APOL1

Chr 22AD

apolipoprotein L1

Also known as: APO-L, APOL, APOL-I, FSGS4

NCBI Gene: 8542ENSG00000100342UniProt: O14791

This gene encodes a secreted high density lipoprotein which binds to apolipoprotein A-I. Apolipoprotein A-I is a relatively abundant plasma protein and is the major apoprotein of HDL. It is involved in the formation of most cholesteryl esters in plasma and also promotes efflux of cholesterol from cells. This apolipoprotein L family member may play a role in lipid exchange and transport throughout the body, as well as in reverse cholesterol transport from peripheral cells to the liver. Several different transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2008]

Primary Disease Associations & Inheritance

{Glomerulosclerosis, focal segmental, 4, susceptibility to}MIM #612551
AD
UniProtFocal segmental glomerulosclerosis 4
233
ClinVar variants
15
Pathogenic / LP
0.00
pLI score
8
Active trials
Clinical Summary— APOL1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
15 Pathogenic / Likely Pathogenic· 103 VUS of 233 total submissions
💊
Clinical Trials
8 active or recruiting trials — potential therapeutic options may be available
Some data sources returned errors (1)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.73LOEUF
pLI 0.000
Z-score -0.02
OE 1.01 (0.59–1.73)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.58Z-score
OE missense 1.11 (1.00–1.23)
259 obs / 233.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.1.01 (0.59–1.73)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.11 (1.00–1.23)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.13
0≤1.21.6
LoF obs/exp: 8 / 7.9Missense obs/exp: 259 / 233.9Syn Z: -0.95

ClinVar Variant Classifications

233 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic14
Likely Pathogenic1
VUS103
Likely Benign55
Benign39
Conflicting7
14
Pathogenic
1
Likely Pathogenic
103
VUS
55
Likely Benign
39
Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
14
0
14
Likely Pathogenic
0
0
1
0
1
VUS
3
85
15
0
103
Likely Benign
0
9
12
34
55
Benign
1
9
26
3
39
Conflicting
—7
Total41036837219

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

APOL1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
APOLIPOPROTEIN L1; APOL1
MIM #603743 · *

{Glomerulosclerosis, focal segmental, 4, susceptibility to}

MIM #612551

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Podocytopathies.
Kopp JB et al.·Nat Rev Dis Primers
2020Review
APOL1 Nephropathy: From Genetics to Clinical Applications.
Friedman DJ et al.·Clin J Am Soc Nephrol
2021Review
Focal Segmental Glomerulosclerosis.
Rosenberg AZ et al.·Clin J Am Soc Nephrol
2017Review
The Pathogenesis of African Trypanosomiasis.
Pays E et al.·Annu Rev Pathol
2023Review
Genome-Wide Association Study of CKD Progression.
Robinson-Cohen C et al.·J Am Soc Nephrol
2023Meta-analysis
Collapsing Glomerulopathy.
Koirala A et al.·Adv Kidney Dis Health
2024Review
Evolutionary history of sickle-cell mutation: implications for global genetic medicine.
Esoh K et al.·Hum Mol Genet
2021Review
The nephropathy of sickle cell trait and sickle cell disease.
Ataga KI et al.·Nat Rev Nephrol
2022Review
APOL1 Bi- and Monoallelic Variants and Chronic Kidney Disease in West Africans.
Gbadegesin RA et al.·N Engl J Med
2025
Genetic Inhibition of APOL1 Pore-Forming Function Prevents APOL1-Mediated Kidney Disease.
Hung AM et al.·J Am Soc Nephrol
2023Meta-analysis
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
APOL1-Mediated Kidney Disease

Dose-Ranging Safety, Tolerability, and Efficacy Study of AZD2373 in Participants With APOL1-Mediated Kidney Disease

RECRUITING
NCT06824987Phase PHASE2AstraZenecaStarted 2025-03-05
AZD2373-Arm 1AZD2373-Arm 2Placebo
AsthmaAtherosclerosisMetabolic Syndrome

Study of the Effect of Innate on the Inflammatory Response to Endotoxin

RECRUITING
NCT01143480National Institute of Environmental Health Sciences (NIEHS)Started 2012-07-30
End Stage Kidney Disease

Duke APOL1 Research Biorepository

RECRUITING
NCT04160507Duke UniversityStarted 2019-12-13
Biorepository
HIV NephropathyKidney InjuryKidney Diseases

Genetic Determinants of Kidney Disease in People of African Ancestry With HIV

ACTIVE NOT RECRUITING
NCT05685810King's College Hospital NHS TrustStarted 2018-05-01
Kidney DiseasesKidney FailureKidney Disease, Chronic

APOL1 Long-term Kidney Transplantation Outcomes Network (APOLLO)

RECRUITING
NCT03615235Wake Forest University Health SciencesStarted 2019-03-21
Nephrotic SyndromeFocal Segmental GlomerulosclerosisAPOL1 Associated Kidney Disease

Predictive Determinants of Nephrotic Syndrome Remission in Patients With At-risk Polymorphism of APOL1

NOT YET RECRUITING
NCT06443034Assistance Publique - Hôpitaux de ParisStarted 2024-06-30
Genetic PredispositionChronic Kidney DiseasesNephropathy

APOL1 Genetic Testing in African Americans

RECRUITING
NCT05656261St. Louis UniversityStarted 2019-01-24
Assessment of the frequency of APOL-1 renal risk variant in the black population, and evaluating their attitudes about genetic testing and APOL1 genotype via self-administered surveys
Diabetic Kidney Disease

Role of Finerenone in African American Veterans With Diabetic Kidney Disease

NOT YET RECRUITING
NCT07155694Phase PHASE4Washington D.C. Veterans Affairs Medical CenterStarted 2025-09
Finerenone 10 MGEmpagliflozin 10 MG

External Resources

Links to major genomics databases and tools