LPA

Summary

LPA (lipoprotein(a), HGNC:6667) is a protein-coding gene on chromosome 6q25.3-q26, encoding Apolipoprotein(a) (P08519). Apo(a) is the main constituent of lipoprotein(a) (Lp(a)).

The protein encoded by this gene is a serine proteinase that inhibits the activity of tissue-type plasminogen activator I. The encoded protein constitutes a substantial portion of lipoprotein(a) and is proteolytically cleaved, resulting in fragments that attach to atherosclerotic lesions and promote thrombogenesis. Elevated plasma levels of this protein are linked to atherosclerosis. Depending on the individual, the encoded protein contains 2-43 copies of kringle-type domains. The allele represented here contains 15 copies of the kringle-type repeats and corresponds to that found in the reference genome sequence.

Source: NCBI Gene 4018 — RefSeq curated summary.

At a glance

• GWAS associations: 209
• Clinical variants (ClinVar): 315 total — 1 pathogenic, 1 likely-pathogenic
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 1 cancer types
• MANE Select transcript: NM_005577

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6667
Approved symbol	LPA
Name	lipoprotein(a)
Location	6q25.3-q26
Locus type	gene with protein product
Status	Approved
Aliases	Lp(a)
Ensembl gene	ENSG00000198670
Ensembl biotype	protein_coding
OMIM	152200
Entrez	4018

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000316300, ENST00000870146, ENST00000870147

RefSeq mRNA: 1 — MANE Select: NM_005577 NM_005577

CCDS: CCDS43523

Canonical transcript exons

ENST00000316300 — 39 exons

Exon	Start	End
ENSE00001148607	160532531	160532649
ENSE00001359822	160531482	160531890
ENSE00001402184	160590944	160591101
ENSE00002430355	160646214	160646395
ENSE00002432905	160537855	160537961
ENSE00002444938	160611562	160611721
ENSE00002447320	160595354	160595535
ENSE00002452215	160556025	160556184
ENSE00002456517	160650338	160650497
ENSE00002457013	160664166	160664275
ENSE00002460169	160628207	160628366
ENSE00002468174	160633753	160633912
ENSE00002469872	160622663	160622822
ENSE00002472858	160557390	160557571
ENSE00002475891	160578523	160578704
ENSE00002477787	160624030	160624211
ENSE00002477874	160547789	160547937
ENSE00002479378	160600917	160601098
ENSE00002479407	160593958	160594117
ENSE00002481720	160545440	160545533
ENSE00002485091	160586449	160586630
ENSE00002487272	160585046	160585205
ENSE00002489570	160617117	160617276
ENSE00002493515	160639300	160639459
ENSE00002495884	160612932	160613113
ENSE00002497648	160589553	160589712
ENSE00002499491	160605046	160605205
ENSE00002503232	160548478	160548659
ENSE00002517864	160599500	160599659
ENSE00002518025	160606477	160606658
ENSE00002518398	160635123	160635304
ENSE00002520717	160618484	160618665
ENSE00002524793	160577136	160577295
ENSE00002525359	160629574	160629755
ENSE00002527643	160640667	160640848
ENSE00002536648	160644847	160645006
ENSE00003627443	160541107	160541181
ENSE00003673632	160542688	160542808
ENSE00003691587	160540043	160540183

Expression profiles

Bgee: expression breadth broad, 100 present calls, max score 90.86.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0120 / max 10.8245, expressed in 3 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
76554	0.0120	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
liver	UBERON:0002107	90.86	gold quality
right lobe of liver	UBERON:0001114	87.39	gold quality
adrenal tissue	UBERON:0018303	87.07	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.45	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	73.89	gold quality
palpebral conjunctiva	UBERON:0001812	60.62	gold quality
lower lobe of lung	UBERON:0008949	54.02	silver quality
prefrontal cortex	UBERON:0000451	53.67	gold quality
Brodmann (1909) area 10	UBERON:0013541	50.76	gold quality
frontal pole	UBERON:0002795	50.41	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality
paraflocculus	UBERON:0005351	50.18	gold quality
thymus	UBERON:0002370	49.95	gold quality
quadriceps femoris	UBERON:0001377	49.91	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	49.73	gold quality
body of pancreas	UBERON:0001150	49.72	gold quality
vastus lateralis	UBERON:0001379	49.45	gold quality
colonic epithelium	UBERON:0000397	49.38	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
cerebellar vermis	UBERON:0004720	49.25	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
hair follicle	UBERON:0002073	49.18	gold quality
adult mammalian kidney	UBERON:0000082	49.01	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
urinary bladder	UBERON:0001255	48.89	gold quality
choroid plexus epithelium	UBERON:0003911	48.89	gold quality
myocardium	UBERON:0002349	48.87	gold quality
frontal cortex	UBERON:0001870	48.86	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.89

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HNF1A, HNF4A, NR1H4

miRNA regulators (miRDB)

28 targeting LPA, 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-4789-5P	99.98	70.76	2721
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-373-3P	99.84	70.68	1668
HSA-MIR-520E-3P	99.84	70.55	1698
HSA-MIR-372-3P	99.83	70.58	1691
HSA-MIR-520A-3P	99.83	70.59	1687
HSA-MIR-520B-3P	99.83	70.56	1699
HSA-MIR-520C-3P	99.83	70.56	1699
HSA-MIR-520D-3P	99.83	70.78	1676
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-519A-3P	99.67	71.67	1868
HSA-MIR-519B-3P	99.67	71.67	1868
HSA-MIR-519C-3P	99.67	71.67	1870
HSA-MIR-425-5P	99.59	67.67	900
HSA-MIR-6733-3P	99.54	67.80	1281
HSA-MIR-21-5P	99.46	70.54	1035
HSA-MIR-590-5P	99.25	70.76	930
HSA-MIR-6876-3P	98.97	65.69	765
HSA-MIR-4801	98.96	69.42	2096
HSA-MIR-626	98.89	66.21	762
HSA-MIR-5707	96.34	66.10	89

Literature-anchored findings (GeneRIF, showing 40)

• children’s group with BMI > 30 and with family history of CVD presented higher levels in comparison to the less obese group with family history of CVD (PMID:11822583)
• data suggest that Lp(a) and peroxidative stress may be involved as cofactors in essential hypertension, with a mechanism that remains to be elucidated (PMID:11833851)
• Lipoprotein (a) promotes large vessel atheromatosis rather than small vessel arteriolosclerosis and favors thrombosis on atheromatous plaques by suppressing local fibrinolysis. (PMID:11865151)
• Type of diabetes and waist-hip ratio are important determinants of levels in diabetic patients [LIPOPROTEIN (A)] (PMID:11947970)
• Plasma lipoprotein (a) levels are significantly elevated in patients with coronary artery disease as compared to controls. The contribution of lipoprotein (a) phenotype to the lipoprotein (a) levels in our population, if any, is modest. (PMID:11999088)
• Positive correlation of Lp(a) between type 2 diabetic patients and their offspring, suggesting a potential genetic control for Lp(a) levels in type 2 diabetics families. (PMID:12482643)
• Lp(a) and apo(a) polymorphisms do not appear to be reliable markers of restenosis in patients with Type 2 diabetes mellitus. (PMID:12738397)
• Blood levels are higher in coronary artery disease patients compared with normal values. (PMID:12940514)
• apo(a) mediates the Lp(a)-induced biphasic response in platelet c-AMP as the result of platelet exposure to increasing levels of Lp(a), up to a concentration of 25 mg/dl Lp(a) (PMID:15041277)
• Our findings suggest that Lp(a) is more strongly associated with aCAD+ in women than in men. (PMID:15479125)
• Changes in Lp(a) levels were found and perhaps these changes may be related to the episodic inflammation affecting patients on hemodialysis. (PMID:15515480)
• Stimulation of PMNs by apo(a) results in the formation of elastase-derived apo(a) fragments that produce a concentration-dependent decrease in the formation of plasmin (PMID:15543335)
• mechanism by which increased circulating levels of Lp[a] could contribute to atherogenesis (PMID:15654123)
• Data suggest that laminin may bind to apolipoprotein (a) in the atherosclerotic intima, thus contributing to the selective retention of lipoprotein (a) in this milieu. (PMID:15708348)
• high levels of apo(a)/Lp(a), perhaps acting via a specific cell-surface binding domain, inhibit hepatic clearance of remnants, leading to high plasma levels of remnant lipoproteins and markedly enhanced atherosclerosis (PMID:15905467)
• Lp(a) is an independent risk factor for the progression of diabetic nephropathy in type 2 diabetic patients with overt proteinuria. (PMID:15983325)
• lipoprotein(a) has a role in homocysteine-enhanced antifibrinolysis in human plasma (PMID:16113787)
• Lp (a) levels may have a pathogenetic role in the development of gangrenous foot lesions in patients with diabetes mellitus. (PMID:16122830)
• binding sites responsible for binding to fibronection (PMID:16150826)
• Lp(a) levels and Apo(a) isoforms may have roles in ischaemic stroke in the elderly (PMID:16197951)
• Suggest connection between peroxisomal enzyme activity & presence of human LPA gene in murine genome. Effect may be result of changes in oxidative processes in lipid metabolism rather than from direct effect of LPA gene on peroximal gene expression. (PMID:16202171)
• data demonstrate that Lp(a), via its apo(a) moiety, is a ligand for the beta2-integrin Mac-1, thereby facilitating inflammatory cell recruitment to atherosclerotic plaques; these observations suggest a novel mechanism for atherogenic properties of Lp(a) (PMID:16403785)
• elevated Lp(a) levels alone do not contribute to increased cardiovascular risk by promoting early atherogenesis in vivo (PMID:16497311)
• The finding of high levels of LP(a) and MDA with low levels of nitric oxide in the peripheral and cavernous venous blood of diabetic men with erectile dysfunction (ED)correlates strongly with severity of ED as measured by PPDU (PMID:16625232)
• Multiple low-prevalence alleles in LPA can account for the large between-population difference in serum Lp(a) levels between European Americans and African Americans. (PMID:16840570)
• Cultured human hepatoma cells secrete an oxidase activity that dramatically enhances the rate of covalent Lp(a) assembly. (PMID:16893192)
• In a relatively small population of elderly subjects, the association of high lipoprotein(a) and fibrinogen levels appears to carry an increased risk of pooled coronary heart disease and stroke mortality. (PMID:17145597)
• Lp(a) lipoprotein levels do not have a clear role in development of coronary artery disease in older men (PMID:17460176)
• Major 5-polymorphic compound genotypes are not associated with restricted range of Lp(a) levels. (PMID:17462619)
• This meta-analysis suggests that elevated Lp(a) is a risk factor for incident stroke. (PMID:17478739)
• Data show that galectin-1, an endogenous lectin produced by arterial cells, binds lipoprotein(a) [Lp(a)] in situ. (PMID:17537433)
• The LPA I4399M Single Nucleotide Polymorphism is associated with severe Coronary Artery Disease and plasma lipoprotein(a) levels (PMID:17569884)
• lower Lipoprotein A (LPA) concentrations were observed in subjects carrying the T allele of the Liproprotein A 93C>T polymorphism and consuming a high intake of fish (PMID:17603063)
• Lipoprotein a polymorphism may confer a potential risk for cardiovascular disease. (PMID:17683612)
• Aspirin lowers the increased Lp(a) levels in patients with ischemic stroke. (PMID:17845920)
• Lp(a) concentration was significantly lower and negatively correlated with triglycerides among Omani diabetic compared to non-diabetic subjects. (PMID:17908332)
• The relationship between LPA and thyroid function status in the general population was studied. (PMID:17923276)
• study shows that the 93T allele of the LPA gene is associated with a reduced risk of peripheral arterial disease and low Lp(a) levels (PMID:17942087)
• observed a stepwise increase in risk of MI with increasing levels of lipoprotein(a), with no evidence of a threshold effect (PMID:18086931)
• human apolipoprotein(a) carboxyl-terminal kringle IV-10-kringle V fusion protein is an effective inhibitor of angiogenesis and angiogenesis-dependent tumor growth. (PMID:18163888)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
mus_musculus	5430401F13Rik	ENSMUSG00000094113
mus_musculus	Gm6619	ENSMUSG00000095577
rattus_norvegicus	Lpal2	ENSRNOG00000024508
drosophila_melanogaster	CG33458	FBGN0053458
drosophila_melanogaster	CG33459	FBGN0053459

Paralogs (1): PRSS56 (ENSG00000237412)

Protein

Protein identifiers

Apolipoprotein(a) — P08519 (reviewed: P08519)

All UniProt accessions (1): P08519

UniProt curated annotations — full annotation on UniProt →

Function. Apo(a) is the main constituent of lipoprotein(a) (Lp(a)). It has serine proteinase activity and is able of autoproteolysis. Inhibits tissue-type plasminogen activator 1. Lp(a) may be a ligand for megalin/Gp 330.

Subunit / interactions. Disulfide-linked to apo-B100. Binds to fibronectin and decorin.

Post-translational modifications. N- and O-glycosylated. The N-glycans are complex biantennary structures present in either a mono- or disialylated state. The O-glycans are mostly (80%) represented by the monosialylated core type I structure, NeuNAcalpha2-3Galbeta1-3GalNAc, with smaller amounts of disialylated and non-sialylated O-glycans also detected.

