ANGPTL4 E40K - GET-Evidence

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

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Curation:
Currentness:

ANGPTL4 E40K

(ANGPTL4 Glu40Lys)


Short summary

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

Variant evidence
Computational

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

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

Impact

Insufficiently evaluated pathogenic

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

Inheritance pattern

dominant

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)

Publications
 

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.

Genomes
 

 

 

Other external references
 

    dbSNP
  • rs116843064
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    PolyPhen-2
  • 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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