LDLR Gene

HGNC Family	Low density lipoprotein receptors
Name	low density lipoprotein receptor
Description	The low density lipoprotein receptor (LDLR) gene family consists of cell surface proteins involved in receptor-mediated endocytosis of specific ligands. The encoded protein is normally bound at the cell membrane, where it binds low density lipoprotein/cholesterol and is taken into the cell. Lysosomes release the cholesterol, which is made available for repression of microsomal enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, the rate-limiting step in cholesterol synthesis. At the same time, a reciprocal stimulation of cholesterol ester synthesis takes place. Mutations in this gene cause the autosomal dominant disorder, familial hypercholesterolemia. Alternate splicing results in multiple transcript variants.[provided by RefSeq, May 2022]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n The low‐density lipoprotein receptor (LDLR) is a pivotal cell‐surface receptor that mediates the uptake of circulating low‐density lipoprotein (LDL) and apolipoprotein E–rich lipoproteins, thereby playing a central role in cholesterol homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " Its extracellular domain comprises multiple LDL‐A (LA) modules that cooperatively bind ligand in a calcium‐dependent manner; in particular, studies on the LA3–LA5 region underscore the importance of specific residues that ensure high‐affinity interactions with apolipoprotein E and proper endocytic function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Genetic and biochemical investigations have demonstrated that mutations in LDLR disrupt proper folding, weaken ligand binding, or impair the receptor’s intracellular trafficking; such defects are a well‐established cause of familial hypercholesterolemia."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "7"}]}, {"type": "t", "text": " Furthermore, computational structure‐based analyses are increasingly being used to assess the pathogenicity of novel LDLR variants by predicting how specific amino acid substitutions can alter the receptor’s binding interface and its calcium‐mediated conformational transitions. Notably, studies in nonmammalian species have identified LDLR‐like proteins that perform analogous functions in maternal cholesterol uptake, reinforcing the fundamental role of LDLR in lipid metabolism across diverse organisms."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " \n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Together, these findings illuminate the multifaceted role of LDLR in the clearance of atherogenic lipoproteins and underscore its significance as a therapeutic target in lipid‐lowering strategies.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Luca A Lotta, Stephen J Sharp, Stephen Burgess, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association Between Low-Density Lipoprotein Cholesterol-Lowering Genetic Variants and Risk of Type 2 Diabetes: A Meta-analysis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "JAMA (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1001/jama.2016.14568"}], "href": "https://doi.org/10.1001/jama.2016.14568"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27701660"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27701660"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Miklos Guttman, J Helena Prieto, Johnny E Croy, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Decoding of lipoprotein-receptor interactions: properties of ligand binding modules governing interactions with apolipoprotein E."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochemistry (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/bi9017208"}], "href": "https://doi.org/10.1021/bi9017208"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20030366"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20030366"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Miklos Guttman, Elizabeth A Komives "}, {"type": "b", "children": [{"type": "t", "text": "The structure, dynamics, and binding of the LA45 module pair of the low-density lipoprotein receptor suggest an important role for LA4 in ligand release."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochemistry (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/bi2014486"}], "href": "https://doi.org/10.1021/bi2014486"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22091758"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22091758"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Sarah Leigh, Marta Futema, Ros Whittall, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The UCL low-density lipoprotein receptor gene variant database: pathogenicity update."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Med Genet (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/jmedgenet-2016-104054"}], "href": "https://doi.org/10.1136/jmedgenet-2016-104054"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27821657"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27821657"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Zhenze Zhao, Peter Michaely "}, {"type": "b", "children": [{"type": "t", "text": "Role of an intramolecular contact on lipoprotein uptake by the LDL receptor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbalip.2011.04.002"}], "href": "https://doi.org/10.1016/j.bbalip.2011.04.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21511053"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21511053"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Vladimir Espinosa Angarica, Modesto Orozco, Javier Sancho "}, {"type": "b", "children": [{"type": "t", "text": "Exploring the complete mutational space of the LDL receptor LA5 domain using molecular dynamics: linking SNPs with disease phenotypes in familial hypercholesterolemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddw004"}], "href": "https://doi.org/10.1093/hmg/ddw004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26755827"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26755827"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Eric W Klee, Michael T Zimmermann "}, {"type": "b", "children": [{"type": "t", "text": "Molecular modeling of LDLR aids interpretation of genomic variants."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Med (Berl) (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00109-019-01755-3"}], "href": "https://doi.org/10.1007/s00109-019-01755-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30778614"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30778614"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Maria R Rivero, Silvana L Miras, Rodrigo Quiroga, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Giardia lamblia low-density lipoprotein receptor-related protein is involved in selective lipoprotein endocytosis and parasite replication."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Microbiol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1365-2958.2010.07512.x"}], "href": "https://doi.org/10.1111/j.1365-2958.2010.07512.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21205007"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21205007"}]}]}]}
Synonyms	LDLCQ2
Proteins	LDLR_HUMAN
NCBI Gene ID	3949
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

LDLR has 19,778 functional associations with biological entities spanning 8 categories (molecular profile, organism, functional term, phrase or reference, disease, phenotype or trait, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 136 datasets.

Click the + buttons to view associations for LDLR from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

LDLR Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of LDLR gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of LDLR gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of LDLR gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of LDLR gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of LDLR gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving LDLR protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of LDLR gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of LDLR gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of LDLR gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of LDLR gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with LDLR gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with LDLR protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with LDLR gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of LDLR gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of LDLR gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of LDLR gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with LDLR gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with LDLR gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of LDLR gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing LDLR protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing LDLR protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing LDLR protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with LDLR protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with LDLR protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of LDLR gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with LDLR gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with LDLR gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with LDLR gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with LDLR gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of LDLR protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by LDLR gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving LDLR gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with LDLR gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with LDLR gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with LDLR gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with LDLR gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with LDLR gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with LDLR gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for LDLR protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at LDLR gene from the ENCODE Histone Modification Site Profiles dataset.