Polymorphism. LPA genetic variants, including variations in the number of Kringle domains, define the lipoprotein(a) quantitative trait locus (LPAQTL) and influence lipoprotein(a) levels in plasma [MIM:618807]. Depending on the individual, the encoded protein contains 2-43 copies of kringle IV-2 repeats. Often the assignement of amino acids in lipoprotein(a) is based on a long allele that contains 37 copies of the kringle-type repeats. The reference allele represented here contains 15 copies of the kringle-type repeats.

Miscellaneous. Apo(a) is known to be proteolytically cleaved, leading to the formation of the so-called mini-Lp(a). Apo(a) fragments accumulate in atherosclerotic lesions, where they may promote thrombogenesis. O-glycosylation may limit the extent of proteolytic fragmentation. Homology with plasminogen kringles IV and V is thought to underlie the atherogenicity of the protein, because the fragments are competing with plasminogen for fibrin(ogen) binding.

Similarity. Belongs to the peptidase S1 family. Plasminogen subfamily.

RefSeq proteins (1): NP_005568* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000001	Kringle	Domain
IPR001254	Trypsin_dom	Domain
IPR001314	Peptidase_S1A	Family
IPR009003	Peptidase_S1_PA	Homologous_superfamily
IPR013806	Kringle-like	Homologous_superfamily
IPR018056	Kringle_CS	Conserved_site
IPR018114	TRYPSIN_HIS	Active_site
IPR033116	TRYPSIN_SER	Active_site
IPR038178	Kringle_sf	Homologous_superfamily
IPR043504
IPR050759	Serine_protease_kringle	Family

Pfam: PF00051, PF00089

UniProt features (143 total): disulfide bond 52, strand 27, domain 17, glycosylation site 17, sequence variant 11, turn 9, region of interest 3, active site 3, helix 2, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

16 structures.

PDB	Method	Resolution (Å)
8TCE	X-RAY DIFFRACTION	1.07
8V9B	X-RAY DIFFRACTION	1.19
1I71	X-RAY DIFFRACTION	1.45
4BVC	X-RAY DIFFRACTION	1.6
6RX7	X-RAY DIFFRACTION	1.63
4BVD	X-RAY DIFFRACTION	1.68
4BV7	X-RAY DIFFRACTION	1.7
3KIV	X-RAY DIFFRACTION	1.8
4BVV	X-RAY DIFFRACTION	1.8
4BVW	X-RAY DIFFRACTION	2
8V8Z	X-RAY DIFFRACTION	2.01
1KIV	X-RAY DIFFRACTION	2.1
4BV5	X-RAY DIFFRACTION	2.1
4KIV	X-RAY DIFFRACTION	2.2
1JFN	SOLUTION NMR
2FEB	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P08519-F1	61.12	0.12

Functional residue map

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

Catalytic / active sites (3): 1861 (charge relay system); 1904 (charge relay system); 1990 (charge relay system)

Disulfide bonds (52): 28–105, 49–88, 77–100, 142–219, 163–202, 191–214, 256–333, 277–316, 305–328, 370–447, 391–430, 419–442, 484–561, 505–544, 533–556, 598–675, 619–658, 647–670, 712–789, 733–772 …

Glycosylation sites (17): 61, 101, 215, 329, 443, 557, 671, 785, 899, 1013, 1127, 1241, 1347, 1381, 1461, 1575, 1689

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-8964041	LDL remodeling
R-HSA-174824	Plasma lipoprotein assembly, remodeling, and clearance
R-HSA-382551	Transport of small molecules
R-HSA-8963899	Plasma lipoprotein remodeling

MSigDB gene sets: 56 (showing top): GOBP_CIRCULATORY_SYSTEM_PROCESS, VART_KSHV_INFECTION_ANGIOGENIC_MARKERS_UP, HSIAO_LIVER_SPECIFIC_GENES, chr6q26, CAIRO_HEPATOBLASTOMA_DN, GOBP_LIPID_METABOLIC_PROCESS, GOMF_GLYCOSAMINOGLYCAN_BINDING, GOBP_LIPID_LOCALIZATION, GOMF_HEPARIN_BINDING, PID_AMB2_NEUTROPHILS_PATHWAY, CAMPS_COLON_CANCER_COPY_NUMBER_DN, GOBP_PROTEOLYSIS, GOCC_PROTEIN_LIPID_COMPLEX, GOMF_PEPTIDASE_REGULATOR_ACTIVITY, GOMF_SULFUR_COMPOUND_BINDING

GO Biological Process (4): proteolysis (GO:0006508), lipid metabolic process (GO:0006629), lipid transport (GO:0006869), blood circulation (GO:0008015)

GO Molecular Function (9): fibronectin binding (GO:0001968), serine-type endopeptidase activity (GO:0004252), endopeptidase inhibitor activity (GO:0004866), heparin binding (GO:0008201), apolipoprotein binding (GO:0034185), protein binding (GO:0005515), peptidase activity (GO:0008233), serine-type peptidase activity (GO:0008236), hydrolase activity (GO:0016787)

GO Cellular Component (2): extracellular region (GO:0005576), plasma lipoprotein particle (GO:0034358)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Plasma lipoprotein remodeling	1
Transport of small molecules	1
Plasma lipoprotein assembly, remodeling, and clearance	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	2
endopeptidase activity	2
protein metabolic process	1
primary metabolic process	1
transport	1
lipid localization	1
circulatory system process	1
serine-type peptidase activity	1
peptidase inhibitor activity	1
endopeptidase regulator activity	1
glycosaminoglycan binding	1
sulfur compound binding	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
serine hydrolase activity	1
catalytic activity	1
cellular anatomical structure	1
extracellular protein-containing complex	1
lipoprotein particle	1

Protein interactions and networks

STRING

1190 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LPA	APOB	P04114	999
LPA	APOA1	P02647	914
LPA	APOE	P02649	902
LPA	APOA2	P02652	883
LPA	APOC3	P02656	811
LPA	ABCA1	O95477	740
LPA	MTTP	P55157	727
LPA	CETP	P11597	713
LPA	LPAR2	Q9HBW0	713
LPA	PCSK9	Q8NBP7	697
LPA	FUCA2	Q9BTY2	693
LPA	TFPI	P10646	676
LPA	LPAR1	P78351	667
LPA	ABCG1	P45844	659
LPA	CRP	P02741	653

IntAct

10 interactions, top by confidence:

