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50 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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TERT
telomerase reverse transcriptase
Chromosome 5 · 5p15.33
NCBI Gene: 7015Ensembl: ENSG00000164362.22HGNC: HGNC:11730UniProt: O14746
2,102PubMed Papers
25Diseases
2Drugs
165Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
RESEARCH IMPACT
Highly StudiedTrendingVariant-Rich
CLINICAL
FDA Approved TargetOMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
negative regulation of extrinsic apoptotic signaling pathway in absence of ligandnucleusnucleoplasmnucleolusdyskeratosis congenita, autosomal dominant 2pulmonary fibrosis and/or bone marrow failure, telomere-related, 1idiopathic pulmonary fibrosisautosomal recessive dyskeratosis congenita 4
✦AI Summary

TERT (telomerase reverse transcriptase) is the catalytic subunit of telomerase, a ribonucleoprotein enzyme that maintains chromosome 5 by synthesizing telomeric repeats (TTAGGG) onto 3' chr5 termini through reverse transcriptase activity 1. Beyond telomere synthesis, TERT functions as a transcriptional co-regulator affecting aging pathways and cellular senescence 2. TERT operates through a bilobar structure involving interaction with telomerase RNA (TER) and is recruited to telomeres via the shelterin protein TPP1, which stabilizes TERT's TEN and TRAP domains 1. In cancer, TERT reactivation occurs through multiple mechanisms including promoter mutations, gene amplifications, and epigenetic alterations that increase telomerase activity, enabling replicative immortality 3. TERT promotes cancer progression through telomere-dependent and independent mechanisms; coexpression with BRAF mutations accelerates thyroid cancer dedifferentiation by enhancing ribosomal biogenesis and protein synthesis 4. DNA methylation of the TERT promoter represents an epigenetic regulatory mechanism of telomerase activation in cancers 5. Clinically, TERT mutations associate with telomere-related bone marrow failure, dyskeratosis congenita, and pulmonary fibrosis. Activating TERT expression in aged cells mitigates aging hallmarks and neuroinflammation 2, while correcting TERT promoter mutations via base editing suppresses hepatocellular carcinoma growth 6, suggesting both therapeutic and diagnostic potential.

Sources cited
1
TERT acts as transcriptional co-regulator in aging; TERT activation promotes telomere synthesis, reduces cellular senescence and inflammatory cytokines, and preserves cognitive function
PMID: 38908367
2
TERT reactivation in cancer occurs through gene amplifications, structural variants, promoter mutations, and epigenetic changes; TERT expression regulates telomerase activity
PMID: 33329574
3
TERT is the catalytic component of telomerase that synthesizes TTAGGG repeats; forms bilobal structure with TER; recruits and activates via TPP1 binding to TEN and TRAP domains
PMID: 35418675
4
TERT reactivation accelerates cancer progression through ribosomal biogenesis; BRAF-TERT coexpression promotes thyroid cancer dedifferentiation
PMID: 37647391
5
DNA methylation of TERT promoter serves as epigenetic regulatory mechanism of telomerase activation in cancer
PMID: 32114294
6
Correcting TERT promoter mutations via base editing suppresses telomerase activity and inhibits hepatocellular carcinoma tumor growth
PMID: 38016019
Disease Associationsⓘ25
dyskeratosis congenita, autosomal dominant 2Open Targets
0.86Strong
pulmonary fibrosis and/or bone marrow failure, telomere-related, 1Open Targets
0.81Strong
idiopathic pulmonary fibrosisOpen Targets
0.72Strong
autosomal recessive dyskeratosis congenita 4Open Targets
0.71Strong
