LPA
protein-codinglipoprotein(a)
Gene summary
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. [provided by RefSeq, Dec 2009]
- LP
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~132.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
Clinical Genomic Database (CGD)
Manifestation: General
Intervention: General
Rationale: The clinical relevance of the condition is unclear
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to LPA variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005577.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 4 | 5 | |||
| missense | 270 | 22 | 3 | 295 | ||
| nonsense | 1 | 1 | 1 | 3 | ||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 1 | 3 | |||
| Total | 1 | 1 | 274 | 26 | 4 | 306 |
Highest pathogenic variant AF is 0.000042139498
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005568.2 | 39 | MANE Select | |
| Ensembl | ENSP00000321334.6 | 39 | MANE Select | |
| Ensembl | ENSP00000540205.1 | 39 | Standard | |
| Ensembl | ENSP00000540205.1 | 39 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Cholesterol metabolism - Homo sapiens (human)
- LDL remodeling
- Transport of small molecules
- Plasma lipoprotein assembly, remodeling, and clearance
- Plasma lipoprotein remodeling
Biological Process
- proteolysis
- lipid metabolic process
- lipid transport
- blood circulation
- negative regulation of endopeptidase activity
Molecular Function
- fibronectin binding
- serine-type endopeptidase activity
- endopeptidase inhibitor activity
- protein binding
- heparin binding
Cellular Component
- extracellular region
- plasma lipoprotein particle
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000447678
- Coding exons
- 39
- Length
- 134893
- Individuals with no LoFs
- 114094
- Homozygous LoFs
- 346
- Heterozygous LoFs
- 11308
- Defined
- 125748
- p
- 0.0475
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -3.27 | 1015 | 761 | 1.33 | 0.0000418 | 13062 |
| Missense (PolyPhen) | 481 | 333.06 | 1.4442 | 5596 | ||
| Synonymous | -6.19 | 413 | 281 | 1.47 | 0.0000167 | 4017 |
| Loss of Function | -2.71 | 118 | 90.2 | 1.31 | 0.00000562 | 1320 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.017 | 0.015 | notable |
| Latino/Admixed American | 0.11 | 0.11 | notable |
| Ashkenazi Jewish | 0.029 | 0.029 | notable |
| East Asian | 0.0042 | 0.0040 | notable |
| Finnish | 0.078 | 0.078 | notable |
| European (Non-Finnish) | 0.039 | 0.039 | notable |
| South Asian | 0.047 | 0.045 | notable |
| Other | 0.043 | 0.043 | notable |
dbNSFP Gene Annotations
Source:
- Function
- 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. {ECO:0000269|PubMed:2531657}.;
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.678
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | High | Medium | High |
| Cancer | High | Medium | High |