LRP1B
Chr 2LDL receptor related protein 1B
Also known as: LRP-1B, LRP-DIT, LRPDIT
The LRP1B protein is a low-density lipoprotein receptor family member that binds and internalizes ligands through receptor-mediated endocytosis at the cell surface. Mutations cause neurodevelopmental disorders with intellectual disability and autism spectrum disorder features, inherited in an autosomal dominant pattern. This gene is highly constrained against loss-of-function variants in the population, indicating intolerance to such mutations.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
400 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 | 1 | 0 | 1 |
Likely Pathogenic | 0 | 5 | 2 | 1 | 8 |
VUS | 1 | 274 | 3 | 0 | 278 |
Likely Benign | 0 | 21 | 7 | 33 | 61 |
Benign | 0 | 14 | 13 | 22 | 49 |
| Total | 1 | 314 | 26 | 56 | 397 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
LRP1B · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
External Resources
Links to major genomics databases and tools