standard; the practical consequence of the Hodgkin and mediastinal finding is that it explains why checkpoint blockade works there.