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10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
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LDLRAP1
low density lipoprotein receptor adaptor protein 1
Chromosome 1 Β· 1p36.11
NCBI Gene: 26119Ensembl: ENSG00000157978.13HGNC: HGNC:18640UniProt: A0ABB0MVA8
73PubMed Papers
21Diseases
0Drugs
68Pathogenic Variants
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
amyloid-beta bindingphosphotyrosine residue bindingprotein bindingphosphatidylinositol-4,5-bisphosphate bindinghomozygous familial hypercholesterolemiafamilial hypercholesterolemiaAbnormality of the cardiovascular systemHypercholesterolemia
✦AI Summary

LDLRAP1 (low density lipoprotein receptor adaptor protein 1) is a clathrin-associated sorting protein essential for efficient endocytosis of the LDL receptor in polarized cells such as hepatocytes and lymphocytes 1. The protein functions as an adapter within the clathrin endocytic machinery, facilitating LDL receptor internalization by stabilizing interactions between receptors and coated pit structural components and binding phosphoinositides that regulate clathrin bud assembly 1. LDLRAP1 mutations cause autosomal recessive hypercholesterolemia (ARH), characterized by elevated plasma LDL cholesterol levels and increased atherosclerotic cardiovascular disease risk, though generally less severe and more responsive to therapy than dominant familial hypercholesterolemia 123. ARH patients typically exhibit LDL receptor accumulation at the cell surface with impaired LDL internalization in some cell types 1. Beyond lipid metabolism, LDLRAP1 deletion impacts metabolic homeostasisβ€”LDLRAP1-knockout mice demonstrate increased weight gain, insulin resistance, and dysregulated adipose tissue function, suggesting LDLRAP1 links hypercholesterolemia with obesity and metabolic dysfunction comorbidities 4. Additionally, exogenous plant microRNAs can suppress LDLRAP1 expression, potentially affecting LDL clearance from circulation 5. Early diagnosis and LDL-lowering therapy targeting LDLRAP1-associated hypercholesterolemia are critical for reducing atherosclerotic disease burden.

Sources cited
1
LDLRAP1 is an adaptor protein required for LDL receptor-dependent internalization; mutations cause autosomal recessive hypercholesterolemia with cell surface receptor accumulation
PMID: 15630633
2
LDLRAP1 mutations cause familial hypercholesterolemia with elevated LDL-C levels and increased ASCVD risk
PMID: 34480646
3
ARH caused by LDLRAP1 mutations presents phenotypic features similar to LDLR-defective homozygous FH with variable severity
PMID: 32977124
4
LDLRAP1 deletion induces atherosclerotic plaque formation, insulin resistance, and dysregulated adipose tissue metabolism
PMID: 35460615
5
Plant-derived microRNA MIR168a can suppress LDLRAP1 expression and decrease LDL clearance from plasma
PMID: 21931358
6
LDLRAP1 is one of the genes responsible for rare autosomal recessive forms of familial hypercholesterolemia
PMID: 36196022
Disease Associationsβ“˜21
homozygous familial hypercholesterolemiaOpen Targets
0.79Strong
familial hypercholesterolemiaOpen Targets
0.74Strong
Abnormality of the cardiovascular systemOpen Targets
0.53Moderate
HypercholesterolemiaOpen Targets
0.46Moderate
Crohn's diseaseOpen Targets
0.41Moderate
hypercholesterolemia, familial, 1Open Targets
0.15Weak
preeclampsiaOpen Targets
0.10Suggestive
hypertriglyceridemia 2Open Targets
0.09Suggestive
neoplasmOpen Targets
0.08Suggestive
cancerOpen Targets
0.07Suggestive
thyroid hormone metabolism, abnormal, 2Open Targets
0.07Suggestive
Combined hyperlipidemiaOpen Targets
0.06Suggestive
sitosterolemia 2Open Targets
0.06Suggestive
hyperlipidemia due to hepatic triglyceride lipase deficiencyOpen Targets
0.06Suggestive
Hyperlipoproteinemia type 1Open Targets
0.06Suggestive
hypercholesterolemia, autosomal dominant, 3Open Targets
0.05Suggestive
pancreatic triacylglycerol lipase deficiencyOpen Targets
0.05Suggestive
hypercholesterolemia, autosomal dominant, type BOpen Targets
0.05Suggestive
familial apolipoprotein C-II deficiencyOpen Targets
0.05Suggestive
cholelithiasisOpen Targets
0.05Suggestive
Hypercholesterolemia, familial, 4UniProt
Pathogenic Variants68
NM_015627.3(LDLRAP1):c.603dup (p.Ser202fs)Pathogenic
