LRP1

Chr 12

LDL receptor related protein 1

Also known as: A2MR, APOER, APR, CD91, DDH3, IGFBP-3R, IGFBP3R, IGFBP3R1

NCBI Gene: 4035ENSG00000123384UniProt: Q07954

This gene encodes a member of the low-density lipoprotein receptor family of proteins. The encoded preproprotein is proteolytically processed by furin to generate 515 kDa and 85 kDa subunits that form the mature receptor (PMID: 8546712). This receptor is involved in several cellular processes, including intracellular signaling, lipid homeostasis, and clearance of apoptotic cells. In addition, the encoded protein is necessary for the alpha 2-macroglobulin-mediated clearance of secreted amyloid precursor protein and beta-amyloid, the main component of amyloid plaques found in Alzheimer patients. Expression of this gene decreases with age and has been found to be lower than controls in brain tissue from Alzheimer's disease patients. [provided by RefSeq, Oct 2015]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtKeratosis pilaris atrophicans
UniProtDevelopmental dysplasia of the hip 3

Clinical highlights

Interpreting a novel variant
This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.
1
Active trials
316
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.06
LOEUF· LoF intol.
LOF
Mechanism· predicted
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?
0.06LOEUF
pLI 1.000
Z-score 14.09
OE 0.03 (0.02–0.06)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?
8.25Z-score
OE missense 0.57 (0.55–0.60)
1692 obs / 2953.0 exp
Constrained

Extremely missense-constrained (top ~0.01%)

Observed / Expected Ratios?
LoF OE?0.03 (0.02–0.06)
0≤0.351.4
Missense OE?0.57 (0.55–0.60)
0≤0.61.4
Synonymous OE?0.92
0≤1.21.6
LoF obs/exp: 8 / 246.9Missense obs/exp: 1692 / 2953.0Syn Z: 2.22

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

LRP1 · 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

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients