LPA Gene - Lipoprotein(a)
Genetic determinant of lipoprotein(a) levels and cardiovascular risk
Gene Information Card
| Symbol | LPA |
|---|---|
| Full Name | Lipoprotein(a) |
| Gene Type | protein-coding |
| Chromosomal Location | 6q25.3-q26 |
| NCBI Gene ID | 4018 ncbi.nlm.nih.gov/gene/4018 |
| Ensembl ID | ENSG00000198670 |
| UniProt ID | P08519 |
| OMIM ID | 147200 |
| HGNC ID | 6667 |
| Aliases | APOA, LP, apo(a) |
Description
The LPA gene encodes apolipoprotein(a), a serine protease-like protein that covalently binds to apolipoprotein B-100 to form lipoprotein(a) [Lp(a)]. Lp(a) is a low-density lipoprotein (LDL)-like particle with an additional apo(a) component. The gene is highly polymorphic, with copy number variation in kringle IV type 2 repeats determining isoform size and plasma Lp(a) concentration. Elevated Lp(a) is an independent, causal risk factor for atherosclerotic cardiovascular disease and calcific aortic valve stenosis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Atherosclerotic cardiovascular disease | Elevated Lp(a) promotes prothrombotic and proinflammatory effects via apo(a) kringle domains and oxidized phospholipids | Multiple genome-wide association studies; Mendelian randomization evidence (PMID: 30586733) |
| Calcific aortic valve stenosis | Lp(a) deposition and oxidation in valve leaflets promote calcification | ClinVar; OMIM #147200; PMID: 30586733 |
| Familial hypercholesterolemia | LPA variants can modify LDL cholesterol levels and cardiovascular risk | ClinVar; PMID: 30586733 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 0.1 | Not detected |
| Hepatocytes | 0.1 | Not detected |
| Plasma | N/A | Secreted; measured as Lp(a) concentration |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 0.1 | Hepatocellular carcinoma cell line; minimal endogenous expression |
| Primary hepatocytes | 0.1 | Low expression; LPA is primarily expressed in liver but at very low mRNA levels |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| Kringle IV type 2 repeat expansion | Copy number variation | Variable (common) | Inversely associated with Lp(a) plasma levels; larger isoforms → lower Lp(a) |
| rs10455872 (intronic) | SNP | ~15% in Europeans | Associated with increased Lp(a) levels and CAD risk |
| rs3798220 (missense) | SNP | ~2% in Europeans | Associated with increased Lp(a) levels and CAD risk |
Mutation functional classification
Loss of Function (LOF)
Rare nonsense/frameshift variants that reduce Lp(a) levels are associated with lower cardiovascular risk.
Gain of Function (GOF)
Not clearly defined; increased Lp(a) due to copy number or regulatory variants is considered a gain-of-function risk factor.
Dominant Negative (DN)
Not reported for LPA.
View complete mutation data：
Gene Ontology (GO)
| • extracellular region (GO:0005576) | • serine-type endopeptidase activity (GO:0004252) |
| • zymogen activation (GO:0031638) | • negative regulation of fibrinolysis (GO:0051918) |
Pathways
• Lipoprotein metabolism (Reactome: R-HSA-174824)
• Plasminogen activating cascade (Reactome: R-HSA-75205)
Protein Summary
Apolipoprotein(a) is a large glycoprotein composed of multiple kringle domains (homologous to plasminogen kringle IV and V) followed by an inactive protease-like domain. It binds covalently to apolipoprotein B-100 via a disulfide bond to form Lp(a). The protein inhibits plasminogen activation, contributing to its prothrombotic effects. Isoform size varies from ~200 to >800 kDa due to kringle IV type 2 repeats.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| LPAR3 Knockout HEK293 Cell Line | EDJ-KQ260 | Human | 23566 | Details Get a Quote |
| LPAR1 Knockout HEK293 Cell Line | EDJ-KQ832 | Human | 1902 | Details Get a Quote |
| LPAR2 Knockout HEK293 Cell Line | EDJ-KQ833 | Human | 9170 | Details Get a Quote |
| LPAR4 Knockout HEK293 Cell Line | EDJ-KQ834 | Human | 2846 | Details Get a Quote |
| LPAR5 Knockout HEK293 Cell Line | EDJ-KQ1289 | Human | 57121 | Details Get a Quote |
| LPAR6 Knockout HEK293 Cell Line | EDJ-KQ1722 | Human | 10161 | Details Get a Quote |
| LPA Knockout HEK293 Cell Line | EDJ-KQ3829 | Human | 4018 | Details Get a Quote |
| LPAR5 Knockout HCT 116 Cell Line | EDJ-KQ19344 | Human | 57121 | Details Get a Quote |
| LPAR1 Knockout A-549 Cell Line | EDJ-KQ19610 | Human | 1902 | Details Get a Quote |
| LPAR1 Knockout HCT 116 Cell Line | EDJ-KQ19611 | Human | 1902 | Details Get a Quote |
| LPAR2 Knockout A-549 Cell Line | EDJ-KQ19612 | Human | 9170 | Details Get a Quote |
| LPAR2 Knockout HCT 116 Cell Line | EDJ-KQ19613 | Human | 9170 | Details Get a Quote |
| LPAR2 Knockout HeLa Cell Line | EDJ-KQ19614 | Human | 9170 | Details Get a Quote |
| LPAR3 Knockout HCT 116 Cell Line | EDJ-KQ19616 | Human | 23566 | Details Get a Quote |
| LPAR5 Knockout A-549 Cell Line | EDJ-KQ20688 | Human | 57121 | Details Get a Quote |