A	B	Type	Score
LPA	FN1	psi-mi:“MI:0407”(direct interaction)	0.590
LPA	APOH	psi-mi:“MI:0915”(physical association)	0.590
LPA	APOH	psi-mi:“MI:0407”(direct interaction)	0.590
LPA	FN1	psi-mi:“MI:0915”(physical association)	0.590
APOH	LPA	psi-mi:“MI:0915”(physical association)	0.590
	CD5L	psi-mi:“MI:0915”(physical association)	0.400
	LECT2	psi-mi:“MI:0915”(physical association)	0.400
	DCTN6	psi-mi:“MI:0914”(association)	0.350

ESM2 similar proteins: A0A0H2URK1, A0A0H3HIJ5, A0A1D8PQ86, A1C3L3, A8AWU7, O86487, P05227, P08519, P08640, P0C727, P0C728, P0CG48, P0CG50, P0CG61, P0CG64, P0CG66, P0CG69, P0CG71, P0CH28, P12027, P13821, P15941, P19837, P24856, P32768, P39712, P46804, P62976, Q02192, Q27905, Q2FJ79, Q2G0L5, Q41406, Q49537, Q49538, Q4L9P0, Q54GV8, Q59SG9, Q5HIB4, Q5SSG8

Diamond homologs: A0A182C2Z2, B8V7S0, O08762, O60235, P00747, P00760, P00762, P00765, P00766, P00767, P00774, P03951, P03952, P04070, P04813, P05981, P06867, P06871, P06872, P07146, P07338, P07477, P08217, P08426, P08519, P12545, P14272, P15944, P17538, P19799, P20231, P20918, P26262, P27435, P29786, P35033, P40313, P47796, P50342, P56677

SIGNOR signaling

0 interactions.

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 1 cancer types — PAAD.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	264
Likely benign	28
Benign	9

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
14450	NM_005577.4(LPA):c.109C>T (p.Arg37Ter)	Pathogenic
4070902	NM_005577.4(LPA):c.4390C>T (p.Arg1464Ter)	Likely pathogenic

SpliceAI

4591 predictions. Top by Δscore:

Variant	Effect	Δscore
6:160540050:G:C	donor_gain	1.0000
6:160540109:T:TA	donor_gain	1.0000
6:160541105:A:AC	donor_gain	1.0000
6:160541106:C:CC	donor_gain	1.0000
6:160541106:CTT:C	donor_gain	1.0000
6:160541108:T:TA	donor_gain	1.0000
6:160548657:CCA:C	acceptor_gain	1.0000
6:160548658:CAC:C	acceptor_gain	1.0000
6:160548660:C:CC	acceptor_gain	1.0000
6:160556027:A:AC	donor_gain	1.0000
6:160556028:T:C	donor_gain	1.0000
6:160557572:C:CC	acceptor_gain	1.0000
6:160577134:A:AC	donor_gain	1.0000
6:160577135:C:CC	donor_gain	1.0000
6:160577135:CG:C	donor_gain	1.0000
6:160577207:T:A	donor_gain	1.0000
6:160577291:TGGTG:T	acceptor_gain	1.0000
6:160577294:TG:T	acceptor_gain	1.0000
6:160577296:C:CC	acceptor_gain	1.0000
6:160577302:T:TC	acceptor_gain	1.0000
6:160578518:CTTA:C	donor_loss	1.0000
6:160578519:TTA:T	donor_loss	1.0000
6:160578520:TA:T	donor_loss	1.0000
6:160578522:C:CG	donor_loss	1.0000
6:160578700:GGCCA:G	acceptor_gain	1.0000
6:160578701:GCCA:G	acceptor_gain	1.0000
6:160578702:CCA:C	acceptor_gain	1.0000
6:160578702:CCAC:C	acceptor_gain	1.0000
6:160578703:CA:C	acceptor_gain	1.0000
6:160578703:CAC:C	acceptor_gain	1.0000

AlphaMissense

13217 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000010760 (6:160561291 C>A), RS1000015125 (6:160626622 C>G), RS1000039738 (6:160567525 G>A,T), RS1000048610 (6:160563385 G>A), RS1000052409 (6:160593894 T>C,G), RS1000069846 (6:160536115 A>G), RS1000122768 (6:160553812 C>T), RS1000134207 (6:160607118 C>A), RS1000213310 (6:160607352 G>A,C,T), RS1000243548 (6:160650841 C>T), RS1000265664 (6:160587914 A>G,T), RS1000275739 (6:160554293 T>C), RS1000313613 (6:160664540 T>C), RS1000313806 (6:160585328 C>A,T), RS1000359613 (6:160652843 G>A)

Disease associations

OMIM: gene MIM:152200 | disease phenotypes: MIM:612954

GenCC curated gene-disease

Mondo (3): inherited lipid metabolism disorder (MONDO:0002525), myofibrillar myopathy 6 (MONDO:0013061), thrombocytopenia (MONDO:0002049)

Orphanet (2): Disorder of lipid metabolism (Orphanet:309005), BAG3-related myofibrillar myopathy (Orphanet:199340)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

209 associations (top):

Study	Trait	p-value
GCST000189_20	Protein quantitative trait loci	4.000000e-10
GCST000312_1	Lp (a) levels	4.000000e-11
GCST000341_1	Coronary heart disease	4.000000e-15
GCST000341_2	Coronary heart disease	1.000000e-09
GCST000755_18	HDL cholesterol	3.000000e-08
GCST000759_20	LDL cholesterol	2.000000e-17
GCST000760_35	Cholesterol, total	1.000000e-16
GCST000998_13	Coronary heart disease	3.000000e-11
GCST001048_1	Monocyte early outgrowth colony forming units	6.000000e-07
GCST001218_2	Lp (a) levels	5.000000e-39
GCST001408_2	Response to statins (LDL cholesterol change)	5.000000e-15
GCST001425_1	Response to statin therapy	1.000000e-09
GCST001726_2	Lipoprotein-associated phospholipase A2 activity change in response to statin therapy	2.000000e-16
GCST001865_1	Aortic-valve calcification	3.000000e-11
GCST002221_65	Cholesterol, total	3.000000e-23
GCST002222_35	LDL cholesterol	3.000000e-21
GCST002287_13	Coronary artery disease or ischemic stroke	2.000000e-12
GCST002289_23	Coronary artery disease	1.000000e-06
GCST002290_2	Coronary artery disease or large artery stroke	9.000000e-14
GCST002601_2	Plasma plasminogen levels	2.000000e-15
GCST002601_4	Plasma plasminogen levels	3.000000e-08
GCST002675_3	Response to statins (LDL cholesterol change)	7.000000e-44
GCST002896_12	Cholesterol, total	9.000000e-14
GCST002897_6	Triglycerides	9.000000e-09
GCST002898_16	LDL cholesterol	4.000000e-14
GCST002898_19	LDL cholesterol	5.000000e-06
GCST002899_12	HDL cholesterol	4.000000e-08
GCST003116_13	Coronary artery disease	5.000000e-39
GCST003117_4	Myocardial infarction	9.000000e-27
GCST003127_1	Lipoprotein (a) levels	3.000000e-45

