ITM2B

Chr 13AD

integral membrane protein 2B

Also known as: ABRI, BRI, BRI2, BRICD2B, E25B, E3-16, FBD, RDGCA

NCBI Gene: 9445 ENSG00000136156 UniProt: Q9Y287 OMIM: 603904

ITM2B encodes a transmembrane protein that inhibits amyloid-beta peptide aggregation and regulates processing of amyloid precursor protein, while also promoting neurite outgrowth. Mutations cause autosomal dominant familial British dementia, familial Danish dementia, and retinal dystrophy with inner retinal dysfunction and ganglion cell abnormalities. The gene shows high constraint against loss-of-function variants (LOEUF 0.536), indicating intolerance to protein-truncating mutations.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Amyloid precursor proteins are processed by beta-secretase and gamma-secretase to produce beta-amyloid peptides which form the characteristic plaques of Alzheimer disease. This gene encodes a transmembrane protein which is processed at the C-terminus by furin or furin-like proteases to produce a small secreted peptide which inhibits the deposition of beta-amyloid. Mutations which result in extension 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. [provided by RefSeq, Oct 2009]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?Retinal dystrophy with inner retinal dysfunction and ganglion cell abnormalitiesMIM #616079

Dementia, familial BritishMIM #176500

Dementia, familial DanishMIM #117300

UniProtCerebral amyloid angiopathy, ITM2B-related 1

UniProtCerebral amyloid angiopathy, ITM2B-related 2

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.54

LOEUF

LOF

Mechanism· predicted