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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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STN1
STN1 subunit of CST complex
Chromosome 10 · 10q24.33
NCBI Gene: 79991Ensembl: ENSG00000107960.13HGNC: HGNC:26200UniProt: Q9H668
79PubMed Papers
21Diseases
0Drugs
2Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
nucleusCST complexprotein bindingtelomeric repeat DNA bindingCoats plus syndromeuterine fibroidcancermelanoma
✦AI Summary

STN1 is a core component of the CTC1-STN1-TEN1 (CST) complex, a single-stranded DNA-binding protein essential for telomere maintenance and genome stability 1. As part of the CST complex, STN1 binds telomeric DNA with high affinity and works with DNA polymerase α/primase to perform fill-in synthesis at the 5' ends of chr10, complementing telomerase's 3' end extension 12. Beyond telomeres, STN1 protects stalled replication forks from aberrant nucleolytic degradation through phosphorylation-dependent mechanisms involving CaMKK2 and ATR-CHK1 kinases 3. The CST complex also regulates DNA double-strand break repair pathway choice by suppressing DNA end resection, thereby favoring non-homologous end joining over homologous recombination 4. Notably, STN1 exhibits context-dependent functions independent of its CST complex role: it promotes pancreatic cancer metastasis by activating EMT transcription factor ZEB1 through R-loop-mediated STAT3 recruitment 5, and facilitates proper DSB repair and cell cycle checkpoint maintenance in KRAS-driven pancreatic cancer 6. Mutations in STN1 cause Coats plus, a telomere biology disorder characterized by pathological telomere shortening 2, and STN1 expression is tightly regulated by upstream overlapping reading frames that reduce protein levels 7.

Sources cited
1
CST-Polα/Primase structure, function, and role as second telomere maintenance machine performing fill-in synthesis
PMID: 37495394
2
POT1 recruitment of CST complex, telomere extension mechanisms, and Coats plus disease association
PMID: 38838667
3
CST complex role in DSB repair pathway choice by blocking DNA end resection
PMID: 40403056
4
STN1 promotes pancreatic cancer metastasis via EMT-activator ZEB1 transcription through R-loop and STAT3
PMID: 40841373
5
STN1 phosphorylation by CaMKK2 and CHK1 protects stalled replication forks from MRE11-mediated degradation
PMID: 38036565
6
STN1 CST-complex-independent roles in DSB repair, cell cycle checkpoint, and ATM stabilization in pancreatic cancer
PMID: 41036624
7
STN1 expression regulation by upstream overlapping reading frames via NMD pathway
PMID: 30067734
8
STN1 mutations in dyskeratosis congenita affecting CTC1-STN1-TEN1 complex protein-protein interactions
PMID: 39198715
Disease Associationsⓘ21
Coats plus syndromeOpen Targets
0.77Strong
uterine fibroidOpen Targets
0.55Moderate
cancerOpen Targets
0.53Moderate
melanomaOpen Targets
0.52Moderate
prostate carcinomaOpen Targets
0.49Moderate
thyroid cancerOpen Targets
0.48Moderate
lung adenocarcinomaOpen Targets
0.48Moderate
coronary artery diseaseOpen Targets
0.48Moderate
basal cell carcinomaOpen Targets
0.48Moderate
cutaneous melanomaOpen Targets
0.48Moderate
benign prostatic hyperplasiaOpen Targets
0.48Moderate
lipomaOpen Targets
0.46Moderate
dyskeratosis congenitaOpen Targets
0.46Moderate
minimally differentiated acute myeloblastic leukemiaOpen Targets
0.46Moderate
meningeal neoplasmOpen Targets
0.44Moderate
hypertensionOpen Targets
0.43Moderate
nontoxic goiterOpen Targets
0.43Moderate
renal carcinomaOpen Targets
0.43Moderate
coronary atherosclerosisOpen Targets
0.43Moderate
lung cancerOpen Targets
0.42Moderate
Cerebroretinal microangiopathy with calcifications and cysts 2UniProt
Pathogenic Variants2
NM_024928.5(STN1):c.707T>C (p.Leu236Pro)Likely pathogenic
Brain disorder
★☆☆☆2019→ Residue 236
NM_024928.5(STN1):c.404G>C (p.Arg135Thr)Pathogenic
Cerebroretinal microangiopathy with calcifications and cysts 2
☆☆☆☆2017→ Residue 135
View on ClinVar ↗
Related Genes
PCNAProtein interaction100%RAD52Protein interaction100%RPA1Protein interaction100%XPAProtein interaction100%SMARCAL1Protein interaction100%MED23Protein interaction99%
Tissue Expression6 tissues
Heart
100%
Lung
84%
Ovary
40%
Brain
36%
Bone Marrow
34%
Liver
29%
Gene Interaction Network
Click a node to explore
STN1PCNARAD52RPA1XPASMARCAL1MED23
PROTEIN STRUCTURE
Preparing viewer…
PDB4JQF · 1.60 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.97LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.67 [0.47–0.97]
RankingsWhere STN1 stands among ~20K protein-coding genes
  • #6,039of 20,598
    Most Researched79
  • #4,360of 5,498
    Most Pathogenic Variants2
  • #9,276of 17,882
    Most Constrained (LOEUF)0.97
Genes detectedSTN1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
CTC1-STN1-TEN1 controls DNA break repair pathway choice via DNA end resection blockade.
PMID: 40403056
Science · 2025
1.00
2
STN1 facilitates metastasis by promoting transcription of EMT-activator ZEB1 in pancreatic cancer.
PMID: 40841373
Nat Commun · 2025
0.90
3
POT1 recruits and regulates CST-Polα/primase at human telomeres.
PMID: 38838667
Cell · 2024
0.80
4
CST-Polα/Primase: the second telomere maintenance machine.
PMID: 37495394
Genes Dev · 2023
0.70
5
CaMKK2 and CHK1 phosphorylate human STN1 in response to replication stress to protect stalled forks from aberrant resection.
PMID: 38036565
Nat Commun · 2023
0.60