EFO canonical traits (34, from GWAS)

EFO ID	Trait name
EFO:0004614	apolipoprotein A 1 measurement
EFO:0006925	lipoprotein A measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004574	total cholesterol measurement
EFO:0004506	monocyte early outgrowth colony forming unit
EFO:0007804	LDL cholesterol change measurement
EFO:0004746	lipoprotein-associated phospholipase A(2) measurement
EFO:0006309	plasma plasminogen measurement
EFO:0004530	triglyceride measurement
EFO:0007796	parental longevity
EFO:0000266	aortic stenosis
EFO:0004340	body mass index
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0009324	APOL1 risk genotype carrier status
EFO:0009925	Antithrombotic agent use measurement
EFO:0009926	Vasodilators used in cardiac diseases use measurement
EFO:0009929	Beta blocking 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:0003912	ankle brachial index
EFO:0005105	lipid or lipoprotein measurement
EFO:0000195	metabolic syndrome
EFO:0004615	apolipoprotein B measurement
EFO:0004285	albuminuria
EFO:0009762	healthspan
EFO:0004458	C-reactive protein measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D013921	Thrombocytopenia	C15.378.140.855; C15.378.243.937
C567843	Myopathy, Myofibrillar, Bag3-Related (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

3 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs10455872	Efficacy	3	rosuvastatin
rs10455872	Efficacy	3	HMG-CoA reductase inhibitors	Coronary Artery Disease
rs10455872	Toxicity	3	HMG-CoA reductase inhibitors	Coronary Artery Disease

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs3798220	LPA		0.00	0
rs10455872	LPA	3	7.00	3	rosuvastatin;HMG-CoA reductase inhibitors
rs41267807	LPA		0.00	0

Binding affinities (BindingDB)

68 measured of 68 human assays (68 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(2S)-3-[3-[2-[bis[2-[3-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]phenyl]ethyl]amino]ethoxy]phenyl]-2-[(3R)-pyrrolidin-3-yl]propanoic acid	IC50	0.54 nM	US-20250179055: Substituted 2-(pyrrolidine-3-yl)acetic acid derivative, preparation method and use thereof
(2S)-3-[3-[2-[2-[3-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]phenoxy]ethyl-[[3-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]phenyl]methyl]amino]-2-oxoethyl]phenyl]-2-[(3R)-pyrrolidin-3-yl]propanoic acid	IC50	0.58 nM	US-20250179055: Substituted 2-(pyrrolidine-3-yl)acetic acid derivative, preparation method and use thereof
US20250179055, Compound 94	IC50	0.65 nM	US-20250179055: Substituted 2-(pyrrolidine-3-yl)acetic acid derivative, preparation method and use thereof
(2S)-3-[3-[[[3-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]phenoxy]carbonyl-[2-[3-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]phenoxy]ethyl]amino]methyl]phenyl]-2-[(3R)-pyrrolidin-3-yl]propanoic acid	IC50	0.66 nM	US-20250179055: Substituted 2-(pyrrolidine-3-yl)acetic acid derivative, preparation method and use thereof
(2S)-3-[3-[[[2-[3-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]phenoxy]acetyl]-[[3-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]phenyl]methyl]amino]methyl]phenyl]-2-[(3R)-pyrrolidin-3-yl]propanoic acid	IC50	0.68 nM	US-20250179055: Substituted 2-(pyrrolidine-3-yl)acetic acid derivative, preparation method and use thereof
(2S)-3-[3-[[[2-[3-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]phenoxy]acetyl]-[2-[3-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]phenoxy]ethyl]amino]methyl]phenyl]-2-[(3R)-pyrrolidin-3-yl]propanoic acid	IC50	0.71 nM	US-20250179055: Substituted 2-(pyrrolidine-3-yl)acetic acid derivative, preparation method and use thereof
(2S)-3-[7-[[bis[[5-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]-1-benzofuran-7-yl]methyl]amino]methyl]-1-benzofuran-5-yl]-2-[(3R)-pyrrolidin-3-yl]propanoic acid	IC50	0.74 nM	US-20250179055: Substituted 2-(pyrrolidine-3-yl)acetic acid derivative, preparation method and use thereof
(2S)-3-[3-[[2-[3-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]phenoxy]ethyl-[3-[3-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]phenyl]propanoyl]amino]methyl]phenyl]-2-[(3R)-pyrrolidin-3-yl]propanoic acid	IC50	0.79 nM	US-20250179055: Substituted 2-(pyrrolidine-3-yl)acetic acid derivative, preparation method and use thereof
(2S)-3-[3-[[bis[[3-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]phenyl]-dideuteriomethyl]amino]methyl]phenyl]-2-[(3R)-pyrrolidin-3-yl]propanoic acid	IC50	0.81 nM	US-20250179055: Substituted 2-(pyrrolidine-3-yl)acetic acid derivative, preparation method and use thereof
(2S)-3-[3-[[bis[[3-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]phenyl]-dideuteriomethyl]amino]-dideuteriomethyl]phenyl]-2-[(3R)-pyrrolidin-3-yl]propanoic acid	IC50	0.83 nM	US-20250179055: Substituted 2-(pyrrolidine-3-yl)acetic acid derivative, preparation method and use thereof
(2S)-3-[3-[[[3-[(2S)-2-carboxy-1,1-dideuterio-2-[(3R)-pyrrolidin-3-yl]ethyl]phenyl]methyl-[[3-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]phenyl]methyl]amino]methyl]phenyl]-3,3-dideuterio-2-[(3R)-pyrrolidin-3-yl]propanoic acid	IC50	0.84 nM	US-20250179055: Substituted 2-(pyrrolidine-3-yl)acetic acid derivative, preparation method and use thereof
(2S)-3-[3-[2-[bis[2-[3-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]phenyl]ethyl]amino]-2-oxoethoxy]phenyl]-2-[(3R)-pyrrolidin-3-yl]propanoic acid	IC50	0.85 nM	US-20250179055: Substituted 2-(pyrrolidine-3-yl)acetic acid derivative, preparation method and use thereof
(2S)-3-[3-[[bis[[3-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]phenyl]methyl]amino]methyl]phenyl]-3,3-dideuterio-2-[(3R)-pyrrolidin-3-yl]propanoic acid	IC50	0.85 nM	US-20250179055: Substituted 2-(pyrrolidine-3-yl)acetic acid derivative, preparation method and use thereof
(2S)-3-[3-[[[2-[3-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]anilino]acetyl]-[2-[3-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]phenoxy]ethyl]amino]methyl]phenyl]-2-[(3R)-pyrrolidin-3-yl]propanoic acid	IC50	0.85 nM	US-20250179055: Substituted 2-(pyrrolidine-3-yl)acetic acid derivative, preparation method and use thereof
(2S)-3-[3-[[2-[3-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]anilino]ethyl-[3-[3-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]phenyl]propanoyl]amino]methyl]phenyl]-2-[(3R)-pyrrolidin-3-yl]propanoic acid	IC50	0.86 nM	US-20250179055: Substituted 2-(pyrrolidine-3-yl)acetic acid derivative, preparation method and use thereof
(2S)-3-[3-[2-[bis[2-[3-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]phenyl]ethyl]amino]ethyl]phenyl]-2-[(3R)-pyrrolidin-3-yl]propanoic acid	IC50	0.87 nM	US-20250179055: Substituted 2-(pyrrolidine-3-yl)acetic acid derivative, preparation method and use thereof
(2S)-3-[3-[[3-[[3-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]phenyl]methoxymethyl]-4-[[3-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]phenyl]methyl]piperazin-1-yl]methyl]phenyl]-2-[(3R)-pyrrolidin-3-yl]propanoic acid	IC50	0.88 nM	US-20250179055: Substituted 2-(pyrrolidine-3-yl)acetic acid derivative, preparation method and use thereof
(2S)-3-[3-[[[6-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]-1-benzothiophen-2-yl]methyl-[[3-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]phenyl]methyl]amino]methyl]phenyl]-2-[(3R)-pyrrolidin-3-yl]propanoic acid	IC50	0.89 nM	US-20250179055: Substituted 2-(pyrrolidine-3-yl)acetic acid derivative, preparation method and use thereof
US20250179055, Compound 127	IC50	0.9 nM	US-20250179055: Substituted 2-(pyrrolidine-3-yl)acetic acid derivative, preparation method and use thereof
US20250179055, Compound 146	IC50	0.93 nM	US-20250179055: Substituted 2-(pyrrolidine-3-yl)acetic acid derivative, preparation method and use thereof
(2S)-3-[6-[[bis[[2-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]-3-methylbenzimidazol-5-yl]methyl]amino]methyl]-1-methylbenzimidazol-2-yl]-2-[(3R)-pyrrolidin-3-yl]propanoic acid	IC50	0.94 nM	US-20250179055: Substituted 2-(pyrrolidine-3-yl)acetic acid derivative, preparation method and use thereof
(2S)-3-[3-[[[3-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]benzoyl]-[2-[3-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]phenyl]ethyl]amino]methyl]phenyl]-2-[(3R)-pyrrolidin-3-yl]propanoic acid	IC50	0.96 nM	US-20250179055: Substituted 2-(pyrrolidine-3-yl)acetic acid derivative, preparation method and use thereof
(2S)-3-[3-[2-[bis[2-[3-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]phenoxy]ethyl]amino]-2-oxoethyl]phenyl]-2-[(3R)-pyrrolidin-3-yl]propanoic acid	IC50	1.02 nM	US-20250179055: Substituted 2-(pyrrolidine-3-yl)acetic acid derivative, preparation method and use thereof
(2S)-3-[3-[[[2-[3-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]phenoxy]ethyl-[[3-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]phenyl]methyl]carbamoyl]amino]methyl]phenyl]-2-[(3R)-pyrrolidin-3-yl]propanoic acid	IC50	1.02 nM	US-20250179055: Substituted 2-(pyrrolidine-3-yl)acetic acid derivative, preparation method and use thereof
(2S)-3-[3-[[bis[[5-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]-1-benzofuran-3-yl]methyl]amino]methyl]-1-benzofuran-5-yl]-2-[(3R)-pyrrolidin-3-yl]propanoic acid	IC50	1.03 nM	US-20250179055: Substituted 2-(pyrrolidine-3-yl)acetic acid derivative, preparation method and use thereof
