ANGPTL3
Chr 1ARangiopoietin like 3
The encoded protein is a hepatokine that regulates lipid and glucose metabolism by inhibiting lipoprotein lipase activity and endothelial lipase, thereby affecting plasma triglyceride clearance and HDL cholesterol levels. Biallelic mutations cause familial hypobetalipoproteinemia type 2, inherited in an autosomal recessive pattern. This gene shows very low constraint against loss-of-function variants in the general population.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
The highest-scoring mechanism for this gene is dominant-negative.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
ANGPTL3 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Physiological Effects of ANGPTL3 Variants in Humans
RECRUITINGStudy to Assess the Effects of Angiopoietin-like Protein 3 (ANGPTL3) Inhibition in Adult Participants With Diabetic Kidney Disease
RECRUITINGA Safety and Tolerability Trial Evaluating CTX310 in Participants With Refractory Dyslipidemias
RECRUITINGStudy of Zodasiran in Adolescent Participants With Homozygous Familial Hypercholesterolemia
NOT YET RECRUITINGA Phase 3 Study of Zodasiran in Adolescent and Adult Subjects With Homozygous Familial Hypercholesterolemia (YOSEMITE)
RECRUITINGA Study of Solbinsiran (LY3561774) in Participants With Severe Hypertriglyceridemia
RECRUITINGGenetic Pathways Leading to Fatty Liver and Atherogenic Dyslipidemia
ENROLLING BY INVITATIONAssessing the Impact of Intensification of Lipid Lowering Therapy With Guidelines-based Evinacumab Administration on Coronary Plaque Volumes Measured by Coronary Computed Tomography Angiography (CCTA) in Patients With Homozygous Familial Hypercholesterolemia (HoFH)
RECRUITINGStudy of ARO-ANG3 in Participants With Homozygous Familial Hypercholesterolemia (HOFH)
ACTIVE NOT RECRUITINGA Dose-exploration Study of EDP167 in HoFH
RECRUITINGPhase 1b Study of VERVE-201 in Patients With Refractory Hyperlipidemia
RECRUITINGCholesterol Disruption in Combination With the Standard of Care in Patients With Advanced Pancreatic Adenocarcinoma
ACTIVE NOT RECRUITINGExternal Resources
Links to major genomics databases and tools