POT1

Summary

POT1 (protection of telomeres 1, HGNC:17284) is a protein-coding gene on chromosome 7q31.33, encoding Protection of telomeres protein 1 (Q9NUX5). Component of the telomerase ribonucleoprotein (RNP) complex that is essential for the replication of chromosome termini. It is a selective cancer dependency (DepMap: 39.6% of cell lines).

This gene is a member of the telombin family and encodes a nuclear protein involved in telomere maintenance. Specifically, this protein functions as a member of a multi-protein complex that binds to the TTAGGG repeats of telomeres, regulating telomere length and protecting chromosome ends from illegitimate recombination, catastrophic chromosome instability, and abnormal chromosome segregation. Increased transcriptional expression of this gene is associated with stomach carcinogenesis and its progression. Alternatively spliced transcript variants have been described.

Source: NCBI Gene 25913 — RefSeq curated summary.

At a glance

• Gene–disease (curated): tumor predisposition syndrome 3 (Definitive, ClinGen) — +4 more curated relationships
• GWAS associations: 9
• Clinical variants (ClinVar): 2,606 total — 152 pathogenic, 55 likely-pathogenic
• Phenotypes (HPO): 47
• Druggable target: yes
• Cancer driver (intOGen): activating (oncogene-like) across 5 cancer types
• Cancer dependency (DepMap): dependent in 39.6% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency emerging evidence, triplosensitivity no evidence
• MANE Select transcript: NM_015450

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17284
Approved symbol	POT1
Name	protection of telomeres 1
Location	7q31.33
Locus type	gene with protein product
Status	Approved
Aliases	hPot1, DKFZp586D211
Ensembl gene	ENSG00000128513
Ensembl biotype	protein_coding
OMIM	606478
Entrez	25913

Gene structure

Transcript identifiers

Ensembl transcripts: 42 — 20 protein_coding, 13 nonsense_mediated_decay, 7 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000357628, ENST00000429326, ENST00000430927, ENST00000436534, ENST00000446993, ENST00000461288, ENST00000466483, ENST00000607932, ENST00000608057, ENST00000608126, ENST00000608200, ENST00000608261, ENST00000608437, ENST00000609106, ENST00000609702, ENST00000610141, ENST00000653241, ENST00000653274, ENST00000653819, ENST00000653892, ENST00000654766, ENST00000655761, ENST00000657333, ENST00000657892, ENST00000661898, ENST00000662531, ENST00000664330, ENST00000664366, ENST00000668382, ENST00000669195, ENST00000867252, ENST00000867253, ENST00000867254, ENST00000928341, ENST00000928342, ENST00000928343, ENST00000928344, ENST00000928345, ENST00000928346, ENST00000947756, ENST00000947757, ENST00000947758

RefSeq mRNA: 2 — MANE Select: NM_015450 NM_001042594, NM_015450

CCDS: CCDS5793

Canonical transcript exons

ENST00000357628 — 19 exons

Exon	Start	End
ENSE00001136130	124851872	124851951
ENSE00001136133	124852972	124853138
ENSE00001136138	124858957	124859112
ENSE00001401958	124898261	124898374
ENSE00001404825	124915574	124915646
ENSE00001405298	124928815	124928999
ENSE00001785664	124870911	124871041
ENSE00001863642	124822386	124824074
ENSE00002441395	124846942	124846998
ENSE00002463467	124829254	124829342
ENSE00002488410	124825252	124825357
ENSE00002489750	124840973	124841178
ENSE00002495808	124827214	124827305
ENSE00002498137	124835279	124835414
ENSE00002511886	124842807	124842963
ENSE00003488402	124897165	124897212
ENSE00003596271	124892266	124892380
ENSE00003688811	124863350	124863640
ENSE00003704554	124929794	124929825

Expression profiles

Bgee: expression breadth ubiquitous, 279 present calls, max score 95.95.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.0932 / max 162.8225, expressed in 1732 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
86010	9.2684	1706
86011	1.8247	940

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	95.95	gold quality
germinal epithelium of ovary	UBERON:0001304	93.12	gold quality
calcaneal tendon	UBERON:0003701	91.28	gold quality
sperm	CL:0000019	91.15	gold quality
choroid plexus epithelium	UBERON:0003911	90.96	gold quality
oocyte	CL:0000023	90.85	gold quality
mucosa of stomach	UBERON:0001199	90.83	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.34	gold quality
tibia	UBERON:0000979	89.50	gold quality
ventricular zone	UBERON:0003053	89.23	gold quality
male germ cell	CL:0000015	88.86	gold quality
adrenal tissue	UBERON:0018303	88.54	gold quality
pigmented layer of retina	UBERON:0001782	87.57	gold quality
corpus callosum	UBERON:0002336	87.23	gold quality
ganglionic eminence	UBERON:0004023	86.96	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.69	gold quality
visceral pleura	UBERON:0002401	86.56	gold quality
parietal pleura	UBERON:0002400	86.36	gold quality
nephron tubule	UBERON:0001231	86.17	gold quality
endometrium	UBERON:0001295	86.13	gold quality
endothelial cell	CL:0000115	86.04	gold quality
pleura	UBERON:0000977	86.01	gold quality
amniotic fluid	UBERON:0000173	85.98	gold quality
esophagus squamous epithelium	UBERON:0006920	85.70	gold quality
tendon	UBERON:0000043	85.59	gold quality
islet of Langerhans	UBERON:0000006	85.54	gold quality
Brodmann (1909) area 23	UBERON:0013554	85.11	gold quality
renal glomerulus	UBERON:0000074	84.82	gold quality
tibial artery	UBERON:0007610	84.66	gold quality
popliteal artery	UBERON:0002250	84.65	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.64

