LDLR

Summary

LDLR (low density lipoprotein receptor, HGNC:6547) is a protein-coding gene on chromosome 19p13.2, encoding Low-density lipoprotein receptor (P01130). Binds low density lipoprotein /LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. It is a selective cancer dependency (DepMap: 10.8% of cell lines) and haploinsufficient (ClinGen: sufficient evidence).

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.

Source: NCBI Gene 3949 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hypercholesterolemia, familial, 1 (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 194
• Clinical variants (ClinVar): 4,833 total — 1233 pathogenic, 617 likely-pathogenic
• Phenotypes (HPO): 37
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 10.8% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_000527

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6547
Approved symbol	LDLR
Name	low density lipoprotein receptor
Location	19p13.2
Locus type	gene with protein product
Status	Approved
Aliases	LDLCQ2
Ensembl gene	ENSG00000130164
Ensembl biotype	protein_coding
OMIM	606945
Entrez	3949

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 21 protein_coding, 4 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000252444, ENST00000455727, ENST00000535915, ENST00000545707, ENST00000557933, ENST00000557958, ENST00000558013, ENST00000558518, ENST00000558528, ENST00000559340, ENST00000560173, ENST00000560467, ENST00000560502, ENST00000560628, ENST00000713991, ENST00000856645, ENST00000856646, ENST00000856647, ENST00000856648, ENST00000913405, ENST00000913406, ENST00000913407, ENST00000913408, ENST00000913409, ENST00000913410, ENST00000913411, ENST00000913412, ENST00000942040

RefSeq mRNA: 5 — MANE Select: NM_000527 NM_000527, NM_001195798, NM_001195799, NM_001195800, NM_001195803

CCDS: CCDS12254, CCDS56083, CCDS56084, CCDS56085, CCDS58651

Canonical transcript exons

ENST00000558518 — 18 exons

Exon	Start	End
ENSE00002553919	11131281	11133820
ENSE00002568469	11113278	11113449
ENSE00003463530	11120370	11120522
ENSE00003464579	11120092	11120233
ENSE00003482036	11116859	11116998
ENSE00003501255	11123174	11123344
ENSE00003509370	11113535	11113762
ENSE00003604878	11116094	11116212
ENSE00003629410	11128008	11128085
ENSE00003652085	11089463	11089615
ENSE00003680438	11129513	11129670
ENSE00004011958	11110652	11110771
ENSE00004011963	11100223	11100345
ENSE00004011965	11105220	11105600
ENSE00004011966	11102664	11102786
ENSE00004011967	11107392	11107514
ENSE00004011968	11111514	11111639
ENSE00004011970	11106565	11106687

Expression profiles

Bgee: expression breadth ubiquitous, 281 present calls, max score 99.53.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 51.1962 / max 582.4371, expressed in 1807 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
173893	33.3337	1761
173894	7.9618	1657
173897	2.0449	776
173895	1.6665	964
173896	1.3827	805
173901	1.2044	418
173902	1.1728	531
173891	0.8366	537
173892	0.6454	377
208690	0.4955	262

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	99.53	gold quality
lower lobe of lung	UBERON:0008949	97.66	gold quality
right adrenal gland	UBERON:0001233	96.45	gold quality
adrenal gland	UBERON:0002369	96.21	gold quality
right adrenal gland cortex	UBERON:0035827	96.05	gold quality
left adrenal gland	UBERON:0001234	95.85	gold quality
endometrium epithelium	UBERON:0004811	95.75	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.66	gold quality
adrenal cortex	UBERON:0001235	95.48	gold quality
left adrenal gland cortex	UBERON:0035825	95.31	gold quality
stromal cell of endometrium	CL:0002255	95.30	gold quality
upper lobe of lung	UBERON:0008948	95.17	gold quality
upper lobe of left lung	UBERON:0008952	95.09	gold quality
lung	UBERON:0002048	94.52	gold quality
mucosa of urinary bladder	UBERON:0001259	94.34	gold quality
right lung	UBERON:0002167	93.94	gold quality
esophagus mucosa	UBERON:0002469	93.66	gold quality
lower esophagus mucosa	UBERON:0035834	93.61	gold quality
islet of Langerhans	UBERON:0000006	93.28	gold quality
left uterine tube	UBERON:0001303	93.21	gold quality
pharyngeal mucosa	UBERON:0000355	92.79	gold quality
mucosa of sigmoid colon	UBERON:0004993	92.79	gold quality
ventricular zone	UBERON:0003053	92.77	gold quality
cartilage tissue	UBERON:0002418	92.67	gold quality
cervix epithelium	UBERON:0004801	92.43	gold quality
liver	UBERON:0002107	92.39	gold quality
decidua	UBERON:0002450	92.36	gold quality
oral cavity	UBERON:0000167	92.09	gold quality
gingival epithelium	UBERON:0001949	91.83	gold quality
amniotic fluid	UBERON:0000173	91.73	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-130473	yes	946.56
E-GEOD-130148	yes	10.99
E-MTAB-7316	no	483.72
E-GEOD-124858	no	69.90
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
ICAM1	Activation
SOCS5	Activation

Upstream regulators (CollecTRI, top): ATF3, BMAL1, CEBPA, CEBPB, CEBPG, CNBP, CREB1, CREBBP, DGKQ, DNMT1, EGR1, ESR1, ESR2, FOS, HES1, HES6, HNF4A, HNRNPK, IKZF1, KLF13, KLF4, KLF9, NFYA, NR1H3, PPARA, PPARG, PPARGC1A, RXRA, SP1, SP3, SREBF1, SREBF2, THRB, TXK, YY1, ZBTB17

miRNA regulators (miRDB)

96 targeting LDLR, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-128-3P	99.95	71.17	2484
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-6783-3P	99.89	67.92	2059

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 10.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• mutations in German patients with familial hypercholesterolemia (PMID:11462246)
• Nineteen mutations were novel: two nonsense, five missense, six nucleotide(s) insertions and six nucleotide(s) deletions. (PMID:11524740)
• mutations in Canadian subjects with familial hypercholesterolemia, but not of French descent (PMID:11668627)
• novel mutations in patients with familial hypercholesterolemia in Spain (PMID:11668640)
• HDL cholesterol levels in patients with molecularly defined familial hypercholesterolemia. LDL receptor gene mutation (81T>G, 858C>A, 1285G>A, 1646G>A, and 1775G>A,) did not significantly influence HDL cholesterol levels. (PMID:11848618)
• These results suggested that polymorphisms of LDL-Rgene might play an independent role of risk factor for hyperlipidemia. (PMID:11860839)
• Eight novel mutations and functional impairments are identified in familial hypercholesterolemia in the north of Japan. (PMID:11916007)
• Review. The proposed association between apoB secretion and FH may, however, be a function of the class of LDL receptor defect. (PMID:11923121)
• LDLR mutations in 350 cases of FH revealed 34 missense, 10 nonsense, 18 frameshift, 2 inframe, 10 splice, and 2 promoter mutations and 10 rearrangements. (PMID:11923123)
• Molecular basis of familial hypercholesterolemia in Brazil: Identification of seven novel LDLR gene mutations (PMID:11933210)
• Defective LDL receptors give rise to a phenotype of elevated LDL cholesterol. Disturbances in IDL metabolism provide the basis for understanding why FDB is less severe than FH. An apoB-LDL receptor interaction is important in the IDL to LDL conversion. (PMID:11947895)
• Critical role of diacylglycerol- and phospholipid-regulated protein kinase C epsilon in induction of low-density lipoprotein receptor transcription in response to depletion of cholesterol. (PMID:11997513)
• Influence of an asparagine to lysine mutation at amino acid 3516 of apolipoprotein B on low-density lipoprotein receptor binding. (PMID:12031600)
• apoE binds to the LDL receptor by interacting with more than one of the receptor ligand-binding repeats. (PMID:12036962)
• human rhinovirus serotype 1A (HRV1A)does not bind to the LDL receptor (PMID:12072496)
• bile acids affect gene expression via a MAPK cascade-mediated stabilization of mRNA (PMID:12149270)
• ARH functions as an adaptor protein that couples LDLR to the endocytic machinery (PMID:12221107)
• Egr1 is the oncostatin M-induced transcription factor that binds to the SIRE sequence of the LDLR promoter (PMID:12235180)
• Two novel missense mutations in the LDL-R gene causing FH were found in two unrelated families from central and southern Tunisia. (PMID:12414836)
• Double mutant allele was founded in 10 out of 458 unrelated patients and not all carriers of the double mutant allele develop hypercholesterolemia. (PMID:12442279)
• crystal structure of the extracellular portion of LDL-R at pH = 5.3 and at 3.7 A resolution; this structure should represent the conformation of LDL-R adopted in endosomes (PMID:12459547)
• restoration of function in cells from patients with autosomal recessive hypercholesterolemia by retroviral expression of ARH1 (PMID:12464675)
• A novel mutation of LDLR gene was reported. This mutation may severely affect the function of LDLR. (PMID:12485531)
• productive LDL-R folding in a cell is not vectorial but is mostly posttranslational, and involves transient long-range non-native disulfide bonds that are isomerized into native short-range cysteine pairs (PMID:12493918)
• fatty acids and rosiglitazone directly stimulate transcription of the LRP gene through activation of PPARgamma and increase functional LRP expression. (PMID:12551936)
• pp90RSK- and protein kinase C-dependent pathway regulates p42/44MAPK-induced LDL receptor transcription in HepG2 cells. (PMID:12562867)
• Deletion in low-density lipoprotein receptor gene is associated with severe familial hypercholesterolemia (PMID:12705331)
• Insulin plays an important role in the in vivo expression of LDL receptors on monocyte cell surface. (PMID:12716819)
• mutation spectrum of the LDLR gene among patients with familial hypercholesterolemia in Morocco (PMID:12730724)
• a new mutation is found, in which a serine residue was replaced by a cysteine at amino acid position 305 (S305C) (PMID:12820708)
• The allelic distribution of the (TA)n polymorphism was significantly different between migraine without aura (MO) and both controls and migraine with aura (MA). (PMID:12873747)
• data presented raise the possibility that the -175g–>t polymorphism in the promoter region of the LDLR gene may have subtle effects that become clinically important within certain genetic and/or environmental contexts (PMID:12944120)
• study provides strong evidence that early growth response 1 regulates low density lipoprotein receptor transcription via a novel mechanism of protein-protein interaction with CCAAT enhancer-binding protein beta (PMID:12947119)
• Doubling transfected human Ldlr expression caused severe atherosclerosis with marked accumulation of cholesterol-rich, apoE-poor remnants in mice with human apoE4, but not apoE3, suggesting that the receptor can trap apoE4. (PMID:12969990)
• data provide an alternative mechanism of LDL receptor gene expression by non-classical estradiol- and tamoxifen-stimulated induction through an ER-alpha/Sp1 complex (PMID:14568562)
• The mean of carotid artery intima-media maximum thicknesses was significantly higher in the 2312-3 C–>A group than in patients with other LDLr mutations (PMID:14624402)
• patients with familial hypercholesterolemia carrying the null LDL receptor have elevation of plasma LDL-cholesterol attributable to both decreased clearance of LDL and increased hepatic production of apoB-100-containing lipoproteins (PMID:14967814)
• cell surface levels of the LDLR mutants were significantly increased upon inhibition of the proteasome degradation pathway (PMID:14993243)
• Point mutations in low density lipoprotein receptor is associated with severe hypercholesterolemia (PMID:15015036)
• a rapid diagnostic assay capable of simultaneously analyzing seven point mutations in the low-density lipoprotein receptor (LDLR) gene, which occur at high frequency in South African familial hypercholesterolemia patients. (PMID:15068387)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:dkey-258f14.3	ENSDARG00000075974
danio_rerio	si:dkey-258f14.7	ENSDARG00000095925
mus_musculus	Ldlr	ENSMUSG00000032193
rattus_norvegicus	Ldlr	ENSRNOG00000009946
drosophila_melanogaster	arr	FBGN0000119
drosophila_melanogaster	Ndg	FBGN0026403

Paralogs (14): LRP6 (ENSG00000070018), LRP2 (ENSG00000081479), NID2 (ENSG00000087303), NID1 (ENSG00000116962), LRP1 (ENSG00000123384), LRP3 (ENSG00000130881), LRP4 (ENSG00000134569), EGF (ENSG00000138798), LRP12 (ENSG00000147650), VLDLR (ENSG00000147852), LRP8 (ENSG00000157193), LRP5 (ENSG00000162337), LRP1B (ENSG00000168702), LRP10 (ENSG00000197324)

Protein

Protein identifiers

Low-density lipoprotein receptor — P01130 (reviewed: P01130)

All UniProt accessions (6): P01130, A0AAQ5BHB8, H0YM92, H0YMD1, H0YMQ3, J3KMZ9

UniProt curated annotations — full annotation on UniProt →

Function. Binds low density lipoprotein /LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must first cluster into clathrin-coated pits. Forms a ternary complex with PGRMC1 and TMEM97 receptors which increases LDLR-mediated LDL internalization. (Microbial infection) Acts as a receptor for hepatitis C virus in hepatocytes, but not through a direct interaction with viral proteins. (Microbial infection) Acts as a receptor for Vesicular stomatitis virus. (Microbial infection) In case of HIV-1 infection, may function as a receptor for extracellular Tat in neurons, mediating its internalization in uninfected cells. (Microbial infection) Acts as a receptor for Crimean-Congo hemorrhagic fever virus (CCHFV). (Microbial infection) Acts as a receptor for many Alphavirus, including Getah virus (GETV), Ross river virus (RRV) and Semliki Forest virus.

Subunit / interactions. Interacts (via NPXY motif) with DAB2 (via PID domain); the interaction is impaired by tyrosine phosphorylation of the NPXY motif. Interacts (via NPXY motif) with LDLRAP1 (via PID domain). Interacts with ARRB1. Interacts with SNX17. Interacts with the full-length immature form of PCSK9 (via C-terminus). Interacts with PGRMC1 and TMEM97; the interaction increases LDL internalization. (Microbial infection) Interacts with C.difficile toxin TcdA, suggesting that it may contribute to TcdA toxin entry into cells. (Microbial infection) Interacts with vesicular stomatitis virus glycoprotein. (Microbial infection) Interacts with Crimean-Congo hemorrhagic fever virus (CCHFV) glycoprotein C. (Microbial infection) Interacts with Getah virus (GETV) E2-E1 spike protein complex. (Microbial infection) May interact with HIV-1 Tat.

Subcellular location. Cell membrane. Membrane. Clathrin-coated pit. Golgi apparatus. Early endosome. Late endosome. Lysosome.

Post-translational modifications. N- and O-glycosylated. Ubiquitinated by MYLIP leading to degradation.

Disease relevance. Hypercholesterolemia, familial, 1 (FHCL1) [MIM:143890] A form of hypercholesterolemia, a disorder of lipoprotein metabolism characterized by elevated serum low-density lipoprotein (LDL) cholesterol levels, which result in excess deposition of cholesterol in tissues and leads to xanthelasma, xanthomas, accelerated atherosclerosis and increased risk of premature coronary heart disease. FHCL1 inheritance is autosomal dominant. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The NPXY motif mediates the interaction with the clathrin adapter DAB2 and with LDLRAP1 which are involved in receptor internalization. A few residues outside the motif also play a role in the interaction.

Similarity. Belongs to the LDLR family.

Isoforms (6)

UniProt ID	Names	Canonical?
P01130-1	1	yes
P01130-2	2
P01130-3	3
P01130-4	4
P01130-5	5
P01130-6	6

RefSeq proteins (5): NP_000518, NP_001182727, NP_001182728, NP_001182729, NP_001182732 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000033	LDLR_classB_rpt	Repeat
IPR000152	EGF-type_Asp/Asn_hydroxyl_site	PTM
IPR000742	EGF	Domain
IPR001881	EGF-like_Ca-bd_dom	Domain
IPR002172	LDrepeatLR_classA_rpt	Repeat
IPR009030	Growth_fac_rcpt_cys_sf	Homologous_superfamily
IPR011042	6-blade_b-propeller_TolB-like	Homologous_superfamily
IPR018097	EGF_Ca-bd_CS	Conserved_site
IPR023415	LDLR_class-A_CS	Conserved_site
IPR036055	LDL_receptor-like_sf	Homologous_superfamily
IPR049883	NOTCH1_EGF-like	Domain
IPR051221	LDLR-related	Family

Pfam: PF00057, PF00058, PF07645, PF14670

UniProt features (394 total): sequence variant 195, strand 72, disulfide bond 30, turn 22, mutagenesis site 17, helix 17, domain 10, splice variant 7, repeat 6, glycosylation site 5, region of interest 4, topological domain 2, signal peptide 1, chain 1, short sequence motif 1, compositionally biased region 1, modified residue 1, sequence conflict 1, transmembrane region 1

Structure

Experimental structures (PDB)

36 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
2FCW	X-RAY DIFFRACTION	1.26
3SO6	X-RAY DIFFRACTION	1.37
1IJQ	X-RAY DIFFRACTION	1.5
1AJJ	X-RAY DIFFRACTION	1.7
5OYL	X-RAY DIFFRACTION	2.25
2W2N	X-RAY DIFFRACTION	2.3
2W2Q	X-RAY DIFFRACTION	2.33
2W2M	X-RAY DIFFRACTION	2.4
3BPS	X-RAY DIFFRACTION	2.41
4NE9	X-RAY DIFFRACTION	2.6
2W2O	X-RAY DIFFRACTION	2.62
2W2P	X-RAY DIFFRACTION	2.62
3GCW	X-RAY DIFFRACTION	2.7
3GCX	X-RAY DIFFRACTION	2.7
3P5B	X-RAY DIFFRACTION	3.3
5OY9	X-RAY DIFFRACTION	3.6
1N7D	X-RAY DIFFRACTION	3.7
9COO	ELECTRON MICROSCOPY	3.73
9BDE	ELECTRON MICROSCOPY	4.18
3P5C	X-RAY DIFFRACTION	4.2
9BD8	ELECTRON MICROSCOPY	4.8
9BDT	ELECTRON MICROSCOPY	5.4
3M0C	X-RAY DIFFRACTION	7.01
1D2J	SOLUTION NMR
1F5Y	SOLUTION NMR
1F8Z	SOLUTION NMR
1HJ7	SOLUTION NMR
1HZ8	SOLUTION NMR
1I0U	SOLUTION NMR
1LDL	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P01130-F1	75.81	0.29

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 724

Disulfide bonds (30): 27–39, 34–52, 46–63, 68–82, 75–95, 89–104, 109–121, 116–134, 128–143, 148–160, 155–173, 167–184, 197–209, 204–222, 216–231, 236–248, 243–261, 255–270, 276–289, 284–302 …

Glycosylation sites (5): 97, 156, 272, 515, 657

Mutagenesis-validated functional residues (17):

Position	Phenotype
165	partial loss of binding to getah virus e2-e1 spike glycoproteins.
168	partial loss of binding to getah virus e2-e1 spike glycoproteins.
175	partial loss of binding to getah virus e2-e1 spike glycoproteins.
208	partial loss of binding to getah virus e2-e1 spike glycoproteins.
214	partial loss of binding to getah virus e2-e1 spike glycoproteins.
217	partial loss of binding to getah virus e2-e1 spike glycoproteins.
224	partial loss of binding to getah virus e2-e1 spike glycoproteins.
811	no change. no change; when associated with r-816 and r-830. insensitive to mylip-triggered degradation; when associated
816	no change. no change; when associated with r-830. no change; when associated with r-811 and r-830. insensitive to mylip-
821	3-fold decreased affinity for ldlrap1.
821	10-fold decreased affinity for ldlrap1.
828	abolishes interaction with arrb2.
829	decreased affinity for ldlrap1.
830	no change. no change; when associated with r-816. no change; when associated with r-811 and r-816. insensitive to mylip-
839	no change. insensitive to mylip-triggered degradation; when associated with r-830. insensitive to mylip-triggered degrad
854	no effect on receptor internalization.
854	enhances interaction with arrb2 and receptor internalization.

Function

Pathways and Gene Ontology

Reactome pathways

15 pathways

ID	Pathway
R-HSA-8856825	Cargo recognition for clathrin-mediated endocytosis
R-HSA-8856828	Clathrin-mediated endocytosis
R-HSA-8964026	Chylomicron clearance
R-HSA-8964038	LDL clearance
R-HSA-975634	Retinoid metabolism and transport
R-HSA-1430728	Metabolism
R-HSA-174824	Plasma lipoprotein assembly, remodeling, and clearance
R-HSA-196854	Metabolism of vitamins and cofactors
R-HSA-199991	Membrane Trafficking
R-HSA-2187338	Visual phototransduction
R-HSA-382551	Transport of small molecules
R-HSA-5653656	Vesicle-mediated transport
R-HSA-6806667	Metabolism of fat-soluble vitamins
R-HSA-8964043	Plasma lipoprotein clearance
R-HSA-9709957	Sensory Perception

MSigDB gene sets: 691 (showing top): GSE45365_NK_CELL_VS_BCELL_UP, GOBP_CELLULAR_RESPONSE_TO_LIPOPROTEIN_PARTICLE_STIMULUS, GOBP_MEMORY, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_DIGESTION, MODULE_52, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_PHOSPHATIDYLCHOLINE_METABOLIC_PROCESS, GOBP_COGNITION, TSENG_IRS1_TARGETS_UP, GOBP_BEHAVIOR, GOBP_REGULATION_OF_TRIGLYCERIDE_METABOLIC_PROCESS

GO Biological Process (45): retinoid metabolic process (GO:0001523), negative regulation of receptor recycling (GO:0001920), lipid metabolic process (GO:0006629), endocytosis (GO:0006897), receptor-mediated endocytosis (GO:0006898), phagocytosis (GO:0006909), long-term memory (GO:0007616), cholesterol metabolic process (GO:0008203), positive regulation of gene expression (GO:0010628), negative regulation of gene expression (GO:0010629), positive regulation of triglyceride biosynthetic process (GO:0010867), regulation of phosphatidylcholine catabolic process (GO:0010899), negative regulation of low-density lipoprotein particle clearance (GO:0010989), phospholipid transport (GO:0015914), intestinal cholesterol absorption (GO:0030299), cholesterol transport (GO:0030301), plasma lipoprotein particle clearance (GO:0034381), low-density lipoprotein particle clearance (GO:0034383), high-density lipoprotein particle clearance (GO:0034384), lipoprotein catabolic process (GO:0042159), cholesterol homeostasis (GO:0042632), artery morphogenesis (GO:0048844), positive regulation of inflammatory response (GO:0050729), regulation of protein metabolic process (GO:0051246), negative regulation of protein metabolic process (GO:0051248), response to caloric restriction (GO:0061771), negative regulation of astrocyte activation (GO:0061889), cholesterol import (GO:0070508), cellular response to fatty acid (GO:0071398), cellular response to low-density lipoprotein particle stimulus (GO:0071404), receptor-mediated endocytosis involved in cholesterol transport (GO:0090118), regulation of cholesterol metabolic process (GO:0090181), amyloid-beta clearance (GO:0097242), amyloid-beta clearance by cellular catabolic process (GO:0150094), negative regulation of microglial cell activation (GO:1903979), positive regulation of lysosomal protein catabolic process (GO:1905167), negative regulation of amyloid fibril formation (GO:1905907), lipid transport (GO:0006869), steroid metabolic process (GO:0008202), negative regulation of macromolecule metabolic process (GO:0010605)

GO Molecular Function (13): amyloid-beta binding (GO:0001540), virus receptor activity (GO:0001618), protease binding (GO:0002020), low-density lipoprotein particle receptor activity (GO:0005041), calcium ion binding (GO:0005509), low-density lipoprotein particle binding (GO:0030169), very-low-density lipoprotein particle receptor activity (GO:0030229), clathrin heavy chain binding (GO:0032050), identical protein binding (GO:0042802), molecular adaptor activity (GO:0060090), lipoprotein particle binding (GO:0071813), protein binding (GO:0005515), protein-containing complex binding (GO:0044877)

GO Cellular Component (21): lysosome (GO:0005764), early endosome (GO:0005769), late endosome (GO:0005770), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), clathrin-coated pit (GO:0005905), external side of plasma membrane (GO:0009897), cell surface (GO:0009986), endosome membrane (GO:0010008), membrane (GO:0016020), basolateral plasma membrane (GO:0016323), clathrin-coated endocytic vesicle membrane (GO:0030669), low-density lipoprotein particle (GO:0034362), endolysosome membrane (GO:0036020), somatodendritic compartment (GO:0036477), signaling receptor complex (GO:0043235), apical part of cell (GO:0045177), sorting endosome (GO:0097443), PCSK9-LDLR complex (GO:1990666), endosome (GO:0005768), endomembrane system (GO:0012505)

Reactome top-level categories

Rollup of top-11 pathways:

Category	Pathways
Plasma lipoprotein clearance	2
Clathrin-mediated endocytosis	1
Membrane Trafficking	1
Visual phototransduction	1
Metabolism of fat-soluble vitamins	1
Transport of small molecules	1
Metabolism	1
Vesicle-mediated transport	1
Sensory Perception	1
Metabolism of vitamins and cofactors	1
Plasma lipoprotein assembly, remodeling, and clearance	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
endosome	4
cellular anatomical structure	4
binding	3
endomembrane system	3
endocytosis	2
gene expression	2
regulation of gene expression	2
plasma lipoprotein particle clearance	2
lipoprotein particle receptor activity	2
membrane	2
protein-containing complex	2
diterpenoid metabolic process	1
receptor recycling	1
regulation of receptor recycling	1
negative regulation of macromolecule metabolic process	1
negative regulation of signaling	1
primary metabolic process	1
vesicle budding from membrane	1
membrane invagination	1
vesicle-mediated transport	1
import into cell	1
memory	1
sterol metabolic process	1
secondary alcohol metabolic process	1
positive regulation of macromolecule biosynthetic process	1
negative regulation of macromolecule biosynthetic process	1
regulation of triglyceride biosynthetic process	1
triglyceride biosynthetic process	1
positive regulation of lipid biosynthetic process	1
positive regulation of triglyceride metabolic process	1
phosphatidylcholine catabolic process	1
regulation of phospholipid catabolic process	1
regulation of phosphatidylcholine metabolic process	1
negative regulation of lipoprotein particle clearance	1
regulation of low-density lipoprotein particle clearance	1
low-density lipoprotein particle clearance	1
lipid transport	1
organophosphate ester transport	1
lipid digestion	1
intestinal lipid absorption	1

Protein interactions and networks

STRING

763 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LDLR	CTSL	P07711	678
LDLR	LDLRAP1	Q5SW96	664
LDLR	PCSK9	Q8NBP7	591
LDLR	CTSS	P25774	461
LDLR	THBS1	P07996	450
LDLR	SCLY	Q96I15	448
LDLR	CTSB	P07858	432
LDLR	CTSV	O60911	335
LDLR	LGMN	Q99538	331
LDLR	EGFR	P00533	325
LDLR	TMPRSS3	P57727	312
LDLR	CTSF	Q9UBX1	311
LDLR	A0A2R8YEI5	A0A2R8YEI5	311
LDLR	CTSK	P43235	301
LDLR	APOB	P04114	295

IntAct

162 interactions, top by confidence:

A	B	Type	Score
TSPAN15	ADAM10	psi-mi:“MI:0914”(association)	0.840
TSPAN5	ADAM10	psi-mi:“MI:0914”(association)	0.800
LDLR	LRPAP1	psi-mi:“MI:0407”(direct interaction)	0.740
LRPAP1	LDLR	psi-mi:“MI:0407”(direct interaction)	0.740
PCSK9	LDLR	psi-mi:“MI:0407”(direct interaction)	0.720
LDLR	PCSK9	psi-mi:“MI:0407”(direct interaction)	0.720
LDLR	APOE	psi-mi:“MI:0407”(direct interaction)	0.710
APOE	LDLR	psi-mi:“MI:0914”(association)	0.710
LDLR	PCSK9	psi-mi:“MI:0407”(direct interaction)	0.680
PCSK9	LDLR	psi-mi:“MI:0407”(direct interaction)	0.680
LDLR	APOH	psi-mi:“MI:0407”(direct interaction)	0.620
Ldlrap1	LDLR	psi-mi:“MI:0407”(direct interaction)	0.560
LDLR	MTIF3	psi-mi:“MI:0915”(physical association)	0.560
LDLR	TLE5	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (501): PCSK9 (Affinity Capture-Western), LDLR (Affinity Capture-MS), LDLR (Affinity Capture-MS), LDLR (Affinity Capture-MS), LDLR (Affinity Capture-MS), LDLR (Affinity Capture-MS), LDLR (Affinity Capture-MS), MYLIP (Affinity Capture-Western), USP2 (Affinity Capture-Western), LDLR (Co-localization), LDLR (Affinity Capture-MS), LDLR (Affinity Capture-MS), LDLR (Affinity Capture-MS), LDLR (Affinity Capture-MS), LDLR (Affinity Capture-MS)

ESM2 similar proteins: A0A6I8RMG7, A2A863, A2VCU8, A7E2Z9, P01130, P01131, P04412, P0CY46, P16144, P18563, P18564, P24043, P35555, P35950, P35952, P35953, P98133, P98155, P98156, P98165, P98166, Q1RPR6, Q28832, Q2KIT5, Q3UZV7, Q4G063, Q4V7M2, Q5XH36, Q60438, Q61220, Q61554, Q62918, Q64632, Q6AYF4, Q6DDW2, Q6UXH1, Q7SXF6, Q7ZXL5, Q863C4, Q8CFM6

Diamond homologs: A2AR95, A2ARV4, A2VEC9, A4IHY6, A4QPB2, A6QNY1, B3EWY9, B3EWZ6, B3M8G0, B3NBB6, B4HVU2, B4L8V5, B4LCX4, B4MLE8, B4PD96, B4QMF4, B5DFC9, C0HL13, G3V928, G4NGN5, O88322, P01130, P07225, P10493, P14543, P15306, P35950, P35951, P35952, P35953, P53813, P86091, P98155, P98157, P98158, P98163, P98164, P98165, P98167, Q00968

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
SREBF2	“up-regulates quantity by expression”	LDLR	“transcriptional regulation”
HNF4A	“up-regulates quantity by expression”	LDLR	“transcriptional regulation”
porfimer	“up-regulates activity”	LDLR	“chemical activation”
MYLIP	“down-regulates quantity by destabilization”	LDLR	ubiquitination
APOB	up-regulates	LDLR	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 158 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	9	8.2×	8e-04
Post-translational protein phosphorylation	7	7.4×	5e-03

GO biological processes:

GO term	Partners	Fold	FDR
extracellular matrix disassembly	5	14.1×	9e-03
protein maturation	7	8.8×	9e-03
canonical Wnt signaling pathway	7	8.2×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

4833 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1233
Likely pathogenic	617
Uncertain significance	1188
Likely benign	880
Benign	88

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1052293	NM_000527.5(LDLR):c.1706A>T (p.Asp569Val)	Pathogenic
1068547	NM_000527.5(LDLR):c.1187-1_1187delinsTA	Pathogenic
1069255	NM_000527.5(LDLR):c.1503_1504dup (p.Asp502fs)	Pathogenic
1069978	NM_000527.5(LDLR):c.2469_2470insTTTTTTTTTTTTTTTTTNNNNNNNNNNTTAGCCAGGATGGTCTCGATCTCCTGACCTCGTGATCCGCCCGCCTCGGCCTCCCAAAGTGCTGGGATTACAAGCGTGAGCCACCGCGCCCGGCCAACAGCATCAACTTT (p.Asp824delinsPhePhePhePhePheXaaXaaXaaXaaLeuAlaArgMetValSerIleSerTer)	Pathogenic
1070723	NC_000019.9:g.(?11213320)(11216296_?)del	Pathogenic
1070724	NC_000019.9:g.(?11213330)(11222326_?)del	Pathogenic
1070725	NC_000019.9:g.(?11217231)(11224448_?)del	Pathogenic
1071946	NM_000527.5(LDLR):c.1411del (p.Arg471fs)	Pathogenic
1072924	NM_000527.5(LDLR):c.1356C>A (p.Cys452Ter)	Pathogenic
1073028	NM_000527.5(LDLR):c.1516dup (p.Val506fs)	Pathogenic
1073362	NM_000527.5(LDLR):c.1824del (p.Phe609fs)	Pathogenic
1074663	NC_000019.9:g.(?11240179)(11241992_?)del	Pathogenic
1074682	NM_000527.5(LDLR):c.2462_2463insTGGCCGGGCGCGGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCCGAGGCGGGTGGATCATGAGGTCAGGAGATCGAGACCATCCTGGCTAACAAGGTGAAACCCCGTCTCTACTAAAAATACAAAAAAAATTAGCCGGGCGCGGTGGCGGGCGCCTGTAGTCCCAGCTACTCGGGAGGCTGAGGCAGGAGAATGGCGTGAACCCGGGAAGCGGAGCTTGCAGTGAGCCGAGATTGCGCCACTGCAGTCCGCAGTCCCGCCTGGGCGACAGAGCGAGACTCCATCTCAAAAAAAAAATAATAATAAAAGAACATCAACAGCAT (p.Ile821_Asn822insGlyArgAlaArgTrpLeuThrProValIleProAlaLeuTrpGluAlaGluAlaGlyGlySerTer)	Pathogenic
1074804	NC_000019.9:g.(?11223944)(11227689_?)del	Pathogenic
1074805	NC_000019.9:g.(?11223948)(11241997_?)del	Pathogenic
1075416	NM_000527.5(LDLR):c.678_681dup (p.Glu228Ter)	Pathogenic
1075455	NM_000527.5(LDLR):c.2530_2542del (p.Gly844fs)	Pathogenic
1076614	NC_000019.9:g.(?11217231)(11218204_?)del	Pathogenic
1076616	NC_000019.9:g.(?11221289)(11221471_?)del	Pathogenic
1076861	NM_000527.5(LDLR):c.1531_1532dup (p.Leu511fs)	Pathogenic
1076971	NM_000527.5(LDLR):c.2449_2453del (p.Asn817fs)	Pathogenic
1120145	Single allele	Pathogenic
1120146	Single allele	Pathogenic
1120147	Single allele	Pathogenic
1120148	Single allele	Pathogenic
1120149	Single allele	Pathogenic
1120150	Single allele	Pathogenic
1120249	NM_000527.5(LDLR):c.1943_1944delinsG (p.Ser648fs)	Pathogenic
1120250	NM_000527.4(LDLR):c.(1845+1_1846-1)_(2140+1_2141-1)del	Pathogenic
1120251	NM_000527.4(LDLR):c.(1586+1_1587-1)_(1845+1_1846-1)del	Pathogenic

SpliceAI

2205 predictions. Top by Δscore:

Variant	Effect	Δscore
19:11089614:AGGTA:A	donor_loss	1.0000
19:11089617:T:A	donor_loss	1.0000
19:11100219:TCA:T	acceptor_loss	1.0000
19:11100220:CAG:C	acceptor_loss	1.0000
19:11100221:A:AG	acceptor_gain	1.0000
19:11100221:AGT:A	acceptor_gain	1.0000
19:11100221:AGTG:A	acceptor_gain	1.0000
19:11100222:G:GA	acceptor_gain	1.0000
19:11100222:GT:G	acceptor_gain	1.0000
19:11100222:GTG:G	acceptor_gain	1.0000
19:11100222:GTGG:G	acceptor_gain	1.0000
19:11100315:G:GT	donor_gain	1.0000
19:11100325:A:G	donor_gain	1.0000
19:11100341:GTGCT:G	donor_gain	1.0000
19:11100343:GCT:G	donor_gain	1.0000
19:11100346:G:GG	donor_gain	1.0000
19:11102659:T:TA	acceptor_gain	1.0000
19:11102659:TGTA:T	acceptor_loss	1.0000
19:11102660:GTAGT:G	acceptor_loss	1.0000
19:11102661:TA:T	acceptor_loss	1.0000
19:11102662:A:AC	acceptor_loss	1.0000
19:11102662:A:AG	acceptor_gain	1.0000
19:11102662:AGT:A	acceptor_gain	1.0000
19:11102663:G:A	acceptor_loss	1.0000
19:11102663:G:GA	acceptor_gain	1.0000
19:11102663:GT:G	acceptor_gain	1.0000
19:11102663:GTG:G	acceptor_gain	1.0000
19:11102663:GTGT:G	acceptor_gain	1.0000
19:11102663:GTGTC:G	acceptor_gain	1.0000
19:11102782:CTGTC:C	donor_gain	1.0000

AlphaMissense

5750 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:11105409:A:C	D168A	0.999
19:11105409:A:T	D168V	0.999
19:11105438:G:T	D178Y	0.999
19:11105518:C:G	C204W	0.999
19:11105570:T:A	C222S	0.999
19:11105571:G:C	C222S	0.999
19:11105572:C:G	C222W	0.999
19:11106597:T:A	C243S	0.999
19:11106598:G:C	C243S	0.999
19:11106651:T:A	C261S	0.999
19:11106652:G:C	C261S	0.999
19:11107419:T:G	F282C	0.999
19:11107424:T:A	C284S	0.999
19:11107425:G:C	C284S	0.999
19:11107460:T:A	C296S	0.999
19:11107461:G:C	C296S	0.999
19:11107478:T:A	C302S	0.999
19:11107479:G:C	C302S	0.999
19:11110696:T:A	C329S	0.999
19:11110697:G:C	C329S	0.999
19:11113677:G:C	A501P	0.999
19:11100250:T:G	F32C	0.998
19:11100291:T:A	C46S	0.998
19:11100292:G:C	C46S	0.998
19:11100309:T:A	C52S	0.998
19:11100310:G:C	C52S	0.998
19:11100324:G:T	D57Y	0.998
19:11102756:T:A	C95S	0.998
19:11102757:G:C	C95S	0.998
19:11102771:G:T	D100Y	0.998

dbSNP variants (sampled 300 via entrez): RS1000111375 (19:11104248 C>T), RS1000130246 (19:11128793 T>C), RS1000194961 (19:11112302 G>T), RS1000204773 (19:11112081 G>A), RS1000311309 (19:11110165 G>C), RS1000320676 (19:11109923 A>C,T), RS1000389252 (19:11095081 G>A), RS1000532406 (19:11111106 C>T), RS1000543829 (19:11110888 G>A,T), RS1000761221 (19:11118242 G>A), RS1000908828 (19:11122579 T>C), RS1001061278 (19:11096286 G>A,T), RS1001108383 (19:11128718 T>C), RS1001131022 (19:11092011 C>T), RS1001297002 (19:11090397 T>C)

Disease associations

OMIM: gene MIM:606945 | disease phenotypes: MIM:143890, MIM:300749, MIM:158350, MIM:144010, MIM:270400, MIM:603813, MIM:617347

GenCC curated gene-disease

Disease	Classification	Inheritance
hypercholesterolemia, familial, 1	Definitive	Autosomal dominant
homozygous familial hypercholesterolemia	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
hypercholesterolemia, familial, 1	Definitive	SD

Mondo (10): familial hypercholesterolemia (MONDO:0005439), hypercholesterolemia, familial, 1 (MONDO:0007750), homozygous familial hypercholesterolemia (MONDO:0018328), syndromic X-linked intellectual disability Najm type (MONDO:0010417), Cowden syndrome 1 (MONDO:0008021), hypercholesterolemia, autosomal dominant, type B (MONDO:0007751), Smith-Lemli-Opitz syndrome (MONDO:0010035), hyperlipidemia (MONDO:0021187), hypercholesterolemia, familial, 4 (MONDO:0011374), hyperlipoproteinemia type 3 (MONDO:0018473)

Orphanet (4): Homozygous familial hypercholesterolemia (Orphanet:391665), X-linked intellectual disability, Najm type (Orphanet:163937), Smith-Lemli-Opitz syndrome (Orphanet:818), Dysbetalipoproteinemia (Orphanet:412)

HPO phenotypes

37 total (30 of 37 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000799	Renal steatosis
HP:0000822	Hypertension
HP:0000991	Xanthomatosis
HP:0001084	Corneal arcus
HP:0001114	Xanthelasma
HP:0001138	Optic neuropathy
HP:0001397	Hepatic steatosis
HP:0001645	Sudden cardiac death
HP:0001653	Mitral regurgitation
HP:0001658	Myocardial infarction
HP:0001677	Coronary artery atherosclerosis
HP:0001681	Angina pectoris
HP:0001920	Renal artery stenosis
HP:0002094	Dyspnea
HP:0002829	Arthralgia
HP:0003077	Hyperlipidemia
HP:0003124	Hypercholesterolemia
HP:0003141	Increased LDL cholesterol concentration
HP:0004381	Supravalvular aortic stenosis
HP:0004416	Precocious atherosclerosis
HP:0004950	Peripheral arterial stenosis
HP:0004963	Calcification of the aorta
HP:0005162	Abnormal left ventricular function
HP:0005177	Premature arteriosclerosis
HP:0005181	Premature coronary artery atherosclerosis
HP:0006693	Myocardial steatosis
HP:0007201	Cerebral artery atherosclerosis
HP:0010874	Tendon xanthomatosis

GWAS associations

194 associations (top):

