ITM2B
Chr 13ADintegral membrane protein 2B
Also known as: ABRI, BRI, BRI2, BRICD2B, E25B, E3-16, FBD, RDGCA
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.
Primary Disease Associations & Inheritance
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
261 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 2 | 1 | 68 | 0 | 71 |
Likely Pathogenic | 1 | 0 | 2 | 0 | 3 |
VUS | 6 | 95 | 15 | 0 | 116 |
Likely Benign | 0 | 1 | 15 | 36 | 52 |
Benign | 0 | 1 | 0 | 4 | 5 |
Conflicting | — | 4 | |||
| Total | 9 | 98 | 100 | 40 | 251 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ITM2B · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools