ITM2B gene

The ITM2B gene (ITM2B stands for Integral Membrane Protein 2B) is a protein-coding gene located on chromosome 13q14.2. The ITM2B gene encodes a transmembrane protein (BRI2) that is processed at the C-terminus by furin or furin-like proteases into a small secreted peptide that inhibits beta-amyloid deposition.

Mature BRI2 (mBRI2) plays a regulatory role in amyloid beta A4 precursor protein (APP) processing and acts as an inhibitor of amyloid beta peptide aggregation and fibril deposition. The protein plays a role in the induction of neurite growth. Furthermore, it acts as a protease inhibitor by blocking the access of secretases to APP cleavage sites.

Mutations that result in elongation of the C-terminal end of the encoded protein, thereby increasing the size of the secreted peptide, are associated with two neurogenerative diseases, familial British dementia and familial Danish dementia(ABri/Dan amyloidosis- see below for hereditary amyloidoses).

1. Michno W et al (2022) Chemical traits of cerebral amyloid angiopathy in familial British-, Danish-, and non-Alzheimer's dementias. J Neurochem 163: 233-246.
2. Yamada M et al (2021) Cerebral amyloid angiopathy. Prog Mol Biol Transl Sci107:41-78.