Study	Trait	p-value
GCST000132_5	LDL cholesterol	4.000000e-26
GCST000134_4	LDL cholesterol	2.000000e-51
GCST000282_8	LDL cholesterol	4.000000e-14
GCST000283_4	LDL cholesterol	2.000000e-07
GCST000285_5	Cholesterol, total	9.000000e-24
GCST000287_2	LDL cholesterol	2.000000e-26
GCST000340_9	Myocardial infarction (early onset)	2.000000e-09
GCST000533_2	Lipid metabolism phenotypes	1.000000e-25
GCST000533_26	Lipid metabolism phenotypes	3.000000e-18
GCST000533_28	Lipid metabolism phenotypes	2.000000e-31
GCST000533_29	Lipid metabolism phenotypes	5.000000e-25
GCST000759_25	LDL cholesterol	4.000000e-117
GCST000760_50	Cholesterol, total	7.000000e-97
GCST000807_8	LDL cholesterol	7.000000e-06
GCST000975_17	LDL cholesterol	7.000000e-08
GCST000998_25	Coronary heart disease	1.000000e-09
GCST001231_11	Carotid intima media thickness	1.000000e-07
GCST001233_11	Metabolite levels	2.000000e-12
GCST001247_19	Cardiovascular disease risk factors	5.000000e-11
GCST001273_2	Lipoprotein-associated phospholipase A2 activity and mass	3.000000e-11
GCST001392_13	Lipid metabolism phenotypes	8.000000e-17
GCST001639_5	Metabolite levels	4.000000e-09
GCST002042_3	LDL cholesterol	2.000000e-17
GCST002193_1	Abdominal aortic aneurysm	2.000000e-10
GCST002220_1	LDL cholesterol	3.000000e-115
GCST002221_62	Cholesterol, total	5.000000e-202
GCST002222_32	LDL cholesterol	4.000000e-262
GCST002287_14	Coronary artery disease or ischemic stroke	3.000000e-12
GCST002289_2	Coronary artery disease	3.000000e-11
GCST002290_4	Coronary artery disease or large artery stroke	2.000000e-11

EFO canonical traits (20, from GWAS)

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004574	total cholesterol measurement
EFO:0004529	lipid measurement
EFO:0004746	lipoprotein-associated phospholipase A(2) measurement
EFO:0004723	coronary artery calcification
EFO:0004458	C-reactive protein measurement
EFO:0005843	cortisol measurement
EFO:0007796	parental longevity
EFO:0009783	carotid atherosclerosis
EFO:0009925	Antithrombotic agent use measurement
EFO:0009931	Agents acting on the renin-angiotensin system use measurement
EFO:0009932	HMG CoA reductase inhibitor use measurement
EFO:0007013	aspirin use measurement
EFO:0004329	alcohol drinking
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0010343	cholesteryl ester 18:0 measurement
EFO:0007804	LDL cholesterol change measurement
EFO:0004615	apolipoprotein B measurement
EFO:0009762	healthspan
EFO:0006925	lipoprotein A measurement

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D000090542	Homozygous Familial Hypercholesterolemia	C16.320.565.398.481.500; C18.452.584.500.500.644.475.500; C18.452.584.563.481.500; C18.452.648.398.481.500
D006949	Hyperlipidemias	C18.452.584.500.500
D019082	Smith-Lemli-Opitz Syndrome	C16.131.077.860; C16.320.565.398.850; C16.320.565.925.875; C18.452.584.500.937; C18.452.584.563.850; C18.452.648.398.850; C18.452.648.925.875
C567466	Mental Retardation And Microcephaly With Pontine And Cerebellar Hypoplasia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3311 (SINGLE PROTEIN), CHEMBL4523996 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 38,627 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL255863	NILOTINIB	4	38,627

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

6 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs14158	Efficacy	3	peginterferon alfa-2a;peginterferon alfa-2b;ribavirin	Chronic hepatitis C virus infection;HIV infectious disease
rs1433099	Efficacy	3	pravastatin	Vascular Diseases
rs2738466	Efficacy	3	pravastatin	Vascular Diseases
rs5925	Efficacy	3	lovastatin
rs688	Efficacy	3	atenolol	Hypertension
rs688	Efficacy	3	lovastatin

PharmGKB variants

6 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs688	LDLR	3	2.75	2	atenolol;lovastatin
rs5925	LDLR	3	2.75	1	lovastatin
rs14158	LDLR	3	2.00	1	peginterferon alfa-2a;peginterferon alfa-2b;ribavirin
rs1433099	LDLR	3	0.00	1	pravastatin
rs2738466	LDLR	3	0.00	1	pravastatin
rs6511720	LDLR		0.00	0

ChEMBL bioactivities

594 potent at pChembl≥5 of 728 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.70	IC50	2	nM	CHEMBL5278292
8.51	IC50	3.1	nM	CHEMBL5268810
8.15	IC50	7	nM	CHEMBL5418494
8.05	IC50	9	nM	CHEMBL5409584
7.85	Ki	14	nM	CHEMBL4789480
7.75	Ki	17.6	nM	CHEMBL4776000
7.63	Ki	23.3	nM	CHEMBL4754486
7.62	Ki	23.9	nM	CHEMBL4795153
7.58	Ki	26.6	nM	CHEMBL4743963
7.57	Ki	26.9	nM	CHEMBL4764247
7.36	Ki	43.5	nM	CHEMBL4789838
7.33	Ki	47.1	nM	CHEMBL4740764
7.32	Ki	48.1	nM	CHEMBL4799936
7.30	IC50	50	nM	CHEMBL5802613
7.30	IC50	50	nM	CHEMBL5780071
7.30	IC50	50	nM	CHEMBL5996876
7.30	IC50	50	nM	CHEMBL6003304
7.30	IC50	50	nM	CHEMBL5956074
7.30	IC50	50	nM	CHEMBL5756628
7.30	IC50	50	nM	CHEMBL6040707
7.30	IC50	50	nM	CHEMBL6039902
7.30	IC50	50	nM	CHEMBL5763767
7.30	IC50	50	nM	CHEMBL5932491
7.30	IC50	50	nM	CHEMBL5743013
7.30	IC50	50	nM	CHEMBL5882670
7.30	IC50	50	nM	CHEMBL5788292
7.30	IC50	50	nM	CHEMBL6021487
7.30	IC50	50	nM	CHEMBL5835110
7.30	IC50	50	nM	CHEMBL6044373
7.30	IC50	50	nM	CHEMBL5902402
7.30	IC50	50	nM	CHEMBL5767193
7.30	IC50	50	nM	CHEMBL5836575
7.30	IC50	50	nM	CHEMBL5926165
7.30	IC50	50	nM	CHEMBL5906583
7.30	IC50	50	nM	CHEMBL5753404
7.30	IC50	50	nM	CHEMBL6044476
7.30	IC50	50	nM	CHEMBL4759663
7.30	IC50	50	nM	CHEMBL5876842
7.30	IC50	50	nM	CHEMBL5827405
7.30	IC50	50	nM	CHEMBL5779731
7.30	IC50	50	nM	CHEMBL5856574
7.30	IC50	50	nM	CHEMBL5815822
7.30	IC50	50	nM	CHEMBL5808401
7.30	IC50	50	nM	CHEMBL5783539
7.30	IC50	50	nM	CHEMBL5910433
7.30	IC50	50	nM	CHEMBL6002292
7.30	IC50	50	nM	CHEMBL5910875
7.30	IC50	50	nM	CHEMBL5758016
7.30	IC50	50	nM	CHEMBL5743459
7.30	IC50	50	nM	CHEMBL5934279

