LRP8

Chr 1

LDL receptor related protein 8

Also known as: APOER2, HSZ75190, LRP-8, MCI1

NCBI Gene: 7804ENSG00000157193UniProt: Q14114

This gene encodes a member of the low density lipoprotein receptor (LDLR) family. Low density lipoprotein receptors are cell surface proteins that play roles in both signal transduction and receptor-mediated endocytosis of specific ligands for lysosomal degradation. The encoded protein plays a critical role in the migration of neurons during development by mediating Reelin signaling, and also functions as a receptor for the cholesterol transport protein apolipoprotein E. Expression of this gene may be a marker for major depressive disorder. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jun 2011]

Primary Disease Associations & Inheritance

{Myocardial infarction, susceptibility to}MIM #608446
153
ClinVar variants
10
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— LRP8
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
10 Pathogenic / Likely Pathogenic· 115 VUS of 153 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.22LOEUF
pLI 1.000
Z-score 5.67
OE 0.11 (0.06–0.22)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.52Z-score
OE missense 0.70 (0.64–0.76)
382 obs / 548.0 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.11 (0.06–0.22)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.70 (0.64–0.76)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.88
0≤1.21.6
LoF obs/exp: 5 / 46.9Missense obs/exp: 382 / 548.0Syn Z: 1.45

ClinVar Variant Classifications

153 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7
Likely Pathogenic3
VUS115
Likely Benign19
Benign8
Conflicting1
7
Pathogenic
3
Likely Pathogenic
115
VUS
19
Likely Benign
8
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
7
0
7
Likely Pathogenic
0
0
3
0
3
VUS
0
112
3
0
115
Likely Benign
0
8
6
5
19
Benign
0
0
1
7
8
Conflicting
—1
Total01202012153

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

LRP8 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

{Myocardial infarction, susceptibility to}

MIM #608446

Molecular basis of disorder known

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Enhanced LRP8 expression induced by Helicobacter pylori drives gastric cancer progression by facilitating β-Catenin nuclear translocation.
Liu B et al.·J Adv Res
2025
LRP8 Regulates Lipid Metabolism to Stimulate Malignant Progression and Cisplatin Resistance in Bladder Cancer.
Wu GF et al.·Kaohsiung J Med Sci
2025
LRP8-dependent cholesterol metabolism modulates mTORC1 signaling and apoptotic pathways in multiple myeloma.
Wang Y et al.·Cell Death Dis
2025
Further evidence for the association between LRP8 and schizophrenia.
Xiao X et al.·Schizophr Res
2020
Selenium and brain aging: A comprehensive review with a focus on hippocampal neurogenesis.
Daneshpour A et al.·Ageing Res Rev
2025Review
Hsa_circ_0005571 promotes the proliferation and invasion of colorectal cancer cells.
Ge H et al.·Sci Rep
2025
The role of LRP8 (ApoER2') in the pathophysiology of the antiphospholipid syndrome.
de Groot PG et al.·Lupus
2010Review
An LRP8 variant is associated with familial and premature coronary artery disease and myocardial infarction.
Shen GQ et al.·Am J Hum Genet
2007
Targeting LRP8 inhibits breast cancer stem cells in triple-negative breast cancer.
Lin CC et al.·Cancer Lett
2018
Therapeutic targeting of the TPX2/TTK network in colorectal cancer.
Shaath H et al.·Cell Commun Signal
2023
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools