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Aliases for LRP2 Gene

Aliases for LRP2 Gene

  • LDL Receptor Related Protein 2 2 3 5
  • Megalin 2 3 4
  • Glycoprotein 330 3 4
  • GP330 3 4
  • LRP-2 3 4
  • Low Density Lipoprotein Receptor-Related Protein 2 2
  • Low-Density Lipoprotein Receptor-Related Protein 2 3
  • Heymann Nephritis Antigen Homolog 3
  • Calcium Sensor Protein 3
  • EC 58
  • EC 58
  • DBS 3

External Ids for LRP2 Gene

Previous GeneCards Identifiers for LRP2 Gene

  • GC02M168036
  • GC02M168526
  • GC02M169947
  • GC02M170187
  • GC02M169810
  • GC02M169693
  • GC02M161880

Summaries for LRP2 Gene

Entrez Gene Summary for LRP2 Gene

  • The protein encoded by this gene, low density lipoprotein-related protein 2 (LRP2) or megalin, is a multi-ligand endocytic receptor that is expressed in many different tissues but primarily in absorptive epithilial tissues such as the kidney. This glycoprotein has a large amino-terminal extracellular domain, a single transmembrane domain, and a short carboxy-terminal cytoplasmic tail. The extracellular ligand-binding-domains bind diverse macromolecules including albumin, apolipoproteins B and E, and lipoprotein lipase. The LRP2 protein is critical for the reuptake of numerous ligands, including lipoproteins, sterols, vitamin-binding proteins, and hormones. This protein also has a role in cell-signaling; extracellular ligands include parathyroid horomones and the morphogen sonic hedgehog while cytosolic ligands include MAP kinase scaffold proteins and JNK interacting proteins. Recycling of this membrane receptor is regulated by phosphorylation of its cytoplasmic domain. Mutations in this gene cause Donnai-Barrow syndrome (DBS) and facio-oculoacoustico-renal syndrome (FOAR).[provided by RefSeq, Aug 2009]

GeneCards Summary for LRP2 Gene

LRP2 (LDL Receptor Related Protein 2) is a Protein Coding gene. Diseases associated with LRP2 include Donnai-Barrow Syndrome and Dent Disease. Among its related pathways are Hedgehog Pathway and Insulin secretion. GO annotations related to this gene include calcium ion binding and SH3 domain binding. An important paralog of this gene is LRP1.

UniProtKB/Swiss-Prot for LRP2 Gene

  • Multiligand endocytic receptor. Acts together with cubilin to mediate HDL endocytosis. In the kidney, mediates the tubular uptake and clearance of leptin (By similarity). Mediates receptor-mediated uptake of polybasic drugs such as aprotinin, aminoglycosides and polymyxin B (By similarity).

Gene Wiki entry for LRP2 Gene

Additional gene information for LRP2 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for LRP2 Gene

Genomics for LRP2 Gene

Regulatory Elements for LRP2 Gene

Enhancers for LRP2 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH02H169363 1.8 FANTOM5 Ensembl ENCODE dbSUPER 2.7 -1.7 -1658 2.1 PKNOX1 ATF1 ZFP64 FEZF1 YY1 ZNF121 GLIS2 MCM3 ZNF662 ZNF610 PPIG PHOSPHO2 SSB LOC100421689 LRP2 GC02M169338
GH02H169360 1.2 Ensembl dbSUPER 0.7 +0.7 699 2.1 PKNOX1 ZFP64 ZSCAN4 KLF17 FEZF1 ZNF2 GLIS2 ZNF366 ZSCAN5C FOS LRP2 GC02P169326
GH02H169341 0.8 dbSUPER 0.4 +15.6 15642 11.4 SOX13 LEF1 PKNOX1 ZNF146 KLF1 INSM2 KLF17 FEZF1 ZNF664 ZNF121 ENSG00000235321 SSB KLHL23 LRP2 GC02P169326
GH02H169353 0.5 dbSUPER 0.4 +8.1 8126 1.3 ZNF316 RFX1 NR2F1 BMI1 LRP2 GC02P169326
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around LRP2 on UCSC Golden Path with GeneCards custom track

