PCSK6
Chr 15proprotein convertase subtilisin/kexin type 6
Also known as: PACE4, SPC4
The encoded protease cleaves proproteins at paired basic amino acids and is constitutively secreted into the extracellular matrix, processing substrates including transforming growth factor beta-related proteins, proalbumin, and von Willebrand factor. Mutations cause autosomal recessive primary congenital glaucoma with developmental abnormalities including cardiac defects and growth retardation. This gene is highly constrained against loss-of-function variants (pLI ~1), indicating that complete loss of function is likely deleterious.
No known disease relationship
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
The highest-scoring mechanism for this gene is dominant-negative.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
139 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 72 | 0 | 72 |
Likely Pathogenic | 0 | 0 | 5 | 0 | 5 |
VUS | 0 | 1 | 12 | 0 | 13 |
Likely Benign | 0 | 3 | 13 | 7 | 23 |
Benign | 1 | 2 | 5 | 1 | 9 |
| Total | 1 | 6 | 107 | 8 | 122 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
PCSK6 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools