TERT

Chr 5ADSomaticAR

telomerase reverse transcriptase

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

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]

OMIMResearchGenerating clinical summary…
LOFmechanismAD/Somatic/ARLOEUF 0.295 OMIM phenotypes
Clinical SummaryTERT
🧬
Gene-Disease Validity (ClinGen)
dyskeratosis congenita, autosomal dominant 2 · SDDefinitive

Definitive — sufficient evidence for diagnostic panels

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.
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Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint?
0.29LOEUF
pLI 0.990
Z-score 5.24
OE 0.16 (0.090.29)
Highly constrained

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

Missense Constraint?
4.88Z-score
OE missense 0.49 (0.450.53)
350 obs / 717.6 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?
LoF OE?0.16 (0.090.29)
00.351.4
Missense OE?0.49 (0.450.53)
00.61.4
Synonymous OE?0.98
01.21.6
LoF obs/exp: 7 / 44.8Missense obs/exp: 350 / 717.6Syn Z: 0.25
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongTERT-related dyskeratosis congenita (monoallelic)LOFAD
strongTERT-related dyskeratosis congenita (biallelic)OTHERAR

This gene — mechanism propensity

DN
0.3395th %ile
GOF
0.3689th %ile
LOF
0.67top 25%

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOFprediction above median · 1 literature citation · LOEUF 0.29
GOF1 literature citation

Literature Evidence

GOFRecently, the gain-of-function mutation of the TERT promoter was identified in many types of human malignancies, and the mutated promoter acquires de novo ETS binding motifs through which the TERT transcription is activated.1
LOFGermline mutations in the gene encoding TERT cause haploinsufficiency with subsequent telomere shortening.2

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants 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.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

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
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 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
Advanced Hepatocellular CarcinomaMetastatic Hepatocellular CarcinomaStage III Hepatocellular Carcinoma AJCC v8

Testing the Addition of an Anti-cancer Drug, Sapanisertib, to the Usual Chemotherapy Treatment (Cabozantinib) in Metastatic Liver Cell Cancer With a Change in Genes for the Protein β-Catenin, The SAPHIRE Trial

RECRUITING
NCT06811116Phase PHASE1, PHASE2National Cancer Institute (NCI)Started 2025-11-17
Biospecimen CollectionCabozantinib S-malateImaging Procedure
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)
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
Heart FailureDilated Cardiomyopathy

Myocardial Telomere Recapping Study for Dilated Cardiomyopathy

ACTIVE NOT RECRUITING
NCT05837143Phase EARLY_PHASE1Shanghai East HospitalStarted 2023-03-30
JV001
Glioma

Clinical Study for the Safety and Therapeutic Efficacy of the AI-QMMM Designed TamavaqTM Personalised Vaccine in Patients With Newly Diagnosed Glioma.

RECRUITING
NCT07077616Phase EARLY_PHASE1Biogenea Pharmaceuticals Ltd.Started 2025-07-01
Biological: personalized vaccine Based on genetic and transcriptional sequencing information, personalized peptide vaccines would be designed and produced;
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
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 2026-06
Dose Level 1 ACU-D1 ointmentDose Level 2 ACU-D1 ointmentDose Level 3 ACU-D1 ointment
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
GlioblastomaGlioblastoma WHO Grade IVGlioblastoma (GBM)

CSF Proteomic Characterization of Glioblastomas

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