ClinGen Dosage Sensitivity Curation Page

PCSK9

  • Curation Status: Complete

Location Information

Select assembly: (NC_000001.10) (NC_000001.11)
  • Haploinsufficiency score: Haploinsufficiency unlikely
  • Strength of Evidence (disclaimer): Haploinsufficiency unlikely
Evidence for haploinsufficiency phenotype
PubMed ID Description
19191301 Nonsense mutations in PCSK9 appear to be polymorphic and confer susceptibility to low LDL cholesterol (hypocholesterolemia) whereas dominant missense mutations predispose to high LDL cholesterol.
15654334 African Americans carry two loss of function changes in PCSK9 with a combined frequency of 2%. These variants resulted in a 40% reduction in plasma levels of LDL cholesterol.

Haploinsufficiency phenotype comments:

Nonsense mutations in PCSK9 appear to be polymorphic and confer susceptibility to low LDL cholesterol (hypocholesterolemia) whereas dominant missense mutations predispose to high LDL cholesterol. There are also multiple reports of deletion CNVs at or near (and could be extending into depending on array resolution) PCSK9 in DGV. There are many PCSK9 frameshift and stop gain changes listed in ExAc (one at high frequency = 33 alleles = p.Tyr142Ter, rs67608943).

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

Triplosensitivity phenotype comment:

There is no evidence at present for triplosensitivity of PCSK9.