LRP2BP

Chr 4

LRP2 binding protein

NCBI Gene: 55805ENSG00000109771UniProt: Q9P2M1

The LRP2BP protein acts as an adapter that regulates LRP2 function and is predicted to be located in the cytoplasm. This gene is extremely intolerant to loss-of-function variants (pLI near 1.0), suggesting that mutations likely cause severe developmental phenotypes, though specific associated diseases have not yet been definitively established in the literature.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
2
Pubs (1 yr)
114
P/LP submissions
0%
P/LP missense
0.97
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— LRP2BP
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
113 unique Pathogenic / Likely Pathogenic· 72 VUS of 200 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.97LOEUF
pLI 0.000
Z-score 1.67
OE 0.60 (0.38–0.97)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.49Z-score
OE missense 0.90 (0.80–1.02)
176 obs / 195.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.60 (0.38–0.97)
0≤0.351.4
Missense OE0.90 (0.80–1.02)
0≤0.61.4
Synonymous OE0.84
0≤1.21.6
LoF obs/exp: 12 / 20.1Missense obs/exp: 176 / 195.2Syn Z: 1.11
DN
0.7227th %ile
GOF
0.80top 10%
LOF
0.2092th %ile

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.

GOFprediction above median
DNprediction above median

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

200 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic103
Likely Pathogenic10
VUS72
Likely Benign7
103
Pathogenic
10
Likely Pathogenic
72
VUS
7
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
103
0
103
Likely Pathogenic
0
0
10
0
10
VUS
0
50
22
0
72
Likely Benign
0
3
4
0
7
Benign
0
0
0
0
0
Total0531390192

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

View in ClinVar →

Protein Context — Lollipop Plot

LRP2BP · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Identification of hub genes associated with pyroptosis in diabetic nephropathy patients using integrated bioinformatic analysis.
Wang Q et al.·Int Urol Nephrol
2025Cohort
Identification of key antifibrotic targets FPR1, TAS2R5, and LRP2BP of valsartan in diabetic nephropathy: A transcriptomics-driven study integrating machine learning, molecular docking, and dynamics simulations.
Wang Z et al.·Int J Biol Macromol
2025
LncRNA-RP11-714G18.1 suppresses vascular cell migration via directly targeting LRP2BP.
Zhang Y et al.·Immunol Cell Biol
2018
Exome-Wide Association Analysis Suggests LRP2BP as a Susceptibility Gene for Endothelial Injury in Systemic Sclerosis in the Han Chinese Population.
Pu W et al.·J Invest Dermatol
2021
Detection of genomic variations and selection signatures in Wagyu using whole-genome sequencing data.
Shi L et al.·Anim Genet
2023
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

Top 5 resultsSearch Europe PMC ↗

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