APOC1
protein-codingapolipoprotein C1, the group of Apolipoproteins
Gene summary
This gene encodes a member of the apolipoprotein C1 family. This gene is expressed primarily in the liver, and it is activated when monocytes differentiate into macrophages. The encoded protein plays a central role in high density lipoprotein (HDL) and very low density lipoprotein (VLDL) metabolism. This protein has also been shown to inhibit cholesteryl ester transfer protein in plasma. A pseudogene of this gene is located 4 kb downstream in the same orientation, on the same chromosome. This gene is mapped to chromosome 19, where it resides within a apolipoprotein gene cluster. Alternative splicing and the use of alternative promoters results in multiple transcript variants. [provided by RefSeq, Sep 2016]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~5.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to APOC1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001645.5. 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 | 1 | ||||
| missense | 10 | 1 | 11 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 12 | 1 | 0 | 13 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001636.1 | 3 | MANE Select | |
| Ensembl | ENSP00000468276.2 | 3 | MANE Select | |
| RefSeq | NP_001307994.1 | 3 | Standard | |
| RefSeq | NP_001307995.1 | 3 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| apoc1 | Danio rerio | Structure: whole organism Quality: malformed abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Cholesterol metabolism - Homo sapiens (human)
- Statin Pathway, Pharmacodynamics
- Statin Pathway
- VLDL assembly
- Plasma lipoprotein assembly
Biological Process
- lipid metabolic process
- triglyceride metabolic process
- cholesterol metabolic process
- positive regulation of cholesterol esterification
- negative regulation of phosphatidylcholine catabolic process
Molecular Function
- phospholipase inhibitor activity
- fatty acid binding
- phosphatidylcholine binding
- lipase inhibitor activity
- phosphatidylcholine-sterol O-acyltransferase activator activity
Cellular Component
- extracellular region
- endoplasmic reticulum
- very-low-density lipoprotein particle
- high-density lipoprotein particle
- chylomicron
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000588750
- Coding exons
- 3
- Length
- 5103
- Individuals with no LoFs
- 125686
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 34
- Defined
- 125720
- p
- 0.000135
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.0858 | 45 | 46.6 | 0.965 | 0.00000258 | 525 |
| Missense (PolyPhen) | 14 | 17.829 | 0.78523 | 223 | ||
| Synonymous | 0.178 | 18 | 19.0 | 0.948 | 9.40e-7 | 168 |
| Loss of Function | 1.07 | 1 | 2.99 | 0.334 | 1.26e-7 | 36 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000064 | 0.000062 | rare |
| Latino/Admixed American | 0.000087 | 0.000087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00054 | 0.00054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000018 | 0.000018 | rare |
| South Asian | 0.00056 | 0.00056 | rare |
| Other | 0.00017 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Inhibitor of lipoprotein binding to the low density lipoprotein (LDL) receptor, LDL receptor-related protein, and very low density lipoprotein (VLDL) receptor. Associates with high density lipoproteins (HDL) and the triacylglycerol-rich lipoproteins in the plasma and makes up about 10% of the protein of the VLDL and 2% of that of HDL. Appears to interfere directly with fatty acid uptake and is also the major plasma inhibitor of cholesteryl ester transfer protein (CETP). Binds free fatty acids and reduces their intracellular esterification. Modulates the interaction of APOE with beta-migrating VLDL and inhibits binding of beta-VLDL to the LDL receptor-related protein. {ECO:0000269|PubMed:17339654, ECO:0000303|PubMed:25160599}.;
Recessive Scores
- pRec
- 0.471
Intolerance Scores
- LoFtool
- 0.758
- RVIS EVS
- -0.05
- RVIS percentile EVS
- 49.39
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.752
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |