Previous symbols: HCHOLA3. Aliases: NARC-1, FH3.
PCSK9 (proprotein convertase subtilisin/kexin type 9) is named by 9 disorder entries.
PCSK9 is a secreted hepatocyte protein that binds the LDL receptor and diverts it to lysosomal degradation. The ai-gene-review record for PCSK9 is being completed upstream, and the pinned ingest snapshot does not yet carry its core functions, so this page makes no claim about them.
Two entries type PCSK9 as causative: Autosomal Dominant Hypercholesterolemia 3; and Hypobetalipoproteinemia. They sit on opposite sides of the gene's dosage: Autosomal Dominant Hypercholesterolemia 3 records a germline gain of function lesion, and ClinGen rates PCSK9 definitive for that disease. In that entry the gene sits on the trigger node Pathogenic PCSK9 Sequence Variant or Duplication and on PCSK9 Binding to the LDL Receptor EGF-A Domain.
PCSK9 is a modifier in Familial Defective Apolipoprotein B-100 and a susceptibility gene in Abdominal Aortic Aneurysm. Four entries carry it with no relationship type: Coronary Artery Disease; Familial Hypercholesterolemia; Hyperlipidemia; and Peripheral Artery Disease. One entry names PCSK9 without a genetic record for it: LDLR-Related Familial Hypercholesterolemia, where it appears as the target of receptor-directed therapy rather than as a cause.
PCSK9 is also a drug target. The KB records the treatments Inclisiran; and Inclisiran (PCSK9-Directed siRNA), and nodes naming the gene conform to the module rnai_gene_silencing.
ClinGen classifies PCSK9 for 1 disease, and no dismech entry matched to it leaves the gene untyped (0). Because the ingest snapshot carries no ai-gene-review core functions for PCSK9, the two layers currently share 0 GO terms by identifier.
Underlined values are claims re-computed from the knowledge base each time this page is built. The tables below are the source of truth.
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 |
|---|---|---|
| Abdominal Aortic Aneurysm | susceptibility |
mechanism: PCSK9 and atherogenic-lipoprotein susceptibility axis
|
| Autosomal Dominant Hypercholesterolemia 3 |
causative
germline
gain of function
CLINGEN: definitive
|
mechanism: PCSK9 Binding to the LDL Receptor EGF-A Domain; Pathogenic PCSK9 Sequence Variant or Duplication
animal model: AAV-hPCSK9(D374Y) mouse; D374Y-PCSK9 transgenic Yucatan minipig
treatment: Inclisiran
|
| Familial Defective Apolipoprotein B-100 | modifier germline | |
| Hypobetalipoproteinemia | causative germline loss of function |
mechanism: PCSK9 Loss-of-Function Variant
subtype: PCSK9 Loss of Function
|
| Coronary Artery Disease |
untyped
Risk Factor
|
|
| Familial Hypercholesterolemia |
untyped
Gain-of-Function Mutations
|
mechanism: PCSK9 Gain-of-Function
treatment: Inclisiran
|
| Hyperlipidemia |
untyped
Monogenic Cause in Familial Hypercholesterolemia and Modifier of LDL-C Burden
|
mechanism: Impaired Hepatic ApoB-Containing Lipoprotein Clearance; PCSK9-Mediated LDL Receptor Degradation
|
| Peripheral Artery Disease |
untyped
Risk Factor
|
|
| LDLR-Related Familial Hypercholesterolemia | no genetic record |
treatment: Inclisiran (PCSK9-Directed siRNA)
|
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 |
|---|---|---|---|
| hypercholesterolemia, autosomal dominant, 3 MONDO:0011369 | AD | Definitive 2018-11-14 |
Identity from HGNC (snapshot 2026-10-01). Page layers are described in the gene pages documentation.