TERF2

Summary

TERF2 (telomeric repeat binding factor 2, HGNC:11729) is a protein-coding gene on chromosome 16q22.1, encoding Telomeric repeat-binding factor 2 (Q15554). Binds the telomeric double-stranded 5’-TTAGGG-3’ repeat and plays a central role in telomere maintenance and protection against end-to-end fusion of chromosomes. It is a common-essential gene (DepMap: required in 96.5% of cancer cell lines).

This gene encodes a telomere specific protein, TERF2, which is a component of the telomere nucleoprotein complex. This protein is present at telomeres in metaphase of the cell cycle, is a second negative regulator of telomere length and plays a key role in the protective activity of telomeres. While having similar telomere binding activity and domain organization, TERF2 differs from TERF1 in that its N terminus is basic rather than acidic.

Source: NCBI Gene 7014 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 59 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 96.5% of screened cell lines (common-essential)
• MANE Select transcript: NM_005652

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11729
Approved symbol	TERF2
Name	telomeric repeat binding factor 2
Location	16q22.1
Locus type	gene with protein product
Status	Approved
Aliases	TRF2
Ensembl gene	ENSG00000132604
Ensembl biotype	protein_coding
OMIM	602027
Entrez	7014

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 11 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000254942, ENST00000564982, ENST00000566051, ENST00000566257, ENST00000566750, ENST00000567130, ENST00000567296, ENST00000567841, ENST00000569280, ENST00000569542, ENST00000569584, ENST00000569611, ENST00000903039, ENST00000930142, ENST00000966429

RefSeq mRNA: 1 — MANE Select: NM_005652 NM_005652

CCDS: CCDS10879

Canonical transcript exons

ENST00000254942 — 10 exons

Exon	Start	End
ENSE00000904612	69357518	69357561
ENSE00000904614	69361404	69361489
ENSE00000904616	69366807	69367199
ENSE00001141451	69355567	69357056
ENSE00003578666	69385391	69385486
ENSE00003638095	69370483	69370629
ENSE00003696379	69368376	69368482
ENSE00003704677	69384580	69384710
ENSE00003786702	69372269	69372355
ENSE00003842710	69385593	69386007

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 94.90.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.6660 / max 169.1686, expressed in 1815 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
157909	11.6005	1792
157907	4.6126	1648
157908	3.8048	1591
157906	0.2416	79
157905	0.2152	89
157903	0.1866	69
157904	0.0047	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	94.90	gold quality
Brodmann (1909) area 46	UBERON:0006483	93.88	gold quality
sural nerve	UBERON:0015488	93.86	gold quality
ventricular zone	UBERON:0003053	93.77	gold quality
ganglionic eminence	UBERON:0004023	92.50	gold quality
postcentral gyrus	UBERON:0002581	92.08	gold quality
colonic epithelium	UBERON:0000397	92.00	gold quality
orbitofrontal cortex	UBERON:0004167	91.69	gold quality
parietal lobe	UBERON:0001872	91.57	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.10	gold quality
prefrontal cortex	UBERON:0000451	90.90	gold quality
gastrocnemius	UBERON:0001388	90.34	gold quality
muscle of leg	UBERON:0001383	90.07	gold quality
frontal cortex	UBERON:0001870	90.04	gold quality
paraflocculus	UBERON:0005351	89.99	gold quality
superior frontal gyrus	UBERON:0002661	89.84	gold quality
hindlimb stylopod muscle	UBERON:0004252	89.83	gold quality
lymph node	UBERON:0000029	89.75	gold quality
neocortex	UBERON:0001950	89.66	gold quality
embryo	UBERON:0000922	89.45	gold quality
frontal pole	UBERON:0002795	89.43	gold quality
tonsil	UBERON:0002372	89.38	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	89.38	gold quality
stromal cell of endometrium	CL:0002255	89.30	gold quality
cerebellum	UBERON:0002037	89.06	gold quality
cingulate cortex	UBERON:0003027	89.03	gold quality
cerebral cortex	UBERON:0000956	89.00	gold quality
anterior cingulate cortex	UBERON:0009835	88.95	gold quality
Brodmann (1909) area 9	UBERON:0013540	88.83	gold quality
cerebellar cortex	UBERON:0002129	88.75	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.71

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
ICAM1	Repression
NOS3	Activation

Upstream regulators (CollecTRI, top): REST, SP1

miRNA regulators (miRDB)

68 targeting TERF2, 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-3613-3P	100.00	76.36	7965
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-2681-5P	99.75	67.64	1655
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-187-5P	99.74	70.26	1404
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-1825	99.72	68.11	1089
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-10393-5P	99.65	68.01	1368
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-497-3P	99.61	69.71	1990
HSA-MIR-4452	99.50	68.45	1493
HSA-MIR-4489	99.50	65.56	785
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-4696	99.48	67.48	1040

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 96.5% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• TRF2-mediated end-capping occurs after telomere replication. (PMID:11577237)
• overexpression of TRF2 increased the rate of telomere shortening in primary cells without accelerating senescence (PMID:11923537)
• Co-localises with the interstitial TTAGGG repeats in interstitial telomeres. (PMID:11938440)
• Results showed that targeting of TRF1 and TRF2 to specific telomeres could be induced, and that targeting leads to telomere shortening. This indicates that these proteins act in cis to repress telomere elongation. (PMID:11971978)
• suggestion that TRF2 functions with WRN, and possibly BLM, in a common pathway at telomeric ends (PMID:12181313)
• Down-regulation of TRF1, TRF2 and TIN2 genes is important to maintain telomeric DNA for gastric cancers. (PMID:12530079)
• upregulation of TRF2 may contribute to telomere maintenance in malignant lymphoma (PMID:12915884)
• data show that the telosome reacts after DNA damage by upregulating telomerase activity and TRF2 expression in malignant cells (PMID:14513051)
• TRF2 is a component of neuroglial cells and appears to be involved in the cytoplasmic process formation that is necessary for neural differentiation. (PMID:14741354)
• PARP-2 physically binds to TRF2 with high affinity (PMID:14749375)
• Atomic force microscopy visualization of DNA end-loop formation by TRF2. (PMID:15005708)
• the nucleolus may sequester TRF2 and thereby influences its telomeric functions (PMID:15265990)
• TIN2 mutants defective in binding of TRF1 or TRF2 induce a DNA damage response and destabilize TRF1 and TRF2 at telomeres in human cells. (PMID:15292264)
• TRF2 binds the ATM kinase and can inhibit the ATM-dependent DNA damage response (PMID:15314656)
• TIN2 binds TRF1 and TRF2 simultaneously and stabilizes the TRF2 complex on telomeres (PMID:15316005)
• The enhancement of endothelial progenitor cell migratory activity by statins depends on TRF2 expression. (PMID:15520325)
• X-ray crystal structures of both TRF1- and TRF2-DNA binding domains in complex with telomeric DNA (2.0 and 1.8 angstroms resolution, respectively) show that they recognize the same TAGGGTT binding site by means of homeodomains (PMID:15608617)
• May be involved in multistep hepatocarcinogenesis by playing crucial role in telomere shortening. (PMID:15632001)
• Our results implicate TRF2 in an initial stage of DSB recognition and processing that occurs before association of ATM with DSBs and activation of the ATM-dependent DSB response network. (PMID:15665826)
• TRF2 may have a role in promoting tumorigenesis by accumulating and contributing to the cells’ ability to maintain an indefinite lifespan (PMID:15735711)
• Linking the induction of TRF2 phosphorylation to the DNA damage-response system, providing an example of direct cross-talk via a signaling pathway between these two major cellular processes. (PMID:16223874)
• Expression of TIN2, a gene regulator is increased in TIN2 expression in adult T-cell leukemia. (PMID:16786598)
• coordinated interactions among TPP1, TIN2, TRF1, and TRF2 may ensure robust assembly of the telosome, telomere targeting of its subunits, and, ultimately, regulated telomere maintenance (PMID:16880378)
• TRF2 binds to model replication forks and four-way junctions in vitro in a structure-specific but sequence-independent manner. (PMID:17052985)
• unanticipated nuclease-independent function of XPF in TRF2-mediated telomere shortening (PMID:17055345)
• Overexpression reduces telomeric, but not genomic, single strand break repair. (PMID:17395247)
• Biochemical fractionation and reconstitution revealed that telomere protection is mediated by a RAP1/TRF2 complex, providing evidence for direct role for human RAP1 in protection of telomeric DNA from nonhomologous end-joining at telomeric DNA ends. (PMID:17499040)
• TRF2 plays an essential role in homologous recombination by facilitating the formation of early recombination intermediates. (PMID:17670947)
• our hypothesis is that when the TRF length becomes shorter during tumour progression, the tumour cells can sustain a better tolerance to shorter telomere with the help of both TRF1 and TRF2, but without immediate activation of the telomerase (PMID:17681636)
• TRF2 is critical for the protection of A549 cells from both telomere erosion and DNA double-strand breaks driven by salvicine. (PMID:18025071)
• In alternative lengthening of telomere cells, TRF2 inactivation/silencing triggers cellular senescence and substantial loss of telomeric DNA upon stable TRF2 knockdown. (PMID:18056407)
• TRF1 and TRF2 bind to the dsDNA of telomeres, whereas POT1 binds to the ssDNA portion (PMID:18178559)
• localized the changes in deuterium uptake of hTRF2 as a function of varying amounts of a model oligodeoxynucleotide (PMID:18197706)
• results indicate that binding to the TRFH docking site involves the sequence F/Y-X-L-X-P in shelterin-associated proteins, which contacts the same molecular recognition surface of the TRFH domains of TRF1 & TRF2 with distinct specificities (PMID:18202258)
• Overexpression of TRF2B induces a p53-dependent DNA damage response in normal but not Werner syndrome fibroblasts. TRF2(DeltaB)-induced telomeric-loop homologous-recombination pathway requires WRN helicase. (PMID:18212065)
• Aurora C phosphorylates TRF2 (PMID:18309533)
• Increased TRF2 expression levels are found in T-cell leukemia cell lines and AML patients with poor prognosis. (PMID:18422278)
• we show that endogenous hSNM1B forms foci which colocalize at telomeres with TRF1 and TRF2 (PMID:18468965)
• The protein hSnm1B is stabilized when bound to the telomere-binding protein TRF2 (PMID:18593705)
• In normal B cells, transcriptional mechanisms exert a critical control over TfR1 and TfR2 expression, whereas in CLL post-transcriptional mechanisms seem to play a complementary and perhaps more important role (PMID:18621559)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	terfa	ENSDARG00000039302
mus_musculus	Terf2	ENSMUSG00000031921
rattus_norvegicus	Terf2	ENSRNOG00000020435

Paralogs (1): TERF1 (ENSG00000147601)

Protein

Protein identifiers

Telomeric repeat-binding factor 2 — Q15554 (reviewed: Q15554)

Alternative names: TTAGGG repeat-binding factor 2, Telomeric DNA-binding protein

All UniProt accessions (9): Q15554, H3BR06, H3BR37, H3BTA7, J3KSJ9, J3KSZ6, J3KTN8, U3KQ35, V9GYM1

UniProt curated annotations — full annotation on UniProt →

Function. Binds the telomeric double-stranded 5’-TTAGGG-3’ repeat and plays a central role in telomere maintenance and protection against end-to-end fusion of chromosomes. In addition to its telomeric DNA-binding role, required to recruit a number of factors and enzymes required for telomere protection, including the shelterin complex, TERF2IP/RAP1 and DCLRE1B/Apollo. Component of the shelterin complex (telosome) that is involved in the regulation of telomere length and protection. Shelterin associates with arrays of double-stranded 5’-TTAGGG-3’ repeats added by telomerase and protects chromosome ends; without its protective activity, telomeres are no longer hidden from the DNA damage surveillance and chromosome ends are inappropriately processed by DNA repair pathways. Together with DCLRE1B/Apollo, plays a key role in telomeric loop (T loop) formation by generating 3’ single-stranded overhang at the leading end telomeres: T loops have been proposed to protect chromosome ends from degradation and repair. Required both to recruit DCLRE1B/Apollo to telomeres and activate the exonuclease activity of DCLRE1B/Apollo. Preferentially binds to positive supercoiled DNA. Together with DCLRE1B/Apollo, required to control the amount of DNA topoisomerase (TOP1, TOP2A and TOP2B) needed for telomere replication during fork passage and prevent aberrant telomere topology. Recruits TERF2IP/RAP1 to telomeres, thereby participating in to repressing homology-directed repair (HDR), which can affect telomere length.

Subunit / interactions. Homodimer. Component of the shelterin complex (telosome) composed of TERF1, TERF2, TINF2, TERF2IP/RAP1, ACD and POT1. Interacts with NBN; interaction takes place with unphosphorylated NBN during G1 phase and prevents to prevent ATM activation and non-homologous end joining repair. Interacts with SLX4/BTBD12. Interacts with DCLRE1B/Apollo and TERF2IP/RAP1; the interaction is direct. Interacts with DSP in the nucleus; the interaction is required for DSP telomere binding.

