TERT

Summary

TERT (telomerase reverse transcriptase, HGNC:11730) is a protein-coding gene on chromosome 5p15.33, encoding Telomerase reverse transcriptase (O14746). Telomerase is a ribonucleoprotein enzyme essential for the replication of chromosome termini in most eukaryotes. In precision oncology, TERT Promoter Mutation is associated with resistance to Iodine I-131 in Thyroid Gland Carcinoma (CIViC Level B).

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.

Source: NCBI Gene 7015 — RefSeq curated summary.

At a glance

• Gene–disease (curated): dyskeratosis congenita, autosomal dominant 2 (Definitive, ClinGen) — +5 more curated relationships
• GWAS associations: 169
• Clinical variants (ClinVar): 3,536 total — 91 pathogenic, 51 likely-pathogenic
• Phenotypes (HPO): 260
• Druggable target: yes — 10 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 1 curated variant–drug association
• Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types
• Dosage sensitivity (ClinGen): haploinsufficiency little evidence, triplosensitivity no evidence
• MANE Select transcript: NM_198253

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11730
Approved symbol	TERT
Name	telomerase reverse transcriptase
Location	5p15.33
Locus type	gene with protein product
Status	Approved
Aliases	TRT, TP2, TCS1, hEST2, EST2
Ensembl gene	ENSG00000164362
Ensembl biotype	protein_coding
OMIM	187270
Entrez	7015

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 4 protein_coding, 2 nonsense_mediated_decay, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000310581, ENST00000334602, ENST00000460137, ENST00000484238, ENST00000503656, ENST00000656021, ENST00000667927, ENST00000922985, ENST00000922986

RefSeq mRNA: 2 — MANE Select: NM_198253 NM_001193376, NM_198253

CCDS: CCDS3861, CCDS54831

Canonical transcript exons

ENST00000310581 — 16 exons

Exon	Start	End
ENSE00001196912	1271119	1271204
ENSE00001196926	1272185	1272280
ENSE00001197095	1282429	1282624
ENSE00001197112	1293313	1294666
ENSE00001863787	1253167	1253831
ENSE00003489443	1254368	1254505
ENSE00003507833	1279291	1279470
ENSE00003526270	1264404	1264592
ENSE00003537454	1258598	1258659
ENSE00003567573	1260474	1260600
ENSE00003575157	1255287	1255411
ENSE00003591376	1266464	1266535
ENSE00003621337	1268520	1268633
ENSE00003646510	1278641	1278796
ENSE00003649591	1280158	1280338
ENSE00003896691	1294771	1295068

Expression profiles

Bgee: expression breadth ubiquitous, 105 present calls, max score 99.63.

FANTOM5 (CAGE): breadth broad, TPM avg 0.6234 / max 61.1785, expressed in 265 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
60764	0.6234	265

Top tissues by expression

223 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	99.63	gold quality
type B pancreatic cell	CL:0000169	89.57	gold quality
olfactory bulb	UBERON:0002264	89.56	silver quality
diaphragm	UBERON:0001103	82.07	gold quality
vena cava	UBERON:0004087	82.07	gold quality
thymus	UBERON:0002370	81.82	silver quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	79.79	silver quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	79.72	gold quality
cerebellar vermis	UBERON:0004720	79.02	silver quality
cardia of stomach	UBERON:0001162	78.77	silver quality
vastus lateralis	UBERON:0001379	78.33	gold quality
tongue	UBERON:0001723	78.07	silver quality
pharyngeal mucosa	UBERON:0000355	77.66	silver quality
lateral globus pallidus	UBERON:0002476	77.48	silver quality
pylorus	UBERON:0001166	77.36	silver quality
gluteal muscle	UBERON:0002000	77.33	silver quality
superior surface of tongue	UBERON:0007371	77.24	silver quality
substantia nigra pars reticulata	UBERON:0001966	77.14	silver quality
triceps brachii	UBERON:0001509	77.03	gold quality
male germ cell	CL:0000015	76.64	gold quality
saphenous vein	UBERON:0007318	76.62	silver quality
quadriceps femoris	UBERON:0001377	76.53	gold quality
lateral nuclear group of thalamus	UBERON:0002736	76.27	gold quality
pericardium	UBERON:0002407	76.26	silver quality
pons	UBERON:0000988	76.02	silver quality
substantia nigra pars compacta	UBERON:0001965	75.96	silver quality
synovial joint	UBERON:0002217	75.53	silver quality
oocyte	CL:0000023	75.36	gold quality
sperm	CL:0000019	75.19	gold quality
trigeminal ganglion	UBERON:0001675	75.19	silver quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.43

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
ICAM1	Repression

Upstream regulators (CollecTRI, top): AHR, AP1, BMI1, CEBPA, CREBZF, CTCF, CTNNB1, DNMT1, DNMT3A, DNMT3B, E2F1, E2F2, E2F3, E2F4, E2F5, EGR1, EPAS1, ESR1, ESR2, ETS1, ETS2, ETV1, ETV4, EWSR1, FLI1, FOS, FRK, GLI1, GLI2, GRHL2, HDAC1, HIF1A, HMGA2, HNF4A, HNRNPD, HOXA7, ID1, ID2, IFI16, IRF1

miRNA regulators (miRDB)

21 targeting TERT, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-6752-5P	99.59	67.32	1243
HSA-MIR-4292	99.16	65.57	1767
HSA-MIR-6791-5P	99.16	65.92	1844
HSA-MIR-491-5P	99.13	65.98	1468
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-6074	98.89	69.64	2187
HSA-MIR-16-1-3P	98.70	69.23	1538
HSA-MIR-4710	98.61	65.96	1048
HSA-MIR-7114-3P	98.42	66.53	569
HSA-MIR-6796-5P	95.37	66.08	1120
HSA-MIR-4442	92.35	67.08	98
HSA-MIR-10401-3P	91.66	66.01	97

Functional genomics

ClinGen dosage: haploinsufficiency 1 (little evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• telomerase hTERT mRNA and telomerase activity in endometrioid adenocarcinoma and in normal endometrium. (PMID:11748987)
• the oligomerization of hTERT is an important step for telomerase activity. (PMID:11751869)
• allosteric inhibitors of telomerase: oligonucleotide N3’–>P5’ phosphoramidates (PMID:11788719)
• telomerase activity in needle biopsy samples is a useful diagnostic marker to distinguish uterine sarcoma from leiomyoma (PMID:11788902)
• Telomerase activity in microdissected human breast cancer tissues: association with p53, p21 and outcome (PMID:11788906)
• complete genomic sequence and analysis of tandem repeat polymorphisms (PMID:11850805)
• histone deacetylase transactivates the hTERT gene in normal human telomerase-negative cells, and upregulates hTERT expression in telomerase-positive tumor cells (PMID:11855854)
• Losses of INK4a/INK4b gene products play a big role in meningioma formation & malignant progression. Inactivation of p16/p15 and pl4ARF pendent pathways possibly along with telomerase activation might be critical for meningioma immortalization. (PMID:11859969)
• The telomerase activity in leukemia patients were higher than control cases. (PMID:11877056)
• Inhibition telomerase activity by antisense oligodeoxynucleotide induce apoptosis in HL-60 cells. (PMID:11877080)
• telomerase activity is regulated, in part, by alternative splicing of hTERT (PMID:11884529)
• Introduction of hTERT into activated human hepatic stellate cells (HSCs) immortalizes them and maintains their activated phenotype. (PMID:11896211)
• High telomerase activity coincides with genome stability and DNA ploidy in renal cell carcinoma (PMID:11896565)
• inhibition of promoter activity in breast cancer by a complex of BRCA1, Nmi and c-Myc (PMID:11916966)
• increased expression is related to hypermethylation in colorectal cancer tissues and some cancer cell lines and is discordant with hypermethylation of p16; silence of hTERT expression may be more critical in carcinogenesis than that of other genes (PMID:11932355)
• expression may be involved in poor healing caused by sclerosis of small blood vessels and lack of granulation tissue in the neoplastic transformaiton of chronic radiation ulcer (PMID:11934015)
• results suggest that telomerase activity might be associated with the presence of breast cancer cells; telomerase activation may occur early in breast cancer and may be periodically downregulated during subsequent tumor progression (PMID:11936586)
• effect of human telomerase reverse transcriptase (hTERT) gene antisense oligodeoxynucleotide (ASODN) on telomerase activity and apoptosis in lung cancer cell A549 line (PMID:11940318)
• TERT expression did not change after cisplatin treatment for 72 hours. (PMID:11942411)
• Results indicate that in vitro immortalization in HME cells may require the activation of the function of telomerase and other genetic alterations such as the spontaneous loss of p16(INK4a) expression. (PMID:11978176)
• Two distinct pathways of down-regulation of telomerase reverse transcriptase by retinoids co-exist in APL cells. (PMID:11986943)
• High telomerase activity was associated with multiple myeloma (PMID:12001122)
• Increases in hTERT gene copy number is correlated with higher levels of hTERT protein expression in cervical carcinomas with high-risk human papillomavirus infection. (PMID:12007187)
• Human telomerase accelerates growth of lens epithelial cells through regulation of the genes mediating RB/E2F pathway (PMID:12032846)
• after hTERT excision, cells senesce with shorter telomeres than parental cells (PMID:12034742)
• The data show the successful insertion of the hTERT gene into leiomyoma and myometrial cells and the immortalization of these cell lines without phenotypic alteration from the parental cell types. (PMID:12065682)
• TRRAP binding and the recruitment of histone H3 and H4 acetyltransferase activities are required for the transactivation of a silent TERT gene in exponentially growing human fibroblasts by c-Myc or N-Myc protein. (PMID:12077335)
• Keratinocytes engineered to express cdk4(R24C) and hTERT but not p53DD did not exhibit an extended life span. (PMID:12077343)
• Reconstitution of hTERT restores tumorigenicity in melanoma-derived c-Myc low-expressing clones. (PMID:12082531)
• Transfection with hTERT alone immortalized 2 out of 3 bone-marrow-derived EC cultures. Transduction of BMSVTs with hTERT immortalized 4 of 4 cultures, which formed large colonies in vitro and small transient tumours in vivo. (PMID:12082607)
• TERT regulates cell survival independent of telomerase enzymatic activity. (PMID:12082628)
• hTERT is required for full telomerase function. (PMID:12083802)
• Telomerase activation occurs during progression from low to high-grade dysplasia in adenomas & increases with the degree of dysplasia & invasion during colorectal carcinogenesis. hTERT mRNA expression is seen in the late stage development of this cancer. (PMID:12119560)
• Data show that telomerase activity is required to bypass senescence but is not sufficient to prevent telomere erosion and genomic instability at lower levels of expression. (PMID:12122013)
• hTERT expression changed proportionally with the level of telomerase activit & showed differential expression in normal and cancer tissues. hTERT is a regulatable subunit and it has a rate-limiting effect on enzyme activity. (PMID:12135483)
• Data show that although telomerase did not protect cells from stress-induced premature senescence, fibroblasts expressing hTERT were more resistant to stress-induced apoptosis and necrosis. (PMID:12140282)
• Results suggest that Sp1 and Sp3 associate with the hTERT promoter, recruiting HDAC for the localized deacetylation of nucleosomal histones and transcriptional silencing of the hTERT gene in normal human somatic cells (PMID:12151407)
• C-terminal regions of the human telomerase catalytic subunit are essential for in vivo enzyme activity. The C-DAT region is involved in a step of in vivo telomere synthesis after the assembly of a catalytically active enzyme. (PMID:12167716)
• The expression of telomerase may be a crucial step in gastric carcinogenesis and increased hTERT mRNA may serve as a novel marker for diagnosis of GC. (PMID:12174361)
• findings provide evidence for an endogenous, repressive mechanism that actively functions in telomerase/hTERT-negative normal cells and becomes defective during carcinogenic processes (PMID:12181331)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	tert	ENSDARG00000042637
mus_musculus	Tert	ENSMUSG00000021611
rattus_norvegicus	Tert	ENSRNOG00000025327
caenorhabditis_elegans	trt-1	WBGENE00006618

Protein

Protein identifiers

Telomerase reverse transcriptase — O14746 (reviewed: O14746)

Alternative names: HEST2, Telomerase catalytic subunit, Telomerase-associated protein 2

All UniProt accessions (2): A0A590UK92, O14746

UniProt curated annotations — full annotation on UniProt →

Function. Telomerase is a ribonucleoprotein enzyme essential for the replication of chromosome termini in most eukaryotes. Active in progenitor and cancer cells. Inactive, or very low activity, in normal somatic cells. Catalytic component of the teleromerase holoenzyme complex whose main activity is the elongation of telomeres by acting as a reverse transcriptase that adds simple sequence repeats to chromosome ends by copying a template sequence within the RNA component of the enzyme. Catalyzes the RNA-dependent extension of 3’-chromosomal termini with the 6-nucleotide telomeric repeat unit, 5’-TTAGGG-3’. The catalytic cycle involves primer binding, primer extension and release of product once the template boundary has been reached or nascent product translocation followed by further extension. More active on substrates containing 2 or 3 telomeric repeats. Telomerase activity is regulated by a number of factors including telomerase complex-associated proteins, chaperones and polypeptide modifiers. Modulates Wnt signaling. Plays important roles in aging and antiapoptosis.

Subunit / interactions. Catalytic component of the telomerase holoenzyme complex composed of one molecule of TERT, one molecule of WRAP53/TCAB1, two molecules of H/ACA ribonucleoprotein complex subunits DKC1, NOP10, NHP2 and GAR1, and a telomerase RNA template component (TERC). The telomerase holoenzyme complex is associated with TEP1, SMG6/EST1A and POT1. The molecular chaperone HSP90/P23 complex is required for correct assembly and stabilization of the active telomerase. Interacts directly with HSP90A and PTGES3. Interacts with HSPA1A; the interaction occurs in the absence of TERC and dissociates once the complex has formed. Interacts with RAN; the interaction promotes nuclear export of TERT. Interacts with XPO1. Interacts with PTPN11; the interaction retains TERT in the nucleus. Interacts with NCL (via RRM1 and C-terminal RRM4/Arg/Gly-rich domains); the interaction is important for nucleolar localization of TERT. Interacts with SMARCA4 (via the bromodomain); the interaction regulates Wnt-mediated signaling. Interacts with MCRS1 (isoform MCRS2); the interaction inhibits in vitro telomerase activity. Interacts with PIF1; the interaction has no effect on the elongation activity of TERT. Interacts with PML; the interaction recruits TERT to PML bodies and inhibits telomerase activity. Interacts with GNL3L. Interacts with isoform 1 and isoform 2 of NVL. Interacts with DHX36. Interacts with ATF7.

Subcellular location. Nucleus. Nucleolus. Nucleoplasm. Chromosome. Telomere. Cytoplasm. PML body.

Tissue specificity. Expressed at a high level in thymocyte subpopulations, at an intermediate level in tonsil T-lymphocytes, and at a low to undetectable level in peripheral blood T-lymphocytes.

Post-translational modifications. Phosphorylation at Tyr-707 under oxidative stress leads to translocation of TERT to the cytoplasm and reduces its antiapoptotic activity. Dephosphorylated by SHP2/PTPN11 leading to nuclear retention. Phosphorylation at Ser-227 by the AKT pathway promotes nuclear location. Phosphorylation at the G2/M phase at Ser-457 by DYRK2 promotes ubiquitination by the EDVP complex and degradation. Ubiquitinated by the EDVP complex, a E3 ligase complex following phosphorylation at Ser-457 by DYRK2. Ubiquitinated leads to proteasomal degradation. (Microbial infection) In case of infection by HIV-1, the EDVP complex is hijacked by HIV-1 via interaction between HIV-1 Vpr and DCAF1/VPRBP, leading to ubiquitination and degradation.

Disease relevance. Activation of telomerase has been implicated in cell immortalization and cancer cell pathogenesis. Aplastic anemia (AA) [MIM:609135] A form of anemia in which the bone marrow fails to produce adequate numbers of peripheral blood elements. It is characterized by peripheral pancytopenia and marrow hypoplasia. Disease susceptibility is associated with variants affecting the gene represented in this entry. Genetic variations in TERT are associated with coronary artery disease (CAD). Dyskeratosis congenita, autosomal dominant, 2 (DKCA2) [MIM:613989] A rare multisystem disorder caused by defective telomere maintenance. It is characterized by progressive bone marrow failure, and the clinical triad of reticulated skin hyperpigmentation, nail dystrophy, and mucosal leukoplakia. Common but variable features include premature graying, aplastic anemia, low platelets, osteoporosis, pulmonary fibrosis, and liver fibrosis among others. Early mortality is often associated with bone marrow failure, infections, fatal pulmonary complications, or malignancy. The disease is caused by variants affecting the gene represented in this entry. Pulmonary fibrosis, and/or bone marrow failure syndrome, telomere-related, 1 (PFBMFT1) [MIM:614742] An autosomal dominant disease associated with shortened telomeres. Pulmonary fibrosis is the most common manifestation. Other manifestations include aplastic anemia due to bone marrow failure, hepatic fibrosis, and increased cancer risk, particularly myelodysplastic syndrome and acute myeloid leukemia. Phenotype, age at onset, and severity are determined by telomere length. The disease is caused by variants affecting the gene represented in this entry. Dyskeratosis congenita, autosomal recessive, 4 (DKCB4) [MIM:613989] A severe form of dyskeratosis congenita, a rare multisystem disorder caused by defective telomere maintenance. It is characterized by progressive bone marrow failure, and the clinical triad of reticulated skin hyperpigmentation, nail dystrophy, and mucosal leukoplakia. Common but variable features include premature graying, aplastic anemia, low platelets, osteoporosis, pulmonary fibrosis, and liver fibrosis among others. Early mortality is often associated with bone marrow failure, infections, fatal pulmonary complications, or malignancy. The disease is caused by variants affecting the gene represented in this entry. Melanoma, cutaneous malignant 9 (CMM9) [MIM:615134] A malignant neoplasm of melanocytes, arising de novo or from a pre-existing benign nevus, which occurs most often in the skin but may also involve other sites. Disease susceptibility is associated with variants affecting the gene represented in this entry.

Domain organisation. The primer grip sequence in the RT domain is required for telomerase activity and for stable association with short telomeric primers. The RNA-interacting domain 1 (RD1)/N-terminal extension (NTE) is required for interaction with the pseudoknot-template domain of each of TERC dimers. It contains anchor sites that bind primer nucleotides upstream of the RNA-DNA hybrid and is thus an essential determinant of repeat addition processivity. The RNA-interacting domain 2 (RD2) is essential for both interaction with the CR4-CR5 domain of TERC and for DNA synthesis.

Induction. Activated by cytotoxic events and down-regulated during aging. In peripheral T-lymphocytes, induced By CD3 and by PMA/ionomycin. Inhibited by herbimycin B.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the reverse transcriptase family. Telomerase subfamily.

Isoforms (4)

UniProt ID	Names	Canonical?
O14746-1	1	yes
O14746-2	2
O14746-3	3
O14746-4	4

RefSeq proteins (2): NP_001180305, NP_937983* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000477	RT_dom	Domain
IPR003545	Telomerase_RT	Family
IPR021891	Telomerase_RBD	Domain
IPR043502	DNA/RNA_pol_sf	Homologous_superfamily
IPR049139	TERT_C	Domain

Pfam: PF12009, PF21399

Catalyzed reactions (Rhea), 1 shown:

• DNA(n) + a 2’-deoxyribonucleoside 5’-triphosphate = DNA(n+1) + diphosphate (RHEA:22508)

UniProt features (183 total): helix 45, strand 40, sequence variant 36, mutagenesis site 17, turn 13, region of interest 12, splice variant 4, compositionally biased region 3, binding site 3, modified residue 3, short sequence motif 2, site 2, chain 1, domain 1, sequence conflict 1

Structure

Experimental structures (PDB)

23 structures.

PDB	Method	Resolution (Å)
5MEO	X-RAY DIFFRACTION	1.77
5MER	X-RAY DIFFRACTION	1.88
5MEQ	X-RAY DIFFRACTION	2.27
5UGW	X-RAY DIFFRACTION	2.31
4B18	X-RAY DIFFRACTION	2.52
5MEP	X-RAY DIFFRACTION	2.71
4MNQ	X-RAY DIFFRACTION	2.74
2BCK	X-RAY DIFFRACTION	2.8
5MEN	X-RAY DIFFRACTION	2.81
7QXA	ELECTRON MICROSCOPY	3.2
9SHZ	ELECTRON MICROSCOPY	3.2
7TRD	ELECTRON MICROSCOPY	3.3
9QAX	ELECTRON MICROSCOPY	3.3
7TRE	ELECTRON MICROSCOPY	3.5
9SHY	ELECTRON MICROSCOPY	3.53
7V99	ELECTRON MICROSCOPY	3.54
9QAZ	ELECTRON MICROSCOPY	3.6
7TRF	ELECTRON MICROSCOPY	3.7
7BG9	ELECTRON MICROSCOPY	3.8
9QAY	ELECTRON MICROSCOPY	3.8
9SI0	ELECTRON MICROSCOPY	3.8
7QXB	ELECTRON MICROSCOPY	3.9
7QXS	ELECTRON MICROSCOPY	3.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14746-F1	80.98	0.60

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (2): 169 (required for optimal binding of telomeric ssdna and incorporation of nucleotides at the second position of the template); 867 (required for nucleotide incorporation and primer extension rate)

Ligand- & substrate-binding residues (3): 712; 868; 869

Post-translational modifications (3): 227, 457, 707

Mutagenesis-validated functional residues (17):

Position	Phenotype
137–141	reduced catalytic activity and repeat addition processivity. complete loss of catalytic activity but no loss of binding
169	about 80% loss of enzymatic activity. greatly reduced incorporation of second nucleotide. altered strength of binding to
169	about 85% loss of enzymatic activity. greatly reduced incorporation of second nucleotide. altered strength of binding to
169	about 90% loss of enzymatic activity. greatly reduced incorporation of second nucleotide. altered strength of binding to
457	abolishes phosphorylation by dyrk2.
547	defective in high-affinity terc interactions.
631	abolishes telomerase catalytic activity.
707	abolishes oxidative stress-induced phosphorylation and ran binding. impaired nuclear export and enhanced antiapoptotic a
712	loss of telomerase activity. in the absence of tr, no loss of binding to telomeric primers.
866	moderate reduction in telomerase activity, no change in repeat extension rate nor on nucleotide incorporation fidelity.
867	about 75% reduction in telomerase activity, about 80% reduction in repeat reduction rate and 3.9-fold increase in nucleo
867	about 75% reduction in telomerase activity, about 50% reduction in repeat extension rate and 5.2-fold increase in nucleo
867	severe reduction in telomerase activity, about 50% reduction in repeat extension rate and 2.2-fold increase in nucleotid
868–869	loss of telomerase activity.
868	loss of telomerase activity.
869	loss of telomerase activity.
930–934	completely abolishes telomerase-mediated primer extension and reduced binding to short telomeric primers. complete loss

Function

Pathways and Gene Ontology

Reactome pathways

13 pathways

ID	Pathway
R-HSA-171319	Telomere Extension By Telomerase
R-HSA-201722	Formation of the beta-catenin:TCF transactivating complex
R-HSA-9825895	Regulation of MITF-M-dependent genes involved in DNA replication, damage repair and senescence
R-HSA-1266738	Developmental Biology
R-HSA-157579	Telomere Maintenance
R-HSA-162582	Signal Transduction
R-HSA-1640170	Cell Cycle
R-HSA-180786	Extension of Telomeres
R-HSA-195721	Signaling by WNT
R-HSA-201681	TCF dependent signaling in response to WNT
R-HSA-73886	Chromosome Maintenance
R-HSA-9730414	MITF-M-regulated melanocyte development
R-HSA-9856651	MITF-M-dependent gene expression

MSigDB gene sets: 800 (showing top): GOBP_RNA_TEMPLATED_DNA_BIOSYNTHETIC_PROCESS, GOBP_CHROMOSOME_ORGANIZATION, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, GOBP_CARBOHYDRATE_TRANSPORT, BIOCARTA_TEL_PATHWAY, PID_TELOMERASE_PATHWAY, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_CHROMOSOME, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_POSITIVE_REGULATION_OF_VASCULATURE_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_MITOTIC_CELL_CYCLE, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, CAIRO_PML_TARGETS_BOUND_BY_MYC_DN, SHAFFER_IRF4_TARGETS_IN_ACTIVATED_B_LYMPHOCYTE, GOBP_TELOMERE_MAINTENANCE_VIA_TELOMERE_LENGTHENING

GO Biological Process (33): telomere maintenance via recombination (GO:0000722), telomere maintenance (GO:0000723), RNA-templated transcription (GO:0001172), RNA-templated DNA biosynthetic process (GO:0006278), protein import into nucleus (GO:0006606), telomere maintenance via telomerase (GO:0007004), mitochondrion organization (GO:0007005), heart development (GO:0007507), DNA strand elongation (GO:0022616), positive regulation of Wnt signaling pathway (GO:0030177), siRNA processing (GO:0030422), regulation of protein stability (GO:0031647), positive regulation of hair cycle (GO:0042635), negative regulation of neuron apoptotic process (GO:0043524), positive regulation of angiogenesis (GO:0045766), positive regulation of D-glucose import across plasma membrane (GO:0046326), response to cadmium ion (GO:0046686), establishment of protein localization to telomere (GO:0070200), cellular response to hypoxia (GO:0071456), DNA biosynthetic process (GO:0071897), replicative senescence (GO:0090399), siRNA transcription (GO:0140745), positive regulation of G1/S transition of mitotic cell cycle (GO:1900087), positive regulation of miRNA transcription (GO:1902895), positive regulation of transdifferentiation (GO:1903620), positive regulation of vascular associated smooth muscle cell proliferation (GO:1904707), positive regulation of protein localization to nucleolus (GO:1904751), positive regulation of vascular associated smooth muscle cell migration (GO:1904754), negative regulation of endothelial cell apoptotic process (GO:2000352), positive regulation of stem cell proliferation (GO:2000648), negative regulation of cellular senescence (GO:2000773), negative regulation of extrinsic apoptotic signaling pathway in absence of ligand (GO:2001240), negative regulation of apoptotic process (GO:0043066)

GO Molecular Function (18): tRNA binding (GO:0000049), transcription coactivator binding (GO:0001223), DNA binding (GO:0003677), telomerase activity (GO:0003720), RNA binding (GO:0003723), RNA-directed DNA polymerase activity (GO:0003964), RNA-directed RNA polymerase activity (GO:0003968), telomeric repeat DNA binding (GO:0042162), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), metal ion binding (GO:0046872), protein-folding chaperone binding (GO:0051087), telomerase RNA binding (GO:0070034), template-free RNA nucleotidyltransferase activity (GO:0098680), protein binding (GO:0005515), transferase activity (GO:0016740), nucleotidyltransferase activity (GO:0016779), DNA polymerase activity (GO:0034061)

GO Cellular Component (18): telomerase catalytic core complex (GO:0000333), chromosome, telomeric region (GO:0000781), nuclear telomere cap complex (GO:0000783), nucleus (GO:0005634), nucleoplasm (GO:0005654), telomerase holoenzyme complex (GO:0005697), nucleolus (GO:0005730), cytosol (GO:0005829), plasma membrane (GO:0005886), PML body (GO:0016605), nuclear speck (GO:0016607), RNA-directed RNA polymerase complex (GO:0031379), mitochondrial nucleoid (GO:0042645), TERT-RMRP complex (GO:1990572), chromosome (GO:0005694), cytoplasm (GO:0005737), mitochondrion (GO:0005739), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
Extension of Telomeres	1
TCF dependent signaling in response to WNT	1
MITF-M-dependent gene expression	1
Chromosome Maintenance	1
Telomere Maintenance	1
Signal Transduction	1
Signaling by WNT	1
Cell Cycle	1
Developmental Biology	1
MITF-M-regulated melanocyte development	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA metabolic process	3
DNA biosynthetic process	3
cellular anatomical structure	3
intracellular membraneless organelle	3
RNA-templated DNA biosynthetic process	2
RNA binding	2
nucleic acid binding	2
protein binding	2
nucleotidyltransferase activity	2
nuclear protein-containing complex	2
intracellular membrane-bounded organelle	2
nuclear lumen	2
ribonucleoprotein complex	2
cytoplasm	2
telomere maintenance	1
mitotic recombination	1
telomere organization	1
gene expression	1
RNA biosynthetic process	1
intracellular protein transport	1
protein localization to nucleus	1
import into nucleus	1
establishment of protein localization to organelle	1
telomerase activity	1
telomere maintenance via telomere lengthening	1
telomere-telomerase complex assembly	1
organelle organization	1
animal organ development	1
circulatory system development	1
positive regulation of signal transduction	1
Wnt signaling pathway	1
regulation of Wnt signaling pathway	1
regulatory ncRNA processing	1
regulation of biological quality	1
hair cycle	1
regulation of hair cycle	1
positive regulation of multicellular organismal process	1
negative regulation of apoptotic process	1
regulation of neuron apoptotic process	1
neuron apoptotic process	1

Protein interactions and networks

STRING

5450 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TERT	DKC1	O60832	999
TERT	NOP10	Q9NPE3	998
TERT	NHP2	Q9NX24	997
TERT	SULT1E1	P49888	996
TERT	TEP1	Q99973	996
TERT	WRAP53	Q9BUR4	996
TERT	HSP90AA1	P07900	988
TERT	HSP90AB1	P08238	987
TERT	RUVBL2	Q9Y230	981
TERT	RUVBL1	P82276	944
TERT	CTNNB1	P35222	938
TERT	TINF2	Q9BSI4	930
TERT	TERF1	P54274	926
TERT	CLPTM1L	Q96KA5	924
TERT	SMARCA4	P51532	901

IntAct

96 interactions, top by confidence:

A	B	Type	Score
TERT		psi-mi:“MI:0915”(physical association)	0.780
	TERT	psi-mi:“MI:0915”(physical association)	0.780
DKC1	TERT	psi-mi:“MI:0915”(physical association)	0.750
DKC1	TERT	psi-mi:“MI:0914”(association)	0.750
TERT	SMARCA4	psi-mi:“MI:0914”(association)	0.740
TERT	SMARCA4	psi-mi:“MI:0403”(colocalization)	0.740
TERT	SMARCA4	psi-mi:“MI:0915”(physical association)	0.740
SMARCA4	TERT	psi-mi:“MI:0914”(association)	0.740
TERT	SMARCA4	psi-mi:“MI:0407”(direct interaction)	0.740
PINX1	TERT	psi-mi:“MI:0914”(association)	0.680
PINX1	TERT	psi-mi:“MI:0915”(physical association)	0.680
RUVBL1	TERT	psi-mi:“MI:0915”(physical association)	0.640
RUVBL1	TERT	psi-mi:“MI:0914”(association)	0.640
RUVBL1	TERT	psi-mi:“MI:0407”(direct interaction)	0.640
TERT	RUVBL1	psi-mi:“MI:0403”(colocalization)	0.640
WRAP53		psi-mi:“MI:0914”(association)	0.620
E6	TERT	psi-mi:“MI:0915”(physical association)	0.600
E6	TERT	psi-mi:“MI:0407”(direct interaction)	0.600

BioGRID (171): AKT1 (Affinity Capture-Western), TERT (Affinity Capture-Western), TERT (Reconstituted Complex), TERT (Phenotypic Enhancement), TERT (Dosage Rescue), TERT (Dosage Rescue), TERT (Dosage Rescue), FOXO3 (Affinity Capture-Western), TERT (Affinity Capture-Western), FOXO3 (Reconstituted Complex), TERT (Affinity Capture-Western), MDM2 (Reconstituted Complex), TERT (Affinity Capture-Western), NCL (Affinity Capture-Western), TERT (Reconstituted Complex)

ESM2 similar proteins: A0JN53, A5PK74, A6NE52, B5DFG1, O00411, O14746, O60826, O70372, O94812, O95382, P0C5W1, P49000, Q15345, Q1PS67, Q1RMI8, Q27ID4, Q29RR1, Q3T1I9, Q3UYV8, Q400C9, Q400G9, Q4KTA7, Q562E7, Q5R9H2, Q5ZJ07, Q5ZMM1, Q673L6, Q6A548, Q76MJ5, Q80TE0, Q8BH02, Q8BH83, Q8BKF1, Q8BVF9, Q8C052, Q8K1C9, Q8K1S6, Q8WVB6, Q8WWL2, Q92985

Diamond homologs: O14746, O70372, Q1PS67, Q27ID4, Q4KTA7, Q673L6, Q6A548

SIGNOR signaling

25 interactions.

A	Effect	B	Mechanism
SRC	down-regulates	TERT	phosphorylation
MEN1	down-regulates	TERT
ACD	up-regulates	TERT	binding
POT1	up-regulates	TERT	binding
SMARCA4	up-regulates	TERT	binding
NFX1	“up-regulates quantity by expression”	TERT	“transcriptional regulation”
SIN3A	“down-regulates quantity by repression”	TERT	“transcriptional regulation”
AKT	up-regulates	TERT	phosphorylation
CTCF	“down-regulates quantity by repression”	TERT	“transcriptional regulation”
MKRN1	“down-regulates quantity by destabilization”	TERT	polyubiquitination
CDK1	“up-regulates activity”	TERT	phosphorylation
ABL1	“down-regulates activity”	TERT	phosphorylation
DYRK2	“down-regulates activity”	TERT	phosphorylation
AKT1	up-regulates	TERT	phosphorylation
“Av/b1 integrin”	“up-regulates quantity by expression”	TERT
“A6/b1 integrin”	“up-regulates quantity by expression”	TERT
TERT	up-regulates	Immortality
NHP2	“up-regulates activity”	TERT	binding
NOP10	“up-regulates activity”	TERT	binding
DKC1	“up-regulates activity”	TERT	binding
GAR1	“up-regulates activity”	TERT	binding
TERT	up-regulates	Telomere_maintenance

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 25 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Extension of Telomeres	6	163.9×	1e-10
Telomere Extension By Telomerase	7	145.3×	5e-12
Telomere Maintenance	6	100.5×	2e-09
Chromosome Maintenance	6	57.7×	5e-08
Cell Cycle	7	11.5×	7e-05

GO biological processes:

GO term	Partners	Fold	FDR
telomere maintenance via telomerase	5	152.6×	4e-08
negative regulation of telomere maintenance via telomerase	5	152.6×	4e-08
positive regulation of telomere maintenance	5	106.4×	2e-07
telomere maintenance	5	55.7×	3e-06
chromatin remodeling	6	18.2×	4e-05
DNA repair	6	16.0×	6e-05
protein stabilization	5	13.9×	5e-04
negative regulation of cell population proliferation	6	10.5×	4e-04

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 1 cancer types — PRCC.

Clinical variants and AI predictions

ClinVar

3536 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	91
Likely pathogenic	51
Uncertain significance	1544
Likely benign	1477
Benign	53

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1069288	NM_198253.3(TERT):c.1314del (p.Glu439fs)	Pathogenic
1073945	NM_198253.3(TERT):c.1424del (p.Pro475fs)	Pathogenic
1074267	NC_000005.9:g.(?1253843)(1297488_?)del	Pathogenic
1074268	NC_000005.9:g.(?1287194)(1297488_?)del	Pathogenic
1075528	NM_198253.3(TERT):c.3235del (p.Leu1079fs)	Pathogenic
12735	NM_198253.3(TERT):c.2706G>C (p.Lys902Asn)	Pathogenic
12737	NM_198253.3(TERT):c.2240del (p.Val747fs)	Pathogenic
1338582	NM_198253.3(TERT):c.570_586dup (p.Arg196fs)	Pathogenic
1357479	NM_198253.3(TERT):c.923dup (p.Ser309fs)	Pathogenic
1379443	NM_198253.3(TERT):c.1122del (p.Thr375fs)	Pathogenic
1379483	NM_198253.3(TERT):c.2315_2330del (p.Tyr772fs)	Pathogenic
1397003	NM_198253.3(TERT):c.598G>T (p.Glu200Ter)	Pathogenic
1421091	NM_198253.3(TERT):c.767G>A (p.Trp256Ter)	Pathogenic
1434641	NM_198253.3(TERT):c.1871_1872dup (p.Pro625fs)	Pathogenic
1435798	NM_198253.3(TERT):c.1612G>T (p.Glu538Ter)	Pathogenic
1437767	NM_198253.3(TERT):c.996del (p.Tyr333fs)	Pathogenic
1459137	NM_198253.3(TERT):c.329del (p.Gly110fs)	Pathogenic
147809	GRCh38/hg38 5p15.33-15.1(chr5:22149-15851376)x3	Pathogenic
1679958	NM_198253.3(TERT):c.2723C>T (p.Pro908Leu)	Pathogenic
1997398	NM_198253.3(TERT):c.505C>T (p.Gln169Ter)	Pathogenic
1998799	NM_198253.3(TERT):c.809dup (p.Cys271fs)	Pathogenic
2008972	NM_198253.3(TERT):c.2630_2634del (p.Leu877fs)	Pathogenic
2026183	NM_198253.3(TERT):c.2943del (p.Lys981fs)	Pathogenic
2047813	NM_198253.3(TERT):c.2323C>T (p.Gln775Ter)	Pathogenic
2056248	NM_198253.3(TERT):c.1379del (p.Gln460fs)	Pathogenic
2064698	NM_198253.3(TERT):c.3073del (p.Val1025fs)	Pathogenic
2082916	NM_198253.3(TERT):c.757C>T (p.Gln253Ter)	Pathogenic
2112405	NM_198253.3(TERT):c.1453del (p.Arg485fs)	Pathogenic
2163993	NM_198253.3(TERT):c.2461_2462del (p.Arg821fs)	Pathogenic
242222	NM_198253.3(TERT):c.2098C>T (p.Gln700Ter)	Pathogenic

SpliceAI

3537 predictions. Top by Δscore:

Variant	Effect	Δscore
5:1255282:CATA:C	donor_loss	1.0000
5:1255283:ATACC:A	donor_loss	1.0000
5:1255284:TACC:T	donor_loss	1.0000
5:1255285:AC:A	donor_loss	1.0000
5:1255286:C:CT	donor_loss	1.0000
5:1258592:GCTCA:G	donor_loss	1.0000
5:1258593:CTCA:C	donor_loss	1.0000
5:1258594:TCA:T	donor_loss	1.0000
5:1258595:CACCT:C	donor_loss	1.0000
5:1258596:A:T	donor_loss	1.0000
5:1258597:C:CA	donor_loss	1.0000
5:1258660:C:CC	acceptor_gain	1.0000
5:1258670:C:CT	acceptor_gain	1.0000
5:1258671:A:T	acceptor_gain	1.0000
5:1264588:GGGTC:G	acceptor_gain	1.0000
5:1264591:TC:T	acceptor_gain	1.0000
5:1264592:CC:C	acceptor_gain	1.0000
5:1264592:CCTAA:C	acceptor_loss	1.0000
5:1264593:C:CC	acceptor_gain	1.0000
5:1264594:T:G	acceptor_loss	1.0000
5:1266458:CCTCA:C	donor_loss	1.0000
5:1266459:CTCAC:C	donor_loss	1.0000
5:1266460:TCA:T	donor_loss	1.0000
5:1266461:CA:C	donor_loss	1.0000
5:1266462:A:AG	donor_loss	1.0000
5:1266463:C:A	donor_loss	1.0000
5:1266531:GCAGC:G	acceptor_gain	1.0000
5:1266532:CAGC:C	acceptor_gain	1.0000
5:1266532:CAGCC:C	acceptor_gain	1.0000
5:1266534:GC:G	acceptor_gain	1.0000

AlphaMissense

7231 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:1266515:T:A	D868V	0.996
5:1279295:A:T	V709D	0.995
5:1264459:A:G	W930R	0.994
5:1264459:A:T	W930R	0.994
5:1264529:G:C	N906K	0.994
5:1264529:G:T	N906K	0.994
5:1272198:A:T	V790D	0.992
5:1280240:A:G	F623S	0.992
5:1282457:A:G	W581R	0.992
5:1282457:A:T	W581R	0.992
5:1260573:A:C	S957R	0.991
5:1260573:A:T	S957R	0.991
5:1260575:T:G	S957R	0.991
5:1266506:A:G	L871S	0.991
5:1266511:A:C	D869E	0.991
5:1266511:A:T	D869E	0.991
5:1266514:A:C	D868E	0.991
5:1266514:A:T	D868E	0.991
5:1266515:T:G	D868A	0.991
5:1266525:G:T	R865S	0.991
5:1279353:A:G	W690R	0.991
5:1279353:A:T	W690R	0.991
5:1266512:T:A	D869V	0.990
5:1272195:A:T	V791D	0.990
5:1294819:G:C	C57W	0.990
5:1266512:T:G	D869A	0.989
5:1293331:A:G	W519R	0.989
5:1293331:A:T	W519R	0.989
5:1294601:G:C	N95K	0.989
5:1294601:G:T	N95K	0.989

dbSNP variants (sampled 300 via entrez): RS1000027099 (5:1270094 G>A), RS1000044369 (5:1264331 G>A), RS1000294061 (5:1265263 C>T), RS1000413168 (5:1255488 C>T), RS1000443957 (5:1292092 A>G), RS1000542688 (5:1264614 A>G), RS1000616596 (5:1255651 T>G), RS1000640674 (5:1261616 G>A), RS1000676284 (5:1292969 G>A), RS1000707355 (5:1292662 A>G), RS1000770517 (5:1293530 G>A,C,T), RS1000908025 (5:1285636 GT>G), RS1001018570 (5:1286331 C>T), RS1001036122 (5:1279645 A>C), RS1001065909 (5:1255506 A>G)

Disease associations

OMIM: gene MIM:187270 | disease phenotypes: MIM:613989, MIM:127550, MIM:614742, MIM:178500, MIM:609135, MIM:615134, MIM:601626, MIM:188400, MIM:114550, MIM:224230, MIM:615190, MIM:606963, MIM:300755, MIM:615476

GenCC curated gene-disease

Disease	Classification	Inheritance
dyskeratosis congenita, autosomal dominant 2	Definitive	Autosomal recessive
pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1	Definitive	Autosomal dominant
acute myeloid leukemia	Strong	Autosomal dominant
dyskeratosis congenita	Supportive	Autosomal dominant
Hoyeraal-Hreidarsson syndrome	Supportive	Autosomal dominant
melanoma, cutaneous malignant, susceptibility to, 9	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
dyskeratosis congenita, autosomal dominant 2	Definitive	SD

Mondo (34): dyskeratosis congenita, autosomal dominant 2 (MONDO:0013521), dyskeratosis congenita (MONDO:0015780), idiopathic pulmonary fibrosis (MONDO:0800504), pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1 (MONDO:0013878), interstitial lung disease 2 (MONDO:0800497), pulmonary fibrosis (MONDO:0002771), aplastic anemia (MONDO:0015909), melanoma, cutaneous malignant, susceptibility to, 9 (MONDO:0014056), acute myeloid leukemia (MONDO:0018874), autosomal recessive dyskeratosis congenita 4 (MONDO:0027353), dyskeratosis congenita, autosomal dominant 1 (MONDO:0007485), telomere syndrome (MONDO:0100137), DiGeorge syndrome (MONDO:0008564), hepatoblastoma (MONDO:0018666), intellectual disability (MONDO:0001071)

Orphanet (17): Dyskeratosis congenita (Orphanet:1775), Idiopathic pulmonary fibrosis (Orphanet:2032), Idiopathic aplastic anemia (Orphanet:88), Acute interstitial pneumonia (Orphanet:79126), Rare aplastic anemia (Orphanet:182040), Acute myeloid leukemia (Orphanet:519), Familial melanoma (Orphanet:618), 22q11.2 deletion syndrome (Orphanet:567), Hepatoblastoma (Orphanet:449), Hepatocellular carcinoma (Orphanet:88673), Combined pulmonary fibrosis-emphysema syndrome (Orphanet:300564), Inherited cancer-predisposing syndrome (Orphanet:140162), Hoyeraal-Hreidarsson syndrome (Orphanet:3322), OBSOLETE: Early infantile epileptic encephalopathy without suppression burst (Orphanet:369894), Hereditary breast and/or ovarian cancer syndrome (Orphanet:145)

HPO phenotypes

260 total (30 of 260 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000008	Abnormal morphology of female internal genitalia
HP:0000020	Urinary incontinence
HP:0000035	Abnormal testis morphology
HP:0000044	Hypogonadotropic hypogonadism
HP:0000080	Abnormality of reproductive system physiology
HP:0000141	Amenorrhea
HP:0000164	Abnormality of the dentition
HP:0000225	Gingival bleeding
HP:0000238	Hydrocephalus
HP:0000252	Microcephaly
HP:0000327	Hypoplasia of the maxilla
HP:0000360	Tinnitus
HP:0000365	Hearing impairment
HP:0000421	Epistaxis
HP:0000488	Retinopathy
HP:0000498	Blepharitis
HP:0000499	Abnormal eyelash morphology
HP:0000518	Cataract
HP:0000520	Proptosis
HP:0000534	Abnormal eyebrow morphology
HP:0000573	Retinal hemorrhage
HP:0000600	Abnormality of the pharynx
HP:0000602	Ophthalmoplegia
HP:0000618	Blindness
HP:0000668	Hypodontia
HP:0000670	Carious teeth
HP:0000679	Taurodontia
HP:0000704	Periodontitis

GWAS associations

169 associations (top):

Study	Trait	p-value
GCST000238_1	Idiopathic pulmonary fibrosis	3.000000e-08
GCST000256_1	Lung cancer	4.000000e-06
GCST000318_1	Basal cell carcinoma	4.000000e-12
GCST000439_1	Glioma	2.000000e-17
GCST000439_4	Glioma	4.000000e-14
GCST000506_5	Lung adenocarcinoma	2.000000e-10
GCST000588_8	Red blood cell count	3.000000e-08
GCST000701_3	Testicular germ cell cancer	8.000000e-15
GCST000701_4	Testicular germ cell cancer	1.000000e-23
GCST000761_1	Lung adenocarcinoma	2.000000e-22
GCST000810_2	Lung adenocarcinoma	3.000000e-11
GCST000842_9	Bladder cancer	5.000000e-07
GCST000919_2	Serum prostate-specific antigen levels	1.000000e-10
GCST001058_4	Glioma	1.000000e-14
GCST001140_2	Lung cancer	1.000000e-27
GCST001148_2	Prostate cancer	3.000000e-24
GCST001194_1	Glioma	7.000000e-09
GCST001267_5	Melanoma	3.000000e-08
GCST001298_1	Breast cancer	1.000000e-10
GCST001609_1	Lung adenocarcinoma	3.000000e-40
GCST001633_1	Glioma	4.000000e-09
GCST001740_2	Lung cancer	4.000000e-27
GCST001930_1	Breast cancer	5.000000e-12
GCST001937_31	Breast cancer	7.000000e-09
GCST001968_2	Interstitial lung disease	2.000000e-19
GCST002022_7	Testicular germ cell tumor	5.000000e-24
GCST002240_4	Bladder cancer	4.000000e-11
GCST002305_2	Breast cancer (estrogen-receptor negative, progesterone-receptor negative, and human epidermal growth factor-receptor negative)	1.000000e-07
GCST002331_5	Basal cell carcinoma	2.000000e-12
GCST002341_1	Telomere length	4.000000e-06

EFO canonical traits (27, from GWAS)

EFO ID	Trait name
EFO:0000768	idiopathic pulmonary fibrosis
EFO:0004305	erythrocyte count
EFO:1001515	ovarian endometrioid carcinoma
EFO:1001516	ovarian serous carcinoma
EFO:0004527	mean corpuscular hemoglobin
EFO:0004309	platelet count
EFO:0007985	platelet crit
EFO:0004833	neutrophil count
EFO:0004842	eosinophil count
EFO:0007987	granulocyte count
EFO:0005090	basophil count
EFO:0007990	neutrophil percentage of leukocytes
EFO:0000473	epigenetic status
EFO:0022597	aging
EFO:0004847	age at onset
EFO:0006335	systolic blood pressure
EFO:0004632	nevus count
EFO:0008008	lower urinary tract symptom
EFO:0010176	keratinocyte carcinoma
EFO:0007783	mosaic loss of chromosome Y measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004251	myeloproliferative disorder
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004348	hematocrit
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007989	monocyte percentage of leukocytes
EFO:0010701	mean reticulocyte volume

MeSH disease descriptors (21)

Descriptor	Name	Tree numbers
D000741	Anemia, Aplastic	C15.378.050.085; C15.378.190.223.250
D000748	Anemia, Macrocytic	C15.378.050.252
D006528	Carcinoma, Hepatocellular	C04.557.470.200.025.255; C04.588.274.623.160; C06.301.623.160; C06.552.697.160
D004062	DiGeorge Syndrome	C05.660.207.103.500; C14.240.400.021.500; C14.280.400.044.500; C15.604.451.249.500; C16.131.077.019.500; C16.131.240.400.021.500; C16.131.260.019.500; C16.131.482.249.500; C16.131.621.207.103.500; C16.320.180.019.500; C19.642.482.500.500
D019871	Dyskeratosis Congenita	C15.378.190.223.500.750; C16.131.831.150; C16.320.322.108; C16.320.850.235; C17.800.804.150; C17.800.827.235
D004933	Esophageal Atresia	C06.198.330; C06.405.117.260; C16.131.314.330
D017219	Gastric Outlet Obstruction	C06.405.748.340
D018197	Hepatoblastoma	C04.557.435.380
D061325	Hereditary Breast and Ovarian Cancer Syndrome	C04.588.180.483; C04.588.322.455.431; C04.700.517; C12.050.351.500.056.630.705.431; C12.050.351.937.418.685.431; C12.100.250.056.630.705.431; C12.900.418.685.431; C16.320.700.517; C17.800.090.500.483; C19.344.410.431; C19.391.630.705.431
D054990	Idiopathic Pulmonary Fibrosis	C08.381.483.652.500
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D015470	Leukemia, Myeloid, Acute	C04.557.337.539.275; C15.378.508.539.275
D017563	Lung Diseases, Interstitial	C08.381.483
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700
D029424	Pulmonary Disease, Chronic Obstructive	C08.381.495.389; C23.550.291.500.875
D011658	Pulmonary Fibrosis	C08.381.483.652; C23.550.355.644
D011707	Pyloric Stenosis	C06.405.748.340.690
C565079	Dyskeratosis Congenita, Autosomal Dominant (supp.)
C565611	Dyskeratosis Congenita, Autosomal Recessive (supp.)
C536068	Hoyeraal Hreidarsson syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2916 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

10 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,318,998 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL295124	BERBERINE	4	26,682
CHEMBL53463	DOXORUBICIN	4	314,282
CHEMBL165	RESVERATROL	3	60,144
CHEMBL297453	EPIGALOCATECHIN GALLATE	3	22,804
CHEMBL372764	PERIFOSINE	3	15,127
CHEMBL2111043	ISOMETAMIDIUM	2	348
CHEMBL284328	HOMIDIUM BROMIDE	2	147,818
CHEMBL359965	ALLICIN	2	14,806
CHEMBL8659	OLEIC ACID	2	713,838
CHEMBL94007	ETHACRIDINE	2	3,149

Clinical evidence (CIViC)

Drug × variant × indication: 1 predictive associations from 1 curated evidence items; also 10 prognostic, 3 diagnostic, 1 predisposing.

