V-set and transmembrane domain-containing protein 1 (VSTM1)

V-set and transmembrane domain-containing protein 1 (VSTM1) is a type I transmembrane protein widely expressed in leukocytes and myeloid cells, with alternative spliced isoforms including VSTM1-v1[1][2]. VSTM1 contains an extracellular immunoglobulin V-like domain and cytoplasmic ITIM motifs, functioning as an inhibitory immune receptor involved in signal transduction and regulation of phagocytes[1][2]. It inhibits cell activation by recruiting SHP-1 and SHP-2 phosphatases, thereby modulating immune responses and reactive oxygen species production[1]. Its cytokine activity also promotes IL-17A secretion by CD4+ T-cells and supports Th17 cell differentiation[5]. VSTM1 is found to be silenced in several hematopoietic malignancies due to CpG promoter hypermethylation, suggesting utility as a diagnostic or prognostic marker; pharmacological demethylation can restore its expression[1]. Although no direct drugs targeting VSTM1 are currently known, antibody-mediated crosslinking inhibits lymphocyte growth, highlighting therapeutic potential for immune and cancer-related disorders[1][2][5].

Other names

SIRL-1Signal inhibitory receptor on leukocytes-1LAIR homologOSCAR-like transcript-1UNQ3033/PRO9835UNQ3033SIRL1VSTM1-v1

Inhibitory signaling via ITIM recruitment of SHP-1/SHP-2 phosphatases (downregulates cell activation, inhibits ROS production and phagocyte microbicidal activity), Promotes IL-17A secretion as cytokine