Subcellular location. Nucleus. Chromosome. Telomere.

Tissue specificity. Ubiquitous. Highly expressed in spleen, thymus, prostate, uterus, testis, small intestine, colon and peripheral blood leukocytes.

Post-translational modifications. Phosphorylated upon DNA damage, most probably by ATM. Phosphorylated TERF2 is not bound to telomeric DNA, and rapidly localizes to damage sites. Methylated by PRMT1 at multiple arginines within the N-terminal Arg-rich region. Methylation may control association with telomeres.

Domain organisation. The TRFH dimerization region mediates the interaction with DCLRE1B/Apollo but not TINF2. The HTH domain is an independent structural unit and mediates binding to telomeric DNA.

Isoforms (2)

UniProt ID	Names	Canonical?
Q15554-3	1	yes
Q15554-4	2

RefSeq proteins (1): NP_005643* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001005	SANT/Myb	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR013867	Telomere_rpt-bd_fac_dimer_dom	Domain
IPR017357	TERF1/2	Family
IPR017930	Myb_dom	Domain
IPR030657	TERF2	Family
IPR031902	TERF2_RBM	Domain
IPR036507	Telomere_rpt-bd_fac_dimer_sf	Homologous_superfamily

Pfam: PF00249, PF08558, PF16772

UniProt features (49 total): helix 17, cross-link 6, turn 5, compositionally biased region 4, modified residue 4, region of interest 4, splice variant 2, strand 2, chain 1, domain 1, DNA-binding region 1, sequence variant 1, short sequence motif 1

Structure

Experimental structures (PDB)

18 structures.

PDB	Method	Resolution (Å)
3SJM	X-RAY DIFFRACTION	1.35
1W0U	X-RAY DIFFRACTION	1.8
3K6G	X-RAY DIFFRACTION	1.95
4M7C	X-RAY DIFFRACTION	2.05
6J67	X-RAY DIFFRACTION	2.05
3BU8	X-RAY DIFFRACTION	2.15
7C5D	X-RAY DIFFRACTION	2.15
1H6P	X-RAY DIFFRACTION	2.2
5XYF	X-RAY DIFFRACTION	2.2
4RQI	X-RAY DIFFRACTION	2.44
3BUA	X-RAY DIFFRACTION	2.5
9Q9K	ELECTRON MICROSCOPY	2.59
9Q9J	ELECTRON MICROSCOPY	2.71
9Q9M	ELECTRON MICROSCOPY	2.81
5WQD	X-RAY DIFFRACTION	3
1VF9	SOLUTION NMR
1VFC	SOLUTION NMR
1XG1	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15554-F1	69.36	0.41

Functional residue map

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

Post-translational modifications (10): 59, 60, 230, 365, 287, 335, 353, 369, 375, 452

Function

Pathways and Gene Ontology

Reactome pathways

28 pathways

ID	Pathway
R-HSA-110328	Recognition and association of DNA glycosylase with site containing an affected pyrimidine
R-HSA-110329	Cleavage of the damaged pyrimidine
R-HSA-110330	Recognition and association of DNA glycosylase with site containing an affected purine
R-HSA-110331	Cleavage of the damaged purine
R-HSA-1221632	Meiotic synapsis
R-HSA-171306	Packaging Of Telomere Ends
R-HSA-171319	Telomere Extension By Telomerase
R-HSA-174411	Polymerase switching on the C-strand of the telomere
R-HSA-174414	Processive synthesis on the C-strand of the telomere
R-HSA-174417	Telomere C-strand (Lagging Strand) Synthesis
R-HSA-174430	Telomere C-strand synthesis initiation
R-HSA-174437	Removal of the Flap Intermediate from the C-strand
R-HSA-2559586	DNA Damage/Telomere Stress Induced Senescence
R-HSA-9670095	Inhibition of DNA recombination at telomere
R-HSA-1474165	Reproduction
R-HSA-1500620	Meiosis
R-HSA-157579	Telomere Maintenance
R-HSA-1640170	Cell Cycle
R-HSA-180786	Extension of Telomeres
R-HSA-2262752	Cellular responses to stress
R-HSA-2559583	Cellular Senescence
R-HSA-73884	Base Excision Repair
R-HSA-73886	Chromosome Maintenance
R-HSA-73894	DNA Repair
R-HSA-73927	Depurination
R-HSA-73928	Depyrimidination
R-HSA-73929	Base-Excision Repair, AP Site Formation
R-HSA-8953897	Cellular responses to stimuli

MSigDB gene sets: 254 (showing top): GOBP_RNA_TEMPLATED_DNA_BIOSYNTHETIC_PROCESS, GOBP_CHROMOSOME_ORGANIZATION, GOBP_REGULATION_OF_DNA_RECOMBINATION, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_AXO_DENDRITIC_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_TELOMERE_MAINTENANCE_VIA_TELOMERASE, chr16q22, PID_TELOMERASE_PATHWAY, GOBP_TELOMERE_CAPPING, REACTOME_MEIOTIC_SYNAPSIS, GOBP_CELL_CYCLE_DNA_REPLICATION, GOBP_NEGATIVE_REGULATION_OF_DNA_REPAIR, GOBP_NEGATIVE_REGULATION_OF_DNA_RECOMBINATION, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, GOBP_TELOMERE_MAINTENANCE_VIA_TELOMERE_LENGTHENING

GO Biological Process (23): telomere maintenance (GO:0000723), in utero embryonic development (GO:0001701), RNA-templated DNA biosynthetic process (GO:0006278), telomere capping (GO:0016233), telomeric loop formation (GO:0031627), protection from non-homologous end joining at telomere (GO:0031848), regulation of telomere maintenance (GO:0032204), negative regulation of telomere maintenance (GO:0032205), positive regulation of telomere maintenance (GO:0032206), negative regulation of telomere maintenance via recombination (GO:0032208), regulation of telomere maintenance via telomerase (GO:0032210), negative regulation of telomere maintenance via telomerase (GO:0032211), negative regulation of telomere maintenance via semi-conservative replication (GO:0032214), telomeric D-loop disassembly (GO:0061820), protein localization to chromosome, telomeric region (GO:0070198), cellular senescence (GO:0090398), axonal transport of messenger ribonucleoprotein complex (GO:0099088), negative regulation of telomere single strand break repair (GO:1903824), negative regulation of telomere capping (GO:1904354), negative regulation of telomere maintenance via telomere lengthening (GO:1904357), negative regulation of t-circle formation (GO:1904430), negative regulation of telomeric D-loop disassembly (GO:1905839), negative regulation of cellular senescence (GO:2000773)

