POT1: Protection of Telomeres 1 — Telomere Maintenance and Cancer Susceptibility Gene
A comprehensive biomedical resource on POT1 gene function, clinical relevance, expression, mutations, and pathways.
Gene Information Card
| Symbol | POT1 |
|---|---|
| Full Name | Protection of Telomeres 1 |
| Gene Type | Protein-coding |
| Chromosomal Location | 7q31.33 |
| NCBI Gene ID | 25913 ncbi.nlm.nih.gov/gene/25913 |
| Ensembl ID | ENSG00000128513 |
| UniProt ID | Q9NUX5 |
| OMIM ID | 606478 |
| HGNC ID | 17284 |
| Aliases | HPOT1, CMM10, DSP1, GLM9 |
Description
POT1 (Protection of Telomeres 1) encodes a protein that is a critical component of the shelterin complex, which protects chromosome ends from DNA damage response and regulates telomere length. POT1 binds to single-stranded telomeric DNA (TTAGGG repeats) and is essential for telomere maintenance. Mutations in POT1 are associated with various cancers, including familial melanoma, chronic lymphocytic leukemia, and glioma, as well as with telomere-related disorders such as Coats plus syndrome and familial idiopathic pulmonary fibrosis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Familial melanoma | Loss-of-function mutations in POT1 lead to telomere elongation and genomic instability, increasing melanoma risk. | ClinVar, OMIM |
| Chronic lymphocytic leukemia (CLL) | Somatic mutations in POT1 are common in CLL, disrupting telomere capping and leading to chromosomal abnormalities. | COSMIC, ClinVar |
| Glioma | POT1 mutations are associated with familial glioma, likely through telomere dysfunction and aberrant cell proliferation. | ClinVar, OMIM |
| Coats plus syndrome | Biallelic mutations in POT1 cause this rare disorder, characterized by retinal telangiectasia and bone abnormalities, due to defective telomere protection. | OMIM, ClinVar |
| Familial idiopathic pulmonary fibrosis | POT1 mutations impair telomere maintenance, leading to pulmonary fibrosis. | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.4 | Medium |
| Bone marrow | 8.2 | Low |
| Lymph node | 7.5 | Low |
| Spleen | 6.9 | Low |
| Brain | 5.1 | Low |
| Liver | 4.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 | 10.5 | Chronic myelogenous leukemia cell line; high expression |
| HeLa | 8.7 | Cervical adenocarcinoma; moderate expression |
| A549 | 7.9 | Lung carcinoma; moderate expression |
| MCF7 | 6.8 | Breast adenocarcinoma; moderate expression |
| HepG2 | 5.4 | Hepatocellular carcinoma; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Arg117Cys | Missense | Rare (0.1% in general population) | Impairs POT1 binding to telomeric DNA, leading to telomere elongation and increased cancer risk. |
| p.Gln94Ter | Nonsense | Rare (0.05%) | Truncates protein, causing loss of function and telomere dysfunction. |
| p.Ser322Asn | Missense | Somatic in CLL (5-10%) | Disrupts interaction with TPP1, affecting telomere length regulation. |
| c.1686_1687del | Frameshift | Somatic in melanoma (2-5%) | Leads to premature stop codon and loss of function. |
Mutation functional classification
Loss of Function (LOF)
Most POT1 mutations are loss-of-function, leading to telomere uncapping, telomere elongation, and genomic instability, which promotes tumorigenesis.
Gain of Function (GOF)
No clear gain-of-function mutations have been reported; all pathogenic variants appear to reduce POT1 function.
Dominant Negative (DN)
Some missense mutations may act in a dominant-negative manner, interfering with wild-type POT1 function in the shelterin complex.
View complete mutation data：
Gene Ontology (GO)
| • telomeric DNA binding | • single-stranded DNA binding |
| • protein binding | • telomere maintenance |
| • negative regulation of telomere maintenance | • regulation of telomere capping |
| • DNA damage response | • cell cycle arrest |
Pathways
• Telomere Maintenance
• Shelterin complex pathway
• Cellular senescence
• DNA damage response
Protein Summary
POT1 is a 634-amino acid protein that contains two oligonucleotide/oligosaccharide-binding (OB) folds at the N-terminus, which mediate sequence-specific binding to single-stranded telomeric DNA. It also has a C-terminal domain that interacts with TPP1 (encoded by ACD), another shelterin component. POT1 is essential for protecting telomere ends from being recognized as DNA double-strand breaks, thereby preventing inappropriate DNA damage responses and homologous recombination. It also regulates telomerase access to telomeres, controlling telomere length. POT1 is widely expressed, with highest levels in testis and bone marrow, and is critical for stem cell function and tissue homeostasis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| POT1 Knockout HEK293 Cell Line | EDJ-KQ7612 | Human | 25913 | Details Get a Quote |
| POT1 Knockout HCT 116 Cell Line | EDJ-KQ34268 | Human | 25913 | Details Get a Quote |
| POT1 Knockout HeLa Cell Line | EDJ-KQ34269 | Human | 25913 | Details Get a Quote |
| POT1 Knockout A-549 Cell Line | EDJ-KQ64337 | Human | 25913 | Details Get a Quote |
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