PCSK1 across dismech

PCSK1 (proprotein convertase subtilisin/kexin type 1) is named by 1 disorder entry.

How the entry records the gene

The single entry naming PCSK1 types it as causative (Obesity Due to MC4R Pathway Disruption) with germline variants (germline). Nothing is left untyped (0), and ClinGen's gene-disease validity table classifies PCSK1 for 0 diseases, so the typing rests on the entry's own cited evidence.

Where the gene sits in the pathograph

PCSK1 appears on one node, MC4R pathway signaling failure, which it shares with LEP, LEPR, POMC, MC4R, SH2B1, NCOA1 and SIM1 — the entry models the whole leptin-melanocortin chain as one mechanism node rather than one node per gene. The process carried by that node is adenylate cyclase-activating G protein-coupled receptor signaling pathway, the receptor-level output; the convertase's own contribution is recorded on the same node as a decreased serine-type endopeptidase activity, since the enzyme acts two steps upstream by cleaving the POMC precursor that yields the MC4R agonist.

No node naming PCSK1 declares conformance to a mechanism module (0), and no treatment record names the gene (0).

Worth noting for future curation: the human PCSK1-deficiency phenotype is broader than this one entry, because PC1/3 matures many precursors besides POMC — neonatal malabsorptive diarrhoea, hypogonadotropic hypogonadism, hypoadrenalism and a raised proinsulin-to-insulin ratio all belong to the same disorder and are not covered by an obesity entry.

Normal function

The ai-gene-review ingest layer currently reports 0 core function terms for PCSK1, because the ingest tables are pinned to an ai-gene-review commit that predates the review of this gene. The upstream review was written in the same round of work as this page and gives serine-type endopeptidase activity in the secretory granule, peptide hormone processing and hormone biosynthesis, the POMC-to-ACTH cleavage upstream of alpha-MSH, and proinsulin conversion as the gene's core functions; those terms will appear here once the ingest pin is advanced. Until then the function layer and the KB layer share 0 GO terms, which reflects the pin rather than a disagreement.