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HNRNPK, NR3C1, TBPL1

miRNA regulators (miRDB)

88 targeting POT1, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-8080	99.82	67.52	1342

Functional genomics

ClinGen dosage: haploinsufficiency 2 (emerging evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 39.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Data show that epitope-tagged human protection of telomeres protein (Pot1) localizes to telomeres in interphase nuclei of human cells, consistent with a direct role in telomere end protection. (PMID:12391173)
• the interaction between the TRF1 complex and POT1 affects the loading of POT1 on the single-stranded telomeric DNA, thus transmitting information about telomere length to the telomere terminus, where telomerase is regulated (PMID:12768206)
• hPOT1 can act as a telomerase-dependent, positive regulator of telomere length (PMID:12781132)
• POT1 has a strong sequence preference for the human telomeric repeat tract and can bind both the 3’ telomeric overhang and the displaced TTAGGG repeats at the base of the t-loop (PMID:14715659)
• Changes in POT1 expression levels may be associated with stomach carcinogenesis and progression. (PMID:14744765)
• Data show that a DAT domain mutant of hTERT is efficiently rescued upon fusion to hPot1. (PMID:15060173)
• PTOP heterodimerizes with POT1 and regulates POT1 telomeric recruitment and telomere length. (PMID:15181449)
• crystal structure at a resolution of 1.73 A of the N-terminal half of human POT1 (hPOT1) protein bound to a telomeric single-stranded DNA (ssDNA) decamer, TTAGGGTTAG, the minimum tight-binding sequence indicated by in vitro binding assays (PMID:15558049)
• Pot1 protects chromosome ends from illegitimate recombination, catastrophic chromosome instability, and abnormal chromosome segregation. (PMID:15620654)
• Data show that protection of telomeres 1 (POT1) negatively affects telomerase activity in vitro, and that the DNA binding activity of POT1 is required for telomerase inhibition. (PMID:15632080)
• The reduction of POT1 by RNA interference led to the loss of telomeric single-stranded overhangs and induced apoptosis, chromosomal instability, and senescence in cells. (PMID:15657433)
• depending on its location relative to the DNA 3’-end, protection of telomeres 1 protein (POT1) can either inhibit telomerase action or form a preferred substrate for telomerase (PMID:15792951)
• determines the structure of the 3’ and 5’ ends of human chromosomes (PMID:15973431)
• POT1 and RecQ helicases WRN and BLM have cooperative roles in resolving DNA structures at telomeric ends, in a manner that protects the telomeric 3’ tail as it is exposed during unwinding (PMID:16030011)
• additional role for POT1 in telomere maintenance: disrupting G-quadruplex structures in telomeric DNA, thereby allowing proper elongation by telomerase (PMID:16043710)
• findings highlight the critical role of TPP1 in telomere maintenance, and support a yin-yang model in which TPP1 and POT1 function as a unit to protect human telomeres, by both positively and negatively regulating telomerase access to telomere DNA (PMID:17237767)
• crystal structure of human TPP1 reveals an oligonucleotide/oligosaccharide-binding fold that is structurally similar to the beta-subunit of the telomere end-binding protein of a ciliated protozoan; TPP1 is the missing beta-subunit of human POT1 (PMID:17237768)
• Tpp1 is required for the protective function of Pot1 proteins. (PMID:17632522)
• Pot1 seems to regulate telomere length through direct interaction with the telomere and by preventing a late S/G2 delay in the cell cycle. (PMID:18066078)
• TRF1 and TRF2 bind to the dsDNA of telomeres, whereas POT1 binds to the ssDNA portion (PMID:18178559)
• Data show that Pot1 production is closely associated with telomere length in gastric mucosa and cancers, and that Pot1 might be a good in situ marker for the examination of cell-specific telomere length. (PMID:18425352)
• Binding of POT1 to telomeric single-stranded DNA and association with TPP1 inhibit the localization of RPA, which can function as a DNA damage sensor, to telomeres. (PMID:18519588)
• Diploid human fibroblasts in which hPOT1 expression has been suppressed harbor telomeres that are longer than control cells. (PMID:18922974)
• study shows that human POT1 combines the features of POT1a and POT1b (PMID:18955498)
• POT1v1 and RPA are capable of stimulating WRN helicase on gapped DNA and 5’-overhang substrates, respectively (PMID:19262689)
• Increased expression of POT1 correlates with resistance to radiation in human laryngeal cancer cell lines. (PMID:19424630)
• Studies indicate that TPP1 and POT1can form heterodimers that bind to the telomeric single-stranded DNA, an activity that is central for telomere end capping. (PMID:19648609)
• the association of POT1 with both ssDNA and TRF2 is critical for telomere length homeostasis. (PMID:19651898)
• POT1 binds with higher affinity to telomeric D-loops with 8-oxo-2’-deoxyguanosine. (PMID:19734539)
• Data support RPA enhancement of branch migration during homologous recombination repair and, conversely, POT1 limitation of inappropriate recombination and branch migration at telomeric ends. (PMID:19812417)
• Ctc1-Stn1-Ten1 is a replication protein A (RPA)-like complex that is not directly involved in conventional DNA replication at forks but plays a role in DNA metabolism frequently required by telomeres. (PMID:19854130)
• role for hPOT1 during telomere replication (PMID:20008939)
• Four single nucleotide polymorphisms in the TERT and POT1 genes were significantly related with overall breast cancer risk. (PMID:20056641)
• Results support a model in which POT1-TPP1 enhances telomerase processivity in a manner markedly different from the sliding clamps used by DNA polymerases. (PMID:20094033)
• the protein network surrounding telomere repeat binding factors, TRF1, TRF2, and POT1 using dual-tag affinity purification (PMID:20811636)
• telomeric tails rarely form the maximum potential number of G4 units provides a structural basis for the coexistence of G4 and POT1 on the same DNA molecule (PMID:21183684)
• 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)
• data suggest that hnRNPA1, TERRA and POT1 act in concert to displace RPA from telomeric ssDNA after DNA replication, and promote telomere capping to preserve genomic integrity (PMID:21399625)
• The human POT1-TPP1 complex is a processivity factor for telomerase. (PMID:21461822)
• Multiple POT1-TPP1 proteins coat and compact long telomeric single-stranded DNA. (PMID:21596049)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pot1	ENSDARG00000079915
mus_musculus	Pot1b	ENSMUSG00000024174
mus_musculus	Pot1a	ENSMUSG00000029676
rattus_norvegicus	Pot1	ENSRNOG00000019986
rattus_norvegicus	Pot1b	ENSRNOG00000047439

Protein

Protein identifiers

Protection of telomeres protein 1 — Q9NUX5 (reviewed: Q9NUX5)

Alternative names: POT1-like telomere end-binding protein

All UniProt accessions (12): Q9NUX5, A0A590UJF2, A0A590UJF7, A0A590UJM4, A0A590UJP0, A0A590UJR1, B7Z7M5, C9JPG9, Q5MJ33, Q5MJ34, Q5MJ35, V9GZ00

UniProt curated annotations — full annotation on UniProt →

Function. Component of the telomerase ribonucleoprotein (RNP) complex that is essential for the replication of chromosome termini. Is a component of the double-stranded telomeric DNA-binding TRF1 complex which is involved in the regulation of telomere length by cis-inhibition of telomerase. Also acts as a single-stranded telomeric DNA-binding protein and thus may act as a downstream effector of the TRF1 complex and may transduce information about telomere maintenance and/or length to the telomere terminus. Component of the shelterin complex (telosome) that is involved in the regulation of telomere length and protection. Shelterin associates with arrays of double-stranded TTAGGG 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. Binds to two or more telomeric single-stranded 5’-TTAGGG-3’ repeats (G-strand) and with high specificity to a minimal telomeric single-stranded 5’-TAGGGTTAG-3’ sequence. Binds telomeric single-stranded sequences internally or at proximity of a 3’-end. Its activity is TERT dependent but it does not increase TERT activity by itself. In contrast, the ACD-POT1 heterodimer enhances telomere elongation by increasing telomerase processivity.

Subunit / interactions. Homodimer or homooligomer. Component of the shelterin complex (telosome) composed of TERF1, TERF2, TINF2, TERF2IP, ACD and POT1. Binds single-stranded telomeric DNA as a monomer. Associated component of the telomerase holoenzyme complex. Found in a complex with TERF1, TINF2 and TNKS1. Interacts with TNKS1. Forms heterodimers with ACD. Identified in a complex with ACD and single-stranded telomeric DNA.

Subcellular location. Nucleus. Chromosome. Telomere.

Tissue specificity. Ubiquitous.

Disease relevance. Tumor predisposition syndrome 3 (TPDS3) [MIM:615848] An autosomal dominant disorder characterized by an increased risk for the development of various types of benign and malignant neoplasms throughout life, with age-dependent penetrance. Affected individuals can develop neoplasms involving epithelial, mesenchymal, and neuronal tissues, as well as lymphoid and myeloid cancers. The disorder is associated with elongated telomeres. Disease susceptibility is associated with variants affecting the gene represented in this entry. Cerebroretinal microangiopathy with calcifications and cysts 3 (CRMCC3) [MIM:620368] An autosomal recessive disorder characterized by intrauterine growth retardation, retinal exudates, global developmental delay, neurologic regression, intracranial calcifications, and leukoencephalopathy. The disease may be caused by variants affecting the gene represented in this entry. Pulmonary fibrosis, and/or bone marrow failure syndrome, telomere-related, 8 (PFBMFT8) [MIM:620367] An autosomal dominant disease associated with shortened telomeres. Pulmonary fibrosis is the most common manifestation. Other features include aplastic anemia due to bone marrow failure, hepatic fibrosis, and increased cancer risk. Phenotype, age at onset, and severity are determined by telomere length. PFBMFT8 is characterized by the onset of progressive pulmonary fibrosis in adulthood, signs of bone marrow failure, such as thrombocytopenia, liver dysfunction, and features of dyskeratosis congenita, including premature graying of the hair, in some affected individuals. The disease may be caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the telombin family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NUX5-1	1, Variant 1	yes
Q9NUX5-2	2, Variant 3

RefSeq proteins (2): NP_001036059, NP_056265* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011564	Telomer_end-bd_POT1/Cdc13	Domain
IPR012340	NA-bd_OB-fold	Homologous_superfamily
IPR028389	POT1	Family
IPR032042	POT1PC	Domain
IPR048953	POT1_C_insert	Domain

Pfam: PF02765, PF16686, PF21375

UniProt features (78 total): strand 30, helix 20, sequence variant 14, turn 5, sequence conflict 3, region of interest 2, splice variant 2, chain 1, site 1

Structure

Experimental structures (PDB)

14 structures.

