LDLR Gene: Low-Density Lipoprotein Receptor
Key regulator of cholesterol homeostasis and genetic basis of familial hypercholesterolemia
Gene Information Card
| Symbol | LDLR |
|---|---|
| Full Name | Low Density Lipoprotein Receptor |
| Gene Type | Protein coding |
| Chromosomal Location | 19p13.2 |
| NCBI Gene ID | 3949 ncbi.nlm.nih.gov/gene/3949 |
| Ensembl ID | ENSG00000130164 |
| UniProt ID | P01130 |
| OMIM ID | 606945 |
| HGNC ID | 6547 |
| Aliases | FH, FHC, LDLCQ2 |
Description
The LDLR gene encodes the low-density lipoprotein receptor, a cell surface protein that mediates the endocytosis of low-density lipoproteins (LDL) and plays a critical role in cholesterol homeostasis. Mutations in this gene are the most common cause of familial hypercholesterolemia, an autosomal dominant disorder characterized by elevated plasma LDL cholesterol levels and increased risk of premature cardiovascular disease.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Familial hypercholesterolemia | Loss-of-function mutations reduce LDL receptor activity, impairing hepatic clearance of LDL from circulation, leading to elevated plasma LDL cholesterol and atherosclerosis. | ClinVar, OMIM |
| Hypercholesterolemia, autosomal dominant, type B | Pathogenic variants in LDLR cause autosomal dominant hypercholesterolemia with variable penetrance. | OMIM |
| Coronary artery disease | LDLR dysfunction contributes to dyslipidemia and accelerates atherosclerotic plaque formation. | ClinVar, literature |
| Myocardial infarction | Elevated LDL due to LDLR mutations increases risk of early-onset myocardial infarction. | ClinVar, literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | High | High expression; primary site of LDL clearance |
| Adrenal gland | Medium | Moderate expression; steroid hormone synthesis |
| Placenta | Medium | Moderate expression |
| Small intestine | Medium | Moderate expression |
| Kidney | Low | Low expression |
| Skeletal muscle | Low | Low expression |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | High | Hepatocyte carcinoma cell line; used for LDLR functional studies |
| Caco-2 | Medium | Intestinal epithelial cells; express LDLR |
| A549 | Low | Lung carcinoma; low expression |
| MCF7 | Low | Breast cancer; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.313+1G>A | Splice donor | Rare | Splice site mutation leading to exon skipping and truncated protein; loss of function |
| p.Asp461Glu | Missense | Rare | Disrupts ligand-binding domain; reduces LDL binding |
| p.Gly592Glu | Missense | Rare | Affects EGF precursor homology domain; impairs receptor recycling |
| p.Arg329X | Nonsense | Rare | Premature stop codon; truncated non-functional receptor |
| c.1846-2A>G | Splice acceptor | Rare | Splice site mutation causing frameshift and loss of function |
Mutation functional classification
Loss of Function (LOF)
Most LDLR mutations are loss-of-function, reducing or abolishing receptor activity, leading to impaired LDL clearance and hypercholesterolemia.
Gain of Function (GOF)
No gain-of-function mutations are reported for LDLR; such mutations would be expected to lower LDL but are not clinically observed.
Dominant Negative (DN)
Some missense mutations may exert a dominant-negative effect by forming non-functional dimers with wild-type receptors, though haploinsufficiency is the primary mechanism.
View complete mutation data：
Gene Ontology (GO)
| • low-density lipoprotein particle receptor activity | • protein binding |
| • clathrin-coated pit | • plasma membrane |
| • receptor-mediated endocytosis | • cholesterol homeostasis |
| • lipid transport |
Pathways
• LDL-mediated lipid transport
• Endocytosis
• Cholesterol metabolism
• Lipoprotein signaling
Protein Summary
The LDL receptor is a mosaic protein composed of multiple domains: ligand-binding domain, EGF precursor homology domain, O-linked sugar domain, transmembrane domain, and cytoplasmic tail. It binds LDL particles at the cell surface and internalizes them via clathrin-mediated endocytosis. The receptor releases LDL in the acidic endosome and is recycled back to the membrane. This process is crucial for maintaining plasma cholesterol levels.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| LDLRAD3 Knockout HEK293T Cell Line | EDJ-KQ158 | Human | 143458 | Details Get a Quote |
| LDLR Knockout HEK293 Cell Line | EDJ-KQ273 | Human | 3949 | Details Get a Quote |
| LDLRAD4 Knockout HEK293 Cell Line | EDJ-KQ4178 | Human | 753 | Details Get a Quote |
| LDLRAP1 Knockout HEK293 Cell Line | EDJ-KQ8415 | Human | 26119 | Details Get a Quote |
| LDLRAD2 Knockout HEK293 Cell Line | EDJ-KQ11659 | Human | 401944 | Details Get a Quote |
| VLDLR Knockout HEK293 Cell Line | EDJ-KQ12141 | Human | 7436 | Details Get a Quote |
| LDLRAD1 Knockout HEK293 Cell Line | EDJ-KQ14050 | Human | 388633 | Details Get a Quote |
| LDLRAD3 Knockout HEK293 Cell Line | EDJ-KQ14051 | Human | 143458 | Details Get a Quote |
| LDLRAD2 Knockout HeLa Cell Line | EDJ-KQ40011 | Human | 401944 | Details Get a Quote |
| LDLR Knockout HCT 116 Cell Line | EDJ-KQ43957 | Human | 3949 | Details Get a Quote |
| LDLR Knockout HeLa Cell Line | EDJ-KQ43958 | Human | 3949 | Details Get a Quote |
| LDLRAD3 Knockout A-549 Cell Line | EDJ-KQ43959 | Human | 143458 | Details Get a Quote |
| LDLRAD3 Knockout HCT 116 Cell Line | EDJ-KQ43960 | Human | 143458 | Details Get a Quote |
| LDLRAD3 Knockout HeLa Cell Line | EDJ-KQ43961 | Human | 143458 | Details Get a Quote |
| LDLRAD4 Knockout HeLa Cell Line | EDJ-KQ25301 | Human | 753 | Details Get a Quote |
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