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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
CTC1
CST telomere replication complex component 1
Chromosome 17 Β· 17p13.1
NCBI Gene: 80169Ensembl: ENSG00000178971.17HGNC: HGNC:26169UniProt: A0A8V8TP86
68PubMed Papers
21Diseases
0Drugs
136Pathogenic Variants
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
chromosome, telomeric regionnucleusnucleoplasmG-rich strand telomeric DNA bindingCoats plus syndromedyskeratosis congenitagenetic disorderinherited bone marrow failure syndrome
✦AI Summary

CTC1 is a core component of the CST (CTC1-STN1-TEN1) complex, a single-stranded DNA-binding protein that functions as a specialized replication factor essential for telomere maintenance and genome stability 1. The CST complex executes two critical functions at telomeres: it recruits and regulates DNA polymerase Ξ±/primase (PolΞ±/primase) to synthesize the complementary C-rich strand through fill-in reactions 21, and it inhibits telomerase to prevent telomere overelongation and maintain telomere length homeostasis 1. Beyond telomeres, CTC1 regulates double-strand break (DSB) repair pathway choice by suppressing DNA end resection through distinct mechanisms that block both EXO1 and BLM-DNA2 nuclease activities, thereby promoting non-homologous end joining over homologous recombination 34. CTC1 also facilitates replication fork recovery and G-quadruplex resolution through cooperation with helicase RECQ4 5, and promotes ATR activation during replication stress by stabilizing TopBP1 6. Pathogenic CTC1 variants cause Coats plus, a telomere biology disorder characterized by pathological telomere shortening and disease mechanisms involving disrupted protein-protein interactions critical for telomere maintenance 7. Enhanced CTC1 expression promotes radioresistance in melanoma by maintaining telomere length 8, highlighting its therapeutic potential as a cancer treatment target.

Sources cited
1
CST-PolΞ±/Primase complex maintains telomeres through fill-in synthesis and controls telomere length by inhibiting telomerase overelongation
PMID: 37495394
2
POT1 recruits CST to telomeres and holds CST-PolΞ±/primase in autoinhibited state; mutations in CST cause Coats plus telomere biology disorder
PMID: 38838667
3
CST suppresses DNA end resection by blocking EXO1 and BLM-DNA2 to control DSB repair pathway choice
PMID: 40403056
4
CST localizes to DNA damage sites downstream of 53BP1-RIF1-shieldin and mediates PolΞ±-dependent fill-in to counteract resection
PMID: 30022158
5
CST cooperates with RECQ4 helicase to resolve G-quadruplexes and maintain telomere stability during replication
PMID: 37493024
6
CTC1 promotes TopBP1 stability and ATR activation in response to telomere dysfunction and replication stress
PMID: 33269665
7
Pathogenic CTC1 variants disrupt protein-protein interactions with CST, PolΞ±/primase, and shelterin complexes in telomere biology disorders
PMID: 39198715
8
Elevated CTC1 increases radioresistance in melanoma by inhibiting telomere shortening and apoptosis
PMID: 24718655
Disease Associationsβ“˜21
Coats plus syndromeOpen Targets
0.84Strong
dyskeratosis congenitaOpen Targets
0.77Strong
genetic disorderOpen Targets
0.51Moderate
inherited bone marrow failure syndromeOpen Targets
0.49Moderate
myelodysplastic syndromeOpen Targets
0.46Moderate
acute myeloid leukemiaOpen Targets
0.46Moderate
Menkes diseaseOpen Targets
0.46Moderate
Bone marrow hypocellularityOpen Targets
0.42Moderate
neurodegenerative diseaseOpen Targets
0.41Moderate
mathematical abilityOpen Targets
0.20Weak
retinopathyOpen Targets
0.12Weak
idiopathic pulmonary fibrosisOpen Targets
0.11Weak
monoclonal gammopathyOpen Targets
0.09Suggestive
alcohol drinkingOpen Targets
0.09Suggestive
lipomaOpen Targets
0.07Suggestive
acute kidney injuryOpen Targets
0.06Suggestive
uterine fibroidOpen Targets
0.04Suggestive
neoplasmOpen Targets
0.04Suggestive
cancerOpen Targets
0.04Suggestive
melanomaOpen Targets
0.03Suggestive
Cerebroretinal microangiopathy with calcifications and cysts 1UniProt
Pathogenic Variants136
NM_025099.6(CTC1):c.19C>T (p.Gln7Ter)Pathogenic
Dyskeratosis congenita|Cerebroretinal microangiopathy with calcifications and cysts 1
β˜…β˜…β˜†β˜†2026β†’ Residue 7
NM_025099.6(CTC1):c.2951GTT[1] (p.Cys985del)Pathogenic
Cerebroretinal microangiopathy with calcifications and cysts 1|Coats plus syndrome|Dyskeratosis congenita|not provided
β˜…β˜…β˜†β˜†2026β†’ Residue 985
NM_025099.6(CTC1):c.1186C>T (p.Arg396Ter)Pathogenic
Dyskeratosis congenita|Cerebroretinal microangiopathy with calcifications and cysts 1
β˜…β˜…β˜†β˜†2026β†’ Residue 396
NM_025099.6(CTC1):c.2T>A (p.Met1Lys)Pathogenic