GO Molecular Function (9): double-stranded telomeric DNA binding (GO:0003691), enzyme binding (GO:0019899), telomeric repeat DNA binding (GO:0042162), protein homodimerization activity (GO:0042803), protein-containing complex binding (GO:0044877), G-rich strand telomeric DNA binding (GO:0098505), DNA binding (GO:0003677), telomerase activity (GO:0003720), protein binding (GO:0005515)

GO Cellular Component (10): chromosome, telomeric region (GO:0000781), nuclear telomere cap complex (GO:0000783), male germ cell nucleus (GO:0001673), nucleus (GO:0005634), nucleoplasm (GO:0005654), nuclear body (GO:0016604), axon (GO:0030424), shelterin complex (GO:0070187), telomere cap complex (GO:0000782), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
Telomere Maintenance	3
Telomere C-strand (Lagging Strand) Synthesis	3
Depyrimidination	2
Depurination	2
Extension of Telomeres	2
Meiosis	1
Processive synthesis on the C-strand of the telomere	1
Cellular Senescence	1
Reproduction	1
Cell Cycle	1
Chromosome Maintenance	1
Cellular responses to stimuli	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
telomere maintenance	5
negative regulation of telomere maintenance	4
telomere capping	2
regulation of telomere maintenance	2
telomere maintenance via telomerase	2
regulation of telomere maintenance via telomere lengthening	2
binding	2
intracellular membraneless organelle	2
DNA metabolic process	1
telomere organization	1
chordate embryonic development	1
DNA biosynthetic process	1
telomere maintenance in response to DNA damage	1
regulation of chromosome organization	1
regulation of DNA metabolic process	1
negative regulation of DNA metabolic process	1
negative regulation of chromosome organization	1
positive regulation of DNA metabolic process	1
positive regulation of chromosome organization	1
telomere maintenance via recombination	1
regulation of telomere maintenance via recombination	1
negative regulation of mitotic recombination	1
negative regulation of DNA recombination at telomere	1
regulation of DNA biosynthetic process	1
regulation of telomere maintenance via telomerase	1
negative regulation of telomere maintenance via telomere lengthening	1
negative regulation of DNA biosynthetic process	1
negative regulation of cell cycle process	1
telomere maintenance via semi-conservative replication	1
regulation of telomere maintenance via semi-conservative replication	1
telomeric loop disassembly	1
protein localization to chromosome	1
cellular process	1
cellular response to stress	1
axonal transport	1
negative regulation of single strand break repair	1
telomere single strand break repair	1
regulation of telomere capping	1
telomere maintenance via telomere lengthening	1
double-stranded DNA binding	1

Protein interactions and networks

STRING

1848 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TERF2	TINF2	Q9BSI4	999
TERF2	TERF2IP	Q9NYB0	999
TERF2	POT1	Q9NUX5	998
TERF2	ACD	Q96AP0	993
TERF2	TERF1	P54274	988
TERF2	DCLRE1B	Q9H816	968
TERF2	TNKS	O95271	859
TERF2	SLX4	Q8IY92	809
TERF2	ATM	Q13315	747
TERF2	WRN	Q14191	739
TERF2	TPP1	O14773	735
TERF2	MUS81	Q96NY9	733
TERF2	EME1	Q96AY2	688
TERF2	SLX4IP	Q5VYV7	683
TERF2	TERT	O14746	678

IntAct

251 interactions, top by confidence:

A	B	Type	Score
TERF2	TERF2IP	psi-mi:“MI:0915”(physical association)	0.970
TERF2IP	TERF2	psi-mi:“MI:0915”(physical association)	0.970
TERF2IP	TERF2	psi-mi:“MI:0914”(association)	0.970
TERF2	TERF2IP	psi-mi:“MI:0407”(direct interaction)	0.970
DCLRE1B	TERF2	psi-mi:“MI:0915”(physical association)	0.920
TERF2	DCLRE1B	psi-mi:“MI:0915”(physical association)	0.920
TERF2	DCLRE1B	psi-mi:“MI:0403”(colocalization)	0.920
DCLRE1B	TERF2	psi-mi:“MI:0403”(colocalization)	0.920
DCLRE1B	TERF2	psi-mi:“MI:0914”(association)	0.920

BioGRID (520): REST (Co-localization), TERF2 (Affinity Capture-Western), EP300 (Affinity Capture-Western), EP300 (Reconstituted Complex), TERF2 (Biochemical Activity), TERF2 (Affinity Capture-Western), TINF2 (Affinity Capture-Western), TERF2 (Affinity Capture-Western), TERF2 (Affinity Capture-MS), TERF2 (Affinity Capture-MS), TERF2 (Affinity Capture-MS), TERF2 (Affinity Capture-MS), TERF2 (Affinity Capture-MS), TERF2 (Affinity Capture-MS), TERF2 (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8HBI7, A0A1L8HJK9, A0A1L8HTT5, A6NP61, A8T6P4, C0SPG1, C3VD30, F1N4E5, K7SGN7, O35144, O35253, O70240, O88406, O88566, Q15554, Q1XFL1, Q3ZC82, Q4KLH3, Q5HZN9, Q5JTV8, Q5PQX1, Q5R7A3, Q62315, Q68DK7, Q6P1H6, Q6PDM1, Q6PG95, Q6ZPF3, Q76N89, Q7T3T8, Q7T3T9, Q7T3U0, Q7TNY7, Q7TP65, Q7TSX9, Q80SU3, Q80VM8, Q86XL3, Q8IVF5, Q8K3I4

Diamond homologs: B4FT40, C0HIA3, F4I7L1, F4IEY4, O55036, P08283, P27806, P37218, P40267, P54274, P70371, Q15554, Q6WLH3, Q6WLH4, Q6WS85, Q8VWK4, Q8W119, Q9FJW5, Q9M2X3, Q9M5W4, Q9PU53, Q43386, Q6C9I6, O35144, P23444, P26568, P26569, Q00423, Q08865, P52551

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
TERF2	“form complex”	“Shelterin complex”	binding
TERF2	down-regulates	Neurogenesis
HNRNPH2	“down-regulates quantity”	TERF2	“post transcriptional regulation”
HNRNPH1	“down-regulates quantity”	TERF2	“post transcriptional regulation”
TERF2	“down-regulates activity”	ATM	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 157 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
Removal of the Flap Intermediate from the C-strand	6	37.0×	5e-07
Processive synthesis on the C-strand of the telomere	5	37.0×	5e-06
Telomere C-strand (Lagging Strand) Synthesis	5	37.0×	5e-06
Telomere Extension By Telomerase	7	31.0×	2e-07
Extension of Telomeres	5	29.2×	2e-05
Telomere Maintenance	6	21.5×	9e-06
Polymerase switching on the C-strand of the telomere	5	20.5×	9e-05
Packaging Of Telomere Ends	9	19.2×	1e-07

GO biological processes:

GO term	Partners	Fold	FDR
telomere maintenance via telomerase	6	31.0×	6e-06
positive regulation of telomere maintenance	7	25.2×	3e-06
double-strand break repair via nonhomologous end joining	7	20.8×	6e-06
telomere maintenance	11	20.7×	4e-09
DNA damage checkpoint signaling	5	13.8×	2e-03
double-strand break repair	9	12.9×	6e-06
double-strand break repair via homologous recombination	7	7.7×	2e-03
DNA replication	6	7.0×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	27
Likely benign	8
Benign	15

Top pathogenic / likely-pathogenic (0)

SpliceAI

1738 predictions. Top by Δscore:

Variant	Effect	Δscore
16:69357559:CTG:C	acceptor_gain	1.0000
16:69357562:C:CC	acceptor_gain	1.0000
16:69361402:AC:A	donor_gain	1.0000
16:69361403:CC:C	donor_gain	1.0000
16:69361488:CT:C	acceptor_gain	1.0000
16:69366805:A:AC	donor_gain	1.0000
16:69366806:C:CC	donor_gain	1.0000
16:69368479:CCAT:C	acceptor_gain	1.0000
16:69368480:CAT:C	acceptor_gain	1.0000
16:69368480:CATC:C	acceptor_gain	1.0000
16:69368504:C:CT	acceptor_gain	1.0000
16:69368505:A:T	acceptor_gain	1.0000
16:69384570:AGAG:A	donor_gain	1.0000
16:69384574:CCTTA:C	donor_loss	1.0000
16:69384575:CTTA:C	donor_loss	1.0000
16:69384576:TTA:T	donor_loss	1.0000
16:69384577:TA:T	donor_loss	1.0000
16:69384578:A:AC	donor_gain	1.0000
16:69384578:A:AT	donor_loss	1.0000
16:69384578:ACAG:A	donor_gain	1.0000
16:69384579:C:CG	donor_gain	1.0000
16:69384579:CA:C	donor_gain	1.0000
16:69384579:CAG:C	donor_gain	1.0000
16:69384579:CAGC:C	donor_gain	1.0000
16:69384584:T:TA	donor_gain	1.0000
16:69384707:CAGT:C	acceptor_gain	1.0000
16:69384711:C:CC	acceptor_gain	1.0000
16:69385385:CCATA:C	donor_loss	1.0000
16:69385386:CATAC:C	donor_loss	1.0000
16:69385387:ATACC:A	donor_loss	1.0000

AlphaMissense

3525 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:69356926:C:G	R534P	1.000
16:69356932:C:G	R532P	1.000
16:69356933:G:T	R532S	1.000
16:69356937:C:A	K530N	1.000
16:69356937:C:G	K530N	1.000
16:69356956:C:G	R524P	1.000
16:69356991:C:A	W512C	1.000
16:69356991:C:G	W512C	1.000
16:69356992:C:G	W512S	1.000
16:69356993:A:G	W512R	1.000
16:69356993:A:T	W512R	1.000
16:69357028:A:T	V500D	1.000
16:69357051:C:A	W492C	1.000
16:69357051:C:G	W492C	1.000
16:69357052:C:G	W492S	1.000
16:69357053:A:G	W492R	1.000
16:69357053:A:T	W492R	1.000
16:69370613:A:G	L237P	1.000
16:69372351:A:T	V204D	1.000
16:69372354:G:T	A203D	1.000
16:69372355:C:G	A203P	1.000
16:69384582:C:G	A202P	1.000
16:69384590:A:T	V199D	1.000
16:69384665:G:T	A174D	1.000
16:69384666:C:G	A174P	1.000
16:69384669:A:G	S173P	1.000
16:69384674:A:G	L171P	1.000
16:69384674:A:T	L171Q	1.000
16:69384677:G:T	P170Q	1.000
16:69384700:A:C	F162L	1.000

dbSNP variants (sampled 300 via entrez): RS1000103752 (16:69380000 G>A,C), RS1000148338 (16:69379165 T>C), RS1000194006 (16:69361592 C>T), RS1000268440 (16:69373737 G>A), RS1000293508 (16:69361722 A>C), RS1000319754 (16:69373536 G>T), RS1000377936 (16:69367714 G>A), RS1000569172 (16:69367386 T>G), RS1000575206 (16:69361940 C>T), RS1000687745 (16:69355104 A>C,G), RS1000741087 (16:69355322 C>A,G), RS1000806130 (16:69355281 G>C), RS1000869870 (16:69383940 C>T), RS1000881535 (16:69371917 A>G,T), RS1000991203 (16:69372613 T>C)

Disease associations

OMIM: gene MIM:602027 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST005951_13	Body mass index	5.000000e-11
GCST007006_16	Logical memory (delayed recall) in normal cognition	7.000000e-07
GCST007269_292	Pulse pressure	3.000000e-09
GCST009856_19	Leukocyte telomere length	5.000000e-10
GCST010703_183	Brain morphology (MOSTest)	5.000000e-11
GCST011494_72	Daytime nap	1.000000e-12

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004874	memory performance
EFO:0005763	pulse pressure measurement
EFO:0004346	neuroimaging measurement
EFO:0007828	daytime rest measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4296012 (SINGLE PROTEIN)

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

ChEMBL bioactivities

25 potent at pChembl≥5 of 55 total, top 24 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.05	Ki	90	nM	CHEMBL4166000
6.68	Ki	210	nM	CHEMBL4163499
6.62	Ki	240	nM	CHEMBL4172926
6.48	Ki	330	nM	CHEMBL4782698
6.47	Ki	340	nM	CHEMBL4176290
6.42	Ki	380	nM	CHEMBL4163072
6.29	Ki	510	nM	CHEMBL4161391
6.14	Ki	720	nM	CHEMBL4161856
5.85	Ki	1400	nM	CHEMBL4159482
5.72	Ki	1890	nM	CHEMBL4160402
5.66	Ki	2200	nM	CHEMBL4168423
5.60	Kd	2500	nM	CHEMBL4745325
5.50	Ki	3200	nM	CHEMBL4167227
5.47	Ki	3400	nM	CHEMBL4169779
5.38	Ki	4200	nM	CHEMBL4745325
5.37	Ki	4300	nM	CHEMBL4792503
5.33	Ki	4700	nM	CHEMBL4168052
5.31	Ki	4900	nM	CHEMBL4759024
5.29	Ki	5100	nM	CHEMBL4746160
5.28	Ki	5200	nM	CHEMBL4750127
5.21	Ki	6100	nM	CHEMBL4166947
5.16	Ki	6900	nM	CHEMBL4745167
5.07	Ki	8500	nM	CHEMBL4165033
5.06	Ki	8800	nM	CHEMBL4779157