Hypercholesterolemia, familial, 4|Familial hypercholesterolemia|not provided|Cardiovascular phenotype
β˜…β˜…β˜†β˜†2026β†’ Residue 202
NM_015627.3(LDLRAP1):c.71del (p.Gly24fs)Pathogenic
Hypercholesterolemia, familial, 4|not provided|Familial hypercholesterolemia|Cardiovascular phenotype
β˜…β˜…β˜†β˜†2025β†’ Residue 24
NM_015627.3(LDLRAP1):c.66G>A (p.Trp22Ter)Pathogenic
Hypercholesterolemia, familial, 4|Familial hypercholesterolemia
β˜…β˜…β˜†β˜†2025β†’ Residue 22
NM_015627.3(LDLRAP1):c.113del (p.Thr38fs)Pathogenic
Hypercholesterolemia, familial, 4|Familial hypercholesterolemia
β˜…β˜…β˜†β˜†2025β†’ Residue 38
NM_015627.3(LDLRAP1):c.143del (p.Phe48fs)Pathogenic
Hypercholesterolemia, familial, 4|Cardiovascular phenotype
β˜…β˜…β˜†β˜†2025β†’ Residue 48
NM_015627.3(LDLRAP1):c.604delinsCC (p.Ser202fs)Pathogenic
Cardiovascular phenotype|Familial hypercholesterolemia
β˜…β˜…β˜†β˜†2025β†’ Residue 202
NM_015627.3(LDLRAP1):c.748-608G>ALikely pathogenic
Cardiovascular phenotype|not provided
β˜…β˜…β˜†β˜†2025
NM_015627.3(LDLRAP1):c.431dup (p.His144fs)Pathogenic
Hypercholesterolemia, familial, 4|not provided|Cardiovascular phenotype|Familial hypercholesterolemia
β˜…β˜…β˜†β˜†2025β†’ Residue 144
NM_015627.3(LDLRAP1):c.89-1G>CPathogenic
Hypercholesterolemia, familial, 4|Familial hypercholesterolemia
β˜…β˜…β˜†β˜†2025
NM_015627.3(LDLRAP1):c.3G>A (p.Met1Ile)Likely pathogenic
Hypercholesterolemia, familial, 4|Familial hypercholesterolemia
β˜…β˜…β˜†β˜†2025β†’ Residue 1
NM_015627.3(LDLRAP1):c.71dup (p.Gly25fs)Pathogenic
Hypercholesterolemia, familial, 4|Familial hypercholesterolemia
β˜…β˜…β˜†β˜†2025β†’ Residue 25
NM_015627.3(LDLRAP1):c.1A>G (p.Met1Val)Likely pathogenic
Hypercholesterolemia, familial, 4|Cardiovascular phenotype|Familial hypercholesterolemia
β˜…β˜…β˜†β˜†2025β†’ Residue 1
NM_015627.3(LDLRAP1):c.649G>T (p.Glu217Ter)Pathogenic
Autosomal recessive inheritance|Hypercholesterolemia, familial, 4|Familial hypercholesterolemia
β˜…β˜…β˜†β˜†2024β†’ Residue 217
NM_015627.3(LDLRAP1):c.402del (p.Ser135fs)Pathogenic
Hypercholesterolemia, familial, 4
β˜…β˜…β˜†β˜†2024β†’ Residue 135
NM_015627.3(LDLRAP1):c.406C>T (p.Gln136Ter)Pathogenic
Hypercholesterolemia, familial, 4|Familial hypercholesterolemia|Cardiovascular phenotype
β˜…β˜…β˜†β˜†2024β†’ Residue 136
NM_015627.3(LDLRAP1):c.65G>A (p.Trp22Ter)Pathogenic
Hypercholesterolemia, familial, 4|Familial hypercholesterolemia
β˜…β˜…β˜†β˜†2024β†’ Residue 22
NM_015627.3(LDLRAP1):c.533-1G>ALikely pathogenic
Hypercholesterolemia, familial, 4|Familial hypercholesterolemia
β˜…β˜…β˜†β˜†2024
NM_015627.3(LDLRAP1):c.112_113del (p.Thr38fs)Pathogenic
not provided|Hypercholesterolemia, familial, 4|Familial hypercholesterolemia
β˜…β˜…β˜†β˜†2024β†’ Residue 38
NM_015627.3(LDLRAP1):c.466del (p.Ala156fs)Pathogenic
Familial hypercholesterolemia|Hypercholesterolemia, familial, 4
β˜…β˜…β˜†β˜†2024β†’ Residue 156
NM_015627.3(LDLRAP1):c.344+1G>APathogenic
Hypercholesterolemia, familial, 4|Cardiovascular phenotype|Familial hypercholesterolemia
β˜…β˜…β˜†β˜†2024
View on ClinVar β†—
Related Genes
APOEProtein interaction100%PCSK9Protein interaction99%LRP2Protein interaction93%AP2B1Protein interaction86%DAB2Protein interaction86%CUBNProtein interaction86%
Tissue Expression6 tissues
Liver
100%
Lung
70%
Heart
47%
Ovary
41%
Bone Marrow
34%
Brain
28%
Gene Interaction Network
Click a node to explore
LDLRAP1APOEPCSK9LRP2AP2B1DAB2CUBN
PROTEIN STRUCTURE
Preparing viewer…
PDB2G30 Β· 1.60 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
1.08LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.79 [0.59–1.08]
RankingsWhere LDLRAP1 stands among ~20K protein-coding genes
  • #6,476of 20,598
    Most Researched73
  • #1,068of 5,498
    Most Pathogenic Variants68 Β· top quartile
  • #11,014of 17,882
    Most Constrained (LOEUF)1.08
Genes detectedLDLRAP1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Genetic and molecular architecture of familial hypercholesterolemia.
PMID: 36196022
J Intern Med Β· 2023
1.00
2
Familial Hypercholesterolemia: Global Burden and Approaches.
PMID: 34480646
Curr Cardiol Rep Β· 2021
0.90
3
Homozygous familial hypercholesterolemia in Italy: Clinical and molecular features.
PMID: 32977124
Atherosclerosis Β· 2020
0.80
4
Exogenous plant MIR168a specifically targets mammalian LDLRAP1: evidence of cross-kingdom regulation by microRNA.
PMID: 21931358
Cell Res Β· 2012
0.70
5
PMID: 27809445
0.60