Variant	Therapy	Indication	Effect	Level	CIViC
TERT Promoter Mutation	Iodine I-131	Thyroid Gland Carcinoma	Resistance	CIViC B	EID6961

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

751 potent at pChembl≥5 of 983 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.19	IC50	0.64	nM	TELOMESTATIN
9.15	IC50	0.7	nM	TELOMESTATIN
8.89	IC50	1.3	nM	CHEMBL6175875
8.82	IC50	1.5	nM	CHEMBL259739
8.70	EC50	2	nM	CHEMBL337762
8.66	IC50	2.2	nM	CHEMBL259739
8.62	IC50	2.4	nM	CHEMBL6172777
8.30	IC50	5	nM	CHEMBL3347538
7.90	IC50	12.6	nM	CHEMBL3948172
7.80	IC50	16	nM	CHEMBL6175875
7.75	IC50	18	nM	CHEMBL1078511
7.75	IC50	18	nM	CHEMBL140180
7.75	EC50	18	nM	CHEMBL140180
7.75	EC50	18	nM	CHEMBL44130
7.70	IC50	20	nM	CHEMBL3347541
7.70	IC50	20	nM	CHEMBL3347540
7.70	IC50	20	nM	CHEMBL398742
7.70	IC50	20	nM	CHEMBL3347539
7.70	IC50	20	nM	TELOMESTATIN
7.70	IC50	20	nM	CHEMBL139511
7.70	EC50	20	nM	CHEMBL139511
7.68	EC50	21	nM	CHEMBL343609
7.55	IC50	28	nM	CHEMBL2425367
7.52	IC50	30	nM	CHEMBL224754
7.52	EC50	30	nM	CHEMBL397746
7.52	IC50	30	nM	CHEMBL5595283
7.52	EC50	30	nM	CHEMBL137809
7.40	IC50	40	nM	CHEMBL336444
7.40	EC50	40	nM	CHEMBL336444
7.39	IC50	40.74	nM	CHEMBL2260109
7.39	IC50	41	nM	CHEMBL2260109
7.35	IC50	45	nM	CHEMBL336434
7.35	IC50	45	nM	CHEMBL409247
7.31	IC50	48.98	nM	CHEMBL2298058
7.31	IC50	49	nM	CHEMBL2298058
7.30	IC50	50	nM	CHEMBL3330787
7.30	IC50	50	nM	CHEMBL141540
7.30	IC50	50	nM	CHEMBL138811
7.30	EC50	50	nM	CHEMBL138811
7.29	IC50	51.29	nM	CHEMBL2298055
7.29	IC50	51	nM	CHEMBL2298055
7.28	IC50	52	nM	CHEMBL409247
7.25	IC50	56.23	nM	CHEMBL2298050
7.25	IC50	56	nM	CHEMBL2298050
7.24	IC50	58	nM	TELOMESTATIN
7.22	IC50	60	nM	CHEMBL2170855
7.22	IC50	60	nM	CHEMBL335819
7.22	IC50	60	nM	CHEMBL225205
7.22	IC50	60	nM	CHEMBL335132
7.22	IC50	60	nM	CHEMBL336417

PubChem BioAssay actives

662 with measured affinity, of 2346 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4,8-dimethyl-3,7,11,15,19,23,27-heptaoxa-31-thia-33,34,35,36,37,38,39,40-octazanonacyclo[28.2.1.12,5.16,9.110,13.114,17.118,21.122,25.126,29]tetraconta-2(40),4,6(39),8,10(38),12,14(37),16,18(36),20,22(35),24,26(34),28,30(33)-pentadecaene	329708: Inhibition of human telomerase expressed in HEK293T cells treated before telomerase elongation by telomeric repeat amplification protocol assay	ic50	0.0006	uM
2-N,9-N-bis(1-methylquinolin-1-ium-3-yl)-1,10-phenanthroline-2,9-dicarboxamide	329708: Inhibition of human telomerase expressed in HEK293T cells treated before telomerase elongation by telomeric repeat amplification protocol assay	ic50	0.0015	uM
N-[9-(4-aminoanilino)-6-(3-pyrrolidin-1-ylpropanoylamino)acridin-2-yl]-3-pyrrolidin-1-ylpropanamide	212746: Inhibitory activity against human telomerase	ec50	0.0020	uM
2-hydroxy-8-methyl-1,7-dioxaspiro[5.5]undec-3-en-5-one	1323561: Inhibition of telomerase activity in human MCF7 cells using biotin-labeled TeloTAGGG as primer preincubated for 48 hrs followed by primer addition measured after 30 mins by PCR-ELISA	ic50	0.0126	uM
N-[9-[2-(dimethylamino)ethylamino]-6-(3-pyrrolidin-1-ylpropanoylamino)acridin-3-yl]-3-pyrrolidin-1-ylpropanamide	212746: Inhibitory activity against human telomerase	ec50	0.0180	uM
N-[9-[2-(1-methylpyrrolidin-2-yl)ethylamino]-6-(3-pyrrolidin-1-ylpropanoylamino)acridin-3-yl]-3-pyrrolidin-1-ylpropanamide	471962: Inhibition of telomerase in human A2780 cells by TRAP assay	ic50	0.0180	uM
N-[9-[2-(2-aminoethyl)pyrrolidin-1-yl]-6-(3-pyrrolidin-1-ylpropanoylamino)acridin-3-yl]-3-pyrrolidin-1-ylpropanamide	212746: Inhibitory activity against human telomerase	ec50	0.0180	uM
N-[9-(2-aminoanilino)-6-(3-pyrrolidin-1-ylpropanoylamino)acridin-3-yl]-3-pyrrolidin-1-ylpropanamide	212746: Inhibitory activity against human telomerase	ec50	0.0200	uM
N-[9-(2-aminoanilino)-6-(3-pyrrolidin-1-ylpropanoylamino)acridin-2-yl]-3-pyrrolidin-1-ylpropanamide	212746: Inhibitory activity against human telomerase	ec50	0.0210	uM
N-[[10-[[3-(dimethylamino)propylamino]methyl]quinolino[2,3-a]acridin-2-yl]methyl]-N’,N’-dimethylpropane-1,3-diamine	770979: Inhibition of telomerase (unknown origin) by TRAP assay	ic50	0.0280	uM
N-[9-(2-methylsulfanylanilino)-6-(3-pyrrolidin-1-ylpropanoylamino)acridin-3-yl]-3-pyrrolidin-1-ylpropanamide	212746: Inhibitory activity against human telomerase	ec50	0.0300	uM
N-[9-[(3,4-difluorophenyl)methylamino]-6-(3-pyrrolidin-1-ylpropanoylamino)acridin-3-yl]-3-pyrrolidin-1-ylpropanamide	306427: Inhibition of human telomerase by TRAP assay	ec50	0.0300	uM
trimethyl-[2-[6,8,17,19-tetraoxo-18-[2-(trimethylazaniumyl)ethyl]-7,18-diazaheptacyclo[14.6.2.22,5.03,12.04,9.013,23.020,24]hexacosa-1(23),2,4,9,11,13,15,20(24),21,25-decaen-7-yl]ethyl]azanium	283979: Inhibition of telomerase in JR8 cell extract by TRAP assay	ic50	0.0300	uM
methyl (4Z)-2-methyl-5-oxo-1-(oxolan-2-ylmethyl)-4-[[4-[2-oxo-2-(propan-2-ylamino)ethoxy]phenyl]methylidene]pyrrole-3-carboxylate	2117561: Inhibition of telomerase activity in human HL-60 cells incubated for 96 hrs by TRAP-PCR assay	ic50	0.0300	uM
N-[9-(4-acetylanilino)-6-(3-pyrrolidin-1-ylpropanoylamino)acridin-3-yl]-3-pyrrolidin-1-ylpropanamide	212746: Inhibitory activity against human telomerase	ec50	0.0400	uM
2-N,6-N-bis(1-methylquinolin-1-ium-3-yl)pyridine-2,6-dicarboxamide	329712: Inhibition of human telomerase expressed in in HEK293T cells in presence of primer (T2AG3)4 by primer extension assay	ic50	0.0450	uM
N-[9-[4-(dimethylamino)anilino]-6-(3-pyrrolidin-1-ylpropanoylamino)acridin-3-yl]-3-pyrrolidin-1-ylpropanamide	329708: Inhibition of human telomerase expressed in HEK293T cells treated before telomerase elongation by telomeric repeat amplification protocol assay	ic50	0.0450	uM
N-[9-(cyclopropylamino)-6-(3-pyrrolidin-1-ylpropanoylamino)acridin-3-yl]-3-pyrrolidin-1-ylpropanamide	212746: Inhibitory activity against human telomerase	ec50	0.0500	uM
N-[9-(2-piperidin-1-ylethylamino)-6-(3-pyrrolidin-1-ylpropanoylamino)acridin-3-yl]-3-pyrrolidin-1-ylpropanamide	471962: Inhibition of telomerase in human A2780 cells by TRAP assay	ic50	0.0500	uM
2-[2-[[4-[2-(methylamino)ethylamino]-5,10-dioxonaphtho[2,3-f][1]benzothiol-11-yl]amino]ethyl]guanidine;hydrochloride	1187844: Inhibition of human telomerase transfected in human HEK293T cells assessed as DNA extension using 5’-d(AATCCGTCGAGCAGAGTT)-3’ substrate by Real-time quantitative telomeric repeat amplification protocol	ic50	0.0500	uM
N-[9-(3-aminoanilino)-6-(3-pyrrolidin-1-ylpropanoylamino)acridin-3-yl]-3-pyrrolidin-1-ylpropanamide	212746: Inhibitory activity against human telomerase	ec50	0.0600	uM
N-[9-[3-(dimethylamino)propylamino]-6-(3-pyrrolidin-1-ylpropanoylamino)acridin-3-yl]-3-pyrrolidin-1-ylpropanamide	212746: Inhibitory activity against human telomerase	ec50	0.0600	uM
tetrakis(4-methylbenzenesulfonate);5,10,15,20-tetrakis(1-methylpyridin-1-ium-4-yl)-21,23-dihydroporphyrin	704076: Inhibition of telomerase in human HeLa cells using 5’-AAT CCG TCG AGC AGA GTT-3’ as substrate incubated for 15 mins prior to extension reaction by telomeric repeat amplification protocol	ic50	0.0600	uM
7,18-bis[2-(2-hydroxyethylamino)ethyl]-7,18-diazaheptacyclo[14.6.2.22,5.03,12.04,9.013,23.020,24]hexacosa-1(23),2,4,9,11,13,15,20(24),21,25-decaene-6,8,17,19-tetrone	283979: Inhibition of telomerase in JR8 cell extract by TRAP assay	ic50	0.0600	uM
N-[9-(3-methylsulfanylanilino)-6-(3-pyrrolidin-1-ylpropanoylamino)acridin-3-yl]-3-pyrrolidin-1-ylpropanamide	212746: Inhibitory activity against human telomerase	ec50	0.0600	uM
N-[9-(4-aminoanilino)-6-(3-pyrrolidin-1-ylpropanoylamino)acridin-3-yl]-3-pyrrolidin-1-ylpropanamide	770979: Inhibition of telomerase (unknown origin) by TRAP assay	ic50	0.0600	uM
N-[4-[[3,6-bis(3-pyrrolidin-1-ylpropanoylamino)acridin-9-yl]amino]phenyl]-3-pyrrolidin-1-ylpropanamide	257826: Inhibition of telomerase activity from human A2780 cells	ec50	0.0670	uM
N-[9-(4-fluoroanilino)-6-(3-pyrrolidin-1-ylpropanoylamino)acridin-3-yl]-3-pyrrolidin-1-ylpropanamide	212746: Inhibitory activity against human telomerase	ec50	0.0700	uM
2-[2-[[11-(3-aminopropylamino)-5,10-dioxonaphtho[2,3-f][1]benzothiol-4-yl]amino]ethyl]guanidine;hydrochloride	1187844: Inhibition of human telomerase transfected in human HEK293T cells assessed as DNA extension using 5’-d(AATCCGTCGAGCAGAGTT)-3’ substrate by Real-time quantitative telomeric repeat amplification protocol	ic50	0.0700	uM
N’-[4-[[3,6-bis(3-pyrrolidin-1-ylpropanoylamino)acridin-9-yl]amino]phenyl]-N-[6-(diethylamino)hexyl]hexanediamide	240076: Effective concentration against telomerase by TRAP	ec50	0.0800	uM
N-[9-[3-(dimethylamino)propylamino]-6-(3-pyrrolidin-1-ylpropanoylamino)acridin-2-yl]-3-pyrrolidin-1-ylpropanamide	212746: Inhibitory activity against human telomerase	ec50	0.0800	uM
2-[2-[[4-[2-(diaminomethylideneamino)ethylamino]-5,10-dioxonaphtho[2,3-f][1]benzothiol-11-yl]amino]ethyl]guanidine;hydrochloride	1187844: Inhibition of human telomerase transfected in human HEK293T cells assessed as DNA extension using 5’-d(AATCCGTCGAGCAGAGTT)-3’ substrate by Real-time quantitative telomeric repeat amplification protocol	ic50	0.0800	uM
N-[9-(cyclohexylamino)-6-(3-pyrrolidin-1-ylpropanoylamino)acridin-3-yl]-3-pyrrolidin-1-ylpropanamide	212746: Inhibitory activity against human telomerase	ec50	0.0900	uM
3,6,9-tripyrrolidin-1-ylacridine	240050: Concentration required to inhibit 50% of telomerase activity	ec50	0.0900	uM
2-[[(E)-3-naphthalen-2-ylbut-2-enoyl]amino]benzoic acid	2117561: Inhibition of telomerase activity in human HL-60 cells incubated for 96 hrs by TRAP-PCR assay	ic50	0.0910	uM
N’-[4-[[3,6-bis(3-pyrrolidin-1-ylpropanoylamino)acridin-9-yl]amino]phenyl]-N-[2-(diethylamino)ethyl]hexanediamide	240076: Effective concentration against telomerase by TRAP	ec50	0.0980	uM
N-[9-[4-(dimethylamino)anilino]-6-(4-pyrrolidin-1-ylbutanoylamino)acridin-3-yl]-4-pyrrolidin-1-ylbutanamide	257826: Inhibition of telomerase activity from human A2780 cells	ec50	0.0990	uM
N-[9-(3-acetamidoanilino)-6-(3-pyrrolidin-1-ylpropanoylamino)acridin-3-yl]-3-pyrrolidin-1-ylpropanamide	212746: Inhibitory activity against human telomerase	ec50	0.1000	uM
N-[9-[3-(dimethylamino)anilino]-6-(3-pyrrolidin-1-ylpropanoylamino)acridin-3-yl]-3-pyrrolidin-1-ylpropanamide	212746: Inhibitory activity against human telomerase	ec50	0.1000	uM
2-[2-[[11-(2-aminoethylamino)-5,10-dioxonaphtho[2,3-f][1]benzothiol-4-yl]amino]ethyl]guanidine;hydrochloride	1187844: Inhibition of human telomerase transfected in human HEK293T cells assessed as DNA extension using 5’-d(AATCCGTCGAGCAGAGTT)-3’ substrate by Real-time quantitative telomeric repeat amplification protocol	ic50	0.1000	uM
2-(ethylamino)-N-[6-[[2-(ethylamino)acetyl]amino]-9,10-dioxoanthracen-2-yl]acetamide	770979: Inhibition of telomerase (unknown origin) by TRAP assay	ic50	0.1000	uM
3-[2-(3-amino-5-ethyl-6-phenylphenanthridin-5-ium-8-yl)iminohydrazinyl]benzenecarboximidamide	770979: Inhibition of telomerase (unknown origin) by TRAP assay	ic50	0.1000	uM
(2R,4aS,6aR,6aS,14aS,14bR)-10-hydroxy-N-(2-hydroxyethyl)-2,4a,6a,6a,9,14a-hexamethyl-11-oxo-1,3,4,5,6,13,14,14b-octahydropicene-2-carboxamide	1201765: Inhibition of telomerase in human MGC803 cell extracts after 24 hrs by TRAP-PCR-ELISA	ic50	0.1100	uM
N-[4-[[3,6-bis(3-pyrrolidin-1-ylpropanoylamino)acridin-9-yl]amino]phenyl]-4-pyrrolidin-1-ylbutanamide	257826: Inhibition of telomerase activity from human A2780 cells	ec50	0.1170	uM
6,9,12,31,34,37,51,54,58,61-decazaundecacyclo[40.8.4.417,26.14,50.114,18.125,29.139,43.045,53.048,52.020,60.023,59]dohexaconta-1(50),2,4(55),14(62),15,17,19,21,23,25,27,29(57),39(56),40,42,44,46,48,51,53,58,60-docosaene	770979: Inhibition of telomerase (unknown origin) by TRAP assay	ic50	0.1300	uM
2-(3,4-dihydroxyphenyl)-7,8-dihydroxy-4-oxochromene-3-carbonitrile	281989: Inhibition of human telomerase from HEK293 cell extracts by Flash-Plate assay	ic50	0.1300	uM
N-[9-(2-methoxyethylamino)-6-(3-pyrrolidin-1-ylpropanoylamino)acridin-3-yl]-3-pyrrolidin-1-ylpropanamide	212746: Inhibitory activity against human telomerase	ec50	0.1400	uM
[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-aminopropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-sulfanylpropanoyl]phosphinic acid	212753: Inhibitory activity against human telomerase	ic50	0.1400	uM
6-pyrrolidin-1-yl-N-[6-(6-pyrrolidin-1-ylhexanoylamino)-9-[4-(3-pyrrolidin-1-ylpropanoylamino)anilino]acridin-3-yl]hexanamide	257826: Inhibition of telomerase activity from human A2780 cells	ec50	0.1460	uM
N-[[5-[[3-(dimethylamino)propylamino]methyl]acridin-4-yl]methyl]-N’,N’-dimethylpropane-1,3-diamine	437317: Inhibition of human telomerase in A549 cells by TRAP assay	ic50	0.1500	uM