Cerebroretinal microangiopathy with calcifications and cysts 1|Dyskeratosis congenita
β˜…β˜…β˜†β˜†2026β†’ Residue 1
NM_025099.6(CTC1):c.2386-1G>ALikely pathogenic
Dyskeratosis congenita|Cerebroretinal microangiopathy with calcifications and cysts 1
β˜…β˜…β˜†β˜†2026
NM_025099.6(CTC1):c.1994T>G (p.Val665Gly)Pathogenic
Cerebroretinal microangiopathy with calcifications and cysts 1|not provided|Dyskeratosis congenita
β˜…β˜…β˜†β˜†2026β†’ Residue 665
NM_025099.6(CTC1):c.1360del (p.Glu454fs)Pathogenic
Dyskeratosis congenita|Cerebroretinal microangiopathy with calcifications and cysts 1
β˜…β˜…β˜†β˜†2026β†’ Residue 454
NM_025099.6(CTC1):c.2831del (p.Pro944fs)Pathogenic
Cerebroretinal microangiopathy with calcifications and cysts 1|Dyskeratosis congenita|not provided|Coats plus syndrome|CTC1-related disorder
β˜…β˜…β˜†β˜†2026β†’ Residue 944
NM_025099.6(CTC1):c.2518C>T (p.Arg840Trp)Likely pathogenic
Cerebroretinal microangiopathy with calcifications and cysts 1|Dyskeratosis congenita|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 840
NM_025099.6(CTC1):c.775G>A (p.Val259Met)Pathogenic
Cerebroretinal microangiopathy with calcifications and cysts 1|Dyskeratosis congenita|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 259
NM_025099.6(CTC1):c.724_727del (p.Lys242fs)Pathogenic
Cerebroretinal microangiopathy with calcifications and cysts 1|Dyskeratosis congenita|not provided|Inborn genetic diseases|CTC1-related disorder
β˜…β˜…β˜†β˜†2025β†’ Residue 242
NM_025099.6(CTC1):c.1213del (p.Asp405fs)Pathogenic
Coats plus syndrome|Dyskeratosis congenita|Cerebroretinal microangiopathy with calcifications and cysts 1
β˜…β˜…β˜†β˜†2025β†’ Residue 405
NM_025099.6(CTC1):c.859C>T (p.Arg287Ter)Pathogenic
Cerebroretinal microangiopathy with calcifications and cysts 1|not provided|Dyskeratosis congenita
β˜…β˜…β˜†β˜†2025β†’ Residue 287
NM_025099.6(CTC1):c.248_251dup (p.His84fs)Pathogenic
Dyskeratosis congenita|Cerebroretinal microangiopathy with calcifications and cysts 1|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 84
NM_025099.6(CTC1):c.3019del (p.Leu1007fs)Pathogenic
Dyskeratosis congenita|not provided|Cerebroretinal microangiopathy with calcifications and cysts 1|Coats plus syndrome|CTC1-related disorder
β˜…β˜…β˜†β˜†2025β†’ Residue 1007
NM_025099.6(CTC1):c.2758+1G>TPathogenic
Dyskeratosis congenita|Cerebroretinal microangiopathy with calcifications and cysts 1
β˜…β˜…β˜†β˜†2025
NM_025099.6(CTC1):c.2996_2997del (p.Pro999fs)Pathogenic
Dyskeratosis congenita|Cerebroretinal microangiopathy with calcifications and cysts 1|CTC1-related disorder|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 999
NM_025099.6(CTC1):c.2959C>T (p.Arg987Trp)Pathogenic
Cerebroretinal microangiopathy with calcifications and cysts 1|Dyskeratosis congenita|not provided|Colon adenocarcinoma
β˜…β˜…β˜†β˜†2025β†’ Residue 987
NM_025099.6(CTC1):c.2452C>T (p.Arg818Ter)Pathogenic
not provided|Dyskeratosis congenita|Cerebroretinal microangiopathy with calcifications and cysts 1
β˜…β˜…β˜†β˜†2025β†’ Residue 818
NM_025099.6(CTC1):c.2176del (p.His726fs)Pathogenic
Cerebroretinal microangiopathy with calcifications and cysts 1|Dyskeratosis congenita
β˜…β˜…β˜†β˜†2025β†’ Residue 726
View on ClinVar β†—
Related Genes
POLA1Protein interaction100%PRIM1Protein interaction100%PRIM2Protein interaction100%TERTProtein interaction100%POLA2Protein interaction100%TERB1Protein interaction99%
Tissue Expression6 tissues
Bone Marrow
100%
Ovary
99%
Lung
94%
Liver
61%
Heart
39%
Brain
27%
Gene Interaction Network
Click a node to explore
CTC1POLA1PRIM1PRIM2TERTPOLA2TERB1
PROTEIN STRUCTURE
Preparing viewer…
PDB5W2L Β· 1.86 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.78LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.65 [0.54–0.78]
RankingsWhere CTC1 stands among ~20K protein-coding genes
  • #6,892of 20,598
    Most Researched68
  • #568of 5,498
    Most Pathogenic Variants136 Β· top quartile
  • #6,324of 17,882
    Most Constrained (LOEUF)0.78
Genes detectedCTC1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
CTC1-STN1-TEN1 controls DNA break repair pathway choice via DNA end resection blockade.
PMID: 40403056
Science Β· 2025
1.00
2
POT1 recruits and regulates CST-PolΞ±/primase at human telomeres.
PMID: 38838667
Cell Β· 2024
0.90
3
CST-PolΞ±/Primase: the second telomere maintenance machine.
PMID: 37495394
Genes Dev Β· 2023
0.80
4
Human CTC1 promotes TopBP1 stability and CHK1 phosphorylation in response to telomere dysfunction and global replication stress.
PMID: 33269665
Cell Cycle Β· 2020
0.70
5
Cooperative interaction of CST and RECQ4 resolves G-quadruplexes and maintains telomere stability.
PMID: 37493024
EMBO Rep Β· 2023
0.60