acute myeloid leukemiaOpen Targets
0.71Strong
aplastic anemiaOpen Targets
0.70Strong
interstitial lung diseaseOpen Targets
0.68Moderate
cutaneous melanomaOpen Targets
0.66Moderate
melanoma, cutaneous malignant, susceptibility to, 9Open Targets
0.65Moderate
dyskeratosis congenitaOpen Targets
0.64Moderate
pulmonary fibrosisOpen Targets
0.63Moderate
prostate carcinomaOpen Targets
0.62Moderate
urinary bladder cancerOpen Targets
0.62Moderate
myelodysplastic syndromeOpen Targets
0.60Moderate
breast carcinomaOpen Targets
0.58Moderate
hepatocellular carcinomaOpen Targets
0.58Moderate
lung carcinomaOpen Targets
0.57Moderate
postinflammatory pulmonary fibrosisOpen Targets
0.56Moderate
lung adenocarcinomaOpen Targets
0.55Moderate
gliomaOpen Targets
0.55Moderate
Aplastic anemiaUniProt
Dyskeratosis congenita, autosomal dominant, 2UniProt
Dyskeratosis congenita, autosomal recessive, 4UniProt
Melanoma, cutaneous malignant 9UniProt
Pulmonary fibrosis, and/or bone marrow failure syndrome, telomere-related, 1UniProt
Pathogenic Variants165
NM_198253.3(TERT):c.2812C>T (p.Arg938Trp)Pathogenic
Abnormal pulmonary interstitial morphology;Short telomere length;Macrocytic anemia;Premature graying of hair|not provided|Pulmonary fibrosis|Dyskeratosis congenita, autosomal dominant 2;Idiopathic Pulmonary Fibrosis|Dyskeratosis congenita
★★☆☆2026→ Residue 938
NM_198253.3(TERT):c.1700C>T (p.Thr567Met)Likely pathogenic
not provided|Idiopathic Pulmonary Fibrosis;Dyskeratosis congenita, autosomal dominant 2|Dyskeratosis congenita|Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1
★★☆☆2026→ Residue 567
NM_198253.3(TERT):c.1122_1134del (p.Thr375fs)Pathogenic
Dyskeratosis congenita, autosomal dominant 2|Dyskeratosis congenita, autosomal dominant 2;Idiopathic Pulmonary Fibrosis
★★☆☆2026→ Residue 375
NM_198253.3(TERT):c.2147C>T (p.Ala716Val)Pathogenic
Aplastic anemia|not provided|Dyskeratosis congenita, autosomal dominant 2;Idiopathic Pulmonary Fibrosis|Dyskeratosis congenita|Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1
★★☆☆2025→ Residue 716
NM_198253.3(TERT):c.1891C>T (p.Arg631Trp)Pathogenic
Acute myeloid leukemia|not provided|Pulmonary fibrosis|Dyskeratosis congenita, autosomal dominant 2;Idiopathic Pulmonary Fibrosis|Dyskeratosis congenita|TERT-related disorder
★★☆☆2025→ Residue 631
NM_198253.3(TERT):c.2110C>T (p.Pro704Ser)Pathogenic
Autosomal recessive dyskeratosis congenita 4|Dyskeratosis congenita, autosomal dominant 1|not provided|Pulmonary fibrosis|Dyskeratosis congenita, autosomal dominant 2;Idiopathic Pulmonary Fibrosis|Dyskeratosis congenita, autosomal dominant 2|Dyskeratosis congenita|TERT-related disorder|Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1
★★☆☆2025→ Residue 704
NM_198253.3(TERT):c.598G>T (p.Glu200Ter)Pathogenic
Dyskeratosis congenita, autosomal dominant 2;Idiopathic Pulmonary Fibrosis|Dyskeratosis congenita
★★☆☆2025→ Residue 200
NM_198253.3(TERT):c.688C>T (p.Arg230Ter)Pathogenic
Dyskeratosis congenita, autosomal dominant 2;Idiopathic Pulmonary Fibrosis|Dyskeratosis congenita
★★☆☆2025→ Residue 230
NM_198253.3(TERT):c.1892G>A (p.Arg631Gln)Pathogenic
Dyskeratosis congenita, autosomal dominant 2|Interstitial lung disease 2|Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1|Dyskeratosis congenita, autosomal dominant 2;Idiopathic Pulmonary Fibrosis|Pulmonary fibrosis|not provided|Telomere syndrome|Dyskeratosis congenita
★★☆☆2025→ Residue 631
NM_198253.3(TERT):c.336dup (p.Glu113fs)Pathogenic
Pulmonary fibrosis|Dyskeratosis congenita, autosomal dominant 2;Idiopathic Pulmonary Fibrosis|7 conditions|Dyskeratosis congenita|Hereditary cancer-predisposing syndrome|not provided
★★☆☆2025→ Residue 113
