APOL1 Gene: Apolipoprotein L1 - Function, Variants, and Disease Association
A comprehensive guide to the APOL1 gene, its protein product, associated diseases, and clinical significance.
Gene Information Card
| Symbol | APOL1 |
|---|---|
| Full Name | Apolipoprotein L1 |
| Gene Type | Protein coding |
| Chromosomal Location | 22q12.3 |
| NCBI Gene ID | 8542 ncbi.nlm.nih.gov/gene/8542 |
| Ensembl ID | ENSG00000134242 |
| UniProt ID | O14791 |
| OMIM ID | 603743 |
| HGNC ID | 618 |
| Aliases | APOL-I, APOL1, FSGS4, apolipoprotein L-I |
Description
The APOL1 gene encodes apolipoprotein L1, a soluble protein that circulates in plasma and is associated with high-density lipoproteins (HDL). It plays a critical role in innate immunity against Trypanosoma brucei, the parasite causing African sleeping sickness. APOL1 also functions in lipid metabolism and autophagy. Two common coding variants (G1 and G2) in the APOL1 gene are strongly associated with an increased risk of focal segmental glomerulosclerosis (FSGS), HIV-associated nephropathy (HIVAN), and other non-diabetic kidney diseases in individuals of African ancestry. These variants confer resistance to trypanosome infection but increase susceptibility to kidney disease.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Focal segmental glomerulosclerosis (FSGS) | APOL1 G1/G2 variants cause gain-of-function toxicity in podocytes, leading to mitochondrial dysfunction and cell death. | Strong association in multiple GWAS and case-control studies; OR 10-30 for high-risk genotypes. |
| HIV-associated nephropathy (HIVAN) | APOL1 risk variants, in the presence of HIV infection, dramatically increase risk of collapsing glomerulopathy. | Case-control studies show high-risk genotype increases HIVAN risk by ~50-fold. |
| Hypertension-attributed end-stage kidney disease (ESKD) | APOL1 risk variants contribute to progressive kidney failure in hypertensive individuals of African descent. | Epidemiological studies show higher ESKD prevalence in carriers. |
| Sickle cell nephropathy | APOL1 risk variants may exacerbate kidney damage in sickle cell disease. | Association studies suggest increased risk of proteinuria and ESKD. |
| Trypanosomiasis resistance | APOL1 G1/G2 variants provide resistance to Trypanosoma brucei rhodesiense infection by enhancing trypanolytic activity. | Functional studies demonstrate trypanolytic activity; evolutionary selection evidence. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | High | High |
| Kidney | Low | Low |
| Pancreas | Low | Low |
| Lung | Low | Low |
| Placenta | Low | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | High | Liver cancer cell line |
| HK-2 | Low | Kidney proximal tubular cell line |
| Podocytes | Low | Primary podocytes |
| A549 | Low | Lung carcinoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| G1 (rs73885319, rs60910145) | Missense (S342G, I384M) | ~30-40% in African populations | Gain-of-function, increased trypanolysis, increased kidney disease risk |
| G2 (rs71785313) | In-frame deletion (N388del, Y389del) | ~10-15% in African populations | Gain-of-function, increased trypanolysis, increased kidney disease risk |
| Wild-type (G0) | Reference | ~50% in African populations | Normal trypanolysis, lower kidney disease risk |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations are rare and not well characterized; complete loss of APOL1 may impair innate immunity but is not typically associated with kidney disease.
Gain of Function (GOF)
The G1 and G2 variants are gain-of-function mutations that confer enhanced trypanolytic activity but also cause podocyte toxicity, leading to kidney disease.
Dominant Negative (DN)
No dominant-negative effects have been described for APOL1 variants.
View complete mutation data：
Gene Ontology (GO)
Pathways
• HDL metabolism
• Autophagy
• Innate immune response
• Lipid transport
Protein Summary
Apolipoprotein L1 (APOL1) is a 398-amino acid protein with a molecular weight of ~44 kDa. It contains a signal peptide, a membrane-interacting domain, and a C-terminal domain that is critical for trypanosome lysis. APOL1 is secreted by the liver and circulates in plasma bound to HDL particles. In the kidney, APOL1 is expressed in podocytes and proximal tubular cells, where risk variants induce mitochondrial dysfunction, endoplasmic reticulum stress, and apoptosis. The protein's trypanolytic activity is mediated by its ability to form pores in the mitochondrial membrane of trypanosomes. APOL1 also participates in autophagy and lipid metabolism.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| APOL1 Knockout HEK293 Cell Line | EDJ-KQ6283 | Human | 8542 | Details Get a Quote |
| APOL1 Knockout A-549 Cell Line | EDJ-KQ30182 | Human | 8542 | Details Get a Quote |
| APOL1 Knockout HeLa Cell Line | EDJ-KQ54937 | Human | 8542 | Details Get a Quote |
| APOL1 Knockout HCT 116 Cell Line | EDJ-KQ71887 | Human | 8542 | Details Get a Quote |
