TERT
Chr 5ADSomaticARtelomerase reverse transcriptase
Also known as: CMM9, DKCA2, DKCB4, EST2, PFBMFT1, TCS1, TP2, TRT
The telomerase reverse transcriptase catalyzes telomere elongation by adding TTAGGG repeats to chromosome ends, functioning as the catalytic component of the telomerase ribonucleoprotein complex. Mutations cause dyskeratosis congenita and pulmonary fibrosis with bone marrow failure syndrome, inherited in both autosomal dominant and recessive patterns depending on the specific variant. This gene is highly constrained against loss-of-function variants (pLI 0.99, LOEUF 0.29), reflecting its essential role in cellular replication and survival.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Highly missense-constrained (top ~0.1%)
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.
Literature Evidence
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
700 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 14 | 0 | 5 | 0 | 19 |
Likely Pathogenic | 12 | 5 | 0 | 0 | 17 |
VUS | 2 | 369 | 39 | 3 | 413 |
Likely Benign | 0 | 14 | 47 | 178 | 239 |
Benign | 0 | 0 | 0 | 0 | 0 |
Conflicting | — | 1 | |||
| Total | 28 | 388 | 91 | 181 | 689 |
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.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Prevalence Of Germline Gene Mutations In Patients With Myeloproliferative Neoplasms With Family History
NOT YET RECRUITINGEvaluation of Risk of hEpatocellular Carcinoma
RECRUITINGINO-5401 and INO-9012 Delivered by Electroporation (EP) in Combination With Cemiplimab (REGN2810) in Newly-Diagnosed Glioblastoma (GBM)
ACTIVE NOT RECRUITINGDinutuximab With Chemotherapy, Surgery and Stem Cell Transplantation for the Treatment of Children With Newly Diagnosed High Risk Neuroblastoma
RECRUITINGEvaluation of the Efficacy of Calcium a -Ketoglutarate(AKG-Ca) in Improving Human Aging
ACTIVE NOT RECRUITINGCSF Proteomic Characterization of Glioblastomas
NOT YET RECRUITINGUse of ACU-D1 in HPV Associated Vulvar and Perianal Lesions in People With HIV
NOT YET RECRUITINGUsing Liquid Biopsy Testing to Identify, Monitor, Predict Recurrence in Urothelial Carcinoma
RECRUITINGTesting 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
RECRUITINGMyocardial Telomere Recapping Study for Dilated Cardiomyopathy
ACTIVE NOT RECRUITINGComprehensive Analysis of Chemotherapy and Targeted Therapy Outcomes in Recurrent Malignant Gliomas
ACTIVE NOT RECRUITINGClinical Study for the Safety and Therapeutic Efficacy of the AI-QMMM Designed TamavaqTM Personalised Vaccine in Patients With Newly Diagnosed Glioma.
RECRUITINGExternal Resources
Links to major genomics databases and tools