(2S)-3-[3-[[bis[[3-[(2S)-2-carboxy-1,1-dideuterio-2-[(3R)-pyrrolidin-3-yl]ethyl]phenyl]methyl]amino]methyl]phenyl]-3,3-dideuterio-2-[(3R)-pyrrolidin-3-yl]propanoic acid	IC50	1.03 nM	US-20250179055: Substituted 2-(pyrrolidine-3-yl)acetic acid derivative, preparation method and use thereof
(2S)-3-[5-[[bis[[2-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]-1-benzothiophen-5-yl]methyl]amino]methyl]-1-benzothiophen-2-yl]-2-[(3R)-pyrrolidin-3-yl]propanoic acid	IC50	1.04 nM	US-20250179055: Substituted 2-(pyrrolidine-3-yl)acetic acid derivative, preparation method and use thereof
(2S)-3-[3-[[bis[[3-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]phenyl]methyl]amino]methyl]phenyl]-2-[(3R)-pyrrolidin-3-yl]propanoic acid	IC50	1.05 nM	US-20250179055: Substituted 2-(pyrrolidine-3-yl)acetic acid derivative, preparation method and use thereof
(2S)-3-[5-[[bis[[4-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]thiophen-2-yl]methyl]amino]methyl]thiophen-3-yl]-2-[(3R)-pyrrolidin-3-yl]propanoic acid	IC50	1.08 nM	US-20250179055: Substituted 2-(pyrrolidine-3-yl)acetic acid derivative, preparation method and use thereof
(2S)-3-[3-[2-[2-[3-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]phenoxy]ethyl-[2-[3-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]phenyl]ethyl]amino]-2-oxoethyl]phenyl]-2-[(3R)-pyrrolidin-3-yl]propanoic acid	IC50	1.12 nM	US-20250179055: Substituted 2-(pyrrolidine-3-yl)acetic acid derivative, preparation method and use thereof
(2S)-3-[3-[[[5-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]-1-benzofuran-3-yl]methyl-[[3-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]phenyl]methyl]amino]methyl]phenyl]-2-[(3R)-pyrrolidin-3-yl]propanoic acid	IC50	1.13 nM	US-20250179055: Substituted 2-(pyrrolidine-3-yl)acetic acid derivative, preparation method and use thereof
(2S)-3-[3-[bis[2-[3-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]phenyl]ethyl]carbamoyl]phenyl]-2-[(3R)-pyrrolidin-3-yl]propanoic acid	IC50	1.16 nM	US-20250179055: Substituted 2-(pyrrolidine-3-yl)acetic acid derivative, preparation method and use thereof
(2S)-3-[3-[[[3-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]-5-fluorobenzoyl]-[[3-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]phenyl]methyl]amino]methyl]phenyl]-2-[(3R)-pyrrolidin-3-yl]propanoic acid	IC50	1.17 nM	US-20250179055: Substituted 2-(pyrrolidine-3-yl)acetic acid derivative, preparation method and use thereof
(2S)-3-[3-[2-[[2-[3-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]phenoxy]acetyl]-[2-[3-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]phenoxy]ethyl]amino]ethoxy]phenyl]-2-[(3R)-pyrrolidin-3-yl]propanoic acid	IC50	1.17 nM	US-20250179055: Substituted 2-(pyrrolidine-3-yl)acetic acid derivative, preparation method and use thereof
(2S)-3-[6-[[bis[[3-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]-1,2-benzoxazol-6-yl]methyl]amino]methyl]-1,2-benzoxazol-3-yl]-2-[(3R)-pyrrolidin-3-yl]propanoic acid	IC50	1.18 nM	US-20250179055: Substituted 2-(pyrrolidine-3-yl)acetic acid derivative, preparation method and use thereof
(2S)-3-[3-[[2-[3-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]phenoxy]ethyl-[[3-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]phenyl]carbamoyl]amino]methyl]phenyl]-2-[(3R)-pyrrolidin-3-yl]propanoic acid	IC50	1.19 nM	US-20250179055: Substituted 2-(pyrrolidine-3-yl)acetic acid derivative, preparation method and use thereof
(2S)-3-[3-[[[2-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]-1-benzofuran-5-yl]methyl-[[3-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]phenyl]methyl]amino]methyl]phenyl]-2-[(3R)-pyrrolidin-3-yl]propanoic acid	IC50	1.26 nM	US-20250179055: Substituted 2-(pyrrolidine-3-yl)acetic acid derivative, preparation method and use thereof
(2S)-3-[3-[2-[2-[3-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]-5-fluorophenoxy]ethyl-[[3-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]-5-fluorophenyl]methyl]amino]-2-oxoethyl]-5-fluorophenyl]-2-[(3R)-pyrrolidin-3-yl]propanoic acid	IC50	1.26 nM	US-20250179055: Substituted 2-(pyrrolidine-3-yl)acetic acid derivative, preparation method and use thereof
(2S)-3-[3-[2-[2-[3-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]phenoxy]ethyl-[[4-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]thiophen-2-yl]methyl]amino]-2-oxoethyl]phenyl]-2-[(3R)-pyrrolidin-3-yl]propanoic acid	IC50	1.26 nM	US-20250179055: Substituted 2-(pyrrolidine-3-yl)acetic acid derivative, preparation method and use thereof
(2S)-3-[5-[[bis[[3-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]-1-benzothiophen-5-yl]methyl]amino]methyl]-1-benzothiophen-3-yl]-2-[(3R)-pyrrolidin-3-yl]propanoic acid	IC50	1.34 nM	US-20250179055: Substituted 2-(pyrrolidine-3-yl)acetic acid derivative, preparation method and use thereof
(2S)-3-[3-[2-[2-[[3-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]phenyl]methoxy]ethyl-[[3-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]phenyl]methyl]amino]-2-oxoethyl]phenyl]-2-[(3R)-pyrrolidin-3-yl]propanoic acid	IC50	1.37 nM	US-20250179055: Substituted 2-(pyrrolidine-3-yl)acetic acid derivative, preparation method and use thereof
(2S)-3-[3-[[[3-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]phenyl]methyl-[2-[3-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]phenyl]-2-oxoethyl]amino]methyl]phenyl]-2-[(3R)-pyrrolidin-3-yl]propanoic acid	IC50	1.45 nM	US-20250179055: Substituted 2-(pyrrolidine-3-yl)acetic acid derivative, preparation method and use thereof
US20250179055, Compound 97	IC50	1.46 nM	US-20250179055: Substituted 2-(pyrrolidine-3-yl)acetic acid derivative, preparation method and use thereof
(2S)-3-[3-[2-[2-[3-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]phenoxy]ethyl-[3-[3-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]phenyl]propanoyl]amino]ethoxy]phenyl]-2-[(3R)-pyrrolidin-3-yl]propanoic acid	IC50	1.5 nM	US-20250179055: Substituted 2-(pyrrolidine-3-yl)acetic acid derivative, preparation method and use thereof
(2S)-3-[3-[2-[2-[3-[(2S)-2-carboxy-2-[(3S)-pyrrolidin-3-yl]ethyl]phenoxy]ethyl-[[3-[(2S)-2-carboxy-2-[(3S)-pyrrolidin-3-yl]ethyl]phenyl]methyl]amino]-2-oxoethyl]phenyl]-2-[(3S)-pyrrolidin-3-yl]propanoic acid	IC50	1.52 nM	US-20250179055: Substituted 2-(pyrrolidine-3-yl)acetic acid derivative, preparation method and use thereof
(2S)-3-[5-[[bis[[2-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]-1,3-thiazol-5-yl]methyl]amino]methyl]-1,3-thiazol-2-yl]-2-[(3R)-pyrrolidin-3-yl]propanoic acid	IC50	1.53 nM	US-20250179055: Substituted 2-(pyrrolidine-3-yl)acetic acid derivative, preparation method and use thereof
US20250179055, Compound 158	IC50	1.65 nM	US-20250179055: Substituted 2-(pyrrolidine-3-yl)acetic acid derivative, preparation method and use thereof
(2S)-3-[3-[2-[bis[2-[3-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]phenyl]ethyl]amino]-2-oxoethyl]phenyl]-2-[(3R)-pyrrolidin-3-yl]propanoic acid	IC50	1.66 nM	US-20250179055: Substituted 2-(pyrrolidine-3-yl)acetic acid derivative, preparation method and use thereof
(2S)-3-[3-[2-[3-[3-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]phenoxy]propyl-[[3-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]phenyl]methyl]amino]-2-oxoethyl]phenyl]-2-[(3R)-pyrrolidin-3-yl]propanoic acid	IC50	1.68 nM	US-20250179055: Substituted 2-(pyrrolidine-3-yl)acetic acid derivative, preparation method and use thereof
US20250179055, Compound 145	IC50	1.72 nM	US-20250179055: Substituted 2-(pyrrolidine-3-yl)acetic acid derivative, preparation method and use thereof

