TERT

telomerase reverse transcriptase

28 disorders 16 untyped 8 somatic driver 2 causative 1 unknown 1 no genetic record 5p15.33 gene with protein product

HGNC:11730 Monarch NCBI Gene 7015 ENSG00000164362 UniProt O14746 OMIM 187270

Aliases: TRT, TP2, TCS1, hEST2, EST2.

Normal function · from ai-gene-review (O14746, commit 79fe13b38970) · AI-generated, not KB evidence

TERT (Telomerase Reverse Transcriptase) is the catalytic protein subunit of telomerase, a ribonucleoprotein enzyme essential for telomere maintenance. TERT catalyzes the template-directed addition of TTAGGG repeats to the 3' ends of telomeres using RNA-directed DNA polymerase activity, with the telomerase RNA component (TERC) providing the template. The enzyme operates as part of the telomerase holoenzyme complex containing TERT, TERC, DKC1, NOP10, NHP2, GAR1, and WRAP53/TCAB1. TERT is essential for cellular immortalization and is reactivated in ~90% of cancers. Beyond telomere maintenance, TERT exhibits non-canonical functions including RNA-dependent RNA polymerase activity when complexed with RMRP RNA, modulation of Wnt signaling, mitochondrial DNA protection, and regulation of cellular senescence and apoptosis. Germline mutations in TERT cause dyskeratosis congenita, aplastic anemia, and pulmonary fibrosis due to defective telomere maintenance.

TERT functions as the catalytic subunit of the telomerase ribonucleoprotein complex, where it exhibits telomerase activity (GO:0003720). TERT catalyzes telomere maintenance via telomerase (GO:0007004) by adding TTAGGG repeats to the 3' ends of chromosomes. This activity occurs within the telomerase holoenzyme complex (GO:0005697) localized to the nucleoplasm (GO:0005654).

molecular function: telomerase activity · directly involved in: telomere maintenance via telomerase · locations: nucleoplasm · in complex: telomerase holoenzyme complex

In the knowledge base · computed from kb/ at build time

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.

Disorder	Relationship	Where the gene appears
Adenoid Cystic Carcinoma	somatic driver somatic	mechanism: TERT Promoter Mutation as an Alternative Oncogenic Route
Anaplastic Thyroid Carcinoma	somatic driver somatic	mechanism: TERT Reactivation and Telomere Maintenance
Bone Giant Cell Tumor	somatic driver somatic
Choroid Plexus Neoplasm	somatic driver somatic	mechanism: Adult-Specific TERT Promoter Activation
Chromophobe Renal Cell Carcinoma	somatic driver somatic
Cri-du-Chat Syndrome	unknown	mechanism: TERT Haploinsufficiency
Dyskeratosis Congenita	causative germline	mechanism: Impaired Telomere Maintenance subtype: TERT scoped to subtype: TERT
Idiopathic Pulmonary Fibrosis	causative	mechanism: Alveolar epithelial telomere dysfunction
Ocular Melanoma	somatic driver somatic	mechanism: UV-Associated BRAF/NRAS/NF1 Driver Activation scoped to subtype: Conjunctival Melanoma
Oligoastrocytoma	somatic driver somatic
Thyroid Follicular Carcinoma	somatic driver	mechanism: TERT Promoter Mutation in Tumor Progression
Adult Granulosa Cell Tumor of Ovary	untyped Promoter mutation (C228T/C250T) is the commonest secondary event, found in roughly 40-43% of tumors, enriched in recurrences, and independently associated with shorter progression-free survival after first recurrence. somatic
BRAF-Mutant Papillary Thyroid Cancer	untyped Somatic Promoter Modifier Mutation
Glioblastoma, IDH-Wildtype	untyped Promoter Mutation
Glioma	untyped Promoter Mutation
Hepatoblastoma	untyped Somatic Promoter Mutation
IDH-Mutant and 1p/19q-Codeleted Oligodendroglioma	untyped Promoter Mutation
Inherited Aplastic Anemia	untyped Telomerase reverse transcriptase catalytic subunit, mutated in autosomal dominant DC and idiopathic aplastic anemia germline	scoped to subtype: Dyskeratosis Congenita
Malignant Sertoli-Leydig Cell Tumor of Ovary	untyped TERT promoter mutation is an uncommon third lesion in Sertoli-Leydig cell tumor, found in 2 of 37 tumors in one series. It is the same lesion that is the commonest secondary event in adult granulosa cell tumor, so it is a shared secondary event across the sex cord-stromal family rather than a histotype-defining driver. somatic
Medulloblastoma, SHH-Activated	untyped Promoter Mutation
Melanoma_in_Congenital_Melanocytic_Nevus	untyped Promoter mutations
Meningioma	untyped Promoter mutation associated with WHO grade 3 biology	mechanism: TERT Promoter Mutation-Associated Grade 3 Biology
Neuroblastoma	untyped Telomere Maintenance Activation
Papillary Thyroid Carcinoma	untyped Somatic Promoter Mutations
Transitional Cell Carcinoma	untyped somatic
Urinary Bladder Small Cell Neuroendocrine Carcinoma	untyped Somatic TERT Promoter Mutation
Vulvar Carcinoma	untyped Somatic Promoter Alteration somatic	mechanism: HPV-Independent Somatic Driver Accumulation
Familial Nonmedullary Thyroid Carcinoma	no genetic record	mechanism: Telomere-Telomerase Imbalance and Chromosome Fragility

ClinGen gene–disease validity · snapshot 2026-10-03 · matched to entries by MONDO

An entry matches when ClinGen's MONDO disease is the entry's own disease term, a subtype term, or an exact-match mapping. An amber status marks an entry ClinGen supports the gene for (Definitive, Strong or Moderate) whose own record does not type it. A Limited, Disputed or Refuted tier on such an entry is not a gap.

ClinGen disease	MOI	Classification	dismech entry
dyskeratosis congenita, autosomal dominant 2 MONDO:0013521	SD	Definitive 2020-07-30	no dismech entry

Mechanism modules · computed from kb/

enabling_replicative_immortality via Adenoid Cystic Carcinoma, Anaplastic Thyroid Carcinoma
genome_instability_mutation via Familial Nonmedullary Thyroid Carcinoma
telomere_attrition via Idiopathic Pulmonary Fibrosis

Identity from HGNC (snapshot 2026-10-01). Page layers are described in the gene pages documentation.