LRP1B

Chr 2

LDL receptor related protein 1B

NCBI Gene: 53353ENSG00000168702UniProt: Q9NZR2

Potential cell surface proteins that bind and internalize ligands in the process of receptor-mediated endocytosis

468
ClinVar variants
13
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— LRP1B
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.26) despite low pLI — interpret in context.
📋
ClinVar Variants
13 Pathogenic / Likely Pathogenic· 333 VUS of 468 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

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.
0.32LOEUF
pLI 0.000
Z-score 10.77
OE 0.26 (0.21–0.32)
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.
1.93Z-score
OE missense 0.89 (0.86–0.92)
2148 obs / 2414.6 exp
Tolerant

Mild missense constraint

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.0.26 (0.21–0.32)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.89 (0.86–0.92)
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.1.11
0≤1.21.6
LoF obs/exp: 63 / 244.9Missense obs/exp: 2148 / 2414.6Syn Z: -2.56

ClinVar Variant Classifications

468 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic10
Likely Pathogenic3
VUS333
Likely Benign67
Benign53
Conflicting2
10
Pathogenic
3
Likely Pathogenic
333
VUS
67
Likely Benign
53
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
10
0
10
Likely Pathogenic
0
0
3
0
3
VUS
1
319
13
0
333
Likely Benign
0
22
10
35
67
Benign
0
15
14
24
53
Conflicting
—2
Total13565059468

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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Clinical characteristics and prognostic analysis of SMARCA4-deficient non-small cell lung cancer.
Liang X et al.·Cancer Med
2023
Total Neoadjuvant Therapy With PD-1 Blockade for High-Risk Proficient Mismatch Repair Rectal Cancer.
Li Y et al.·JAMA Surg
2024Clinical trial
Integrated analyses of multi-omic data derived from paired primary lung cancer and brain metastasis reveal the metabolic vulnerability as a novel therapeutic target.
Duan H et al.·Genome Med
2024
Multi-omics Analysis Reveals Immune Features Associated with Immunotherapy Benefit in Patients with Squamous Cell Lung Cancer from Phase III Lung-MAP S1400I Trial.
Parra ER et al.·Clin Cancer Res
2024Cohort
Mutational spectrum and precision oncology for biliary tract carcinoma.
Lin J et al.·Theranostics
2021
LRP1B Suppresses Immunotherapy Efficacy in Lung Adenocarcinoma by Preventing Ferroptosis.
Ke ZH et al.·Cancer Med
2024
Comprehensive genetic variant analysis reveals combination of KRAS and LRP1B as a predictive biomarker of response to immunotherapy in patients with non-small cell lung cancer.
Eklund EA et al.·J Exp Clin Cancer Res
2025Cohort
Molecular Characterization of NUT Carcinoma: A Report from the NUT Carcinoma Registry.
Kim JJ et al.·Clin Cancer Res
2025
Antitumor immunity and prognosis value elicited by FAT3 and LRP1B co-mutation in endometrial cancer.
Jiang Z et al.·Gynecol Oncol
2024
Genomic profiling of aggressive pathologic features in lung adenocarcinoma.
Lin YD et al.·Lung Cancer
2025
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
Cocaine Use Disorder

CRACK-TARGET 1: Descriptive Study of Observed Behavioral Sensitization and Expectations

RECRUITING
NCT06050304Phase NAAssistance Publique - Hôpitaux de ParisStarted 2025-03-04
Observation of behavior and search of biomarkers with 3 blood tests.3 weeks wearing an actimeter3 blood tests

External Resources

Links to major genomics databases and tools