PubChem BioAssay actives

25 with measured affinity, of 63 total; 23 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
(3S,6S,9S,17S,20S)-9-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]propanoyl]amino]-4-methylpentanoyl]amino]-6-aminohexanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-N,N,3-trimethyl-6-(2-methylpropyl)-2,5,8,19-tetraoxo-1,4,7,18-tetrazabicyclo[18.3.0]tricosane-17-carboxamide	1355116: Displacement of 5-((2R,6S,9S,12S,15S,18S,21S,24S)-3-((S)-2-((S)-1-amino-3-methyl-1-oxobutan-2-ylcarbamoyl)pyrrolidine-1-carbonyl)-15-(4-aminobutyl)-2-hydroxy-12-(4-hydroxybenzyl)-6,9,18,24-tetraisobutyl-21-methyl-5,8,11,14,17,20,23,26,29-nonaoxo-4,7,10,13,16,19,22,25,28-nonaazatetratriacontan-34-ylcarbamoyl)-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid from TRF2 TRFH domain (unknown origin) after 30 mins by fluorescence polarization assay	ki	0.0900	uM
(2S)-1-[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]propanoyl]amino]-4-methylpentanoyl]amino]-6-aminohexanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-methylpentanoyl]amino]-2-cyclohexylacetyl]amino]-3-hydroxybutanoyl]-N-[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]pyrrolidine-2-carboxamide	1355116: Displacement of 5-((2R,6S,9S,12S,15S,18S,21S,24S)-3-((S)-2-((S)-1-amino-3-methyl-1-oxobutan-2-ylcarbamoyl)pyrrolidine-1-carbonyl)-15-(4-aminobutyl)-2-hydroxy-12-(4-hydroxybenzyl)-6,9,18,24-tetraisobutyl-21-methyl-5,8,11,14,17,20,23,26,29-nonaoxo-4,7,10,13,16,19,22,25,28-nonaazatetratriacontan-34-ylcarbamoyl)-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid from TRF2 TRFH domain (unknown origin) after 30 mins by fluorescence polarization assay	ki	0.2100	uM
(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]propanoyl]amino]-4-methylpentanoyl]amino]-6-aminohexanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]propanoyl]-N-[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]pyrrolidine-2-carboxamide	1355116: Displacement of 5-((2R,6S,9S,12S,15S,18S,21S,24S)-3-((S)-2-((S)-1-amino-3-methyl-1-oxobutan-2-ylcarbamoyl)pyrrolidine-1-carbonyl)-15-(4-aminobutyl)-2-hydroxy-12-(4-hydroxybenzyl)-6,9,18,24-tetraisobutyl-21-methyl-5,8,11,14,17,20,23,26,29-nonaoxo-4,7,10,13,16,19,22,25,28-nonaazatetratriacontan-34-ylcarbamoyl)-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid from TRF2 TRFH domain (unknown origin) after 30 mins by fluorescence polarization assay	ki	0.2400	uM
(2S)-1-[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]propanoyl]amino]-4-methylpentanoyl]amino]-6-aminohexanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxybutanoyl]-N-[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]pyrrolidine-2-carboxamide	1675871: Binding affinity to TRFH domain of TRF2 (residues 42 to 245) (unknown origin) by FP based assay	ki	0.3300	uM
(2S)-2-[[(2S)-1-[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]propanoyl]amino]-4-methylpentanoyl]amino]-6-aminohexanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxybutanoyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoic acid	1355116: Displacement of 5-((2R,6S,9S,12S,15S,18S,21S,24S)-3-((S)-2-((S)-1-amino-3-methyl-1-oxobutan-2-ylcarbamoyl)pyrrolidine-1-carbonyl)-15-(4-aminobutyl)-2-hydroxy-12-(4-hydroxybenzyl)-6,9,18,24-tetraisobutyl-21-methyl-5,8,11,14,17,20,23,26,29-nonaoxo-4,7,10,13,16,19,22,25,28-nonaazatetratriacontan-34-ylcarbamoyl)-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid from TRF2 TRFH domain (unknown origin) after 30 mins by fluorescence polarization assay	ki	0.3400	uM
(2S)-2-[[(2S)-1-[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(2-aminoacetyl)amino]-4-methylpentanoyl]amino]propanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxybutanoyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoic acid	1355116: Displacement of 5-((2R,6S,9S,12S,15S,18S,21S,24S)-3-((S)-2-((S)-1-amino-3-methyl-1-oxobutan-2-ylcarbamoyl)pyrrolidine-1-carbonyl)-15-(4-aminobutyl)-2-hydroxy-12-(4-hydroxybenzyl)-6,9,18,24-tetraisobutyl-21-methyl-5,8,11,14,17,20,23,26,29-nonaoxo-4,7,10,13,16,19,22,25,28-nonaazatetratriacontan-34-ylcarbamoyl)-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid from TRF2 TRFH domain (unknown origin) after 30 mins by fluorescence polarization assay	ki	0.3800	uM
(2S)-1-[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]propanoyl]amino]-4-methylpentanoyl]amino]-6-aminohexanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-methylpentanoyl]amino]-2-cyclopentylacetyl]amino]-3-hydroxybutanoyl]-N-[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]pyrrolidine-2-carboxamide	1355116: Displacement of 5-((2R,6S,9S,12S,15S,18S,21S,24S)-3-((S)-2-((S)-1-amino-3-methyl-1-oxobutan-2-ylcarbamoyl)pyrrolidine-1-carbonyl)-15-(4-aminobutyl)-2-hydroxy-12-(4-hydroxybenzyl)-6,9,18,24-tetraisobutyl-21-methyl-5,8,11,14,17,20,23,26,29-nonaoxo-4,7,10,13,16,19,22,25,28-nonaazatetratriacontan-34-ylcarbamoyl)-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid from TRF2 TRFH domain (unknown origin) after 30 mins by fluorescence polarization assay	ki	0.5100	uM
