TERT

Chr 5

telomerase reverse transcriptase

Also known as: CMM9, DKCA2, DKCB4, EST2, PFBMFT1, TCS1, TP2, TRT

NCBI Gene: 7015ENSG00000164362UniProt: O14746

Telomerase is a ribonucleoprotein polymerase that maintains telomere ends by addition of the telomere repeat TTAGGG. The enzyme consists of a protein component with reverse transcriptase activity, encoded by this gene, and an RNA component which serves as a template for the telomere repeat. Telomerase expression plays a role in cellular senescence, as it is normally repressed in postnatal somatic cells resulting in progressive shortening of telomeres. Deregulation of telomerase expression in somatic cells may be involved in oncogenesis. Studies in mouse suggest that telomerase also participates in chromosomal repair, since de novo synthesis of telomere repeats may occur at double-stranded breaks. Alternatively spliced variants encoding different isoforms of telomerase reverse transcriptase have been identified; the full-length sequence of some variants has not been determined. Alternative splicing at this locus is thought to be one mechanism of regulation of telomerase activity. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

UniProtAplastic anemia
UniProtDyskeratosis congenita, autosomal dominant, 2
UniProtPulmonary fibrosis, and/or bone marrow failure syndrome, telomere-related, 1
UniProtDyskeratosis congenita, autosomal recessive, 4
3924
ClinVar variants
33
Pathogenic / LP
0.99
pLI score· haploinsufficient
12
Active trials
Clinical Summary— TERT
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
33 Pathogenic / Likely Pathogenic· 323 VUS of 3924 total submissions
💊
Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available
Some data sources returned errors (2)

omim: Error: OMIM fetch failed: 429

pubmed: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
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.
0.29LOEUF
pLI 0.990
Z-score 5.24
OE 0.16 (0.09–0.29)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

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.
4.88Z-score
OE missense 0.49 (0.45–0.53)
350 obs / 717.6 exp
Constrained

Highly missense-constrained (top ~0.1%)

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.0.16 (0.09–0.29)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.49 (0.45–0.53)
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.0.98
0≤1.21.6
LoF obs/exp: 7 / 44.8Missense obs/exp: 350 / 717.6Syn Z: 0.25

ClinVar Variant Classifications

3924 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic20
Likely Pathogenic13
VUS323
Likely Benign230
Conflicting3
20
Pathogenic
13
Likely Pathogenic
323
VUS
230
Likely Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
15
0
5
0
20
Likely Pathogenic
9
4
0
0
13
VUS
2
297
21
3
323
Likely Benign
0
9
54
167
230
Benign
0
0
0
0
0
Conflicting
—3
Total2631080170589

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

View in ClinVar →

Protein Context — Lollipop Plot

TERT · protein map & ClinVar variants

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

Gene2Phenotype Curations

TERT-related dyskeratosis congenita (monoallelic)

strong
ADLoss Of FunctionAbsent Gene Product, Altered Gene Product Structure
Dev. DisordersCancer
G2P ↗

TERT-related dyskeratosis congenita (biallelic)

strong
ARUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

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

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Machine Learning-Based Preoperative Predicting TERT Promoter Mutation and EGFR Gene Amplification Phenotype in IDH Wild-Type Glioblastoma Using Advanced MR Habitat Imaging.
Su Y et al.·AJNR Am J Neuroradiol
2026
Conformational studies of 1,2-di-tert-butoxyethane with special attention to the gauche oxygen effect.
Furuya H et al.·Phys Chem Chem Phys
2026
Study of tert-butyl bromide hydrolysis in the 1-propanol/water system using the fundamental thermodynamic equation of chemical reactivity.
Wiseman FL et al.·Phys Chem Chem Phys
2026
Biodegradation of 2,4-di-tert-butylphenol in continuous cropping field: Impacts on sustainable cultivation of Liliumbrownii.
Zhong S et al.·J Environ Manage
2026
Chalcogen bond-driven self-assembly of a 4-tert-butylcalix[4]arene-ebselen conjugate.
Ravi R et al.·Dalton Trans
2026
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
NASHHCCGenetic Predisposition

