TERF2IP

Summary

TERF2IP (TERF2 interacting protein, HGNC:19246) is a protein-coding gene on chromosome 16q23.1, encoding Telomeric repeat-binding factor 2-interacting protein 1 (Q9NYB0). Acts both as a regulator of telomere function and as a transcription regulator.

Enables G-rich strand telomeric DNA binding activity and phosphatase binding activity. Involved in several processes, including positive regulation of non-canonical NF-kappaB signal transduction; protection from non-homologous end joining at telomere; and regulation of primary metabolic process. Located in chromosome, telomeric region; cytoplasm; and nuclear body. Part of shelterin complex.

Source: NCBI Gene 54386 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 856 total — 1 likely-pathogenic
• Phenotypes (HPO): 11
• Druggable target: yes
• MANE Select transcript: NM_018975

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19246
Approved symbol	TERF2IP
Name	TERF2 interacting protein
Location	16q23.1
Locus type	gene with protein product
Status	Approved
Aliases	RAP1
Ensembl gene	ENSG00000166848
Ensembl biotype	protein_coding
OMIM	605061
Entrez	54386

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 6 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000300086, ENST00000564671, ENST00000569234, ENST00000653858, ENST00000659145, ENST00000898755, ENST00000898756, ENST00000912662

RefSeq mRNA: 1 — MANE Select: NM_018975 NM_018975

CCDS: CCDS32491

Canonical transcript exons

ENST00000300086 — 3 exons

Exon	Start	End
ENSE00001107207	75656207	75657432
ENSE00001107212	75647773	75648552
ENSE00003533850	75654273	75654397

Expression profiles

Bgee: expression breadth ubiquitous, 300 present calls, max score 99.51.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 69.0978 / max 1004.7530, expressed in 1825 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
155039	38.1765	1821
155038	28.5018	1822
155037	1.7646	992
155041	0.5157	213
155036	0.1393	65

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
middle temporal gyrus	UBERON:0002771	99.51	gold quality
Brodmann (1909) area 23	UBERON:0013554	99.41	gold quality
substantia nigra pars compacta	UBERON:0001965	99.26	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.22	gold quality
superior vestibular nucleus	UBERON:0007227	99.11	gold quality
pons	UBERON:0000988	99.09	gold quality
medial globus pallidus	UBERON:0002477	99.02	gold quality
cortical plate	UBERON:0005343	98.97	gold quality
globus pallidus	UBERON:0001875	98.95	gold quality
lateral nuclear group of thalamus	UBERON:0002736	98.87	gold quality
Brodmann (1909) area 9	UBERON:0013540	98.82	gold quality
superior frontal gyrus	UBERON:0002661	98.79	gold quality
medulla oblongata	UBERON:0001896	98.77	gold quality
CA1 field of hippocampus	UBERON:0003881	98.77	gold quality
ventral tegmental area	UBERON:0002691	98.72	gold quality
cerebellar hemisphere	UBERON:0002245	98.70	gold quality
cerebellar cortex	UBERON:0002129	98.69	gold quality
lateral globus pallidus	UBERON:0002476	98.69	gold quality
hypothalamus	UBERON:0001898	98.68	gold quality
ganglionic eminence	UBERON:0004023	98.66	gold quality
occipital lobe	UBERON:0002021	98.65	gold quality
cerebellum	UBERON:0002037	98.65	gold quality
orbitofrontal cortex	UBERON:0004167	98.65	gold quality
prefrontal cortex	UBERON:0000451	98.63	gold quality
parietal lobe	UBERON:0001872	98.63	gold quality
postcentral gyrus	UBERON:0002581	98.61	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	98.61	gold quality
primary visual cortex	UBERON:0002436	98.59	gold quality
nucleus accumbens	UBERON:0001882	98.58	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	98.58	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-7316	yes	15.43
E-MTAB-9221	yes	13.68
E-HCAD-9	yes	7.16
E-GEOD-84465	yes	6.88
E-HCAD-5	no	950.41
E-CURD-97	no	822.94
E-MTAB-10042	no	208.50
E-GEOD-93593	no	11.00
E-CURD-46	no	10.20
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

38 targeting TERF2IP, 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-196A-1-3P	99.99	72.15	2772
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-187-5P	99.74	70.26	1404
HSA-MIR-10393-3P	99.72	66.56	961
HSA-MIR-6801-5P	99.72	66.50	981
HSA-MIR-5003-5P	99.61	69.13	1624
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-4727-5P	99.23	67.55	1154
HSA-MIR-4477B	99.23	70.49	1733
HSA-MIR-5587-5P	99.07	68.58	838
HSA-MIR-625-5P	99.02	68.64	2031
HSA-MIR-3922-5P	98.77	66.53	1059
HSA-MIR-6882-3P	98.23	67.01	1119
HSA-MIR-637	97.91	64.05	1517
HSA-MIR-450A-2-3P	97.91	67.56	1459
HSA-MIR-585-5P	97.54	69.02	955
HSA-MIR-4639-3P	97.54	67.12	787

Literature-anchored findings (GeneRIF, showing 40)

• OZF overexpression in tumours may alter the balance between hRap1 and other telomeric proteins (PMID:15838871)
• 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)
• Suggest a role for cAMP/Epac1/Rap1 pathway in regulating proliferation of pancreatic carcinoma cells. (PMID:18580452)
• Rap1-induced activation of both alpha4beta1 and alphaLbeta2 is defective, autocrine VEGF and chemokine are necessary to activate alpha4beta1 for ligand binding. (PMID:18922916)
• Data show that actin bundle formation and subsequent linkage between actin bundles and VE-cadherin through alpha- and beta-catenins are important for the stabilization of VE-cadherin at the cell-cell contacts in cAMP-Epac-Rap1 signal-activated cells. (PMID:20032304)
• Findings provide the first demonstration that the interplay between Rap1 and E-cadherin along the endocytic recycling pathway serves as a timely and efficient mechanism to regulate hESC self-renewal. (PMID:20039365)
• play a role in telomere regulation and may contribute to the telomeric fusions and chromosomal abnormalities observed in ulcerative colitis; a biomarker for associated cancer risk (PMID:20061197)
• TRF2/RAP1 prevents classical-non-homologous end-joining-mediated end fusion at the initial DNA-dependent protein kinase end binding and activation step. (PMID:20407424)
• Data found that Rap1 binds to both telomeres and to extratelomeric sites through the (TTAGGG)(2) consensus motif. Extratelomeric Rap1-binding sites were enriched at subtelomeric regions. (PMID:20622869)
• levels of Rap1 are positively regulated by NF-kappaB, and human breast cancers with NF-kappaB hyperactivity show elevated levels of cytoplasmic Rap1. (PMID:20622870)
• Mouse gene deletion experiments revealed DNA-damage-response pathways that threaten chromosome ends and how the components of the telomeric shelterin complex prevent activation of these pathways.[Shelterin] (PMID:21209389)
• Rap1 controls cadherin function to regulate somal translocation in the neocortex. (PMID:21315259)
• Study investigated the binding sites of telomeric proteins along human chromosomes; RAP1 and TRF2 could be found on a small number of interstitial sites, including regions that are proximal to genes. (PMID:21423278)
• Lyn controls spatial activation of Rap1 by recruiting the CrkL-C3G protein complex to the leading edge (PMID:21628423)
• N-terminal myr-tagged SKAP1 for membrane binding facilitated constitutive RapL membrane and Rap1 binding and effectively substituted for PI3K and TCR ligation in the activation of LFA-1 in T cells. (PMID:21669874)
• Data uncover a new Epac-Rap1-dependent pathway by which endothelial cells can regulate WPB exocytosis in response to agonists that signal through cAMP. (PMID:22511766)
• as hTRF2 recruits hRap1 to telomeric sequences, hRap1 alters the affinity of hTRF2 and its binding preference on telomeric DNA. Moreover, the TRF2-Rap1 complex has higher ability to re-model telomeric DNA (PMID:23086976)
• these results demonstrate PRL-3 as a novel regulator of NF-kappaB signaling pathway through RAP1. (PMID:23178297)
• Mesenchymal high-grade glioma is maintained by the ID-RAP1 axis. (PMID:23241957)
• These data provide evidence for the involvement of the Epac/Rap1 signaling pathway in cAMP-mediated decidualization of human endometrial stromal cells. (PMID:23352189)
• results reveal an effector pathway for Rap1 in the modulation of Rho signaling and actin dynamics, through which Rap1 modulates endothelial barrier function (PMID:23798437)
• chemokine unresponsiveness in chronic lymphocytic leukemia lymphocytes results from failure of Arf1/phospholipase D1-mediated translocation of Rap1 to the plasma membrane for GTP loading and may be a specific feature of anergy induced by DNA Ags. (PMID:23804711)
• Loss of epithelial integrity in tumorigenesis involves activation of RAP1 via exchange protein directly activated by cAMP (EPAC). (PMID:24316969)
• results indicate that Rap1 miRNA can effectively enhance sensitivity of HepG2 cell line to 5-FU chemotherapy (PMID:24549317)
• These findings reveal Pkp3 as a coordinator of desmosome and adherens junction assembly and maturation through its functional association with Rap1. (PMID:25208567)
• a detailed analysis of individual focal adhesion parameters identified focal adhesion size, sliding and intensity as primary targets of Rap1. (PMID:25447308)
• the conservation of Rap1 reflects its role in transcriptional regulation rather than a function at telomeres. (PMID:25453752)
• Nonsense mutations in the TERF2IP gene in familial melanoma: four families carried TERF2IP variants, which included nonsense mutations in both genes (p.Q320X and p.R364X, respectively). (PMID:25505254)
• C3G/RAP1 activity is involved in the metastatic spread of epithelial ovarian cancer. (PMID:25617801)
• Data show that full-length repressor activator protein 1 (Rap1) binds to full-length telomeric repeat binding factor 2 (TRF2) with high affinity and equimolar ratio. (PMID:25675958)
• Data show that isoform beta2 of the heregulin (HRGbeta2) localizes at telomeres with the telomere-associated proteins TRF2 and RAP1. (PMID:26318724)
• Data indicate telomere-binding protein RAP1 as an interacting partner of isoform beta2 of the heregulin (HRGbeta2). (PMID:26327598)
• In pro-inflammatory macrophages, Rap1 promotes cytokine production via NFkappaB activation favoring a pro-inflammatory environment which may contribute to the development and progression of atherosclerosis. (PMID:26505215)
• Through a combination of biochemical, biophysical and structural approaches, we unveiled a unique mode of assembly between RAP1 and TRF2 (PMID:26748096)
• Rap1 may induce hepatic ischemia reperfusion injury (IRI) through promoting neutrophils inflammatory response. Rap1 may be the potential therapeutic target of attenuating hepatic IRI. (PMID:27050284)
• The Rap1-RIAM-talin axis of integrin activation and blood cell function (PMID:27207789)
• Rap1 activation was dependent on PKA and required Src family kinases and the Rap1 exchanger C3G. (PMID:27531745)
• Rap1GAP functions as a novel suppressor of epithelial mesenchymal transformation and tumor metastasis in gastric cancer, and loss of Rap1GAP predicts poor prognosis. (PMID:28009991)
• RAP1 promotes colorectal cell migration through the regulation of Vimentin and RAP1 may act as a potential target for the diagnosis and therapy of CRC. (PMID:28381157)
• the cytoplasmic RAP1-NF-kappaB-BCL2 axis represents a key pathway to cisplatin resistance in non-small cell lung cancer cells. (PMID:28518145)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	terf2ip	ENSDARG00000103977
mus_musculus	Terf2ip	ENSMUSG00000033430
rattus_norvegicus	Terf2ip	ENSRNOG00000010712

Protein

Protein identifiers

Telomeric repeat-binding factor 2-interacting protein 1 — Q9NYB0 (reviewed: Q9NYB0)

Alternative names: Dopamine receptor-interacting protein 5, Repressor/activator protein 1 homolog

All UniProt accessions (4): Q9NYB0, A0A590UJT3, H3BMI8, H3BR63

UniProt curated annotations — full annotation on UniProt →

Function. Acts both as a regulator of telomere function and as a transcription regulator. Involved in the regulation of telomere length and protection as a component of the shelterin complex (telosome). In contrast to other components of the shelterin complex, it is dispensible for telomere capping and does not participate in the protection of telomeres against non-homologous end-joining (NHEJ)-mediated repair. Instead, it is required to negatively regulate telomere recombination and is essential for repressing homology-directed repair (HDR), which can affect telomere length. Does not bind DNA directly: recruited to telomeric double-stranded 5’-TTAGGG-3’ repeats via its interaction with TERF2. Independently of its function in telomeres, also acts as a transcription regulator: recruited to extratelomeric 5’-TTAGGG-3’ sites via its association with TERF2 or other factors, and regulates gene expression. When cytoplasmic, associates with the I-kappa-B-kinase (IKK) complex and acts as a regulator of the NF-kappa-B signaling by promoting IKK-mediated phosphorylation of RELA/p65, leading to activate expression of NF-kappa-B target genes.

Subunit / interactions. Associates with the I-kappa-B-kinase (IKK) core complex, composed of CHUK, IKBKB and IKBKG. Homodimer. Component of the shelterin complex (telosome) composed of TERF1, TERF2, TINF2, TERF2IP ACD and POT1. Interacts with TERF2; the interaction is direct. Does not interact with TERF1. Interacts with SLX4/BTBD12.

Subcellular location. Nucleus. Cytoplasm. Chromosome. Telomere.

Tissue specificity. Ubiquitous. Highly expressed.

Miscellaneous. Shares a bidirectional promoter with KARS1.

Similarity. Belongs to the RAP1 family.

RefSeq proteins (1): NP_061848* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001357	BRCT_dom	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR015010	TERF2IP_Myb	Domain
IPR021661	Rap1_C	Domain
IPR036420	BRCT_dom_sf	Homologous_superfamily
IPR038104	Rap1_C_sf	Homologous_superfamily
IPR039595	TE2IP/Rap1	Family

Pfam: PF08914, PF11626, PF16589

UniProt features (46 total): helix 12, modified residue 7, strand 7, cross-link 6, region of interest 3, domain 2, turn 2, compositionally biased region 2, initiator methionine 1, chain 1, sequence variant 1, sequence conflict 1, short sequence motif 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
3K6G	X-RAY DIFFRACTION	1.95
4RQI	X-RAY DIFFRACTION	2.44
8RD4	ELECTRON MICROSCOPY	3.58
1FEX	SOLUTION NMR
7OZ0	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NYB0-F1	72.76	0.37

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 (13): 2, 36, 43, 154, 156, 203, 206, 114, 194, 208, 212, 240, 372

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: 225 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, GOBP_RNA_TEMPLATED_DNA_BIOSYNTHETIC_PROCESS, GOBP_CHROMOSOME_ORGANIZATION, GOBP_REGULATION_OF_DNA_RECOMBINATION, PID_TELOMERASE_PATHWAY, GOBP_TELOMERE_CAPPING, REACTOME_MEIOTIC_SYNAPSIS, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_NEGATIVE_REGULATION_OF_DNA_RECOMBINATION, GOBP_TELOMERE_MAINTENANCE_VIA_TELOMERE_LENGTHENING, GOBP_TELOMERE_ORGANIZATION, GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR_VIA_HOMOLOGOUS_RECOMBINATION, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_DNA_REPAIR

GO Biological Process (17): telomere maintenance (GO:0000723), regulation of DNA-templated transcription (GO:0006355), telomere maintenance via telomerase (GO:0007004), regulation of double-strand break repair via homologous recombination (GO:0010569), telomere maintenance via telomere lengthening (GO:0010833), telomere capping (GO:0016233), 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), intracellular signal transduction (GO:0035556), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), negative regulation of DNA recombination at telomere (GO:0048239), protein localization to chromosome, telomeric region (GO:0070198), negative regulation of protein phosphorylation (GO:0001933), obsolete positive regulation of NF-kappaB transcription factor activity (GO:0051092), positive regulation of non-canonical NF-kappaB signal transduction (GO:1901224)

GO Molecular Function (4): phosphatase binding (GO:0019902), telomeric repeat DNA binding (GO:0042162), G-rich strand telomeric DNA binding (GO:0098505), protein binding (GO:0005515)

GO Cellular Component (10): nuclear chromosome (GO:0000228), chromosome, telomeric region (GO:0000781), nuclear telomere cap complex (GO:0000783), male germ cell nucleus (GO:0001673), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), nuclear body (GO:0016604), shelterin complex (GO:0070187), 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
regulation of telomere maintenance	2
intracellular anatomical structure	2
positive regulation of intracellular signal transduction	2
nuclear lumen	2
cellular anatomical structure	2
intracellular membraneless organelle	2
DNA metabolic process	1
telomere organization	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
telomerase activity	1
RNA-templated DNA biosynthetic process	1
telomere maintenance via telomere lengthening	1
telomere-telomerase complex assembly	1
regulation of DNA recombination	1
double-strand break repair via homologous recombination	1
regulation of double-strand break repair	1
telomere capping	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
signal transduction	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
negative regulation of DNA recombination	1
regulation of DNA recombination at telomere	1
protein localization to chromosome	1
regulation of protein phosphorylation	1
protein phosphorylation	1
negative regulation of protein modification process	1
negative regulation of phosphorylation	1
non-canonical NF-kappaB signal transduction	1
regulation of non-canonical NF-kappaB signal transduction	1
enzyme binding	1

Protein interactions and networks

STRING

1719 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TERF2IP	TERF2	Q15554	999
TERF2IP	TINF2	Q9BSI4	998
TERF2IP	TERF1	P54274	997
TERF2IP	POT1	Q9NUX5	970
TERF2IP	ACD	Q96AP0	967
TERF2IP	SLX4IP	Q5VYV7	823
TERF2IP	SLX4	Q8IY92	814
TERF2IP	SLX1A	Q9BQ83	778
TERF2IP	DCLRE1B	Q9H816	755
TERF2IP	TNKS	O95271	754
TERF2IP	TPP1	O14773	744
TERF2IP	MUS81	Q96NY9	723
TERF2IP	EME1	Q96AY2	697
TERF2IP	SUN1	O94901	655
TERF2IP	TERT	O14746	608

IntAct

302 interactions, top by confidence:

A	B	Type	Score
TERF2	TERF2IP	psi-mi:“MI:0915”(physical association)	0.970
TERF2IP	XRCC6	psi-mi:“MI:0915”(physical association)	0.660
POT1	TERF1	psi-mi:“MI:0914”(association)	0.530
PRX	TERF2IP	psi-mi:“MI:0915”(physical association)	0.510
HNRNPK	TERF2IP	psi-mi:“MI:0915”(physical association)	0.510
RABIF	TERF2IP	psi-mi:“MI:0915”(physical association)	0.510
HAGH	TERF2IP	psi-mi:“MI:0915”(physical association)	0.510
MRTO4	TERF2IP	psi-mi:“MI:0915”(physical association)	0.510
RGMA	TERF2IP	psi-mi:“MI:0915”(physical association)	0.510
COTL1	TERF2IP	psi-mi:“MI:0915”(physical association)	0.510
TERF2IP	PEA15	psi-mi:“MI:0915”(physical association)	0.510
SMARCC2	TERF2IP	psi-mi:“MI:0915”(physical association)	0.510
MCM2	TERF2IP	psi-mi:“MI:0915”(physical association)	0.510
TERF2IP	AKR1A1	psi-mi:“MI:0915”(physical association)	0.510
NUDT14	TERF2IP	psi-mi:“MI:0915”(physical association)	0.510
OGFR	TERF2IP	psi-mi:“MI:0915”(physical association)	0.510
BCL7B	TERF2IP	psi-mi:“MI:0915”(physical association)	0.510
TERF2IP	NASP	psi-mi:“MI:0915”(physical association)	0.510
CTBP1	TERF2IP	psi-mi:“MI:0915”(physical association)	0.510
LANCL2	TERF2IP	psi-mi:“MI:0915”(physical association)	0.510
MAGOHB	TERF2IP	psi-mi:“MI:0915”(physical association)	0.510
TOR1AIP1	TERF2IP	psi-mi:“MI:0915”(physical association)	0.510
TERF2IP	XAGE2	psi-mi:“MI:0915”(physical association)	0.510
CRK	TERF2IP	psi-mi:“MI:0915”(physical association)	0.510
TERF2IP	UCHL1	psi-mi:“MI:0915”(physical association)	0.510
TWF2	TERF2IP	psi-mi:“MI:0915”(physical association)	0.510
PPP6R3	TERF2IP	psi-mi:“MI:0915”(physical association)	0.510
IL1RN	TERF2IP	psi-mi:“MI:0915”(physical association)	0.510

BioGRID (675): TERF2 (Affinity Capture-Western), TERF2IP (Affinity Capture-MS), TERF2IP (Affinity Capture-MS), TERF2IP (Affinity Capture-MS), TERF2IP (Affinity Capture-MS), TERF2IP (Affinity Capture-MS), TERF2IP (Two-hybrid), TERF2IP (Co-fractionation), GGCX (Affinity Capture-MS), PPP1R10 (Affinity Capture-MS), TERF2 (Affinity Capture-MS), SLC16A3 (Affinity Capture-MS), WDFY3 (Affinity Capture-MS), POT1 (Affinity Capture-MS), TINF2 (Affinity Capture-MS)

ESM2 similar proteins: A0JNA8, A2AFR3, A2AWP8, F1LXF1, O15034, O94844, O94967, O95267, P11274, P28028, Q01826, Q08BT5, Q14161, Q14CM0, Q15139, Q3UGM2, Q3UHE1, Q4R4I0, Q5R5M3, Q5VUG0, Q5XIS9, Q60611, Q62101, Q66H91, Q68FF6, Q6NZQ4, Q6PAJ1, Q6PB44, Q6ZW49, Q6ZWH5, Q80U28, Q8BWW9, Q8BZ03, Q8CGF6, Q8TCU6, Q8VDD9, Q8VI24, Q96GD3, Q9BZ71, Q9BZL6

Diamond homologs: B8QB46, Q0VCT3, Q4R4I0, Q5EAN7, Q6NYJ3, Q71M44, Q7T0L4, Q91VL8, Q9NYB0

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
TERF2IP	“form complex”	“Shelterin complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 135 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
Processive synthesis on the C-strand of the telomere	5	42.8×	1e-05
Telomere C-strand (Lagging Strand) Synthesis	5	42.8×	1e-05
Removal of the Flap Intermediate from the C-strand	5	35.6×	2e-05
Telomere Extension By Telomerase	6	30.8×	1e-05
Polymerase switching on the C-strand of the telomere	5	23.8×	2e-04
Recognition and association of DNA glycosylase with site containing an affected purine	6	13.8×	3e-04
Cleavage of the damaged purine	6	13.8×	3e-04
Packaging Of Telomere Ends	5	12.3×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of telomere maintenance via telomerase	5	29.3×	1e-04
positive regulation of telomere maintenance	5	20.4×	8e-04
telomere maintenance	7	15.0×	1e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	528
Likely benign	304
Benign	10

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1697789	NM_018975.4(TERF2IP):c.670+1G>A	Likely pathogenic

SpliceAI

602 predictions. Top by Δscore:

Variant	Effect	Δscore
16:75648456:GAGCA:G	donor_gain	1.0000
16:75654267:TAACA:T	acceptor_gain	1.0000
16:75654268:A:AG	acceptor_gain	1.0000
16:75654268:AACAG:A	acceptor_gain	1.0000
16:75654269:A:G	acceptor_gain	1.0000
16:75654269:ACAGA:A	acceptor_gain	1.0000
16:75654270:C:G	acceptor_gain	1.0000
16:75654270:CA:C	acceptor_gain	1.0000
16:75654271:A:AG	acceptor_gain	1.0000
16:75654271:A:T	acceptor_gain	1.0000
16:75654272:G:GC	acceptor_gain	1.0000
16:75654272:G:T	acceptor_gain	1.0000
16:75654272:GA:G	acceptor_gain	1.0000
16:75654272:GAA:G	acceptor_gain	1.0000
16:75654272:GAAC:G	acceptor_gain	1.0000
16:75654272:GAACC:G	acceptor_gain	1.0000
16:75654368:G:GT	donor_gain	1.0000
16:75654379:G:GT	donor_gain	1.0000
16:75654389:G:GT	donor_gain	1.0000
16:75654398:G:GG	donor_gain	1.0000
16:75654398:G:T	donor_loss	1.0000
16:75654399:T:G	donor_loss	1.0000
16:75648525:G:GT	donor_gain	0.9900
16:75648549:GGGG:G	donor_gain	0.9900
16:75648550:GGG:G	donor_gain	0.9900
16:75648550:GGGG:G	donor_gain	0.9900
16:75648551:GGG:G	donor_gain	0.9900
16:75648558:GAGGC:G	donor_gain	0.9900
16:75648561:GC:G	donor_gain	0.9900
16:75654389:G:T	donor_gain	0.9900

AlphaMissense

2603 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:75656495:T:A	W362R	1.000
16:75656495:T:C	W362R	1.000
16:75656497:G:C	W362C	1.000
16:75656497:G:T	W362C	1.000
16:75656589:G:T	R393M	1.000
16:75656590:G:C	R393S	1.000
16:75656590:G:T	R393S	1.000
16:75647944:T:C	F21S	0.999
16:75647973:T:C	F31L	0.999
16:75647974:T:C	F31S	0.999
16:75647975:C:A	F31L	0.999
16:75647975:C:G	F31L	0.999
16:75647976:T:G	Y32D	0.999
16:75647999:G:C	K39N	0.999
16:75647999:G:T	K39N	0.999
16:75648019:T:A	I46N	0.999
16:75648028:G:A	G49D	0.999
16:75648073:T:A	L64Q	0.999
16:75648133:T:A	I84N	0.999
16:75648372:T:A	W164R	0.999
16:75648372:T:C	W164R	0.999
16:75648411:T:A	W177R	0.999
16:75648411:T:C	W177R	0.999
16:75656406:T:A	V332D	0.999
16:75656421:T:C	L337P	0.999
16:75656425:A:C	K338N	0.999
16:75656425:A:T	K338N	0.999
16:75656496:G:C	W362S	0.999
16:75656510:G:C	D367H	0.999
16:75656511:A:T	D367V	0.999

dbSNP variants (sampled 300 via entrez): RS1000165150 (16:75649105 G>A,T), RS1000302079 (16:75649639 C>G), RS1000379607 (16:75654085 G>T), RS1000400061 (16:75651171 C>T), RS1000410971 (16:75654301 G>A,C), RS1000499646 (16:75646483 G>A,C), RS1000855639 (16:75651360 C>G,T), RS1001385854 (16:75652878 T>G), RS1001539120 (16:75649332 T>G), RS1001709982 (16:75648620 G>A,C), RS1002228917 (16:75645872 T>A), RS1002312849 (16:75647525 C>A,G), RS1002388630 (16:75651754 A>G,T), RS1002463113 (16:75655583 T>C), RS1002963082 (16:75655916 A>C,G)

Disease associations

OMIM: gene MIM:605061 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

11 total (11 of 11 shown, HPO-id order):

HPO	Term
HP:0000488	Retinopathy
HP:0000958	Dry skin
HP:0001480	Freckling
HP:0001595	Abnormal hair morphology
HP:0002071	Abnormality of extrapyramidal motor function
HP:0002861	Melanoma
HP:0002894	Neoplasm of the pancreas
HP:0003764	Nevus
HP:0006753	Neoplasm of the stomach
HP:0100013	Neoplasm of the breast
HP:0100763	Abnormality of the lymphatic system

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST006190_3	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	7.000000e-08
GCST006192_51	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	1.000000e-12
GCST006192_74	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	1.000000e-18
GCST006193_36	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	2.000000e-07
GCST006195_18	Systolic blood pressure x smoking status (current vs non-current) interaction (2df test)	2.000000e-12
GCST006195_68	Systolic blood pressure x smoking status (current vs non-current) interaction (2df test)	2.000000e-18
GCST006195_80	Systolic blood pressure x smoking status (current vs non-current) interaction (2df test)	4.000000e-06
GCST007327_7	Smoking status (ever vs never smokers)	2.000000e-08
GCST010796_402	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-09
GCST012053_7	Weight	8.000000e-08
GCST90000047_240	Age at first sexual intercourse	3.000000e-09

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0006336	diastolic blood pressure
EFO:0006527	smoking status measurement
EFO:0006335	systolic blood pressure
EFO:0004318	smoking behavior
EFO:0004327	electrocardiography
EFO:0004338	body weight
EFO:0009749	age at first sexual intercourse measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3751647 (SINGLE PROTEIN)

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

ChEMBL bioactivities

35 potent at pChembl≥5 of 51 total, top 35 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.15	Ki	7	nM	CHEMBL3752561
7.96	Kd	11	nM	CHEMBL4299462
7.96	Kd	11	nM	CHEMBL4299367
7.80	Ki	16	nM	CHEMBL4299459
7.72	Ki	19	nM	CHEMBL3751889
7.72	Ki	19	nM	CHEMBL3752814
7.66	Ki	22	nM	CHEMBL3752958
7.50	Ki	32	nM	CHEMBL3752264
7.28	Ki	53	nM	CHEMBL3754578
7.27	Kd	53.9	nM	CHEMBL5653589
7.27	ED50	53.9	nM	CHEMBL5653589
7.19	IC50	65	nM	CHEMBL3752561
7.00	IC50	100	nM	CHEMBL4299459
6.92	IC50	120	nM	CHEMBL3751889
6.92	IC50	120	nM	CHEMBL3752814
6.89	Ki	130	nM	CHEMBL4299434
6.89	IC50	130	nM	CHEMBL3752958
6.85	Ki	140	nM	CHEMBL4299460
6.75	IC50	180	nM	CHEMBL3752264
6.55	IC50	280	nM	CHEMBL3754578
6.52	Kd	300	nM	CHEMBL3752569
6.21	IC50	610	nM	CHEMBL4299434
6.16	IC50	700	nM	CHEMBL4299460
5.80	Ki	1600	nM	CHEMBL3752803
5.75	Ki	1800	nM	CHEMBL3752883
5.70	Ki	2000	nM	CHEMBL3752069
5.68	Ki	2100	nM	CHEMBL3754122
5.66	Kd	2200	nM	CHEMBL4299443
5.52	Ki	3000	nM	CHEMBL3753586
5.24	Ki	5800	nM	CHEMBL3753717
5.21	Ki	6200	nM	CHEMBL4299431
5.15	IC50	7100	nM	CHEMBL3752803
5.08	IC50	8300	nM	CHEMBL3752883
5.03	IC50	9300	nM	CHEMBL3752069
5.01	IC50	9700	nM	CHEMBL3754122

PubChem BioAssay actives

34 with measured affinity, of 55 total; 21 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
(6S,9S,12S,15S,18R)-6-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[2-[[2-[[(2S,3R)-2-[[(2S,3R)-2-acetamido-3-hydroxybutanoyl]amino]-3-hydroxybutanoyl]amino]-3-(2-chlorophenyl)propanoyl]amino]acetyl]amino]-4-methylsulfanylbutanoyl]amino]-4-methylsulfanylbutanoyl]amino]-3-hydroxybutanoyl]amino]-4-methylpentanoyl]amino]-6-aminohexanoyl]amino]-15-(4-aminobutyl)-N-[(2S)-1-[[(2S)-1-amino-3-hydroxy-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]-12-benzyl-9-methyl-7,10,13,16-tetraoxo-1,8,11,14,17,21,22-heptazabicyclo[18.2.1]tricosa-20(23),21-diene-18-carboxamide	1271752: Competitive binding to RAP1 (unknown origin) incubated for 1 hr by fluorescence polarization-based binding assay	ki	0.0070	uM
4-[[5-[3-[3-[[(2S)-2-[[(2S)-2-[[(6R,9S,12R,15R,18R)-6-[[(2R)-2-[[(2R)-2-[[(2R,3S)-2-[[(2R)-2-[[(2R)-2-[[2-[[(2S)-2-[[(2S,3R)-2-[[(2S,3R)-2-acetamido-3-hydroxybutanoyl]amino]-3-hydroxybutanoyl]amino]-3-phenylpropanoyl]amino]acetyl]amino]-4-methylsulfanylbutanoyl]amino]-4-methylsulfanylbutanoyl]amino]-3-hydroxybutanoyl]amino]-4-methylpentanoyl]amino]-6-aminohexanoyl]amino]-15-(4-aminobutyl)-12-benzyl-9-methyl-7,10,13,16-tetraoxo-1,8,11,14,17,21,22-heptazabicyclo[18.2.1]tricosa-20(23),21-diene-18-carbonyl]amino]-4-methylpentanoyl]amino]-3-hydroxypropanoyl]amino]propanoylamino]propanoylamino]-6-amino-6-oxohexyl]carbamoyl]-2-(3-hydroxy-6-oxoxanthen-9-yl)benzoic acid	1271755: Binding affinity to RAP1 (unknown origin) incubated for 1 to 2 hrs by fluorescence polarization assay	kd	0.0110	uM
4-[[3-[[3-[[(2R,3R)-1-[[(2R,3R)-1-[[(2R)-1-[[2-[[(2R)-1-[[(2R)-1-[[(2R,3R)-1-[[(2R)-1-[[(2R)-6-amino-1-[[(6R,9S,12R,15R,18R)-15-(4-aminobutyl)-18-[[(2S)-1-[[(2R)-1-amino-3-hydroxy-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamoyl]-12-benzyl-9-methyl-7,10,13,16-tetraoxo-1,8,11,14,17,21,22-heptazabicyclo[18.2.1]tricosa-20(23),21-dien-6-yl]amino]-1-oxohexan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-2-oxoethyl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-3-oxopropyl]amino]-3-oxopropyl]carbamoyl]-2-(3-hydroxy-6-oxoxanthen-9-yl)benzoic acid	1271755: Binding affinity to RAP1 (unknown origin) incubated for 1 to 2 hrs by fluorescence polarization assay	kd	0.0110	uM
(6R,9R,12S,15R,18S)-6-[[(2R)-2-[[(2R)-2-[[(2R,3S)-2-[[(2R)-2-[[(2R)-2-[[2-[[2-[[(2S,3S)-2-[[(2S,3S)-2-acetamido-3-hydroxybutanoyl]amino]-3-hydroxybutanoyl]amino]-3-naphthalen-2-ylpropanoyl]amino]acetyl]amino]-4-methylsulfanylbutanoyl]amino]-4-methylsulfanylbutanoyl]amino]-3-hydroxybutanoyl]amino]-4-methylpentanoyl]amino]-6-aminohexanoyl]amino]-15-(4-aminobutyl)-N-[(2R)-1-[[(2S)-1-amino-3-hydroxy-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]-12-benzyl-9-methyl-7,10,13,16-tetraoxo-1,8,11,14,17,21,22-heptazabicyclo[18.2.1]tricosa-20(23),21-diene-18-carboxamide	1271752: Competitive binding to RAP1 (unknown origin) incubated for 1 hr by fluorescence polarization-based binding assay	ki	0.0160	uM
(6S,9S,12S,15S,18R)-6-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[2-[[2-[[(2S,3R)-2-[[(2S,3R)-2-acetamido-3-hydroxybutanoyl]amino]-3-hydroxybutanoyl]amino]-3-phenylpropanoyl]amino]acetyl]amino]-4-methylsulfanylbutanoyl]amino]-4-methylsulfanylbutanoyl]amino]-3-hydroxybutanoyl]amino]-4-methylpentanoyl]amino]-6-aminohexanoyl]amino]-15-(4-aminobutyl)-N-[(2S)-1-[[(2S)-1-amino-3-hydroxy-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]-12-benzyl-9-methyl-7,10,13,16-tetraoxo-1,8,11,14,17,21,22-heptazabicyclo[18.2.1]tricosa-20(23),21-diene-18-carboxamide	1271752: Competitive binding to RAP1 (unknown origin) incubated for 1 hr by fluorescence polarization-based binding assay	ki	0.0190	uM
(6S,9S,12S,15S,18R)-6-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[2-[[2-[[(2S,3R)-2-[[(2S,3R)-2-acetamido-3-hydroxybutanoyl]amino]-3-hydroxybutanoyl]amino]-3-(3-chlorophenyl)propanoyl]amino]acetyl]amino]-4-methylsulfanylbutanoyl]amino]-4-methylsulfanylbutanoyl]amino]-3-hydroxybutanoyl]amino]-4-methylpentanoyl]amino]-6-aminohexanoyl]amino]-15-(4-aminobutyl)-N-[(2S)-1-[[(2S)-1-amino-3-hydroxy-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]-12-benzyl-9-methyl-7,10,13,16-tetraoxo-1,8,11,14,17,21,22-heptazabicyclo[18.2.1]tricosa-20(23),21-diene-18-carboxamide	1271752: Competitive binding to RAP1 (unknown origin) incubated for 1 hr by fluorescence polarization-based binding assay	ki	0.0190	uM
(6S,9S,12S,15S,18R)-6-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[2-[[2-[[(2S,3R)-2-[[(2S,3R)-2-acetamido-3-hydroxybutanoyl]amino]-3-hydroxybutanoyl]amino]-3-(4-chlorophenyl)propanoyl]amino]acetyl]amino]-4-methylsulfanylbutanoyl]amino]-4-methylsulfanylbutanoyl]amino]-3-hydroxybutanoyl]amino]-4-methylpentanoyl]amino]-6-aminohexanoyl]amino]-15-(4-aminobutyl)-N-[(2S)-1-[[(2S)-1-amino-3-hydroxy-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]-12-benzyl-9-methyl-7,10,13,16-tetraoxo-1,8,11,14,17,21,22-heptazabicyclo[18.2.1]tricosa-20(23),21-diene-18-carboxamide	1271752: Competitive binding to RAP1 (unknown origin) incubated for 1 hr by fluorescence polarization-based binding assay	ki	0.0220	uM
(6S,9S,12S,15S,18R)-6-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[2-[[2-[[(2S,3R)-2-[[(2S,3R)-2-acetamido-3-hydroxybutanoyl]amino]-3-hydroxybutanoyl]amino]-3-cyclohexylpropanoyl]amino]acetyl]amino]-4-methylsulfanylbutanoyl]amino]-4-methylsulfanylbutanoyl]amino]-3-hydroxybutanoyl]amino]-4-methylpentanoyl]amino]-6-aminohexanoyl]amino]-15-(4-aminobutyl)-N-[(2S)-1-[[(2S)-1-amino-3-hydroxy-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]-12-benzyl-9-methyl-7,10,13,16-tetraoxo-1,8,11,14,17,21,22-heptazabicyclo[18.2.1]tricosa-20(23),21-diene-18-carboxamide	1271752: Competitive binding to RAP1 (unknown origin) incubated for 1 hr by fluorescence polarization-based binding assay	ki	0.0320	uM
(6S,9S,12S,15S,18R)-6-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[2-[[2-[[(2S,3R)-2-[[(2S,3R)-2-acetamido-3-hydroxybutanoyl]amino]-3-hydroxybutanoyl]amino]-4,4-dimethylpentanoyl]amino]acetyl]amino]-4-methylsulfanylbutanoyl]amino]-4-methylsulfanylbutanoyl]amino]-3-hydroxybutanoyl]amino]-4-methylpentanoyl]amino]-6-aminohexanoyl]amino]-15-(4-aminobutyl)-N-[(2S)-1-[[(2S)-1-amino-3-hydroxy-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]-12-benzyl-9-methyl-7,10,13,16-tetraoxo-1,8,11,14,17,21,22-heptazabicyclo[18.2.1]tricosa-20(23),21-diene-18-carboxamide	1271752: Competitive binding to RAP1 (unknown origin) incubated for 1 hr by fluorescence polarization-based binding assay	ki	0.0530	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149570: Binding affinity to human TERF2IP incubated for 45 mins by Kinobead based pull down assay	kd	0.0539	uM
(6R,9R,12S,15R,18S)-6-[[(2R)-2-[[(2R)-2-[[(2R,3R)-2-[[(2R)-2-[[(2R)-2-[[2-[[2-[[(2S,3R)-2-[[(2S,3R)-2-acetamido-3-hydroxybutanoyl]amino]-3-hydroxybutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]acetyl]amino]-4-methylsulfanylbutanoyl]amino]-4-methylsulfanylbutanoyl]amino]-3-hydroxybutanoyl]amino]-4-methylpentanoyl]amino]-6-aminohexanoyl]amino]-15-(4-aminobutyl)-N-[(2R)-1-[[(2S)-1-amino-3-hydroxy-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]-12-benzyl-9-methyl-7,10,13,16-tetraoxo-1,8,11,14,17,21,22-heptazabicyclo[18.2.1]tricosa-20(23),21-diene-18-carboxamide	1271752: Competitive binding to RAP1 (unknown origin) incubated for 1 hr by fluorescence polarization-based binding assay	ki	0.1300	uM
(6R,9S,12R,15R,18R)-6-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3R)-2-[[(2S,3R)-2-[[(2S,3R)-2-acetamido-3-hydroxybutanoyl]amino]-3-hydroxybutanoyl]amino]-3-methylpentanoyl]amino]acetyl]amino]-4-methylsulfanylbutanoyl]amino]-4-methylsulfanylbutanoyl]amino]-3-hydroxybutanoyl]amino]-4-methylpentanoyl]amino]-6-aminohexanoyl]amino]-15-(4-aminobutyl)-N-[(2S)-1-[[(2R)-1-amino-3-hydroxy-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]-12-benzyl-9-methyl-7,10,13,16-tetraoxo-1,8,11,14,17,21,22-heptazabicyclo[18.2.1]tricosa-20(23),21-diene-18-carboxamide	1271752: Competitive binding to RAP1 (unknown origin) incubated for 1 hr by fluorescence polarization-based binding assay	ki	0.1400	uM
4-[[3-[[3-[[(2S,3R)-1-[[(2S,3R)-1-[[(2S,3S)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S,3R)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2R,3R)-1-[[(2S)-1-[[(2S)-1-amino-3-hydroxy-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-2-oxoethyl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-3-oxopropyl]amino]-3-oxopropyl]carbamoyl]-2-(3-hydroxy-6-oxoxanthen-9-yl)benzoic acid	1271755: Binding affinity to RAP1 (unknown origin) incubated for 1 to 2 hrs by fluorescence polarization assay	kd	0.3000	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3S)-2-[[(2S,3R)-2-[[(2S,3R)-2-acetamido-3-hydroxybutanoyl]amino]-3-hydroxybutanoyl]amino]-3-methylpentanoyl]amino]acetyl]amino]-4-methylsulfanylbutanoyl]amino]-4-methylsulfanylbutanoyl]amino]-3-hydroxybutanoyl]amino]-4-methylpentanoyl]amino]-6-aminohexanoyl]amino]propanoyl]amino]propanoyl]amino]-3-phenylpropanoyl]amino]-6-aminohexanoyl]amino]-6-amino-N-[(2S)-1-[[(2S)-1-amino-3-hydroxy-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]hexanamide	1271752: Competitive binding to RAP1 (unknown origin) incubated for 1 hr by fluorescence polarization-based binding assay	ki	1.6000	uM
(2S)-2-[[(2S)-2-[[2-[[(2S,3S)-2-[[(2S,3R)-2-[[(2S,3R)-2-acetamido-3-hydroxybutanoyl]amino]-3-hydroxybutanoyl]amino]-3-methylpentanoyl]amino]acetyl]amino]-4-methylsulfanylbutanoyl]amino]-6-amino-N-[(2S,3R)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S,3R)-1-[[(2S)-1-[[(2S)-1-amino-3-hydroxy-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]hexanamide	1271752: Competitive binding to RAP1 (unknown origin) incubated for 1 hr by fluorescence polarization-based binding assay	ki	1.8000	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3S)-2-[[(2S,3R)-2-[[(2S,3R)-2-acetamido-3-hydroxybutanoyl]amino]-3-hydroxybutanoyl]amino]-3-methylpentanoyl]amino]acetyl]amino]-4-methylsulfanylbutanoyl]amino]-4-methylsulfanylbutanoyl]amino]-3-hydroxybutanoyl]amino]-4-methylpentanoyl]amino]-6-aminohexanoyl]amino]propanoyl]amino]propanoyl]amino]-3-phenylpropanoyl]amino]-6-amino-N-[(2S,3R)-1-[[(2S)-1-[[(2S)-1-amino-3-hydroxy-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]hexanamide	