HomeAboutRankingsData Sources
© 2026 GeneE
🧬
GeneE
10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
ⓘGeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
PCSK1N
proprotein convertase subtilisin/kexin type 1 inhibitor
Chromosome X · Xp11.23
NCBI Gene: 27344Ensembl: ENSG00000102109.10HGNC: HGNC:17301UniProt: Q9UHG2
30PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
GO:0005615endopeptidase inhibitor activitysignaling receptor bindingtrans-Golgi networktype 2 diabetes mellituspancreatic intraductal papillary-mucinous neoplasmneoplasmBarrett's esophagus
✦AI Summary

PCSK1N encodes proSAAS, an endogenous inhibitor of proprotein convertase 1/3 (PC1/3) that plays critical roles in prohormone processing and metabolic regulation. As an endogenous ligand for GPR83, PCSK1N is involved in feeding regulation 1. The gene directly inhibits PC1/3 activity by interfering with its C-terminal cleavage, thereby modulating proinsulin processing 2. PCSK1N expression is transcriptionally regulated by Pax6, which binds the Pcsk1n promoter to suppress its expression; Pax6 mutations lead to elevated PCSK1N, compromising PC1/3 function and glucose metabolism 2. In type 2 diabetes, PCSK1N knockout in human β-like cells associates with altered insulin production 1. PCSK1N also serves as a biomarker in neuroendocrine tumors: it is elevated in silent corticotroph adenomas and correlates with tumor size, functioning as part of the adaptive endoplasmic reticulum stress response 3. In MYCN-amplified neuroblastoma, PCSK1N overexpression associates with poor prognosis and correlates with MYCN expression 4. Additionally, cerebrospinal fluid PCSK1N levels are altered in dementia with Lewy bodies, contributing to a diagnostic biomarker panel 5. In the hypothalamus, Pcsk1n expression decreases during recurrent hypoglycemia-induced impairment of counterregulatory responses 6.

Sources cited
1
PCSK1N is associated with insulin production in β-cell functional studies
PMID: 37214922
2
PCSK1N (proSAAS) inhibits PC1/3 activity and C-terminal cleavage, and is directly downregulated by Pax6 transcription factor
PMID: 23056534
3
PCSK1N is elevated in silent corticotroph adenomas, correlates with tumor size, and is part of ER stress adaptive response
PMID: 39288010
4
PCSK1N overexpression associates with poor prognosis and MYCN amplification in neuroblastoma
PMID: 40600620
5
PCSK1N is a candidate cerebrospinal fluid biomarker for dementia with Lewy bodies
PMID: 32552841
6
Pcsk1n expression decreases in hypothalamic neurons during recurrent hypoglycemia-induced impairment
PMID: 38017352
Disease Associationsⓘ20
type 2 diabetes mellitusOpen Targets
0.28Weak
pancreatic intraductal papillary-mucinous neoplasmOpen Targets
0.06Suggestive
neoplasmOpen Targets
0.05Suggestive
Barrett's esophagusOpen Targets
0.05Suggestive
Alzheimer diseaseOpen Targets
0.05Suggestive
Pick diseaseOpen Targets
0.04Suggestive
synucleinopathyOpen Targets
0.04Suggestive
N-acetylaspartate deficiencyOpen Targets
0.04Suggestive
intellectual disability, autosomal recessive 58Open Targets
0.04Suggestive
autism spectrum disorderOpen Targets
0.03Suggestive
behavioral variant of frontotemporal dementiaOpen Targets
0.03Suggestive
spinocerebellar ataxia type 27Open Targets
0.03Suggestive
autismOpen Targets
0.03Suggestive
AnxietyOpen Targets
0.03Suggestive
Parkinson diseaseOpen Targets
0.03Suggestive
15q11q13 microduplication syndromeOpen Targets
0.03Suggestive
intellectual disability, autosomal dominant 50Open Targets
0.03Suggestive
clear cell renal carcinomaOpen Targets
0.03Suggestive
papillary thyroid carcinomaOpen Targets
0.03Suggestive
Nijmegen breakage syndromeOpen Targets
0.03Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
CPEProtein interaction90%GPR171Protein interaction86%PCSK1Protein interaction85%SCG2Protein interaction72%POMCProtein interaction72%CHGBProtein interaction72%
Tissue Expression6 tissues
Brain
100%
Ovary
2%
Lung
1%
Liver
1%
Heart
0%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
PCSK1NCPEGPR171PCSK1SCG2POMCCHGB
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q9UHG2
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.37LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.76 [0.44–1.37]
RankingsWhere PCSK1N stands among ~20K protein-coding genes
  • #11,997of 20,598
    Most Researched30
  • #14,253of 17,882
    Most Constrained (LOEUF)1.37
Genes detectedPCSK1N
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
PCSK1N as a Tumor Size Marker and an ER Stress Response Protein in Corticotroph Pituitary Adenomas.
PMID: 39288010
J Clin Endocrinol Metab · 2025
1.00
2
Functional interrogation of twenty type 2 diabetes-associated genes using isogenic human embryonic stem cell-derived β-like cells.
PMID: 37858332
Cell Metab · 2023
0.90
3
Pax6 directly down-regulates Pcsk1n expression thereby regulating PC1/3 dependent proinsulin processing.
PMID: 23056534
PLoS One · 2012
0.80
4
Transcriptional subtypes on immune microenvironment and predicting postoperative recurrence and metastasis in human pheochromocytoma and paraganglioma.
PMID: 41400463
Elife · 2025
0.70
5
Identification of Crucial Genes Associated With MYCN-Driven Neuroblastoma Based on Single-Cell Analysis and Machine Learning.
PMID: 40600620
Cancer Med · 2025
0.60