ANGPTL4 E40K - GET-Evidence

Note: This variant has not been sufficiently evaluated by a GET-Evidence editor.

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(ANGPTL4 Glu40Lys)

Short summary

This dominant protective variant reduces the mean plasma triglyceride level by 15% in heterozygous carriers.

Variant evidence

PolyPhen-2 reports: Unable to locate protein entry angptl4 in the available version of UniProtKB.

Functional -
Case/Control -
Familial -
Clinical importance
Severity -
Treatability -
Penetrance -


Insufficiently evaluated pathogenic

(The "insufficiently evaluated" qualifier is assigned automatically based on the above evidence and importance scores.)

Inheritance pattern


Summary of published research, and additional commentary


Allele frequency

  • A @ chr19:8429323: 1.1% (109/10230) in EVS
  • A @ chr19:8335322: 0.8% (1/126) in GET-Evidence
  • Frequency shown in summary reports: 1.1% (109/10230)


Romeo S, Pennacchio LA, Fu Y, Boerwinkle E, Tybjaerg-Hansen A, Hobbs HH, Cohen JC. Population-based resequencing of ANGPTL4 uncovers variations that reduce triglycerides and increase HDL. Nat Genet. 2007 Apr;39(4):513-6. Epub 2007 Feb 25. PubMed PMID: 17322881; PubMed Central PMCID: PMC2762948.

The ANGPTL4-E40K variant is present in about 3% of European Americans and is associated with lower triglyceride levels and higher levels of HDL cholesterol in three independent populations.

Smart-Halajko MC, Kelley-Hedgepeth A, Montefusco MC, Cooper JA, Kopin A, McCaffrey JM, Balasubramanyam A, Pownall HJ, Nathan DM, Peter I, Talmud PJ, Huggins GS; Look AHEAD Study. ANGPTL4 variants E40K and T266M are associated with lower fasting triglyceride levels in Non-Hispanic White Americans from the Look AHEAD Clinical Trial. BMC Med Genet. 2011 Jun 29;12:89. doi: 10.1186/1471-2350-12-89. PubMed PMID: 21714923; PubMed Central PMCID: PMC3146919.

This study shows that ANGPTL4-E40K carriers have a 17% reduction of triglyceride levels in a population of patients with Type 2 diabetes.




Other external references

  • rs116843064
  • Score: 0.98 (probably damaging)

Other in silico analyses

  • NBLOSUM100 score = 0
  • GET-Evidence autoscore = 4

Edit history

Gene search

"GENE" or "GENE A123C":

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