LDLRAD3
Chr 11low density lipoprotein receptor class A domain containing 3
Also known as: LRAD3
The LDLRAD3 protein binds amyloid-beta and regulates APP processing through receptor-mediated endocytosis, potentially influencing the production of amyloidogenic peptides. Mutations cause autosomal recessive early-onset Alzheimer disease, representing one of the rare monogenic forms of this neurodegenerative condition in children and young adults. The gene shows relatively low constraint to loss-of-function variation in the general population.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
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
84 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 | 14 | 0 | 14 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 0 | 42 | 10 | 0 | 52 |
Likely Benign | 0 | 1 | 0 | 3 | 4 |
Benign | 0 | 3 | 0 | 0 | 3 |
| Total | 0 | 46 | 25 | 3 | 74 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
LDLRAD3 · 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