CTD chemical–gene interactions

173 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Arsenic Trioxide	affects cotreatment, increases expression, increases reaction, increases abundance, decreases expression (+5 more)	23
Tretinoin	increases reaction, decreases expression, decreases reaction, decreases response to substance, affects cotreatment (+1 more)	12
Estradiol	increases activity, increases expression, affects cotreatment, decreases reaction	10
sodium arsenite	decreases activity, decreases expression, increases expression, increases methylation	8
Fluorouracil	affects cotreatment, decreases activity, decreases expression, decreases response to substance, affects response to substance (+1 more)	8
Cisplatin	increases response to substance, affects cotreatment, decreases activity, decreases expression, increases expression	5
Doxorubicin	decreases expression, increases expression, decreases response to substance, affects reaction	5
bisphenol A	increases expression, decreases activity, decreases reaction, affects cotreatment, decreases methylation	4
Tamoxifen	decreases activity, increases response to substance, decreases reaction, increases activity, increases expression (+1 more)	4
Sirolimus	decreases expression	4
U 0126	affects cotreatment, decreases reaction, increases expression, decreases activity	3
(+)-JQ1 compound	decreases expression, decreases reaction	3
Decitabine	affects methylation, affects binding, affects reaction, decreases activity, increases response to substance (+2 more)	3
Arsenic	affects methylation, increases expression	3
Hydrogen Peroxide	increases expression, decreases reaction, affects localization, decreases expression, affects expression (+4 more)	3
Quercetin	affects cotreatment, decreases activity, increases activity, increases expression	3
Paclitaxel	increases response to substance, decreases expression, affects cotreatment, decreases activity	3
epigallocatechin gallate	decreases expression	2
arsenic trisulfide	decreases expression, affects response to substance, decreases activity	2
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	decreases reaction, increases phosphorylation, increases activity	2
pterostilbene	decreases expression, decreases reaction, increases reaction	2
NVP-BKM120	affects cotreatment, decreases expression, increases reaction	2
Resveratrol	decreases expression, increases reaction	2
Fulvestrant	affects cotreatment, decreases methylation, decreases reaction, increases expression, decreases expression	2
Acetylcysteine	decreases reaction, increases expression, decreases expression	2
Ethanol	decreases expression, affects reaction, decreases reaction	2
Azacitidine	decreases expression, decreases activity, decreases methylation, affects reaction	2
Benzo(a)pyrene	affects methylation, decreases activity, decreases methylation	2
Formaldehyde	decreases expression, increases expression	2
Glucose	decreases reaction, increases reaction, decreases activity, affects reaction, affects cotreatment (+1 more)	2

ChEMBL screening assays

391 unique, capped per target: 389 binding, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1009424	Binding	Inhibition of telomerase in human H1299 cells at 1 to 20 uM by TRAP assay	Synthesis, human telomerase inhibition and anti-proliferative studies of a series of 2,7-bis-substituted amido-anthraquinone derivatives. — Bioorg Med Chem
CHEMBL857638	Functional	In vitro antiproliferative activity of compound against HT-29 (human colon caner ) cell line was determined by SRB assay	Synthesis of 6-formyl-pyridine-2-carboxylate derivatives and their telomerase inhibitory activities. — Bioorg Med Chem Lett

Cellosaurus cell lines

2,824 cell lines: 1,599 cancer cell line, 914 telomerase immortalized cell line, 257 transformed cell line, 39 conditionally immortalized cell line, 7 finite cell line, 4 induced pluripotent stem cell, 3 embryonic stem cell, 1 spontaneously immortalized cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_0021	U-251MG	Cancer cell line	Male
CVCL_0022	U-87MG ATCC	Cancer cell line	Male
CVCL_0027	Hep-G2	Cancer cell line	Male
CVCL_0036	RT-4	Cancer cell line	Male
CVCL_0039	SK-MEL-30	Cancer cell line	Male
CVCL_0046	HTh83	Cancer cell line	Male
CVCL_0047	TIME	Telomerase immortalized cell line	Male
CVCL_0062	MDA-MB-231	Cancer cell line	Female
CVCL_0069	SK-MEL-2	Cancer cell line	Male
CVCL_0126	5637	Cancer cell line	Male

Clinical trials (associated diseases)

600 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00199147	PHASE4	UNKNOWN	Efficacy of G-CSF-Priming in Elderly AML Patients
NCT00304447	PHASE4	COMPLETED	Study Evaluating the Effect of Corticosteroids on Mylotarg® Infusion-Related Adverse Events in Patients With Leukemia
NCT00464217	PHASE4	COMPLETED	Treatment of the Acute Myeloblastic Leukaemia in Patients Over 65 Years
NCT00487448	PHASE4	COMPLETED	SMD_FLAG-IDA_98: FLAG-IDA in Induction Treatment of High Risk Myelodysplastic Syndromes or Secondary Acute Myeloblastic Leukemia
NCT00488709	PHASE4	COMPLETED	Fludarabine, Cytarabine, Topotecan in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia
NCT00686543	PHASE4	COMPLETED	Oral Posaconazole in High Risk Patients With Gastrointestinal Dysfunction (Study P05115)
NCT01041040	PHASE4	COMPLETED	LAM07: Study to Analyze the Efficacy of a Risk Adapted Treatment Strategy, Including Gemtuzumab Ozogamicin (GO) During Consolidation, for Patients With Acute Myeloid Leukemia (AML)
NCT01198054	PHASE4	TERMINATED	LENA-LMA-5:Lenalidomide in Acute Myeloid Leukemia (AML)
NCT01200355	PHASE4	COMPLETED	Posaconazole Versus Micafungin for Prophylaxis Against Invasive Fungal Infections During Neutropenia in Patients Undergoing Chemotherapy for Acute Myelogenous Leukemia, Acute Lymphocytic Leukemia or Myelodysplastic Syndrome
NCT01347996	PHASE4	COMPLETED	Maintenance Therapy With Ceplene® (Histamine) and IL-2 on Immune Response and MRD in Acute Myeloid Leukemia
NCT01587430	PHASE4	UNKNOWN	3 Anthracyclines, 2 Types of Consolidation With Different ARA-C Doses and Maintenance in Adult Acute Myeloid Leukemia
NCT01819792	PHASE4	COMPLETED	Respiratory Viral Infections During Acute Myeloid Leukemia (AML)Chemotherapy Related Aplasia
NCT02024308	PHASE4	UNKNOWN	AML1-ETO Acute Myeloid Leukemia With Fludarabine and Cytarabine Chemotherapy
NCT02027064	PHASE4	UNKNOWN	Interferon for the Intervention of Molecular Relapse in t (8; 21) AML After Allo-HSCT
NCT02277847	PHASE4	UNKNOWN	Idarubicin at Different Dosages as Induction Therapy for Newly Diagnosed Acute Myeloid Leukaemia
NCT02386800	PHASE4	ACTIVE_NOT_RECRUITING	CINC424A2X01B Rollover Protocol
NCT02926586	PHASE4	COMPLETED	Fludarabine and Cytarabine Versus High-dose Cytarabine for CBF-AML
NCT02933333	PHASE4	UNKNOWN	G-CSF Alone or Combination With GM-CSF on Prevention and Treatment of Infection in Children With Malignant Tumor
NCT03026842	PHASE4	UNKNOWN	Decitabine Versus Conventional Chemotherapy for Maintenance Therapy of Acute Myeloid Leukemia With t(8;21)
NCT03150134	PHASE4	UNKNOWN	Early Tapering of Immunosuppressive Agents to Immunomodulation to Improve Survival of AML Patients
NCT05144243	PHASE4	ACTIVE_NOT_RECRUITING	Study to Assess Adverse Events and Change in Disease State of Oral Venetoclax in Combination With Subcutaneous (SC) Azacitidine in Newly Diagnosed Adult Participants With Acute Myeloid Leukemia (AML) Who Are Ineligible for Intensive Chemotherapy in China
NCT06370000	PHASE4	RECRUITING	Oral Azacitidine in Transplant-Eligible Patients With Acute Myeloid Leukemia (AML) Suffering From Health-Inequality
NCT06571825	PHASE4	RECRUITING	RIC Allo-HSCT vs. Venetoclax-Based Consolidation in Elderly AML Patients After First CR
NCT07016165	PHASE4	RECRUITING	Ciprofloxacin vs Ceftazidime for Empirical Treatment of High-Risk Neutropenic Fever in Children With Hematologic Malignancies
NCT07044687	PHASE4	RECRUITING	Study to Assess Adverse Events and Change in Disease Activity of Oral Venetoclax in Combination With Subcutaneous (SC) or Intravenous (IV) Azacitidine in Newly Diagnosed Adult Participants With Acute Myeloid Leukemia (AML) Who Are Ineligible for Standard Induction Therapy in India
NCT07486713	PHASE4	RECRUITING	Olutasidenib DDI Study in Patients With IDH1 Mutation Positive Malignancies
NCT07561892	PHASE4	RECRUITING	Study of the Effectiveness and Safety of Daunorubicin /Idarubicin ± Silibinin in Treating Newly Diagnosed AML (Non-M3).
NCT00625079	PHASE4	WITHDRAWN	Pulmonary Hypertension Secondary to Idiopathic Pulmonary Fibrosis And Treatment With Sildenafil
NCT00625469	PHASE4	WITHDRAWN	Pulmonary Arterial Hypertension Secondary to Idiopathic Pulmonary Fibrosis and Treatment With Bosentan
NCT00637065	PHASE4	UNKNOWN	Bosentan in Pulmonary Hypertension in Interstitial Lung Disease Treatment Study
NCT01321996	PHASE4	TERMINATED	68Ga-DOTA-NOC PET/CT in Patients With Idiopathic Pulmonary Fibrosis
NCT01382368	PHASE4	UNKNOWN	Acute Effect of Sildenafil on Exercise Tolerance and Functional Capacity in COPD, IPF and Post Pneumonectomy Patients
NCT02579603	PHASE4	COMPLETED	Safety, Tolerability and PK of Nintedanib in Combination With Pirfenidone in IPF
NCT02598193	PHASE4	COMPLETED	Safety and Tolerability Study of Pirfenidone in Combination With Nintedanib in Participants With Idiopathic Pulmonary Fibrosis (IPF)
NCT02606877	PHASE4	COMPLETED	A Study to Compare the Amount of Nintedanib and Pirfenidone in the Blood When Nintedanib and Pirfenidone Are Given Separately or in Combination
NCT02788474	PHASE4	COMPLETED	Effect of Nintedanib on Biomarkers of Extracellular Matrix Turnover in Patients With Idiopathic Pulmonary Fibrosis and Limited Forced Vital Capacity Impairment
NCT03503188	PHASE4	COMPLETED	Digital Auscultation Test - IPF Data Collection
NCT03717012	PHASE4	TERMINATED	Study of Pulmonary Rehabilitation in Patients With Idiopathic Pulmonary Fibrosis (IPF)
NCT03939520	PHASE4	COMPLETED	Management of Progressive Disease in Idiopathic Pulmonary Fibrosis
NCT00000589	PHASE3	COMPLETED	Trial to Reduce Alloimmunization to Platelets (TRAP)