PDB	Method	Resolution (Å)
1XJV	X-RAY DIFFRACTION	1.73
3KJO	X-RAY DIFFRACTION	1.8
3KJP	X-RAY DIFFRACTION	1.8
5H65	X-RAY DIFFRACTION	2.1
5UN7	X-RAY DIFFRACTION	2.1
8SH0	X-RAY DIFFRACTION	2.16
7S1O	X-RAY DIFFRACTION	2.55
7S1U	X-RAY DIFFRACTION	2.55
8SH1	X-RAY DIFFRACTION	2.6
7S1T	X-RAY DIFFRACTION	2.9
8SOJ	ELECTRON MICROSCOPY	3.8
7QXB	ELECTRON MICROSCOPY	3.9
7QXS	ELECTRON MICROSCOPY	3.9
8SOK	ELECTRON MICROSCOPY	4.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NUX5-F1	87.63	0.69

Functional residue map

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

Catalytic / active sites (1): 243 (dna-binding)

Function

Pathways and Gene Ontology

Reactome pathways

14 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

MSigDB gene sets: 293 (showing top): GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, GOBP_RNA_TEMPLATED_DNA_BIOSYNTHETIC_PROCESS, GOBP_CHROMOSOME_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_DNA_BIOSYNTHETIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_TELOMERE_MAINTENANCE_VIA_TELOMERASE, PID_TELOMERASE_PATHWAY, GOBP_TELOMERE_CAPPING, REACTOME_MEIOTIC_SYNAPSIS, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_CHROMOSOME, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_TELOMERE_MAINTENANCE_VIA_TELOMERE_LENGTHENING, GOBP_TELOMERE_ORGANIZATION, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE

GO Biological Process (13): telomere maintenance via telomerase (GO:0007004), telomere capping (GO:0016233), telomere assembly (GO:0032202), positive regulation of telomere maintenance (GO:0032206), regulation of telomere maintenance via telomerase (GO:0032210), negative regulation of telomere maintenance via telomerase (GO:0032211), positive regulation of telomere maintenance via telomerase (GO:0032212), positive regulation of DNA strand elongation (GO:0060383), telomeric D-loop disassembly (GO:0061820), establishment of protein localization to telomere (GO:0070200), positive regulation of telomeric D-loop disassembly (GO:1905840), regulation of double-strand break repair via nonhomologous end joining (GO:2001032), telomere maintenance (GO:0000723)

GO Molecular Function (10): telomerase inhibitor activity (GO:0010521), DEAD/H-box RNA helicase binding (GO:0017151), telomeric repeat DNA binding (GO:0042162), single-stranded telomeric DNA binding (GO:0043047), telomeric D-loop binding (GO:0061821), G-rich strand telomeric DNA binding (GO:0098505), 8-hydroxy-2’-deoxyguanosine DNA binding (GO:1905773), G-rich single-stranded DNA binding (GO:1990955), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (6): chromosome, telomeric region (GO:0000781), nuclear telomere cap complex (GO:0000783), nucleoplasm (GO:0005654), shelterin complex (GO:0070187), nucleus (GO:0005634), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-8 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
telomere maintenance via telomerase	3
telomerase activity	2
telomere maintenance	2
telomere organization	2
positive regulation of DNA metabolic process	2
regulation of telomere maintenance via telomerase	2
RNA-templated DNA biosynthetic process	1
telomere maintenance via telomere lengthening	1
telomere-telomerase complex assembly	1
cellular component assembly	1
regulation of telomere maintenance	1
positive regulation of chromosome organization	1
regulation of telomere maintenance via telomere lengthening	1
regulation of DNA biosynthetic process	1
negative regulation of telomere maintenance via telomere lengthening	1
negative regulation of DNA biosynthetic process	1
positive regulation of telomere maintenance via telomere lengthening	1
positive regulation of DNA biosynthetic process	1
DNA strand elongation	1
regulation of DNA strand elongation	1
telomeric loop disassembly	1
establishment of protein localization to chromosome	1
telomeric D-loop disassembly	1
positive regulation of telomeric loop disassembly	1
regulation of telomeric D-loop disassembly	1
double-strand break repair via nonhomologous end joining	1
regulation of double-strand break repair	1
DNA metabolic process	1
enzyme inhibitor activity	1
enzyme binding	1
sequence-specific DNA binding	1
telomeric repeat DNA binding	1
sequence-specific single stranded DNA binding	1
D-loop DNA binding	1
single-stranded telomeric DNA binding	1
oxidized purine DNA binding	1
single-stranded DNA binding	1
nucleic acid binding	1
binding	1
chromosomal region	1

Protein interactions and networks

STRING

1298 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
POT1	TINF2	Q9BSI4	999
POT1	TERF1	P54274	999
POT1	TERF2	Q15554	998
POT1	ACD	Q96AP0	998
POT1	TPP1	O14773	992
POT1	TERF2IP	Q9NYB0	970
POT1	NUPR2	A6NF83	868
POT1	TNKS	O95271	828
POT1	WRN	Q14191	820
POT1	DCLRE1B	Q9H816	750
POT1	TERT	O14746	742
POT1	CTC1	Q2NKJ3	733
POT1	PINX1	Q96BK5	647
POT1	NOP10	Q9NPE3	646
POT1	GAR1	Q9NY12	604

IntAct

246 interactions, top by confidence:

