ITM2B

Chr 13AD

integral 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.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.543 OMIM phenotypes
Clinical SummaryITM2B
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.63) — some intolerance to loss-of-function variants.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.54LOEUF
pLI 0.626
Z-score 2.64
OE 0.17 (0.070.54)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.04Z-score
OE missense 0.75 (0.640.89)
107 obs / 141.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.17 (0.070.54)
00.351.4
Missense OE0.75 (0.640.89)
00.61.4
Synonymous OE0.84
01.21.6
LoF obs/exp: 2 / 11.8Missense obs/exp: 107 / 141.9Syn Z: 0.87
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedITM2B-related retinal dystrophy with inner retinal dysfunction and ganglion cell abnormalitiesOTHERAD
DN
0.3892th %ile
GOF
0.4578th %ile
LOF
0.4726th %ile

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOF1 literature citation

Literature Evidence

LOFMutations in integral membrane protein 2B (ITM2b/BRI2) gene cause familial British and Danish dementia (FBD and FDD), autosomal dominant disorders characterized by progressive cognitive deterioration. Two pathogenic mechanisms, which may not be mutually exclusive, have been proposed for FDD and FBD:PMID:33172889

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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