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Niacin	affects cotreatment, decreases expression	7
Aspirin	decreases expression, affects response to substance	3
lovastatin-niacin combination	decreases expression	2
Copper	affects cotreatment, decreases expression, increases oxidation, decreases secretion, increases secretion	2
Lovastatin	affects cotreatment, decreases expression	2
pimagedine	decreases expression, decreases reaction, increases expression	1
terbufos	increases methylation	1
CGP 52608	affects binding, increases reaction	1
obeticholic acid	decreases expression	1
abrine	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Butylated Hydroxytoluene	decreases expression, decreases reaction, increases expression	1
Carbon Disulfide	increases expression	1
Fonofos	increases methylation	1
Formaldehyde	decreases expression	1
Parathion	increases methylation	1
Superoxides	affects cotreatment, increases oxidation, decreases secretion	1
Aflatoxin B1	decreases expression	1
Hydroxyl Radical	affects cotreatment, increases oxidation, decreases secretion	1
Sodium Selenite	decreases expression	1
Copper Sulfate	decreases expression	1
Simvastatin	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00079638	PHASE4	COMPLETED	Comparative Efficacy Evaluation of Lipids When Treated With Niaspan & Statin or Other Lipid-Modifying Therapies-COMPELL
NCT00125125	PHASE4	COMPLETED	Fluvastatin in Adults With Dislipidemia With History of Muscle Problems
NCT00150384	PHASE4	COMPLETED	Clinical Utility of Caduet in Achieving Blood Pressure and Lipid Endpoints in a Specific Patient Population
NCT00171262	PHASE4	COMPLETED	Trial to Evaluate the Efficacy of Fluvastatin on Certain Markers
NCT00171327	PHASE4	COMPLETED	Efficacy and Safety of Fluvastatin or Valsartan and Their Combination in Dyslipidemic Patients With Hypertension and Endothelial Dysfunction
NCT00192621	PHASE4	COMPLETED	Seronegatives and Metabolic Abnormalities Protocol 2 (SAMA002): Study to Compare the Effect of Kaletra and Combivir® in HIV-Negative Healthy Subjects
NCT00194402	PHASE4	COMPLETED	SLIM: Combined Effects of Slo-Niacin and Atorvastatin on Lipoproteins and Inflammatory Markers in Hyperlipidemia
NCT00249938	PHASE4	COMPLETED	Evaluation of Combination Cholesterol Treatments in Patients With High Cholesterol.
NCT00264394	PHASE4	COMPLETED	Cardiovascular Risk Factor Management in HIV Infection
NCT00282659	PHASE4	COMPLETED	The Use of Magnesium to Improve Blood Pressure, Cholesterol, and Glucose Control
NCT00330980	PHASE4	COMPLETED	Effects of Statin Medications on Mental Processes, Behavior, and Serotonin Levels
NCT00332761	PHASE4	COMPLETED	Caduet in an Untreated Subject Population
NCT00345657	PHASE4	COMPLETED	Efficacy Study of Extended-Release Niacin/Lovastatin Versus Usual Care
NCT00346697	PHASE4	COMPLETED	Omega-3 Fatty Acids for High Triglycerides in HIV-infected Patients
NCT00350038	PHASE4	COMPLETED	Irbesartan, Ciprofibrate and Their Combination Onto the Endothelial Functions
NCT00385658	PHASE4	COMPLETED	Efficacy of Fluvastatin and Fenofibrate in Comparison to Simvastatin and Ezetimibe in Patients With Metabolic Syndrome
NCT00412113	PHASE4	COMPLETED	A Multi-Risk Factor Strategy vs a Guideline-Based Approach in Achieving Blood Pressure and Lipid Goals in Hypertensives at Extra Risk
NCT00441480	PHASE4	COMPLETED	Effect of Plant Sterols Esterified to Fish Oil Fatty Acids on Plasma Lipid Levels
NCT00442325	PHASE4	COMPLETED	Benefits Of Using Various Starting Doses Of Atorvastatin On Achievement Of Cholesterol Targets
NCT00442845	PHASE4	COMPLETED	Establish The Benefits Of Using Various Starting Doses Of Atorvastatin On Achievement Of Cholesterol Targets (ACTFAST)
NCT00447070	PHASE4	COMPLETED	Effect of Atazanavir on Endothelial Function in HIV-Infected Patients
NCT00506961	PHASE4	COMPLETED	Evaluate the Efficacy and Safety of Rosuvastatin Versus Simvastatin in Type 2 Diabetic Patients With Dyslipidemia
NCT00540293	PHASE4	COMPLETED	Lipitor Korean Atorvastatin Goal Achievement Across Risk Levels Study
NCT00541554	PHASE4	UNKNOWN	Reversal of Antipsychotic-Induced Hyperprolactinemia, Weight Gain, Hyperglycemia and Dyslipidemia
NCT00644670	PHASE4	COMPLETED	A Study Of The Efficacy Of Atorvastatin For Lowering Cholesterol In High-Risk Patients With High Cholesterol
NCT00644709	PHASE4	COMPLETED	A Study Of Atorvastatin For The Treatment Of High Cholesterol In Patients At High Risk Of Coronary Heart Disease (CHD)
NCT00645151	PHASE4	COMPLETED	A Study Of The Efficacy Of Atorvastatin In Lowering Cholesterol In Latin American Patients With High Cholesterol
NCT00647543	PHASE4	COMPLETED	Atorvastatin Study For The Treatment Of High Cholesterol In Patients From Thailand
NCT00651963	PHASE4	COMPLETED	Open Label Study Evaluating The Use Of Combination Therapy Of Ezetimibe And Statins In Patients With Dyslipidemia In Colombia (0653-141)(COMPLETED)
NCT00665834	PHASE4	COMPLETED	Comparison of Rosuvastatin and Atorvastatin in Patients With Acute Coronary Syndrome
NCT00678743	PHASE4	COMPLETED	An Open-label Extension to Assess the Continued Efficacy of Omacor Plus Simvastatin
NCT00700037	PHASE4	COMPLETED	Change in Plaque Characteristics With Atorvastatin
NCT00708370	PHASE4	COMPLETED	A Study to Evaluate the Efficacy of a Counselling and Advisory Care for Health (COACH) Program in Dyslipidemic Patients.
NCT00712049	PHASE4	UNKNOWN	Effects of Nicotinic Acid Plus Simvastatin Versus Simvastatin Alone on Carotid and Femoral Intima-Media Thickness in Patients With Peripheral Artery Disease (NASCIT)
NCT01010516	PHASE4	UNKNOWN	Comparison of High-Dose Rosuvastatin Versus Low Statin Dose Plus Fenofibrate Versus Low Statin Dose Plus Niacin in the Treatment of Mixed Hyperlipidemia
NCT01025492	PHASE4	TERMINATED	Study of Trilipix Effects on Lipids and Arteries
NCT01029522	PHASE4	COMPLETED	Dyslipidemia in Cardiovascular Disease
NCT01052311	PHASE4	TERMINATED	The Impact of Tredaptive on Flow-Mediated Dilation in Cardiac Patients
NCT01239004	PHASE4	COMPLETED	Colesevelam Treatment for Impaired Fasting Glucose During Niacin Therapy
NCT01256476	PHASE4	COMPLETED	Prevail-Us: A Study Of Pitavastatin 4 mg Vs. Pravastatin 40 mg In Patients With Primary Hyperlipidemia Or Mixed Dyslipidemia