PubChem BioAssay actives

82 with measured affinity, of 362 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
3-[(3S,6S,12R,15S,21S,24S,27S,30S,33S,36S,39S,42S,45S)-6-benzyl-12-(ethylcarbamoyl)-39,42-bis[(1R)-1-hydroxyethyl]-21,27,28,33,34-pentamethyl-2,5,8,14,20,23,26,29,32,35,38,41,44-tridecaoxo-30,36-bis[(4-phenylphenyl)methyl]-3-propan-2-yl-10-thia-1,4,7,13,19,22,25,28,31,34,37,40,43-tridecazatricyclo[43.3.0.015,19]octatetracontan-24-yl]propanoic acid	1933148: Inhibition of PCSK9-LDLR (unknown origin) protein-protein interaction	ic50	0.0020	uM
(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-1-[(2R)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2R)-2-[[2-[[2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S,3R)-2-[(2-aminoacetyl)amino]-3-hydroxybutanoyl]amino]-4-oxobutanoyl]amino]-4-carboxybutanoyl]amino]-3-sulfanylpropanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-4-oxobutanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]acetyl]amino]-3-sulfanylpropanoyl]amino]-3-hydroxypropanoyl]amino]-3-methylpentanoyl]amino]-3-methylbutanoyl]amino]-3-sulfanylpropanoyl]amino]-5-carbamimidamidopentanoyl]amino]hexanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]amino]-3-methylpentanoyl]amino]acetyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-carboxybutanoyl]amino]-3-sulfanylpropanoyl]amino]-4-methylpentanoyl]amino]-3-sulfanylpropanoyl]pyrrolidine-2-carbonyl]amino]-3-carboxypropanoyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]-3-methylbutanoyl]amino]propanoyl]amino]-5-oxopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-sulfanylpropanoyl]amino]pentanedioic acid	1933140: Inhibition of human PCSK9-LDLR protein-protein interaction using EGF peptide as substrate preincubated for 30 mins followed by LDLR addition and measured after 2 hrs by ELISA	ic50	0.0031	uM
5-[5-[1-(4,4-dimethylpentyl)-5-naphthalen-2-ylimidazol-2-yl]-2-iodoimidazol-1-yl]-N-methylpentan-1-amine	1990773: Inhibition of His-tagged PCSK9 to recombinant LDLR (unknown origin) protein-protein interaction incubated for 2 hrs by fluorescence plate reader analysis	ic50	0.0070	uM
5-[5-[1-(4,4-dimethylpentyl)-5-naphthalen-2-ylimidazol-2-yl]-2-ethynylimidazol-1-yl]-N-methylpentan-1-amine	1990773: Inhibition of His-tagged PCSK9 to recombinant LDLR (unknown origin) protein-protein interaction incubated for 2 hrs by fluorescence plate reader analysis	ic50	0.0090	uM
2-[(5R,8S,14S,17S,20S,23S,26S,32S)-32-(4-aminobutyl)-5-carbamoyl-23,26-bis[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-hydroxyphenyl)methyl]-17-(1H-imidazol-5-ylmethyl)-8-methyl-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]acetic acid	1700388: Inhibition of avi-tagged-biotinylated human PCSK9 interaction with His-tagged human LDLR EGFa domain by LANCE Ulight Streptavidin based TR-FRET assay	ki	0.0140	uM
2-[(8S,14S,17S,20S,23S,26S,29R,32S)-32-(4-aminobutyl)-23,26-bis[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-hydroxyphenyl)methyl]-17-(1H-imidazol-5-ylmethyl)-8-methyl-7,13,16,19,22,25,28,31,34-nonaoxo-29-propan-2-yl-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]acetic acid	1700388: Inhibition of avi-tagged-biotinylated human PCSK9 interaction with His-tagged human LDLR EGFa domain by LANCE Ulight Streptavidin based TR-FRET assay	ki	0.0176	uM
2-[(8S,14S,17S,20S,23S,26S,29R,32S)-32-(4-aminobutyl)-23,26-bis[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-hydroxyphenyl)methyl]-17-(1H-imidazol-5-ylmethyl)-8,29-dimethyl-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]acetic acid	1700388: Inhibition of avi-tagged-biotinylated human PCSK9 interaction with His-tagged human LDLR EGFa domain by LANCE Ulight Streptavidin based TR-FRET assay	ki	0.0233	uM
(5R,8S,14S,17S,20S,26S,29S,35S)-35-(4-aminobutyl)-26,29-bis[(5-fluoro-1H-indol-3-yl)methyl]-17-[(1R)-1-hydroxyethyl]-14-[(4-hydroxyphenyl)methyl]-8-methyl-7,13,16,19,25,28,31,34,37-nonaoxo-3,40-dithia-6,12,15,18,24,27,30,33,36-nonazatetracyclo[40.3.1.08,12.020,24]hexatetraconta-1(45),42(46),43-triene-5-carboxamide	1700388: Inhibition of avi-tagged-biotinylated human PCSK9 interaction with His-tagged human LDLR EGFa domain by LANCE Ulight Streptavidin based TR-FRET assay	ki	0.0239	uM
2-[(8S,14S,17S,20S,23S,26S,32S)-32-(4-aminobutyl)-23,26-bis[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-hydroxyphenyl)methyl]-17-(1H-imidazol-5-ylmethyl)-8-methyl-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]acetic acid	1700388: Inhibition of avi-tagged-biotinylated human PCSK9 interaction with His-tagged human LDLR EGFa domain by LANCE Ulight Streptavidin based TR-FRET assay	ki	0.0266	uM
2-[(8S,14S,17S,20S,23S,26S,29R,32S)-32-(4-aminobutyl)-23,26-bis[(5-fluoro-1H-indol-3-yl)methyl]-29-[(1S)-1-hydroxyethyl]-14-[(4-hydroxyphenyl)methyl]-17-(1H-imidazol-5-ylmethyl)-8-methyl-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]acetic acid	1700388: Inhibition of avi-tagged-biotinylated human PCSK9 interaction with His-tagged human LDLR EGFa domain by LANCE Ulight Streptavidin based TR-FRET assay	ki	0.0269	uM
2-[(8S,14S,17S,20S,23S,26S,29R,32S)-32-(4-aminobutyl)-23,26-bis[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-hydroxyphenyl)methyl]-17-(1H-imidazol-5-ylmethyl)-8-methyl-7,13,16,19,22,25,28,31,34-nonaoxo-29-propyl-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]acetic acid	1700388: Inhibition of avi-tagged-biotinylated human PCSK9 interaction with His-tagged human LDLR EGFa domain by LANCE Ulight Streptavidin based TR-FRET assay	ki	0.0435	uM
2-[(5R,8S,14S,17S,20S,23S,26S,32S,35R)-35-acetamido-32-(4-aminobutyl)-5-carbamoyl-23,26-bis[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-hydroxyphenyl)methyl]-17-(1H-imidazol-5-ylmethyl)-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]acetic acid	1700388: Inhibition of avi-tagged-biotinylated human PCSK9 interaction with His-tagged human LDLR EGFa domain by LANCE Ulight Streptavidin based TR-FRET assay	ki	0.0471	uM
2-[(8S,14S,17S,20S,23S,26S,29R,32S)-29-(4-aminobutyl)-23,26-bis[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-hydroxyphenyl)methyl]-17-(1H-imidazol-5-ylmethyl)-8,32-dimethyl-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]acetic acid	1700388: Inhibition of avi-tagged-biotinylated human PCSK9 interaction with His-tagged human LDLR EGFa domain by LANCE Ulight Streptavidin based TR-FRET assay	ki	0.0481	uM
2-[(5R,8S,14S,17S,20S,23S,32S)-32-(4-aminobutyl)-5-carbamoyl-23-[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-hydroxyphenyl)methyl]-17-(1H-imidazol-5-ylmethyl)-26-methyl-26-naphthalen-1-yl-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]acetic acid	1700388: Inhibition of avi-tagged-biotinylated human PCSK9 interaction with His-tagged human LDLR EGFa domain by LANCE Ulight Streptavidin based TR-FRET assay	ki	0.0630	uM
2-[(5R,8S,13S,16S,19S,22S,25S,31S)-31-(4-aminobutyl)-5-carbamoyl-22,25-bis[(5-fluoro-1H-indol-3-yl)methyl]-13-[(4-hydroxyphenyl)methyl]-16-(1H-imidazol-5-ylmethyl)-7,12,15,18,21,24,27,30,33-nonaoxo-3,36-dithia-6,11,14,17,20,23,26,29,32-nonazatricyclo[36.3.1.08,11]dotetraconta-1(41),38(42),39-trien-19-yl]acetic acid	1700388: Inhibition of avi-tagged-biotinylated human PCSK9 interaction with His-tagged human LDLR EGFa domain by LANCE Ulight Streptavidin based TR-FRET assay	ki	0.0675	uM
3-isoquinolin-8-yloxy-4-methyl-N-[3-(4-methylimidazol-1-yl)-5-(4-methylpiperazin-1-yl)phenyl]benzamide	1666983: Inhibition of recombinant human His-tagged PCSK9 interaction with recombinant LDLR AB domain (unknown origin) measured after 3 hrs by horseradish peroxidase-coupled TMB substrate based spectrophotometry	ic50	0.0780	uM
2-[(8S,14S,17S,20S,23S,26S,29R,32S)-23,26-bis[(5-fluoro-1H-indol-3-yl)methyl]-32-(4-hydroxybutyl)-17-(1H-imidazol-5-ylmethyl)-14-[(4-methoxyphenyl)methyl]-8,29-dimethyl-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]acetic acid	1700388: Inhibition of avi-tagged-biotinylated human PCSK9 interaction with His-tagged human LDLR EGFa domain by LANCE Ulight Streptavidin based TR-FRET assay	ki	0.0789	uM
(5R,8S,14S,17S,20S,26S,29S,35S)-35-(4-aminobutyl)-26,29-bis[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-hydroxyphenyl)methyl]-8,17-dimethyl-7,13,16,19,25,28,31,34,37-nonaoxo-3,40-dithia-6,12,15,18,24,27,30,33,36-nonazatetracyclo[40.3.1.08,12.020,24]hexatetraconta-1(45),42(46),43-triene-5-carboxamide	1700388: Inhibition of avi-tagged-biotinylated human PCSK9 interaction with His-tagged human LDLR EGFa domain by LANCE Ulight Streptavidin based TR-FRET assay	ki	0.0883	uM
2-[(5R,8S,14S,17S,20S,23S,26S,32S)-5-carbamoyl-23,26-bis[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-hydroxyphenyl)methyl]-17-(1H-imidazol-5-ylmethyl)-8-methyl-7,13,16,19,22,25,28,31,34-nonaoxo-32-propyl-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]acetic acid	1700388: Inhibition of avi-tagged-biotinylated human PCSK9 interaction with His-tagged human LDLR EGFa domain by LANCE Ulight Streptavidin based TR-FRET assay	ki	0.0947	uM
2-[(5R,8S,14S,17S,20S,23S,26S,32S,35R)-35-acetamido-32-(4-aminobutyl)-5-carbamoyl-23-[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-hydroxyphenyl)methyl]-17-(1H-imidazol-5-ylmethyl)-26-(1H-indol-3-ylmethyl)-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]acetic acid	1700388: Inhibition of avi-tagged-biotinylated human PCSK9 interaction with His-tagged human LDLR EGFa domain by LANCE Ulight Streptavidin based TR-FRET assay	ki	0.1030	uM
2-[(3S,6S,9S,12S,15S,18S,21S,24S,27S,30S,33S,39R,42S)-39-[(2-amino-2-oxoethyl)carbamoyl]-33-benzyl-3-(3-carbamimidamidopropyl)-21,24-bis[(1R)-1-hydroxyethyl]-27-(hydroxymethyl)-9,10,15,16-tetramethyl-2,5,8,11,14,17,20,23,26,29,32,35,41-tridecaoxo-12,18-bis[(4-phenylphenyl)methyl]-30-propan-2-yl-37-thia-1,4,7,10,13,16,19,22,25,28,31,34,40-tridecazabicyclo[40.3.0]pentatetracontan-6-yl]acetic acid	1933161: Inhibition of PCSK9-LDLR protein-protein interaction in human HepG2 cells assessed as increase in LDL uptake	ec50	0.1060	uM
2-[(5R,8S,14S,17S,20S,23S,26S,32S)-32-(4-aminobutyl)-5-carbamoyl-23,26-bis[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-hydroxyphenyl)methyl]-17-(1H-imidazol-5-ylmethyl)-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]acetic acid	1700388: Inhibition of avi-tagged-biotinylated human PCSK9 interaction with His-tagged human LDLR EGFa domain by LANCE Ulight Streptavidin based TR-FRET assay	ki	0.1100	uM
2-[(5R,8S,14S,17S,20S,23S,26S,32S)-32-(4-aminobutyl)-5-carbamoyl-23,26-bis[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-hydroxyphenyl)methyl]-17-(1H-imidazol-5-ylmethyl)-15-methyl-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]acetic acid	1700388: Inhibition of avi-tagged-biotinylated human PCSK9 interaction with His-tagged human LDLR EGFa domain by LANCE Ulight Streptavidin based TR-FRET assay	ki	0.1120	uM
2-[(5R,8S,14S,17S,20S,23S,26S,32S)-32-(3-aminopropyl)-5-carbamoyl-23,26-bis[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-hydroxyphenyl)methyl]-17-(1H-imidazol-5-ylmethyl)-8-methyl-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]acetic acid	1700388: Inhibition of avi-tagged-biotinylated human PCSK9 interaction with His-tagged human LDLR EGFa domain by LANCE Ulight Streptavidin based TR-FRET assay	ki	0.1325	uM
3-[(5R,8S,11S,14S,17S,20S,23S,26S,29S,32S,35S,38R)-38-(2-acetamidohexanoylamino)-35-tert-butyl-5-carbamoyl-8,26-bis[(1R)-1-hydroxyethyl]-14,32-bis[(4-hydroxyphenyl)methyl]-29-(1H-imidazol-5-ylmethyl)-7,10,13,16,19,22,25,28,31,34,37-undecaoxo-11,20-dipropyl-23-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-3,40-dithia-6,9,12,15,18,21,24,27,30,33,36-undecazabicyclo[40.3.1]hexatetraconta-1(45),42(46),43-trien-17-yl]propanoic acid	1700388: Inhibition of avi-tagged-biotinylated human PCSK9 interaction with His-tagged human LDLR EGFa domain by LANCE Ulight Streptavidin based TR-FRET assay	ki	0.1340	uM
3-[(8S,14S,17S,20S,23S,26S,29R,32S)-20-(carboxymethyl)-23,26-bis[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-hydroxyphenyl)methyl]-17-(1H-imidazol-5-ylmethyl)-8,29-dimethyl-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-32-yl]propanoic acid	1700388: Inhibition of avi-tagged-biotinylated human PCSK9 interaction with His-tagged human LDLR EGFa domain by LANCE Ulight Streptavidin based TR-FRET assay	ki	0.2022	uM
2-[(8S,14S,17S,20S,23S,26S,32S)-32-(4-aminobutyl)-23,26-bis[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-hydroxyphenyl)methyl]-17-(1H-imidazol-5-ylmethyl)-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]acetic acid	1700388: Inhibition of avi-tagged-biotinylated human PCSK9 interaction with His-tagged human LDLR EGFa domain by LANCE Ulight Streptavidin based TR-FRET assay	ki	0.2520	uM
2-[(5R,8S,14S,17S,20S,23S,26S,32S)-32-(4-aminobutyl)-5-carbamoyl-23,26-bis[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-hydroxyphenyl)methyl]-17-(1H-imidazol-5-ylmethyl)-33-methyl-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]acetic acid	1700388: Inhibition of avi-tagged-biotinylated human PCSK9 interaction with His-tagged human LDLR EGFa domain by LANCE Ulight Streptavidin based TR-FRET assay	ki	0.3420	uM
2-[(5R,8S,14S,17S,20S,23S,26S,32S)-5-carbamoyl-23,26-bis[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-hydroxyphenyl)methyl]-17-(1H-imidazol-5-ylmethyl)-32-methyl-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]acetic acid	1700388: Inhibition of avi-tagged-biotinylated human PCSK9 interaction with His-tagged human LDLR EGFa domain by LANCE Ulight Streptavidin based TR-FRET assay	ki	0.3920	uM
(5R,8S,14S,17S,20S,23S,26S,32S)-32-(4-aminobutyl)-23,26-bis[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-hydroxyphenyl)methyl]-17-(1H-imidazol-5-ylmethyl)-20-methyl-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-triene-5-carboxamide	1700388: Inhibition of avi-tagged-biotinylated human PCSK9 interaction with His-tagged human LDLR EGFa domain by LANCE Ulight Streptavidin based TR-FRET assay	ki	0.4270	uM
N-[3-[[(3S)-3-aminopiperidin-1-yl]methyl]-5-(4-methylimidazol-1-yl)phenyl]-3-[[4-(4-fluorophenyl)pyrimidin-2-yl]amino]-4-methylbenzamide	1666983: Inhibition of recombinant human His-tagged PCSK9 interaction with recombinant LDLR AB domain (unknown origin) measured after 3 hrs by horseradish peroxidase-coupled TMB substrate based spectrophotometry	ic50	0.4280	uM
4-methyl-N-[3-(4-methylimidazol-1-yl)-5-piperazin-1-ylphenyl]-3-[(4-phenylpyrimidin-2-yl)amino]benzamide	1666983: Inhibition of recombinant human His-tagged PCSK9 interaction with recombinant LDLR AB domain (unknown origin) measured after 3 hrs by horseradish peroxidase-coupled TMB substrate based spectrophotometry	ic50	0.4910	uM
2-[(5R,8S,14S,17S,20S,23S,26S,32S)-32-(4-aminobutyl)-5-carbamoyl-23,26-bis[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-hydroxyphenyl)methyl]-17-methyl-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]acetic acid	1700388: Inhibition of avi-tagged-biotinylated human PCSK9 interaction with His-tagged human LDLR EGFa domain by LANCE Ulight Streptavidin based TR-FRET assay	ki	0.5250	uM
N-[3-[[(3S)-3-aminopiperidin-1-yl]methyl]-5-(4-methylimidazol-1-yl)phenyl]-4-methyl-3-phenoxybenzamide	1666983: Inhibition of recombinant human His-tagged PCSK9 interaction with recombinant LDLR AB domain (unknown origin) measured after 3 hrs by horseradish peroxidase-coupled TMB substrate based spectrophotometry	ic50	0.5370	uM
N-[3-(1,3-benzodioxol-5-ylmethylamino)-4-methylphenyl]-3-cyclohexylpropanamide	102351: Concentration at which one-half of the maximum Low density lipoprotein receptor is upregulated in HepG2 cells	ec50	0.6000	uM
2-[(5R,8S,14S,17S,20S,23S,26S,32S)-32-(4-aminobutyl)-5-carbamoyl-23-[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-hydroxyphenyl)methyl]-17-(1H-imidazol-5-ylmethyl)-26-methyl-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]acetic acid	1700388: Inhibition of avi-tagged-biotinylated human PCSK9 interaction with His-tagged human LDLR EGFa domain by LANCE Ulight Streptavidin based TR-FRET assay	ki	0.6560	uM
N-[3-[(Z)-2-(1,3-benzodioxol-5-yl)-2-cyanoethenyl]-4-methylphenyl]-3-cyclohexylpropanamide	102351: Concentration at which one-half of the maximum Low density lipoprotein receptor is upregulated in HepG2 cells	ec50	0.7000	uM
3-cyclohexyl-N-[3-(6-hydroxy-1H-benzimidazol-2-yl)-4-methylphenyl]propanamide	102351: Concentration at which one-half of the maximum Low density lipoprotein receptor is upregulated in HepG2 cells	ec50	0.7000	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-amino-4-methylpentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-methylpentanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]butanedioic acid	1933148: Inhibition of PCSK9-LDLR (unknown origin) protein-protein interaction	ic50	0.7000	uM
4-methyl-N-[3-(4-methylimidazol-1-yl)-5-[(4-methylpiperazin-1-yl)methyl]phenyl]-3-[(4-phenylpyrimidin-2-yl)amino]benzamide	1666983: Inhibition of recombinant human His-tagged PCSK9 interaction with recombinant LDLR AB domain (unknown origin) measured after 3 hrs by horseradish peroxidase-coupled TMB substrate based spectrophotometry	ic50	0.7140	uM
4-methyl-N-[3-(4-methylimidazol-1-yl)-5-(4-methylpiperazin-1-yl)phenyl]-3-[(4-phenylpyrimidin-2-yl)amino]benzamide	1666983: Inhibition of recombinant human His-tagged PCSK9 interaction with recombinant LDLR AB domain (unknown origin) measured after 3 hrs by horseradish peroxidase-coupled TMB substrate based spectrophotometry	ic50	0.7580	uM
4-methyl-N-[3-(4-methylimidazol-1-yl)-5-(4-methylpiperazin-1-yl)phenyl]-3-phenoxybenzamide	1666983: Inhibition of recombinant human His-tagged PCSK9 interaction with recombinant LDLR AB domain (unknown origin) measured after 3 hrs by horseradish peroxidase-coupled TMB substrate based spectrophotometry	ic50	0.7590	uM
(4S)-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-acetamido-3-hydroxybutanoyl]amino]-3-methylbutanoyl]amino]-3-phenylpropanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-4-carboxybutanoyl]amino]-5-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	1933148: Inhibition of PCSK9-LDLR (unknown origin) protein-protein interaction	ic50	0.8000	uM
2-[(5R,8S,14S,17S,20S,23S,26S,32S,35R)-35-[[(2S)-2-[[(2S)-2-acetamido-3-(1H-imidazol-5-yl)propanoyl]-methylamino]-3-(4-fluorophenyl)propanoyl]amino]-32-(4-aminobutyl)-5-carbamoyl-23,26-bis[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-hydroxyphenyl)methyl]-17-(1H-imidazol-5-ylmethyl)-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]acetic acid	1700388: Inhibition of avi-tagged-biotinylated human PCSK9 interaction with His-tagged human LDLR EGFa domain by LANCE Ulight Streptavidin based TR-FRET assay	ki	0.9560	uM
2-[(5R,8S,15S,18S,21S,24S,27S,33S)-33-(4-aminobutyl)-5-carbamoyl-24,27-bis[(5-fluoro-1H-indol-3-yl)methyl]-15-[(4-hydroxyphenyl)methyl]-18-(1H-imidazol-5-ylmethyl)-7,14,17,20,23,26,29,32,35-nonaoxo-3,38-dithia-6,13,16,19,22,25,28,31,34-nonazatricyclo[38.3.1.08,13]tetratetraconta-1(43),40(44),41-trien-21-yl]acetic acid	1700388: Inhibition of avi-tagged-biotinylated human PCSK9 interaction with His-tagged human LDLR EGFa domain by LANCE Ulight Streptavidin based TR-FRET assay	ki	0.9690	uM
N-[3-[(Z)-2-cyano-2-pyridin-3-ylethenyl]-4-methylphenyl]-3-cyclohexylpropanamide	102351: Concentration at which one-half of the maximum Low density lipoprotein receptor is upregulated in HepG2 cells	ec50	1.0000	uM
2-[(5R,8S,14S,17S,20S,23S,26S,32S,35R)-35-acetamido-32-(4-aminobutyl)-5-carbamoyl-26-[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-hydroxyphenyl)methyl]-17-(1H-imidazol-5-ylmethyl)-23-(1H-indol-3-ylmethyl)-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]acetic acid	1700388: Inhibition of avi-tagged-biotinylated human PCSK9 interaction with His-tagged human LDLR EGFa domain by LANCE Ulight Streptavidin based TR-FRET assay	ki	1.0700	uM
5-[5-[1-(cyclohexylmethyl)-5-naphthalen-2-ylimidazol-2-yl]-2-ethynylimidazol-1-yl]-N-methylpentan-1-amine	1990773: Inhibition of His-tagged PCSK9 to recombinant LDLR (unknown origin) protein-protein interaction incubated for 2 hrs by fluorescence plate reader analysis	ic50	1.1800	uM
N-[5-(3-cyclohexylpropanoylamino)-2-methylphenyl]pyridine-3-carboxamide	102351: Concentration at which one-half of the maximum Low density lipoprotein receptor is upregulated in HepG2 cells	ec50	1.2000	uM
N-[3-(1H-benzimidazol-2-yl)-4-methylphenyl]-3-cyclohexylpropanamide	102351: Concentration at which one-half of the maximum Low density lipoprotein receptor is upregulated in HepG2 cells	ec50	1.3000	uM

CTD chemical–gene interactions

227 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Simvastatin	affects expression, affects response to substance, increases reaction, affects cotreatment, increases expression (+3 more)	15
Cyclosporine	decreases reaction, increases degradation, increases expression, affects cotreatment, affects binding	7
fatostatin	decreases expression, increases reaction, increases response to substance	6
bisphenol A	affects expression, decreases expression, increases expression	5
Valproic Acid	affects expression, affects methylation, decreases expression	5
sodium arsenite	decreases expression, increases expression	4
25-hydroxycholesterol	increases activity, decreases activity, increases reaction, increases response to substance, decreases reaction (+4 more)	3
perfluorooctane sulfonic acid	decreases expression	3
Atorvastatin	increases activity, increases expression	3
Troglitazone	affects binding, decreases expression, increases activity, increases expression	3
Fluvastatin	affects binding, increases reaction, increases activity, affects cotreatment, affects response to substance	3
Acetaminophen	affects binding, increases reaction, increases degradation, increases expression, affects cotreatment (+1 more)	3
Cisplatin	increases expression, decreases expression, decreases reaction, affects cotreatment	3
Curcumin	decreases expression, decreases reaction, increases activity, increases expression	3
Lovastatin	increases activity, increases expression, increases reaction	3
triphenyl phosphate	affects expression, increases expression	2
cobaltous chloride	decreases expression, increases expression	2
perfluorooctanoic acid	decreases expression, increases expression	2
potassium chromate(VI)	affects cotreatment, decreases expression	2
Air Pollutants	affects cotreatment, decreases expression, increases abundance, increases expression, decreases reaction	2
Ethanol	increases abundance, decreases reaction, decreases expression, affects cotreatment	2
Aspirin	decreases reaction, increases abundance, increases reaction, affects binding, increases degradation	2
Benzo(a)pyrene	decreases expression	2
Cholesterol	decreases activity, increases response to substance, increases chemical synthesis, increases reaction, increases uptake (+1 more)	2
Dexamethasone	decreases reaction, affects reaction, decreases expression, increases expression	2
Estradiol	increases expression	2
Hydrogen Peroxide	increases expression, affects cotreatment	2
Lipopolysaccharides	affects expression, affects response to substance, increases expression, decreases reaction	2
Nickel	increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2

ChEMBL screening assays

55 unique, capped per target: 54 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2091225	Binding	Displacement of S-tagged Ac-DSGL[CMPRLRGC]cDPR-NH2 from human DsRed2-fused LDLR expressed in CHO cells at 10 uM after 1 hr by FRET assay	Chemical optimization of new ligands of the low-density lipoprotein receptor as potential vectors for central nervous system targeting. — J Med Chem
CHEMBL706292	Functional	Capability of derepressing the transcription of Low density lipoprotein receptor promoter in the presence of 25-hydroxycholesterol in CHO cells measured as maximum activity at 20 ug/mL	Synthesis and biological evaluation of a new series of sterols as potential hypocholesterolemic agents. — J Med Chem

Cellosaurus cell lines

48 cell lines: 23 finite cell line, 15 induced pluripotent stem cell, 6 cancer cell line, 4 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_1V08	GM02000	Finite cell line	Female
CVCL_4N05	GM00700	Finite cell line	Female
CVCL_4N06	GM00701	Finite cell line	Female
CVCL_4N13	GM01448	Transformed cell line	Female
CVCL_4N16	GM01460	Transformed cell line	Female
CVCL_4N19	GM01915	Finite cell line	Female
CVCL_4N35	GM03040	Finite cell line	Male
CVCL_4N38	GM03064	Finite cell line	Male
CVCL_4N39	GM03065	Finite cell line	Female
CVCL_7288	GM00483	Finite cell line	Female

Clinical trials (associated diseases)

182 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT06231459	PHASE4	COMPLETED	Expression of Pro- and Anti-inflammatory Cytokines During Anti-PCSK9 in Familial Hypercholesterolemia
NCT00655265	PHASE4	COMPLETED	A Study of the Safety and Efficacy of Patients With Familial Hypercholesterolaemia Taking Colesevelam as add-on Therapy to Their Existing Medication
NCT00916643	PHASE4	COMPLETED	Low-Density Lipoprotein (LDL) Apheresis Using H.E.L.P. Therapy
NCT03331666	PHASE4	TERMINATED	Impact of LDL-cholesterol Lowering on Platelet Activation
NCT05465278	PHASE4	COMPLETED	Alirocumab and Plaque Burden In Familial Hypercholesterolaemia
NCT00000594	PHASE3	COMPLETED	NHLBI Type II Coronary Intervention Study
NCT00092833	PHASE3	TERMINATED	Investigational Drug in Patients With Hypercholesterolemia or in Patients With Sitosterolemia (0653-026)(COMPLETED)
NCT00134485	PHASE3	COMPLETED	Study To Evaluate The Safety And Efficacy Of Torcetrapib/Atorvastatin In Subjects With Familial Hypercholerolemia
NCT00134511	PHASE3	COMPLETED	Study To Evaluate The Effect Of Torcetrapib/Atorvastatin In Patients With Genetic High Cholesterol Disorder
NCT00136981	PHASE3	COMPLETED	Carotid B-Mode Ultrasound Study to Compare Anti-Atherosclerotic Effect of Torcetrpib/Atorvastatin to Atorvastatin Alone.
NCT00384293	PHASE3	TERMINATED	Carotid IMT (Intima Media Thickening) Study (0524A-041)(TERMINATED)
NCT01524289	PHASE3	COMPLETED	Study to Assess the Tolerability and Efficacy of Anacetrapib (MK-0859) Co-Administered With Statin in Participants With Heterozygous Familial Hypercholesterolemia (MK-0859-020)
NCT00730236	PHASE3	COMPLETED	A Safety and Efficacy Study of AEGR-733 to Treat Homozygous Familial Hypercholesterolemia (FH)
NCT01841684	PHASE3	TERMINATED	Efficacy and Tolerability of Anacetrapib Added to Ongoing Lipid-Lowering Therapy in Adult Participants With Homozygous Familial Hypercholesterolemia (HoFH) (MK-0859-042)
NCT02226198	PHASE3	COMPLETED	A Study to Evaluate the Efficacy and Safety of Rosuvastatin in Children and Adolescents With Homozygous Familial Hypercholesterolemia
NCT02434497	PHASE3	COMPLETED	A Study to Evaluate the Safety of Rosuvastatin in Children and Adolescents With Homozygous Familial Hypercholesterolemia
NCT02765841	PHASE3	WITHDRAWN	Evaluate the Efficacy and Safety of Lomitapide in Pediatric Patients With Homozygous Familial Hypercholesterolemia on Stable Lipid-lowering Therapy
NCT03156621	PHASE3	COMPLETED	Study in Participants With Homozygous Familial Hypercholesterolemia (HoFH)
NCT03399786	PHASE3	COMPLETED	Efficacy and Safety of Evinacumab in Patients With Homozygous Familial Hypercholesterolemia
NCT03409744	PHASE3	COMPLETED	Evaluate the Long-Term Safety and Efficacy of Evinacumab in Patients With Homozygous Familial Hypercholesterolemia
NCT03814187	PHASE3	COMPLETED	Trial to Assess the Effect of Long Term Dosing of Inclisiran in Subjects With High CV Risk and Elevated LDL-C
NCT03851705	PHASE3	COMPLETED	A Study of Inclisiran in Participants With Homozygous Familial Hypercholesterolemia (HoFH)
NCT04034485	PHASE3	COMPLETED	Phase 3 Study to Evaluate the Efficacy and Safety of LIB003 With Evolocumab in HoFH
NCT04233918	PHASE3	COMPLETED	Evaluate the Efficacy and Safety of Evinacumab in Pediatric Patients With Homozygous Familial Hypercholesterolemia
NCT05611528	PHASE3	COMPLETED	Safety and Effectiveness of Evinacumab for the Treatment of Homozygous Familial Hypercholesterolemia
NCT05682378	PHASE3	RECRUITING	Long-term Safety and Tolerability of Inclisiran in Participants With HeFH or HoFH Who Have Completed the Pediatric ORION-16, ORION-13, ORION-20, or ORION-19 Studies
NCT06712771	PHASE3	ACTIVE_NOT_RECRUITING	A Phase 3 Clinical Trial to Evaluate the Efficacy and Safety of VSA003 in Chinese HoFH Patients
NCT06723652	PHASE3	COMPLETED	A Multicenter, Randomized, Double-blind, Placebo-controlled Phase III Clinical Study Evaluating the Efficacy and Safety of SHR-1918 in Patients With Homozygous Familial Hypercholesterolemia
NCT07037771	PHASE3	RECRUITING	A Phase 3 Study of Zodasiran in Adolescent and Adult Subjects With Homozygous Familial Hypercholesterolemia (YOSEMITE)
NCT07473843	PHASE3	NOT_YET_RECRUITING	Study of Zodasiran in Adolescent Participants With Homozygous Familial Hypercholesterolemia
NCT00355615	PHASE3	COMPLETED	PLUTO: Pediatric Lipid-redUction Trial of rOsuvastatin
NCT00552097	PHASE3	COMPLETED	Effect of Ezetimibe Plus Simvastatin Versus Simvastatin Alone on Atherosclerosis in the Carotid Artery (ENHANCE)(P02578)
NCT00607373	PHASE3	COMPLETED	Study to Assess the Safety and Efficacy of ISIS 301012 (Mipomersen) in Homozygous Familial Hypercholesterolemia
NCT00694109	PHASE3	COMPLETED	An Open-label Extension Study to Assess the Long-term Safety and Efficacy of ISIS 301012 (Mipomersen) in Patients With Familial Hypercholesterolemia or Severe-Hypercholesterolemia
NCT00827606	PHASE3	COMPLETED	Atorvastatin Three Year Pediatric Study
NCT00943306	PHASE3	COMPLETED	Long Term, Follow-on Study of Lomitapide in Patients With Homozygous Familial Hypercholesterolemia
NCT01813006	PHASE3	COMPLETED	Effect of Omega-3 Fatty Acid on Endothelial Function
NCT02624869	PHASE3	COMPLETED	Safety, Tolerability and Efficacy of Evolocumab (AMG 145) in Children With Inherited Elevated Low-density Lipoprotein Cholesterol (Familial Hypercholesterolemia)
NCT02748057	PHASE3	COMPLETED	A Clinical Trial to Assess the Long Term Safety and Tolerability of MK-0653H in Japanese Participants With Hypercholesterolemia (MK-0653H-833)
NCT03884452	PHASE3	COMPLETED	Ezetimibe (SCH 58235) Taken With Either Atorvastatin or Simvastatin in Participants With Familial Hypercholesterolemia (MK-0653-018)