CTC1

Chr 17AR

CST telomere replication complex component 1

Also known as: AAF-132, AAF132, C17orf68, CRMCC, tmp494178

NCBI Gene: 80169ENSG00000178971UniProt: Q2NKJ3

This gene encodes a component of the CST complex. This complex plays an essential role in protecting telomeres from degradation. This protein also forms a heterodimer with the CST complex subunit STN1 to form the enzyme alpha accessory factor. This enzyme regulates DNA replication. Mutations in this gene are the cause of cerebroretinal microangiopathy with calcifications and cysts. Alternate splicing results in both coding and non-coding variants. [provided by RefSeq, Mar 2012]

Primary Disease Associations & Inheritance

Cerebroretinal microangiopathy with calcifications and cystsMIM #612199
AR
584
ClinVar variants
52
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— CTC1
🧬
Gene-Disease Validity (ClinGen)
cerebroretinal microangiopathy with calcifications and cysts 1 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
52 Pathogenic / Likely Pathogenic· 275 VUS of 584 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.63LOEUF
pLI 0.000
Z-score 3.97
OE 0.46 (0.34–0.63)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.50Z-score
OE missense 0.95 (0.89–1.01)
645 obs / 682.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.46 (0.34–0.63)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.95 (0.89–1.01)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.00
0≤1.21.6
LoF obs/exp: 29 / 63.0Missense obs/exp: 645 / 682.0Syn Z: -0.04

ClinVar Variant Classifications

584 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic32
Likely Pathogenic20
VUS275
Likely Benign240
Benign7
Conflicting10
32
Pathogenic
20
Likely Pathogenic
275
VUS
240
Likely Benign
7
Benign
10
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
17
0
15
0
32
Likely Pathogenic
17
1
2
0
20
VUS
1
221
47
6
275
Likely Benign
1
0
104
135
240
Benign
0
0
6
1
7
Conflicting
—10
Total36222174142584

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

View in ClinVar →

Protein Context — Lollipop Plot

CTC1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

CTC1-related dyskeratosis congenita

definitive
ARLoss Of FunctionAbsent Gene Product, Altered Gene Product Structure
Cancer
G2P ↗

CTC1-related cerebroretinal microangiopathy with calcifications and cysts

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersEye
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Cerebroretinal microangiopathy with calcifications and cysts

MIM #612199

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — CTC1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
CTC1-STN1-TEN1 controls DNA break repair pathway choice via DNA end resection blockade.
Rogers CM et al.·Science
2025
The evolving genetic landscape of telomere biology disorder dyskeratosis congenita.
Tummala H et al.·EMBO Mol Med
2024
The Clinical and Genetic Landscape of Hereditary Cancer: Experience from a Single Clinical Diagnostic Laboratory.
Tsoulos N et al.·Cancer Genomics Proteomics
2024
Molecular mechanisms of telomere biology disorders.
Grill S et al.·J Biol Chem
2021Review
Childhood-inherited white matter disorders with calcification.
Livingston JH·Handb Clin Neurol
2024Review
Underlying Disease in Atypical Retinopathy of Prematurity.
Cruz NFSD et al.·Am J Ophthalmol
2025
Pathogenic CTC1 mutations cause global genome instabilities under replication stress.
Wang Y et al.·Nucleic Acids Res
2018
Genetic Polymorphisms Associated with Fetal Hemoglobin (HbF) Levels and F-Cell Numbers: A Systematic Review of Genome-Wide Association Studies.
Stephanou C et al.·Int J Mol Sci
2024Review
Structural genomics approach to investigate deleterious impact of nsSNPs in conserved telomere maintenance component 1.
Choudhury A et al.·Sci Rep
2021
CTC1 mutations in a Brazilian family with progeroid features and recurrent bone fractures.
Sargolzaeiaval F et al.·Mol Genet Genomic Med
2018Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools