Mutasi pada gen ''proprotein convertase subtilisin/kexin type 9'' (''PCSK9'') dikaitkan dengan [[Gen dominan|autosomal dominan]] (yaitu hanya membutuhkan satu salinan abnormal) FH dalam laporan tahun 2003.<ref name="Rader20036">{{Cite journal|year=2003|title=Monogenic hypercholesterolemia: new insights in pathogenesis and treatment|journal=J. Clin. Invest.|volume=111|issue=12|pages=1795–803|doi=10.1172/JCI18925|pmc=161432|pmid=12813012|vauthors=Rader DJ, Cohen J, Hobbs HH}}</ref><ref>{{Cite journal|last=Abifadel M|last2=Varret M|last3=Rabès JP|last4=Allard|first4=Delphine|last5=Ouguerram|first5=Khadija|last6=Devillers|first6=Martine|last7=Cruaud|first7=Corinne|last8=Benjannet|first8=Suzanne|last9=Wickham|first9=Louise|displayauthors=3|year=2003|title=Mutations in PCSK9 cause autosomal dominant hypercholesterolemia|url=https://www.researchgate.net/publication/10774079_Mutations_in_PCSK9_cause_autosomal_dominant_hypercholesterolemia|journal=Nat. Genet.|volume=34|issue=2|pages=154–6|doi=10.1038/ng1161|pmid=12730697}}</ref> Gen tersebut terletak pada kromosom pertama (1p34.1-p32) dan menyandi protein dengan 666 asam amino yang diekspresikan di hati. Telah dikemukakan bahwa PCSK9 menyebabkan FH terutama dengan mengurangi jumlah reseptor LDL pada sel-sel hati.<ref>{{Cite journal|last=Choi|first=Seungbum|last2=Korstanje|first2=Ron|date=2013-12|title=Proprotein convertases in high-density lipoprotein metabolism|url=https://biomarkerres.biomedcentral.com/articles/10.1186/2050-7771-1-27|journal=Biomarker Research|language=en|volume=1|issue=1|pages=27|doi=10.1186/2050-7771-1-27|issn=2050-7771|pmc=PMC4177610|pmid=24252756}}</ref>