A	B	Type	Score
ACD	POT1	psi-mi:“MI:0915”(physical association)	0.930
POT1	ACD	psi-mi:“MI:0915”(physical association)	0.930
TERF2	TINF2	psi-mi:“MI:0914”(association)	0.890
POT1	TERF2	psi-mi:“MI:0914”(association)	0.890
POT1	TERF2	psi-mi:“MI:0915”(physical association)	0.890
POT1	TINF2	psi-mi:“MI:0915”(physical association)	0.740
TINF2	POT1	psi-mi:“MI:0915”(physical association)	0.740
TERF2	MCPH1	psi-mi:“MI:0914”(association)	0.580
CFL2	POT1	psi-mi:“MI:0915”(physical association)	0.560
POT1	CFL2	psi-mi:“MI:0915”(physical association)	0.560
POT1	TERF1	psi-mi:“MI:0914”(association)	0.530
POT1	PHYKPL	psi-mi:“MI:0915”(physical association)	0.510
POT1	GFPT2	psi-mi:“MI:0915”(physical association)	0.510
POT1	SYAP1	psi-mi:“MI:0915”(physical association)	0.510
PIPOX	POT1	psi-mi:“MI:0915”(physical association)	0.510
POT1	PROSER2	psi-mi:“MI:0915”(physical association)	0.510
POT1	CNST	psi-mi:“MI:0915”(physical association)	0.510
SULT4A1	POT1	psi-mi:“MI:0915”(physical association)	0.510
POT1	HLCS	psi-mi:“MI:0915”(physical association)	0.510
POT1	MAP4K2	psi-mi:“MI:0915”(physical association)	0.510
POT1	MADD	psi-mi:“MI:0915”(physical association)	0.510
POT1	MAGEA4	psi-mi:“MI:0915”(physical association)	0.510
POT1	PACSIN1	psi-mi:“MI:0915”(physical association)	0.510
POT1	KIAA1191	psi-mi:“MI:0915”(physical association)	0.510
POT1	DOK2	psi-mi:“MI:0915”(physical association)	0.510
POT1	PYM1	psi-mi:“MI:0915”(physical association)	0.510
ALDH3A1	POT1	psi-mi:“MI:0915”(physical association)	0.510

BioGRID (298): POT1 (Affinity Capture-Western), POT1 (Reconstituted Complex), POT1 (Two-hybrid), POT1 (Affinity Capture-MS), ACD (Two-hybrid), POT1 (Reconstituted Complex), PRKDC (Affinity Capture-MS), TERF1 (Affinity Capture-MS), TERF2 (Affinity Capture-MS), AVL9 (Affinity Capture-MS), POT1 (Affinity Capture-MS), POT1 (Affinity Capture-MS), POT1 (Affinity Capture-MS), POT1 (Affinity Capture-MS), POT1 (Affinity Capture-MS)

ESM2 similar proteins: O60939, P01134, P08887, P23510, P25291, P26012, P48030, P51641, P54900, P55259, P78380, Q07212, Q08E08, Q1A730, Q29108, Q2KHT6, Q3SXP7, Q56A07, Q58DF9, Q5H8A4, Q5M7U7, Q5SQ64, Q5ZMH6, Q62522, Q6MG56, Q7M729, Q7M730, Q7YR73, Q7Z6K3, Q864L3, Q86WI3, Q8BHK2, Q8C525, Q8IWT1, Q8R092, Q8TBF5, Q8VE33, Q95K48, Q969P5, Q96IK5

Diamond homologs: P62597, Q91WC1, Q95K48, Q9NUX5

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
POT1	“form complex”	POT1/ACD	binding
POT1	up-regulates	TERT	binding
POT1	“down-regulates activity”	RPA2	binding
POT1	“down-regulates activity”	RPA1	binding
POT1	“down-regulates activity”	RPA3	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 161 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	35.6×	2e-05
Telomere C-strand (Lagging Strand) Synthesis	5	35.6×	2e-05
Removal of the Flap Intermediate from the C-strand	5	29.6×	5e-05
Extension of Telomeres	5	28.1×	5e-05
Telomere Extension By Telomerase	6	25.6×	2e-05
Polymerase switching on the C-strand of the telomere	5	19.8×	3e-04
Telomere Maintenance	5	17.2×	4e-04
Meiosis	5	13.3×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of telomere maintenance	5	17.6×	2e-03
cellular response to heat	7	16.6×	5e-05
glycolytic process	5	13.2×	4e-03
telomere maintenance	7	12.9×	2e-04
substantia nigra development	5	12.6×	4e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 5 cancer types — ANGS, CLLSLL, LGGNOS, MEL, SOFT_TISSUE.

Clinical variants and AI predictions

ClinVar

2606 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	152
Likely pathogenic	55
Uncertain significance	1290
Likely benign	827
Benign	56

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1003943	NM_015450.3(POT1):c.285_286insCT (p.Ile96fs)	Pathogenic
1025033	NC_000007.13:g.(?124510955)(124537227_?)del	Pathogenic
1035359	NM_015450.3(POT1):c.1414_1415insT (p.Ser472fs)	Pathogenic
1036448	NC_000007.13:g.(?124482851)(124483027_?)del	Pathogenic
1036449	NC_000007.13:g.(?124499001)(124511105_?)del	Pathogenic
1042147	NM_015450.3(POT1):c.1262C>A (p.Ser421Ter)	Pathogenic
1045392	NM_015450.3(POT1):c.1030G>T (p.Glu344Ter)	Pathogenic
1052329	NM_015450.3(POT1):c.329dup (p.Leu110fs)	Pathogenic
1052949	NM_015450.3(POT1):c.9+4A>G	Pathogenic
1055178	NM_015450.3(POT1):c.1672dup (p.Tyr558fs)	Pathogenic
1055219	NM_015450.3(POT1):c.1502_1503del (p.Tyr501fs)	Pathogenic
1056550	NM_015450.3(POT1):c.744_745insA (p.Gln249fs)	Pathogenic
1057927	NM_015450.3(POT1):c.777_781del (p.Leu259fs)	Pathogenic
1063217	NM_015450.3(POT1):c.873_885del (p.Asp291fs)	Pathogenic
1064274	NC_000007.13:g.(?124486986)(124537227_?)del	Pathogenic
1315512	NM_015450.3(POT1):c.595C>T (p.Gln199Ter)	Pathogenic
1348991	NM_015450.3(POT1):c.631dup (p.His211fs)	Pathogenic
1360495	NM_015450.3(POT1):c.562_563del (p.Arg188fs)	Pathogenic
139524	NM_015450.3(POT1):c.818G>T (p.Arg273Leu)	Pathogenic
139526	NM_015450.3(POT1):c.1869G>C (p.Gln623His)	Pathogenic
1395307	NM_015450.3(POT1):c.1615C>T (p.Gln539Ter)	Pathogenic
1428610	NM_015450.3(POT1):c.669C>G (p.Tyr223Ter)	Pathogenic
1439061	NM_015450.3(POT1):c.719del (p.Arg240fs)	Pathogenic
1451603	NM_015450.3(POT1):c.1381_1382del (p.Leu460_Ser461insTer)	Pathogenic
1451887	NM_015450.3(POT1):c.118G>T (p.Gly40Ter)	Pathogenic
1451927	NM_015450.3(POT1):c.1593del (p.Ala532fs)	Pathogenic
1452034	NM_015450.3(POT1):c.279_280del (p.Gln94fs)	Pathogenic
1453462	NM_015450.3(POT1):c.258dup (p.Gln87fs)	Pathogenic
1454851	NM_015450.3(POT1):c.1272G>A (p.Trp424Ter)	Pathogenic
1457879	NM_015450.3(POT1):c.1379_1380del (p.Leu460fs)	Pathogenic

SpliceAI

3243 predictions. Top by Δscore:

Variant	Effect	Δscore
7:124824070:TGCAT:T	acceptor_gain	1.0000
7:124824072:CAT:C	acceptor_gain	1.0000
7:124824073:ATCT:A	acceptor_loss	1.0000
7:124824074:TCT:T	acceptor_loss	1.0000
7:124824075:C:CC	acceptor_gain	1.0000
7:124824075:CT:C	acceptor_loss	1.0000
7:124825248:CTA:C	donor_loss	1.0000
7:124825249:TACCA:T	donor_loss	1.0000
7:124825250:A:AC	donor_gain	1.0000
7:124825251:C:CA	donor_loss	1.0000
7:124825251:C:CC	donor_gain	1.0000
7:124825251:CCAAT:C	donor_gain	1.0000
7:124825260:ATT:A	donor_gain	1.0000
7:124825262:T:A	donor_gain	1.0000
7:124825280:AT:A	donor_gain	1.0000
7:124825281:T:C	donor_gain	1.0000
7:124825357:CCT:C	acceptor_gain	1.0000
7:124825359:T:C	acceptor_gain	1.0000
7:124825359:T:TC	acceptor_gain	1.0000
7:124825365:A:AC	acceptor_gain	1.0000
7:124825365:A:C	acceptor_gain	1.0000
7:124825367:G:C	acceptor_gain	1.0000
7:124825367:G:GC	acceptor_gain	1.0000
7:124825368:T:C	acceptor_gain	1.0000
7:124825368:T:TC	acceptor_gain	1.0000
7:124825371:C:CT	acceptor_gain	1.0000
7:124825372:A:AC	acceptor_gain	1.0000
7:124825372:A:C	acceptor_gain	1.0000
7:124825372:A:T	acceptor_gain	1.0000
7:124827212:A:AC	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000003108 (7:124925510 A>G,T), RS1000029700 (7:124928577 C>T), RS1000059775 (7:124848199 G>T), RS1000065795 (7:124930142 G>A), RS1000074577 (7:124848545 A>T), RS1000083991 (7:124849959 C>A,G), RS1000116937 (7:124888859 T>C), RS1000150696 (7:124835786 C>G), RS1000186084 (7:124890378 A>G), RS1000223474 (7:124880383 A>T), RS1000234076 (7:124922500 G>A), RS1000312264 (7:124856176 A>G), RS1000345308 (7:124907144 C>T), RS1000346445 (7:124842739 T>G), RS1000365344 (7:124824431 C>A)

Disease associations

OMIM: gene MIM:606478 | disease phenotypes: MIM:615848, MIM:616568, MIM:620367, MIM:620368, MIM:263200, MIM:615134, MIM:127550, MIM:155600, MIM:137800

GenCC curated gene-disease

Disease	Classification	Inheritance
tumor predisposition syndrome 3	Definitive	Autosomal dominant
pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 8	Strong	Autosomal dominant
thyroid gland carcinoma	Limited	Autosomal dominant
glioma susceptibility 9	Limited	Autosomal dominant
cerebroretinal microangiopathy with calcifications and cysts 3	Limited	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
tumor predisposition syndrome 3	Definitive	AD

