ANGPTL3

angiopoietin like 3

1 disorder 1 causative 1p31.3 gene with protein product

HGNC:491 Monarch NCBI Gene 27329 ENSG00000132855 UniProt Q9Y5C1 OMIM 604774

Previous symbols: ANGPT5.

Curated summary · agent-written · kb/genes/curated/hgnc_491.md

All 12 claims checked against the KB draft

ANGPTL3 across dismech

ANGPTL3 (angiopoietin like 3) is named by 1 disorder entry: Hypobetalipoproteinemia.

Normal function

ai-gene-review gives ANGPTL3's core molecular function as lipase inhibitor activity, in the extracellular region, acting in cholesterol homeostasis; phospholipid homeostasis; and triglyceride homeostasis.

Familial combined hypolipidemia

Hypobetalipoproteinemia types ANGPTL3 as causative with a germline variant origin and a functional impact of loss of function. ClinGen rates the gene definitive for familial hypobetalipoproteinemia 2, which the entry carries as its ANGPTL3 subtype. The gene sits on the node ANGPTL3 Loss-of-Function Variant, which records lipase inhibitor activity as decreased. Downstream nodes record increased lipoprotein lipase activity and increased triglyceride catabolism.

Underlined values are claims re-computed from the knowledge base each time this page is built. The tables below are the source of truth.

Normal function · from ai-gene-review (Q9Y5C1, commit 79fe13b38970) · AI-generated, not KB evidence

ANGPTL3 is a secreted glycoprotein produced predominantly by the liver that regulates circulating lipoproteins. Its N-terminal region inhibits lipoprotein lipase and endothelial lipase, helping maintain plasma triglyceride, cholesterol and phospholipid levels. Association with ANGPTL8 supports potent inhibition of intravascular lipoprotein lipase, while endothelial lipase inhibition can occur independently of ANGPTL8. Its C-terminal fibrinogen-like domain binds integrin alpha-v/beta-3 and supports endothelial adhesion, migration and angiogenic responses in experimental systems. Proteolytic processing generates fragments with distinct activities but is not obligatory for every inhibitory mechanism. Biallelic loss-of-function variants cause familial combined hypolipidemia.

Inhibits extracellular lipases through the N-terminal region: ANGPTL3 cooperates with ANGPTL8 to suppress lipoprotein lipase and also inhibits endothelial lipase. These activities regulate plasma triglyceride turnover and HDL phospholipid/cholesterol homeostasis. Activity depends on oligomer composition and the local lipase-stabilizing environment. Human-protein biophysics supports ATP-independent unfolding of LPL; the later EL mutagenesis predominantly tests mouse ANGPTL3 and is distinguished from human plasma oligomer measurements.

molecular function: lipase inhibitor activity · directly involved in: triglyceride homeostasis; cholesterol homeostasis; phospholipid homeostasis · locations: extracellular region

In the knowledge base · computed from kb/ at build time

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.

Disorder	Relationship	Where the gene appears
Hypobetalipoproteinemia	causative germline loss of function CLINGEN: definitive (ANGPTL3 Deficiency)	mechanism: ANGPTL3 Loss-of-Function Variant subtype: ANGPTL3 Deficiency

ClinGen gene–disease validity · snapshot 2026-10-03 · matched to entries by MONDO

An entry matches when ClinGen's MONDO disease is the entry's own disease term, a subtype term, or an exact-match mapping. An amber status marks an entry ClinGen supports the gene for (Definitive, Strong or Moderate) whose own record does not type it. A Limited, Disputed or Refuted tier on such an entry is not a gap.

ClinGen disease	MOI	Classification	dismech entry
familial hypobetalipoproteinemia 2 MONDO:0011505	AR	Definitive 2022-11-21	Hypobetalipoproteinemia causative

Identity from HGNC (snapshot 2026-10-01). Page layers are described in the gene pages documentation.