(2S)-1-[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]propanoyl]amino]-4-methylpentanoyl]amino]-6-aminohexanoyl]amino]-3-(4-aminophenyl)propanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxybutanoyl]-N-[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]pyrrolidine-2-carboxamide	1355116: Displacement of 5-((2R,6S,9S,12S,15S,18S,21S,24S)-3-((S)-2-((S)-1-amino-3-methyl-1-oxobutan-2-ylcarbamoyl)pyrrolidine-1-carbonyl)-15-(4-aminobutyl)-2-hydroxy-12-(4-hydroxybenzyl)-6,9,18,24-tetraisobutyl-21-methyl-5,8,11,14,17,20,23,26,29-nonaoxo-4,7,10,13,16,19,22,25,28-nonaazatetratriacontan-34-ylcarbamoyl)-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid from TRF2 TRFH domain (unknown origin) after 30 mins by fluorescence polarization assay	ki	0.7200	uM
(2S)-1-[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]propanoyl]amino]-4-methylpentanoyl]amino]-6-aminohexanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-methylpentanoyl]amino]-3-cyclohexylpropanoyl]amino]-3-hydroxybutanoyl]-N-[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]pyrrolidine-2-carboxamide	1355116: Displacement of 5-((2R,6S,9S,12S,15S,18S,21S,24S)-3-((S)-2-((S)-1-amino-3-methyl-1-oxobutan-2-ylcarbamoyl)pyrrolidine-1-carbonyl)-15-(4-aminobutyl)-2-hydroxy-12-(4-hydroxybenzyl)-6,9,18,24-tetraisobutyl-21-methyl-5,8,11,14,17,20,23,26,29-nonaoxo-4,7,10,13,16,19,22,25,28-nonaazatetratriacontan-34-ylcarbamoyl)-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid from TRF2 TRFH domain (unknown origin) after 30 mins by fluorescence polarization assay	ki	1.4000	uM
(2S)-1-[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]propanoyl]amino]-4-methylpentanoyl]amino]-6-aminohexanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxybutanoyl]pyrrolidine-2-carboxylic acid	1355116: Displacement of 5-((2R,6S,9S,12S,15S,18S,21S,24S)-3-((S)-2-((S)-1-amino-3-methyl-1-oxobutan-2-ylcarbamoyl)pyrrolidine-1-carbonyl)-15-(4-aminobutyl)-2-hydroxy-12-(4-hydroxybenzyl)-6,9,18,24-tetraisobutyl-21-methyl-5,8,11,14,17,20,23,26,29-nonaoxo-4,7,10,13,16,19,22,25,28-nonaazatetratriacontan-34-ylcarbamoyl)-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid from TRF2 TRFH domain (unknown origin) after 30 mins by fluorescence polarization assay	ki	1.8900	uM
(2S)-2-[[(2S)-1-[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-4-methylpentanoyl]amino]propanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxybutanoyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoic acid	1355116: Displacement of 5-((2R,6S,9S,12S,15S,18S,21S,24S)-3-((S)-2-((S)-1-amino-3-methyl-1-oxobutan-2-ylcarbamoyl)pyrrolidine-1-carbonyl)-15-(4-aminobutyl)-2-hydroxy-12-(4-hydroxybenzyl)-6,9,18,24-tetraisobutyl-21-methyl-5,8,11,14,17,20,23,26,29-nonaoxo-4,7,10,13,16,19,22,25,28-nonaazatetratriacontan-34-ylcarbamoyl)-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid from TRF2 TRFH domain (unknown origin) after 30 mins by fluorescence polarization assay	ki	2.2000	uM
(3S,6S,9S,18S,21S)-9-[[3-(cyclopropylmethoxy)-5-phenylmethoxybenzoyl]amino]-N,N,3-trimethyl-6-(2-methylpropyl)-2,5,8,20-tetraoxo-11,16-dioxa-1,4,7,19-tetrazabicyclo[19.3.0]tetracosane-18-carboxamide	1675870: Binding affinity to biotinylated TRF2 (unknown origin) by biolayer interferometry assay	kd	2.5000	uM
(2S)-1-[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]propanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxybutanoyl]-N-[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]pyrrolidine-2-carboxamide	1355116: Displacement of 5-((2R,6S,9S,12S,15S,18S,21S,24S)-3-((S)-2-((S)-1-amino-3-methyl-1-oxobutan-2-ylcarbamoyl)pyrrolidine-1-carbonyl)-15-(4-aminobutyl)-2-hydroxy-12-(4-hydroxybenzyl)-6,9,18,24-tetraisobutyl-21-methyl-5,8,11,14,17,20,23,26,29-nonaoxo-4,7,10,13,16,19,22,25,28-nonaazatetratriacontan-34-ylcarbamoyl)-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid from TRF2 TRFH domain (unknown origin) after 30 mins by fluorescence polarization assay	ki	3.2000	uM
(2S)-1-[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]propanoyl]amino]-4-methylpentanoyl]amino]-6-aminohexanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxybutanoyl]-N-[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]pyrrolidine-2-carboxamide	1355116: Displacement of 5-((2R,6S,9S,12S,15S,18S,21S,24S)-3-((S)-2-((S)-1-amino-3-methyl-1-oxobutan-2-ylcarbamoyl)pyrrolidine-1-carbonyl)-15-(4-aminobutyl)-2-hydroxy-12-(4-hydroxybenzyl)-6,9,18,24-tetraisobutyl-21-methyl-5,8,11,14,17,20,23,26,29-nonaoxo-4,7,10,13,16,19,22,25,28-nonaazatetratriacontan-34-ylcarbamoyl)-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid from TRF2 TRFH domain (unknown origin) after 30 mins by fluorescence polarization assay	ki	3.4000	uM
(3S,6S,9S,18S,21S)-9-[[3-(cyclobutylmethoxy)-5-phenylmethoxybenzoyl]amino]-N,N,3-trimethyl-6-(2-methylpropyl)-2,5,8,20-tetraoxo-11,16-dioxa-1,4,7,19-tetrazabicyclo[19.3.0]tetracosane-18-carboxamide	1675871: Binding affinity to TRFH domain of TRF2 (residues 42 to 245) (unknown origin) by FP based assay	ki	4.3000	uM
(2S)-1-[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]propanoyl]amino]-4-methylpentanoyl]amino]-6-aminohexanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-methylpentanoyl]amino]pentanoyl]amino]-3-hydroxybutanoyl]-N-[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]pyrrolidine-2-carboxamide	1355116: Displacement of 5-((2R,6S,9S,12S,15S,18S,21S,24S)-3-((S)-2-((S)-1-amino-3-methyl-1-oxobutan-2-ylcarbamoyl)pyrrolidine-1-carbonyl)-15-(4-aminobutyl)-2-hydroxy-12-(4-hydroxybenzyl)-6,9,18,24-tetraisobutyl-21-methyl-5,8,11,14,17,20,23,26,29-nonaoxo-4,7,10,13,16,19,22,25,28-nonaazatetratriacontan-34-ylcarbamoyl)-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid from TRF2 TRFH domain (unknown origin) after 30 mins by fluorescence polarization assay	ki	4.7000	uM
