STIM1 Gene

The STIM1 gene (STIM1 stands for "Stromal Interaction Molecule 1") is a protein-coding gene located on chromosome 11p15.4. Alternative splicing of this gene results in multiple transcript variants.

The STIM1 gene encodes a type 1 transmembrane protein that mediates Ca2+ influx after depletion of intracellular Ca2+ stores by gating store-operated Ca2+ influx channels (SOCs). It is one of several genes located in gene domain of 11p15.5, an important tumor suppressor gene region.

STIM-Orai channels have recently been identified as the underlying molecular mechanism of store-operated calcium entry (SOCE). STIM (stromal interaction molecule) proteins are Ca2+ sensors in the endoplasmic reticulum. Orai proteins are STIM binding partners that form the channel pore.

The protein encoded by the STIM1 gene is a protein with a single transmembrane domain that crosses mainly the endoplasmic/sarcoplasmic reticulum but also the cell membrane. Its N-terminus is located in the endoplasmic/sarcoplasmic reticulum, while the C-terminus is located in the cytoplasm. The STIM1 monomer binds Ca2+ with low affinity. Ca2+ consumption leads to unfolding of the STIM1 protein as well as dimerization and multimerization. The C-terminal part of STIM1 consists of three coiled-coil domains CC1, CC2, and CC3, serine/valine (SP) and lysine (K)-rich regions, an inhibitory domain (ID), and a functional TRIP structure. Since the second CC structure has been shown to be the smallest segment with the ability to activate the Orai1 channel, it is also called SOAR (STIM1-ORAI1 Activation Region).

Diseases associated with STIM1 include Stormorken syndrome/OMIM: 1850709. Stormorken syndrome is a rare autosomal dominant genetic disorder with a complex phenotype that includes muscle fatigue, bleeding tendency associated with thrombocytopathy or thrombocytopenia, asplenia, miosis, anemia, migraine, dyslexia, ichthyosis , and short stature.

1. Jiang Li-Jun et al.(2021) Stormorken Syndrome Caused by a Novel STIM1 Mutation: A Case Report. "Frontiers in neurology 12: 522513.
2. Markello T et al. (2015) York platelet syndrome is a CRAC channelopathy due to gain-of-function mutations in STIM1. Molec Genet Metab 114: 474-482.
3. Misceo D et al (2014) A dominant STIM1 mutation causes Stormorken syndrome. Hum. Mutat. 35: 556-564.
4. Mizobuchi M et al (2000) Muscle involvement of Stormorken's syndrome. Rinsho Shinkeigaku 40: 915-920.