Evaluation of Risk of hEpatocellular Carcinoma

RECRUITING
NCT06523179Phase NAFondazione IRCCS Ca' Granda, Ospedale Maggiore PoliclinicoStarted 2018-01-01
quantify the impact of genetic risk factors
Recurrent Malignant GliomaGlioblastomaAnaplastic Astrocytoma

Comprehensive Analysis of Chemotherapy and Targeted Therapy Outcomes in Recurrent Malignant Gliomas

ACTIVE NOT RECRUITING
NCT07448480Blokhin's Russian Cancer Research CenterStarted 2026-02-01
Bevacizumab-Containing RegimensNon-Bevacizumab RegimensBRAF ± MEK Targeted Therapy
Human Papilloma VirusHuman Immunodeficiency VirusAnal Intraepithelial Neoplasia

Use of ACU-D1 in HPV Associated Vulvar and Perianal Lesions in People With HIV

NOT YET RECRUITING
NCT06233331Phase PHASE1Emory UniversityStarted 2025-11
Dose Level 1 ACU-D1 ointmentDose Level 2 ACU-D1 ointmentDose Level 3 ACU-D1 ointment
Bladder Cancer

Antitumor T Cell Responses in Patients With Bladder Cancer

NOT YET RECRUITING
NCT06334406Centre Hospitalier Universitaire de BesanconStarted 2024-04-02
Biological samples
Urothelial Carcinoma (UC)Bladder (Urothelial, Transitional Cell) CancerLiquid Biopsy

Using Liquid Biopsy Testing to Identify, Monitor, Predict Recurrence in Urothelial Carcinoma

RECRUITING
NCT07441499Tianjin Medical University Second HospitalStarted 2026-03
Multi-Component Liquid Biopsy for Urothelial Carcinoma
Heart FailureDilated Cardiomyopathy

Myocardial Telomere Recapping Study for Dilated Cardiomyopathy

ACTIVE NOT RECRUITING
NCT05837143Phase EARLY_PHASE1Shanghai East HospitalStarted 2023-03-30
JV001
Polycythemia VeraEssential ThrombocythaemiaMyelofibrosis

Prevalence Of Germline Gene Mutations In Patients With Myeloproliferative Neoplasms With Family History

NOT YET RECRUITING
NCT06923670Phase NAFondazione Policlinico Universitario Agostino Gemelli IRCCSStarted 2025-05-21
NGS testingNGS analysis for mutations in genes involved in familial predisposition to hematological malignancies
Recurrent Glioblastoma

Tislelizumab (One Anti-PD-1 Antibody) Plus Low-dose Bevacizumab for Bevacizumab Refractory Recurrent Glioblastoma

NOT YET RECRUITING
NCT05540275Phase PHASE2Henan Provincial People's HospitalStarted 2023-10-05
Tislelizumab plus Bevacizumab
Ganglioneuroblastoma, NodularNeuroblastoma

Dinutuximab With Chemotherapy, Surgery and Stem Cell Transplantation for the Treatment of Children With Newly Diagnosed High Risk Neuroblastoma

RECRUITING
NCT06172296Phase PHASE3National Cancer Institute (NCI)Started 2024-04-19
Biospecimen CollectionBone Marrow AspirationBone Marrow Biopsy
GlioblastomaGlioblastoma WHO Grade IVGlioblastoma (GBM)

CSF Proteomic Characterization of Glioblastomas

NOT YET RECRUITING
NCT06845020Univeridad Autonoma de GuadalajaraStarted 2025-03-01
Aging

Evaluation of the Efficacy of Calcium a -Ketoglutarate(AKG-Ca) in Improving Human Aging

ACTIVE NOT RECRUITING
NCT07114536Phase NAShenzhen Hygieia Biotech Co., LtdStarted 2025-08-20
Calcium-a-ketoglutaratePlacebo(starch)
Idiopathic Interstitial Pneumopathy/Pneumopathy Interstitial DiffusePaediatric and Adult Patients

RaDiCo PID Cohort (RaDiCo-ILD Cohort in English)

RECRUITING
NCT04238871Institut National de la Santé Et de la Recherche Médicale, FranceStarted 2017-06-21

External Resources

Links to major genomics databases and tools