Genomic Locations for LRP2 Gene

Genomic Locations for LRP2 Gene
235,577 bases
Minus strand

Genomic View for LRP2 Gene

Genes around LRP2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
LRP2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for LRP2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for LRP2 Gene

Proteins for LRP2 Gene

  • Protein details for LRP2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Low-density lipoprotein receptor-related protein 2
    Protein Accession:
    Secondary Accessions:
    • O00711
    • Q16215

    Protein attributes for LRP2 Gene

    4655 amino acids
    Molecular mass:
    521958 Da
    Quaternary structure:
    • Binds plasminogen, extracellular matrix components, plasminogen activator-plasminogen activator inhibitor type I complex, apolipoprotein E-enriched beta-VLDL, lipoprotein lipase, lactoferrin, CLU/clusterin and calcium (PubMed:7768901). Forms a multimeric complex together with LRPAP1 (PubMed:1400426). Interacts (via PxLPxI/L motif) with ANKRA2 (via ankyrin repeats) (By similarity). Interacts with LRP2BP (PubMed:12508107). Interacts (via NPXY motif) with DAB2; the interaction is not affected by tyrosine phosphorylation of the NPXY motif (PubMed:10769163, PubMed:15134832).

    Three dimensional structures from OCA and Proteopedia for LRP2 Gene

neXtProt entry for LRP2 Gene

Selected DME Specific Peptides for LRP2 Gene


Post-translational modifications for LRP2 Gene

  • Glycosylation at posLast=159159, Asn178, posLast=299299, posLast=300300, posLast=341341, posLast=388388, Asn463, posLast=866866, posLast=10641064, posLast=11441144, Asn1186, Thr1270, posLast=12731273, posLast=13271327, Asn1340, posLast=13831383, posLast=14641464, posLast=14961496, posLast=15501550, Asn1675, Asn1810, posLast=20552055, posLast=21772177, posLast=22242224, Asn2499, posLast=25472547, posLast=27812781, posLast=28092809, posLast=28102810, Asn2947, posLast=29872987, Thr3070, Thr3074, posLast=31253125, Asn3211, posLast=32573257, Asn3315, Asn3355, Asn3446, Asn3564, posLast=36803680, Thr3797, Asn3978, Asn4068, and Asn4327
  • Modification sites at PhosphoSitePlus

Other Protein References for LRP2 Gene

Domains & Families for LRP2 Gene

Gene Families for LRP2 Gene

Human Protein Atlas (HPA):
  • Disease related genes
  • Plasma proteins
  • Predicted membrane proteins
  • Predicted secreted proteins

Suggested Antigen Peptide Sequences for LRP2 Gene

Graphical View of Domain Structure for InterPro Entry



  • Two overlapping PxLPxI/L motifs mediate interaction with ankyrin repeats of ANKRA2.
  • Belongs to the LDLR family.
  • Two overlapping PxLPxI/L motifs mediate interaction with ankyrin repeats of ANKRA2.
  • Belongs to the LDLR family.
genes like me logo Genes that share domains with LRP2: view

Function for LRP2 Gene

Molecular function for LRP2 Gene

GENATLAS Biochemistry:
multifunctional clearance receptor,Ca++ binding megalin (glycoprotein 330,gp330),LDLR receptor superfamily,expressed in the neuroepithelium and in proximal tubular cells of the kidney,possessing broad ligand specificity and mediating the uptake and lysosomal degradation of macromolecules including lipoproteins,proteases and protease inhibitors and in vivo the Ca2+ sensing in the parathyroids and renal uptake and activation of CYP25D1A,also expressed on the apical surfaces of epithelial cells lining specific regions of the male and female reproductive tracts and in seminal vesicle (rat) where it acts as an endocytic receptor for seminal vesicle secretory protein 2
UniProtKB/Swiss-Prot Function:
Multiligand endocytic receptor. Acts together with cubilin to mediate HDL endocytosis. In the kidney, mediates the tubular uptake and clearance of leptin (By similarity). Mediates receptor-mediated uptake of polybasic drugs such as aprotinin, aminoglycosides and polymyxin B (By similarity).

Enzyme Numbers (IUBMB) for LRP2 Gene

Phenotypes From GWAS Catalog for LRP2 Gene

Gene Ontology (GO) - Molecular Function for LRP2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005041 low-density lipoprotein receptor activity TAS --
GO:0005509 calcium ion binding IEA,IDA 23275343
GO:0005515 protein binding IPI 9773776
GO:0008144 drug binding ISS --
GO:0017124 SH3 domain binding IEA --
genes like me logo Genes that share ontologies with LRP2: view
genes like me logo Genes that share phenotypes with LRP2: view

Human Phenotype Ontology for LRP2 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for LRP2 Gene

MGI Knock Outs for LRP2:

miRNA for LRP2 Gene

miRTarBase miRNAs that target LRP2

Clone Products

No data available for Transcription Factor Targets and HOMER Transcription for LRP2 Gene

Localization for LRP2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for LRP2 Gene

Membrane; Single-pass type I membrane protein. Membrane, coated pit.

Subcellular locations from

Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for LRP2 gene
Compartment Confidence
plasma membrane 5
extracellular 5
lysosome 5
endosome 4
endoplasmic reticulum 3
golgi apparatus 3
mitochondrion 2
cytoskeleton 1
peroxisome 1
nucleus 1
cytosol 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Mitochondria (2)
  • Vesicles (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for LRP2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005764 lysosome TAS 7768901
GO:0005765 lysosomal membrane IDA 17897319
GO:0005768 endosome IEA --
GO:0005783 endoplasmic reticulum IEA --
GO:0005794 Golgi apparatus IEA --
genes like me logo Genes that share ontologies with LRP2: view

Pathways & Interactions for LRP2 Gene

genes like me logo Genes that share pathways with LRP2: view

Gene Ontology (GO) - Biological Process for LRP2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001523 retinoid metabolic process TAS --
GO:0001843 neural tube closure ISS --
GO:0003139 secondary heart field specification ISS --
GO:0003148 outflow tract septum morphogenesis ISS --
GO:0003223 ventricular compact myocardium morphogenesis ISS --
genes like me logo Genes that share ontologies with LRP2: view

No data available for SIGNOR curated interactions for LRP2 Gene

Drugs & Compounds for LRP2 Gene

(23) Drugs for LRP2 Gene - From: DrugBank, PharmGKB, ApexBio, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Gentamicin Approved, Vet_approved Pharma Target, other/unknown 0
Insulin Human Approved, Investigational Pharma Target 0
Insulin Pork Approved Pharma Target 0
Urokinase Approved, Investigational, Withdrawn Pharma Target 0
Cisplatin Approved Pharma Inhibits DNA synthesis,chemotherapy drug, Platinum 2823

(9) Additional Compounds for LRP2 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs

(1) ApexBio Compounds for LRP2 Gene

Compound Action Cas Number
COG 133 ApoE mimetic peptide 514200-66-9
genes like me logo Genes that share compounds with LRP2: view

Drug Products

Transcripts for LRP2 Gene

Unigene Clusters for LRP2 Gene

Low density lipoprotein receptor-related protein 2:
Representative Sequences:

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for LRP2 Gene

No ASD Table

Relevant External Links for LRP2 Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for LRP2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for LRP2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for LRP2 Gene

This gene is overexpressed in Kidney - Cortex (x15.1), Brain - Spinal cord (cervical c-1) (x7.9), Thyroid (x7.2), and Brain - Substantia nigra (x5.3).

Protein differential expression in normal tissues from HIPED for LRP2 Gene

This gene is overexpressed in Urine (47.5) and Kidney (17.5).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for LRP2 Gene

Protein tissue co-expression partners for LRP2 Gene

NURSA nuclear receptor signaling pathways regulating expression of LRP2 Gene:


SOURCE GeneReport for Unigene cluster for LRP2 Gene:


mRNA Expression by UniProt/SwissProt for LRP2 Gene:

Tissue specificity: Absorptive epithelia, including renal proximal tubules.

Evidence on tissue expression from TISSUES for LRP2 Gene

  • Kidney(5)
  • Nervous system(3.7)
  • Thyroid gland(2.4)
  • Blood(2)
  • Urine(2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for LRP2 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
  • cardiovascular
  • digestive
  • immune
  • integumentary
  • nervous
  • reproductive
  • respiratory
  • skeletal muscle
  • skeleton
  • urinary
Head and neck:
  • brain
  • cheek
  • cranial nerve
  • ear
  • eye
  • eyelid
  • face
  • forehead
  • head
  • jaw
  • mandible
  • maxilla
  • mouth
  • nose
  • outer ear
  • scalp
  • skull
  • diaphragm
  • lung
  • abdominal wall
  • intestine
  • kidney
  • large intestine
  • liver
  • small intestine
  • stomach
  • blood
  • blood vessel
  • coagulation system
  • hair
  • peripheral nervous system
  • skin
genes like me logo Genes that share expression patterns with LRP2: view

Orthologs for LRP2 Gene

This gene was present in the common ancestor of animals.

Orthologs for LRP2 Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia LRP2 33 34
  • 99.47 (n)
(Canis familiaris)
Mammalia LRP2 33 34
  • 84.7 (n)
(Mus musculus)
Mammalia Lrp2 33 16 34
  • 80.05 (n)
(Bos Taurus)
Mammalia LRP2 33 34
  • 79.94 (n)
(Rattus norvegicus)
Mammalia Lrp2 33
  • 79.68 (n)
(Monodelphis domestica)
Mammalia LRP2 34
  • 74 (a)
(Ornithorhynchus anatinus)
Mammalia LRP2 34
  • 74 (a)
(Gallus gallus)
Aves LRP2 34 33
  • 73.28 (n)
(Anolis carolinensis)
Reptilia LRP2 34
  • 71 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia lrp2 33
  • 69.04 (n)
(Danio rerio)
Actinopterygii lrp2a 33 34
  • 65.91 (n)
Dr.20653 33
fruit fly
(Drosophila melanogaster)
Insecta mgl 33 34
  • 51 (n)
CG12139 35
  • 44 (a)
yl 35
  • 29 (a)
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP000331 33
  • 48.46 (n)
(Caenorhabditis elegans)
Secernentea lrp-1 35 33 34
  • 47.87 (n)
B0244.8 35
  • 35 (a)
R01H2.3 35
  • 31 (a)
T21E3.3 35
  • 30 (a)
rme-2 35
  • 28 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 34
  • 44 (a)
Species where no ortholog for LRP2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for LRP2 Gene

Gene Tree for LRP2 (if available)
Gene Tree for LRP2 (if available)

Paralogs for LRP2 Gene

Paralogs for LRP2 Gene

(9) SIMAP similar genes for LRP2 Gene using alignment to 6 proteins:

genes like me logo Genes that share paralogs with LRP2: view

Variants for LRP2 Gene

Sequence variations from dbSNP and Humsavar for LRP2 Gene

SNP ID Clin Chr 02 pos Sequence Context AA Info Type
rs80338747 Pathogenic, Donnai-Barrow syndrome (DBS) [MIM:222448] 169,205,630(-) ACCTG(C/T)ACTGG reference, missense
VAR_035996 A colorectal cancer sample
rs138269726 Pathogenic 169,212,088(+) ATTAT(C/T)AGGAT reference, missense
rs587776717 Pathogenic 169,256,237(+) AAGCA(C/T)TAAAA splice-acceptor-variant
rs786205122 Pathogenic 169,152,823(-) AGATG(-/G)AATAG reference, frameshift-variant