Mondo (18): tumor predisposition syndrome 3 (MONDO:0014368), hereditary neoplastic syndrome (MONDO:0015356), pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 8 (MONDO:0957263), cerebroretinal microangiopathy with calcifications and cysts 3 (MONDO:0957264), polycystic kidney disease 4 (MONDO:0033004), melanoma, cutaneous malignant, susceptibility to, 9 (MONDO:0014056), high-grade astrocytoma with piloid features (MONDO:0858958), dyskeratosis congenita (MONDO:0015780), familial melanoma (MONDO:0018961), pleomorphic xanthoastrocytoma (MONDO:0016690), diffuse midline glioma, H3 K27-altered (MONDO:1060171), melanoma, cutaneous malignant, susceptibility to, 1 (MONDO:0007963), breast carcinoma (MONDO:0004989), glioma susceptibility 1 (MONDO:0024498), Hoyeraal-Hreidarsson syndrome (MONDO:0018045)

Orphanet (7): Familial melanoma (Orphanet:618), Inherited cancer-predisposing syndrome (Orphanet:140162), Dyskeratosis congenita (Orphanet:1775), Pleomorphic xanthoastrocytoma (Orphanet:251607), Hoyeraal-Hreidarsson syndrome (Orphanet:3322), Rare constitutional aplastic anemia (Orphanet:68383), Hereditary isolated aplastic anemia (Orphanet:397692)

HPO phenotypes

47 total (30 of 47 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000020	Urinary incontinence
HP:0000488	Retinopathy
HP:0000958	Dry skin
HP:0001082	Cholecystitis
HP:0001147	Retinal exudate
HP:0001217	Clubbing
HP:0001344	Absent speech
HP:0001399	Hepatic failure
HP:0001409	Portal hypertension
HP:0001480	Freckling
HP:0001511	Intrauterine growth retardation
HP:0001595	Abnormal hair morphology
HP:0001744	Splenomegaly
HP:0001873	Thrombocytopenia
HP:0002040	Esophageal varix
HP:0002071	Abnormality of extrapyramidal motor function
HP:0002094	Dyspnea
HP:0002206	Pulmonary fibrosis
HP:0002216	Premature graying of hair
HP:0002239	Gastrointestinal hemorrhage
HP:0002352	Leukoencephalopathy
HP:0002514	Cerebral calcification
HP:0002540	Inability to walk
HP:0002757	Recurrent fractures
HP:0002861	Melanoma
HP:0002894	Neoplasm of the pancreas
HP:0003581	Adult onset
HP:0003596	Middle age onset

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST002299_5	Chronic lymphocytic leukemia	3.000000e-08
GCST003061_10	Cutaneous malignant melanoma	5.000000e-07
GCST003809_4	Response to selective serotonin reuptake inhibitors and depression	1.000000e-06
GCST004146_11	Chronic lymphocytic leukemia	9.000000e-09
GCST008366_10	Leukocyte telomere length	3.000000e-10
GCST008366_18	Leukocyte telomere length	2.000000e-11
GCST009856_6	Leukocyte telomere length	1.000000e-13
GCST010002_262	Refractive error	4.000000e-08
GCST011828_1	Telomere length	1.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005658	response to selective serotonin reuptake inhibitor

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D029502	Anemia, Hypoplastic, Congenital	C15.378.050.085.080; C15.378.190.223.500.500; C16.320.077
D019871	Dyskeratosis Congenita	C15.378.190.223.500.750; C16.131.831.150; C16.320.322.108; C16.320.850.235; C17.800.804.150; C17.800.827.235
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700
C536068	Hoyeraal Hreidarsson syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5908 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, decreases methylation	4
bisphenol A	decreases methylation, increases expression	2
Benzo(a)pyrene	decreases expression, decreases methylation	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
2-methyl-4-isothiazolin-3-one	decreases expression	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	affects expression, affects cotreatment, increases expression, decreases reaction	1
beta-lapachone	decreases expression, increases expression	1
sodium arsenite	decreases expression, increases abundance	1
3,4,5,3’,4’-pentachlorobiphenyl	affects cotreatment, decreases reaction, increases expression, decreases expression, increases reaction	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
jinfukang	decreases expression	1
Bortezomib	decreases expression, decreases reaction	1
Resveratrol	affects cotreatment, increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	decreases expression, increases abundance	1
Dimethyl Sulfoxide	affects cotreatment, decreases reaction, increases expression	1
Doxorubicin	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Testosterone	decreases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Tetradecanoylphorbol Acetate	increases reaction, affects cotreatment, increases expression, decreases expression	1
Tretinoin	affects cotreatment, decreases reaction, increases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	decreases methylation	1
Copper Sulfate	decreases expression	1
tert-Butylhydroperoxide	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1027378	Binding	Inhibition of human 35S-labeled Pot1 binding to human telomeric DNA	BRACO19 analog dimers with improved inhibition of telomerase and hPot 1. — Bioorg Med Chem

