PCSK1N

Chr X

proprotein convertase subtilisin/kexin type 1 inhibitor

Also known as: BigLEN, PEN, PROSAAS, SAAS, SCG8, SgVIII

The encoded protein functions as a specific inhibitor of prohormone convertase 1 (PCSK1), controlling the proteolytic processing of neuroendocrine peptide precursors including proopiomelanocortin and proenkephalin in the secretory pathway. Mutations in PCSK1N cause autosomal recessive neuronal ceroid lipofuscinosis 14, a form of Batten disease characterized by progressive neurodegeneration with seizures, vision loss, and cognitive decline. The gene shows moderate tolerance to loss-of-function variation with a LOEUF score of 1.25.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 1.25
Clinical SummaryPCSK1N
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.53) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
61 unique Pathogenic / Likely Pathogenic· 55 VUS of 120 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
1.25LOEUF
pLI 0.532
Z-score 1.38
OE 0.00 (0.001.25)
Moderately constrained

Highly tolerant — LoF variants common in population

Missense Constraint
0.81Z-score
OE missense 0.70 (0.550.91)
42 obs / 59.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.001.25)
00.351.4
Missense OE0.70 (0.550.91)
00.61.4
Synonymous OE0.69
01.21.6
LoF obs/exp: 0 / 2.2Missense obs/exp: 42 / 59.7Syn Z: 1.31

ClinVar Variant Classifications

120 submitted variants in ClinVar

Classification Summary

Pathogenic59
Likely Pathogenic2
VUS55
Likely Benign1
59
Pathogenic
2
Likely Pathogenic
55
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
59
0
59
Likely Pathogenic
0
0
2
0
2
VUS
0
45
10
0
55
Likely Benign
0
1
0
0
1
Benign
0
0
0
0
0
Total046710117

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PCSK1N · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC