LDLRAP1
Low Density Lipoprotein Receptor Adaptor Protein 1
Gene Information Card
| Symbol | LDLRAP1 |
|---|---|
| Full Name | Low Density Lipoprotein Receptor Adaptor Protein 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 1p36.11 |
| NCBI Gene ID | 26119 ncbi.nlm.nih.gov/gene/26119 |
| Ensembl ID | ENSG00000157978 |
| UniProt ID | Q5SWZ9 |
| OMIM ID | 605747 |
| HGNC ID | 18640 |
| Aliases | ARH, ARH1, ARH2, FHCB1, FHCL1, MGC34774 |
Description
LDLRAP1 encodes the low density lipoprotein receptor adaptor protein 1, also known as ARH (autosomal recessive hypercholesterolemia protein). This protein is essential for the clathrin-mediated internalization of the LDL receptor (LDLR) in hepatocytes. Mutations in LDLRAP1 cause autosomal recessive hypercholesterolemia (ARH), characterized by elevated plasma LDL cholesterol and premature atherosclerosis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Autosomal recessive hypercholesterolemia (ARH) | Loss-of-function mutations in LDLRAP1 impair LDLR internalization, leading to defective hepatic clearance of LDL cholesterol and severe hypercholesterolemia. | OMIM #603813; ClinVar; PMID: 11574793 |
| Hypercholesterolemia, familial, 4 | Mutations in LDLRAP1 cause a rare form of familial hypercholesterolemia with autosomal recessive inheritance. | OMIM #603813; PMID: 11574793 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Adrenal gland | 8.3 | Medium |
| Placenta | 6.1 | Low |
| Kidney | 4.7 | Low |
| Small intestine | 3.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 10.2 | Hepatocyte cell line |
| HeLa | 5.8 | Cervical carcinoma |
| HEK293 | 4.1 | Embryonic kidney |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.432G>A (p.Trp144*) | Nonsense | Rare | Loss of function; premature stop codon leads to truncated protein |
| c.65G>A (p.Trp22*) | Nonsense | Rare | Loss of function; premature stop codon |
| c.432+1G>A | Splice site | Rare | Loss of function; aberrant splicing |
| c.938C>T (p.Pro313Leu) | Missense | Rare | Loss of function; disrupts protein function |
Mutation functional classification
Loss of Function (LOF)
Most LDLRAP1 mutations are loss-of-function, leading to impaired LDLR internalization and autosomal recessive hypercholesterolemia.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported; disease is recessive.
View complete mutation data：
Gene Ontology (GO)
| • clathrin-coated pit | • clathrin-dependent endocytosis |
| • low-density lipoprotein particle receptor catabolic process | • low-density lipoprotein receptor activity |
| • protein binding | • receptor-mediated endocytosis |
Pathways
• LDL clearance (Reactome: R-HSA-8963898)
• Clathrin-mediated endocytosis (KEGG: hsa04144)
• Lipoprotein metabolism (Reactome: R-HSA-174824)
Protein Summary
LDLRAP1 is a 308-amino acid adaptor protein containing a phosphotyrosine-binding (PTB) domain that interacts with the NPXY motif of the LDL receptor. It recruits clathrin and AP-2 to facilitate LDLR internalization. Defects in this protein cause autosomal recessive hypercholesterolemia.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| LDLRAP1 Knockout HEK293 Cell Line | EDJ-KQ8415 | Human | 26119 | Details Get a Quote |
| LDLRAP1 Knockout A-549 Cell Line | EDJ-KQ34497 | Human | 26119 | Details Get a Quote |
| LDLRAP1 Knockout HCT 116 Cell Line | EDJ-KQ34498 | Human | 26119 | Details Get a Quote |
| LDLRAP1 Knockout HeLa Cell Line | EDJ-KQ34499 | Human | 26119 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