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D9NZ	Ubigene HEK293 POT1 KO	Transformed cell line	Female
CVCL_TF24	HAP1 POT1 (-) 1	Cancer cell line	Male
CVCL_XR74	HAP1 POT1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00604318	PHASE4	COMPLETED	Quality of Life, Recombinant TSH (Thyrogen) and Thyroid Cancer
NCT01496313	PHASE4	COMPLETED	To Compare The Effects Of Two Doses Of Vandetanib In Patients With Advanced Medullary Thyroid Cancer
NCT02946918	PHASE4	TERMINATED	Levothyroxine Replacement With Liquid Gel Capsules vs Tablets Post-thyroidectomy
NCT03065218	PHASE4	TERMINATED	99mTc Sestamibi Scans In Thyroglobulin Positive Scan Negative Differentiated Thyroid Cancer (DTC) Patients
NCT03469310	PHASE4	COMPLETED	Minimizing Narcotic Analgesics After Endocrine Surgery
NCT03969108	PHASE4	COMPLETED	Diagnostic Accuracy Study of Indocyanine Green for Parathyroid Perfusion Assessment
NCT05949424	PHASE4	UNKNOWN	OPTI - DOSE: Optimal Dosing of Oral Anticancer Drugs in Older Adults
NCT06697782	PHASE4	COMPLETED	Aprepitant and Ondansetron Monotherapy or Combination for Postoperative Nausea and Vomiting in Thyroid Cancer
NCT07600580	PHASE4	ACTIVE_NOT_RECRUITING	The Association Between Bilateral Intermediate Cervical Plexus Block During Total Thyroidectomy and Surgical Stress Response
NCT03975829	PHASE4	RECRUITING	Pediatric Long-Term Follow-up and Rollover Study
NCT00014638	PHASE4	COMPLETED	Letrozole in Treating Postmenopausal Women With Metastatic Breast Cancer
NCT00022386	PHASE4	COMPLETED	Epoetin Alfa in Treating Chemotherapy-Related Anemia in Women With Stage I, Stage II, or Stage III Breast Cancer
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00030758	PHASE4	UNKNOWN	Filgrastim or Pegfilgrastim in Preventing Neutropenia in Women Receiving Chemotherapy Following Surgery for Breast Cancer
NCT00082277	PHASE4	COMPLETED	Anastrozole Biphosphonate Study in Postmenopausal Women With Hormone-Receptor-Positive Early Breast Cancer
NCT00087620	PHASE4	TERMINATED	A Study of Capecitabine In Combination With Docetaxel vs Capecitabine Followed by Docetaxel As First-Line Treatment For Metastatic Breast Cancer
NCT00121836	PHASE4	COMPLETED	A Study of Xeloda (Capecitabine) in Women With HER2-Negative Metastatic Breast Cancer
NCT00126360	PHASE4	UNKNOWN	STARS Breast Trial (Study of Anastrozole and Radiotherapy Sequencing Pilot)
NCT00127933	PHASE4	COMPLETED	XeNA Study - A Study of Xeloda (Capecitabine) in Patients With Invasive Breast Cancer
NCT00128297	PHASE4	COMPLETED	Pamidronate Administration in Breast Cancer Patients With Bone Metastases
NCT00129597	PHASE4	UNKNOWN	Effect of Ketalar to Prevent Postoperative Chronic Pain After Mastectomy
NCT00131170	PHASE4	COMPLETED	Paravertebral Block for Breast Surgery
NCT00156039	PHASE4	COMPLETED	Randomized Trial of Follow-up Strategies in Breast Cancer
NCT00160901	PHASE4	COMPLETED	Complementary Therapies for the Reduction of Side Effects During Chemotherapy for Breast Cancer
NCT00171847	PHASE4	TERMINATED	Study of the Efficacy and Safety of Letrozole Combined With Trastuzumab in Patients With Metastatic Breast Cancer
NCT00176046	PHASE4	COMPLETED	Mistletoe Extract in Early or Advanced Breast Cancer, A Feasibility Study
NCT00190697	PHASE4	COMPLETED	A Study of LY353381 (Arzoxifene) for Patients Who Benefitted From This Drug in Other Oncology Trials and Wished to Continue Treatment
NCT00234195	PHASE4	COMPLETED	Wellbutrin XL, Major Depressive Disorder and Breast Cancer
NCT00237133	PHASE4	COMPLETED	Treatment of Locally Advanced Breast Cancer With Letrozole in Postmenopausal Women
NCT00237224	PHASE4	COMPLETED	Open Label Study of Postmenopausal Women With ER and /or PgR Positive Breast Cancer Treated With Letrozole
NCT00241046	PHASE4	TERMINATED	Letrozole in the Treatment of 1st and 2nd Line Hormone Receptor Positive Breast Cancer: Pre-therapeutic Risk Assessment
NCT00277160	PHASE4	COMPLETED	A Study of Primary Prophylaxis With Neulasta (Pegfilgrastim) Versus Secondary Prophylaxis After Chemotherapy in Elderly Subjects (>/= 65 Years Old) With Cancer
NCT00323479	PHASE4	COMPLETED	Arthralgia During Anastrozole Therapy for Breast Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00356148	PHASE4	COMPLETED	The Efficacy of Prophylactic Antibiotic Administration During Breast Cancer Surgery in Overweight Patients.
NCT00372476	PHASE4	COMPLETED	Efficacy and Safety of Imatinib and Vinorelbine in Patients With Advanced Breast Cancer
NCT00413491	PHASE4	UNKNOWN	National Screening in Denmark With MR Versus Mammography and Ultrasound of Women With BRCA1 or BRCA2 Mutations
NCT00484614	PHASE4	UNKNOWN	Study the Role of Positron Emission Mammography in Pre-surgical Planning for Breast Cancer
NCT00485953	PHASE4	COMPLETED	Effect of Bisphosphonate on Bone Loss in Postmenopausal Women With Breast Cancer Initiating Aromatase Inhibitor Therapy
NCT00496678	PHASE4	COMPLETED	Trial of Patient Navigation-Activation