1271752: Competitive binding to RAP1 (unknown origin) incubated for 1 hr by fluorescence polarization-based binding assay	ki	2.0000	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3S)-2-[[(2S,3R)-2-[[(2S,3R)-2-acetamido-3-hydroxybutanoyl]amino]-3-hydroxybutanoyl]amino]-3-methylpentanoyl]amino]acetyl]amino]-4-methylsulfanylbutanoyl]amino]-4-methylsulfanylbutanoyl]amino]-3-hydroxybutanoyl]amino]-4-methylpentanoyl]amino]-6-aminohexanoyl]amino]-6-azidohexanoyl]amino]propanoyl]amino]-3-phenylpropanoyl]amino]-6-amino-N-[(2S)-1-[[(2S)-1-[[(2S)-1-amino-3-hydroxy-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxopent-4-yn-2-yl]hexanamide	1271752: Competitive binding to RAP1 (unknown origin) incubated for 1 hr by fluorescence polarization-based binding assay	ki	2.1000	uM
4-[[5-[3-[3-[[(2R)-2-[[(2R)-2-[[(2S,3S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3R)-2-[[(2S,3R)-2-[[(2S,3R)-2-acetamido-3-hydroxybutanoyl]amino]-3-hydroxybutanoyl]amino]-3-methylpentanoyl]amino]acetyl]amino]-4-methylsulfanylbutanoyl]amino]-4-methylsulfanylbutanoyl]amino]-3-hydroxybutanoyl]amino]-4-methylpentanoyl]amino]-6-aminohexanoyl]amino]propanoyl]amino]propanoyl]amino]-3-phenylpropanoyl]amino]-6-aminohexanoyl]amino]-3-hydroxybutanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxypropanoyl]amino]propanoylamino]propanoylamino]-6-amino-6-oxohexyl]carbamoyl]-2-(3-hydroxy-6-oxoxanthen-9-yl)benzoic acid	1271755: Binding affinity to RAP1 (unknown origin) incubated for 1 to 2 hrs by fluorescence polarization assay	kd	2.2000	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3S)-2-[[(2S,3R)-2-[[(2S,3R)-2-acetamido-3-hydroxybutanoyl]amino]-3-hydroxybutanoyl]amino]-3-methylpentanoyl]amino]acetyl]amino]-4-methylsulfanylbutanoyl]amino]-4-methylsulfanylbutanoyl]amino]-3-hydroxybutanoyl]amino]-4-methylpentanoyl]amino]-6-aminohexanoyl]amino]-6-amino-N-[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S,3R)-1-[[(2S)-1-[[(2S)-1-amino-3-hydroxy-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopropan-2-yl]hexanamide	1271752: Competitive binding to RAP1 (unknown origin) incubated for 1 hr by fluorescence polarization-based binding assay	ki	3.0000	uM
(2S)-2-[[(2S)-2-[[2-[[(2S,3S)-2-[[(2S,3R)-2-[[(2S,3R)-2-acetamido-3-hydroxybutanoyl]amino]-3-hydroxybutanoyl]amino]-3-methylpentanoyl]amino]acetyl]amino]-4-methylsulfanylbutanoyl]amino]-6-amino-N-[(2S,3R)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S,3R)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]hexanamide	1271752: Competitive binding to RAP1 (unknown origin) incubated for 1 hr by fluorescence polarization-based binding assay	ki	5.8000	uM
(6R,9S,12R,15R,18S)-6-[[(2R)-2-[[(2R)-2-[[(2R,3R)-2-[[(2R)-2-[[(2R)-2-[[2-[[(2R,3R)-2-[[(2R,3R)-2-[[(2R,3S)-2-acetamido-3-hydroxybutanoyl]amino]-3-hydroxybutanoyl]amino]-3-methylpentanoyl]amino]acetyl]amino]-4-methylsulfanylbutanoyl]amino]-4-methylsulfanylbutanoyl]amino]-3-hydroxybutanoyl]amino]-4-methylpentanoyl]amino]-6-aminohexanoyl]amino]-15-(4-aminobutyl)-N-[(2R)-1-[[(2S)-1-amino-3-hydroxy-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]-12-benzyl-9-methyl-7,10,13,16-tetraoxo-1,8,11,14,17,21,22-heptazabicyclo[18.2.1]tricosa-20(23),21-diene-18-carboxamide	1271752: Competitive binding to RAP1 (unknown origin) incubated for 1 hr by fluorescence polarization-based binding assay	ki	6.2000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, increases abundance, increases expression	4
Arsenic Trioxide	affects binding, decreases reaction, increases expression	2
Arsenic	increases expression, decreases expression, increases abundance	2
Tobacco Smoke Pollution	increases expression	2
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
potassium chromate(VI)	increases expression, affects cotreatment	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
epigallocatechin gallate	affects cotreatment, increases expression	1
azoxystrobin	decreases expression	1
deguelin	decreases expression	1
fenpyroximate	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
nutlin 3	affects cotreatment, increases secretion	1
abrine	increases expression	1
LDN 193189	affects cotreatment, increases expression	1
picoxystrobin	decreases expression	1
(+)-JQ1 compound	increases expression	1
Acetaminophen	increases expression	1
Caffeine	decreases phosphorylation	1
Dactinomycin	affects cotreatment, increases secretion	1
Doxorubicin	decreases expression	1
Formaldehyde	increases expression	1
Methyl Methanesulfonate	increases expression	1
Thiram	increases expression	1
Urethane	increases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3755499	Binding	Competitive binding to RAP1 (unknown origin) incubated for 1 hr by fluorescence polarization-based binding assay	Design of High-Affinity Stapled Peptides To Target the Repressor Activator Protein 1 (RAP1)/Telomeric Repeat-Binding Factor 2 (TRF2) Protein-Protein Interaction in the Shelterin Complex. — J Med Chem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E2LR	HAP1 TERF2IP (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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