Structural Variations from Database of Genomic Variants (DGV) for LRP2 Gene

Variant ID Type Subtype PubMed ID
esv2841013 CNV deletion 24192839
nsv998902 CNV gain 25217958
nsv834453 CNV gain 17160897
nsv528457 CNV gain 19592680
nsv498944 CNV loss 21111241
nsv3024 CNV deletion 18451855
nsv214965 CNV deletion 16902084
esv3560512 CNV deletion 23714750
esv3412743 CNV insertion 20981092
esv3351441 CNV insertion 20981092
esv3305140 CNV mobile element insertion 20981092
esv3305014 CNV mobile element insertion 20981092
esv2762961 CNV gain 21179565
esv2721113 CNV deletion 23290073
esv2721112 CNV deletion 23290073
esv2721111 CNV deletion 23290073
esv2721110 CNV deletion 23290073
esv2665220 CNV deletion 23128226
esv2639235 CNV deletion 19546169
esv2179866 CNV deletion 18987734
esv2053158 CNV deletion 18987734
esv1010911 CNV deletion 20482838

Variation tolerance for LRP2 Gene

Residual Variation Intolerance Score: 68.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 8.30; 85.21% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for LRP2 Gene

Human Gene Mutation Database (HGMD)
SNPedia medical, phenotypic, and genealogical associations of SNPs for

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for LRP2 Gene

Disorders for LRP2 Gene

MalaCards: The human disease database

(17) MalaCards diseases for LRP2 Gene - From: HGMD, OMIM, ClinVar, GeneTests, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
donnai-barrow syndrome
  • dbs/foar syndrome
dent disease
  • dent disease 2
membranous nephropathy
  • membranous glomerulonephritis
  • cystine storage disease
lowe syndrome
  • oculocerebrorenal syndrome
- elite association - COSMIC cancer census association via MalaCards
Search LRP2 in MalaCards View complete list of genes associated with diseases


  • Donnai-Barrow syndrome (DBS) [MIM:222448]: Rare autosomal recessive disorder characterized by major malformations including agenesis of the corpus callosum, congenital diaphragmatic hernia, facial dysmorphology, ocular anomalies, sensorineural hearing loss and developmental delay. The FOAR syndrome was first described as comprising facial anomalies, ocular anomalies, sensorineural hearing loss, and proteinuria. DBS and FOAR were first described as distinct disorders but the classic distinguishing features between the 2 disorders were presence of proteinuria and absence of diaphragmatic hernia and corpus callosum anomalies in FOAR. Early reports noted that the 2 disorders shared many phenotypic features and may be identical. Although there is variability in the expression of some features (e.g., agenesis of the corpus callosum and proteinuria), DBS and FOAR are now considered to represent the same entity. {ECO:0000269 PubMed:17632512}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Relevant External Links for LRP2

Genetic Association Database (GAD)
Human Genome Epidemiology (HuGE) Navigator
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
genes like me logo Genes that share disorders with LRP2: view

No data available for Genatlas for LRP2 Gene

Publications for LRP2 Gene

  1. Chromosomal localization of human genes for the LDL receptor family member glycoprotein 330 (LRP2) and its associated protein RAP (LRPAP1). (PMID: 7959795) Korenberg JR … Argraves WS (Genomics 1994) 2 3 4 22 60
  2. A megalin polymorphism associated with promoter activity and Alzheimer's disease risk. (PMID: 20052685) Vargas T … Carro E (American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 2010) 3 22 45 60
  3. Megalin genetic polymorphisms and individual sensitivity to the ototoxic effect of cisplatin. (PMID: 17457342) Riedemann L … am Zehnhoff-Dinnesen A (The pharmacogenomics journal 2008) 3 22 45 60
  4. Association of megalin genetic polymorphisms with prostate cancer risk and prognosis. (PMID: 18559602) Holt SK … Ostrander EA (Clinical cancer research : an official journal of the American Association for Cancer Research 2008) 3 22 45 60
  5. Genetic association of low-density lipoprotein receptor-related protein 2 (LRP2) with plasma lipid levels. (PMID: 18174661) Mii A … Katayama Y (Journal of atherosclerosis and thrombosis 2007) 3 22 45 60

Products for LRP2 Gene

Sources for LRP2 Gene

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