ITM2C
Chr 2integral membrane protein 2C
Also known as: BRI3, BRICD2C, E25, E25C, ITM3
The ITM2C protein negatively regulates amyloid-beta peptide production by inhibiting APP processing through alpha- and beta-secretase pathways. Mutations cause autosomal recessive neurodevelopmental disorders with intellectual disability and developmental delay. The gene shows moderate constraint against loss-of-function variants (pLI 0.70, LOEUF 0.50), suggesting intolerance to complete protein loss.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
ClinVar Variant Classifications
93 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 | 0 | 0 | 29 | 0 | 29 |
Likely Pathogenic | 0 | 0 | 0 | 0 | 0 |
VUS | 0 | 39 | 2 | 0 | 41 |
Likely Benign | 0 | 2 | 0 | 0 | 2 |
Benign | 0 | 0 | 0 | 2 | 2 |
| Total | 0 | 41 | 31 | 2 | 74 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ITM2C · 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