(3S,6S,9S,18S,21S)-9-[(3-cyclobutyloxy-5-phenylmethoxybenzoyl)amino]-N,N,3-trimethyl-6-(2-methylpropyl)-2,5,8,20-tetraoxo-11,16-dioxa-1,4,7,19-tetrazabicyclo[19.3.0]tetracosane-18-carboxamide	1675871: Binding affinity to TRFH domain of TRF2 (residues 42 to 245) (unknown origin) by FP based assay	ki	4.9000	uM
(3S,6S,9S,18S,21S)-9-[(3-cyclopentyloxy-5-phenylmethoxybenzoyl)amino]-N,N,3-trimethyl-6-(2-methylpropyl)-2,5,8,20-tetraoxo-11,16-dioxa-1,4,7,19-tetrazabicyclo[19.3.0]tetracosane-18-carboxamide	1675871: Binding affinity to TRFH domain of TRF2 (residues 42 to 245) (unknown origin) by FP based assay	ki	5.1000	uM
(3S,6S,9S,18S,21S)-N,N,3-trimethyl-9-[[3-(2-methylpropoxy)-5-phenylmethoxybenzoyl]amino]-6-(2-methylpropyl)-2,5,8,20-tetraoxo-11,16-dioxa-1,4,7,19-tetrazabicyclo[19.3.0]tetracosane-18-carboxamide	1675871: Binding affinity to TRFH domain of TRF2 (residues 42 to 245) (unknown origin) by FP based assay	ki	5.2000	uM
(2S)-1-[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]propanoyl]amino]-4-methylpentanoyl]amino]-6-aminohexanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-methylpentanoyl]amino]-4,4-dimethylpentanoyl]amino]-3-hydroxybutanoyl]-N-[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]pyrrolidine-2-carboxamide	1355116: Displacement of 5-((2R,6S,9S,12S,15S,18S,21S,24S)-3-((S)-2-((S)-1-amino-3-methyl-1-oxobutan-2-ylcarbamoyl)pyrrolidine-1-carbonyl)-15-(4-aminobutyl)-2-hydroxy-12-(4-hydroxybenzyl)-6,9,18,24-tetraisobutyl-21-methyl-5,8,11,14,17,20,23,26,29-nonaoxo-4,7,10,13,16,19,22,25,28-nonaazatetratriacontan-34-ylcarbamoyl)-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid from TRF2 TRFH domain (unknown origin) after 30 mins by fluorescence polarization assay	ki	6.1000	uM
(3S,6S,9S,18S,21S)-9-[[3-(cyclopentylmethoxy)-5-phenylmethoxybenzoyl]amino]-N,N,3-trimethyl-6-(2-methylpropyl)-2,5,8,20-tetraoxo-11,16-dioxa-1,4,7,19-tetrazabicyclo[19.3.0]tetracosane-18-carboxamide	1675871: Binding affinity to TRFH domain of TRF2 (residues 42 to 245) (unknown origin) by FP based assay	ki	6.9000	uM
(2S)-1-[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]propanoyl]amino]-4-methylpentanoyl]amino]-6-aminohexanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-methylpentanoyl]amino]-3-phenylpropanoyl]amino]-3-hydroxybutanoyl]-N-[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]pyrrolidine-2-carboxamide	1355116: Displacement of 5-((2R,6S,9S,12S,15S,18S,21S,24S)-3-((S)-2-((S)-1-amino-3-methyl-1-oxobutan-2-ylcarbamoyl)pyrrolidine-1-carbonyl)-15-(4-aminobutyl)-2-hydroxy-12-(4-hydroxybenzyl)-6,9,18,24-tetraisobutyl-21-methyl-5,8,11,14,17,20,23,26,29-nonaoxo-4,7,10,13,16,19,22,25,28-nonaazatetratriacontan-34-ylcarbamoyl)-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid from TRF2 TRFH domain (unknown origin) after 30 mins by fluorescence polarization assay	ki	8.5000	uM
2-[3-[[(3S,6S,9S,18S,21S)-18-(dimethylcarbamoyl)-3-methyl-6-(2-methylpropyl)-2,5,8,20-tetraoxo-11,16-dioxa-1,4,7,19-tetrazabicyclo[19.3.0]tetracosan-9-yl]carbamoyl]-5-phenylmethoxyphenoxy]acetic acid	1675871: Binding affinity to TRFH domain of TRF2 (residues 42 to 245) (unknown origin) by FP based assay	ki	8.8000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, decreases expression	3
Fluorouracil	increases expression	2
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
pirinixic acid	increases activity, increases expression, affects binding	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	affects reaction, increases expression, affects cotreatment, decreases expression	1
3,4,5,3’,4’-pentachlorobiphenyl	decreases expression	1
vanadyl sulfate	decreases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
pazopanib	increases expression	1
Arsenic Trioxide	increases expression	1
Arsenic	decreases expression	1
Cadmium	increases abundance, increases expression	1
Catechin	affects cotreatment, increases expression	1
Cisplatin	decreases expression, increases reaction	1
Dimethyl Sulfoxide	affects cotreatment, decreases expression, increases expression	1
Doxorubicin	decreases expression	1
Formaldehyde	decreases expression	1
Ivermectin	decreases expression	1
Lead	decreases expression	1
Piroxicam	decreases expression, increases reaction	1
Tetradecanoylphorbol Acetate	affects reaction, increases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	affects cotreatment, decreases expression, increases expression	1
Antirheumatic Agents	decreases expression	1
Cadmium Chloride	increases abundance, increases expression	1

ChEMBL screening assays

4 unique, capped per target: 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4150013	Binding	Displacement of 5-((2R,6S,9S,12S,15S,18S,21S,24S)-3-((S)-2-((S)-1-amino-3-methyl-1-oxobutan-2-ylcarbamoyl)pyrrolidine-1-carbonyl)-15-(4-aminobutyl)-2-hydroxy-12-(4-hydroxybenzyl)-6,9,18,24-tetraisobutyl-21-methyl-5,8,11,14,17,20,23,26,29-no	Cyclic Peptidic Mimetics of Apollo Peptides Targeting Telomeric Repeat Binding Factor 2 (TRF2) and Apollo Interaction. — ACS Med Chem Lett

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_WM80	HTC75 T19	Cancer cell line	Male
CVCL_WM81	HTC75 T4	Cancer cell line	Male

Clinical trials (associated diseases)

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