NM_198253.3(TERT):c.2011C>T (p.Arg671Trp)Likely pathogenic
not provided|Hoyeraal-Hreidarsson syndrome;Autosomal recessive dyskeratosis congenita 4|Autosomal recessive dyskeratosis congenita 4|Pulmonary fibrosis|Idiopathic Pulmonary Fibrosis;Dyskeratosis congenita, autosomal dominant 2|Telomere syndrome|Dyskeratosis congenita
★★☆☆2025→ Residue 671
NM_198253.3(TERT):c.3187G>A (p.Gly1063Ser)Pathogenic
not provided|Pulmonary fibrosis|Idiopathic Pulmonary Fibrosis;Dyskeratosis congenita, autosomal dominant 2|Dyskeratosis congenita, autosomal dominant 2
★★☆☆2025→ Residue 1063
NM_198253.3(TERT):c.3110_3111del (p.Ile1036_Ser1037insTer)Pathogenic
Dyskeratosis congenita, autosomal dominant 2;Idiopathic Pulmonary Fibrosis|Dyskeratosis congenita
★★☆☆2025→ Residue 1036
NM_198253.3(TERT):c.570_586dup (p.Arg196fs)Pathogenic
not provided|Dyskeratosis congenita
★★☆☆2025→ Residue 196
NM_198253.3(TERT):c.2320C>T (p.Arg774Ter)Pathogenic
Dyskeratosis congenita, autosomal dominant 2|Dyskeratosis congenita, autosomal dominant 2;Idiopathic Pulmonary Fibrosis|not provided
★★☆☆2025→ Residue 774
NM_198253.3(TERT):c.3026C>T (p.Ala1009Val)Likely pathogenic
Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1|Idiopathic Pulmonary Fibrosis;Dyskeratosis congenita, autosomal dominant 2
★★☆☆2025→ Residue 1009
NM_198253.3(TERT):c.2286+1G>ALikely pathogenic
Idiopathic Pulmonary Fibrosis;Dyskeratosis congenita, autosomal dominant 2|Dyskeratosis congenita|not provided
★★☆☆2025
NM_198253.3(TERT):c.2594G>A (p.Arg865His)Pathogenic
Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1|Interstitial lung disease 2|not provided|Dyskeratosis congenita, autosomal dominant 2;Idiopathic Pulmonary Fibrosis|Pulmonary fibrosis|Dyskeratosis congenita, autosomal dominant 2
★★☆☆2025→ Residue 865
NM_198253.3(TERT):c.2131-2A>GLikely pathogenic
Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1|Idiopathic Pulmonary Fibrosis;Dyskeratosis congenita, autosomal dominant 2|not provided
★★☆☆2025
NM_198253.3(TERT):c.219+2T>ALikely pathogenic
Dyskeratosis congenita, autosomal dominant 2|Dyskeratosis congenita
★★☆☆2025
View on ClinVar ↗
Drug Targets2
IMETELSTATApproved
Telomerase reverse transcriptase inhibitor
anemia
IMETELSTAT SODIUMApproved
Telomerase reverse transcriptase inhibitor
anemia
Related Genes
CTC1Protein interaction100%TP53Protein interaction100%PTENProtein interaction100%RPA1Protein interaction100%MYCProtein interaction100%SULT1E1Protein interaction100%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
7%
Liver
0%
Lung
0%
Ovary
0%
Heart
0%
Gene Interaction Network
Click a node to explore
TERTCTC1TP53PTENRPA1MYCSULT1E1
PROTEIN STRUCTURE
Preparing viewer…
PDB5MEO · 1.77 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.59Moderately Constrained
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.46 [0.35–0.59]
RankingsWhere TERT stands among ~20K protein-coding genes
  • #53of 20,598
    Most Researched2,102 · top 1%
  • #490of 1,025
    FDA-Approved Drug Targets2
  • #448of 5,498
    Most Pathogenic Variants165 · top 10%
  • #4,027of 17,882
    Most Constrained (LOEUF)0.59 · top quartile
Genes detectedTERT
Sources retrieved50 papers
Response time—
📄 Sources
50▼
1
TERT activation targets DNA methylation and multiple aging hallmarks.
PMID: 38908367
Cell · 2024
1.00
2
Human TERT promoter polymorphism rs2853669 is associated with cancers: an updated meta-analysis.
PMID: 33743166
Hum Cell · 2021
0.92
3
TERT-Regulation and Roles in Cancer Formation.
PMID: 33329574
Front Immunol · 2020
0.90
4
Non-Canonical TERT Activity Initiates Osteogenesis in Calcific Aortic Valve Disease.
PMID: 39835393
Circ Res · 2025
0.84
5
TERT promoter mutations in thyroid cancer.
PMID: 37532521
Endocr J · 2023
0.82