PINX1: A Key Regulator of Telomerase and Telomere Integrity
Comprehensive genomic and functional analysis of the PINX1 gene, its role in telomere maintenance, cancer, and cellular senescence.
Gene Information Card
| Symbol | PINX1 |
|---|---|
| Full Name | PIN2/TERF1 interacting telomerase inhibitor 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 8p23.1 |
| NCBI Gene ID | 54984 ncbi.nlm.nih.gov/gene/54984 |
| Ensembl ID | ENSG00000147650 |
| UniProt ID | Q96BK5 |
| OMIM ID | 607149 |
| HGNC ID | 30046 |
| Aliases | LPTS, PIN2, TRF1-interacting protein, telomerase inhibitor |
Description
PINX1 (PIN2/TERF1 interacting telomerase inhibitor 1) encodes a protein that directly binds to the telomerase catalytic subunit (TERT) and inhibits telomerase activity. It also interacts with TRF1 (TERF1) and plays a critical role in telomere length regulation, chromosome stability, and cellular senescence. Loss or mutation of PINX1 is associated with telomere elongation and various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hepatocellular carcinoma | Reduced PINX1 expression leads to telomerase activation and uncontrolled proliferation | PMID: 15601830 |
| Gastric cancer | PINX1 downregulation correlates with poor prognosis and telomere lengthening | PMID: 19351836 |
| Breast cancer | PINX1 loss promotes telomerase activity and tumorigenesis | PMID: 21573163 |
| Colorectal cancer | PINX1 mutations and reduced expression linked to genomic instability | PMID: 22430205 |
| Dyskeratosis congenita | Potential involvement in telomere maintenance disorders | PMID: 23559589 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | Medium |
| Thyroid | 8.3 | Medium |
| Adrenal gland | 7.1 | Medium |
| Liver | 5.6 | Low |
| Breast | 4.2 | Low |
| Lung | 3.8 | Low |
| Colon | 3.5 | Low |
| Brain | 2.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver cancer) | 6.8 | Moderate expression |
| MCF7 (breast cancer) | 5.2 | Low expression |
| A549 (lung cancer) | 4.1 | Low expression |
| HeLa (cervical cancer) | 3.9 | Low expression |
| K562 (leukemia) | 2.5 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.511C>T (p.Arg171*) | Nonsense | <1% | Loss of function; truncated protein |
| c.632G>A (p.Arg211Gln) | Missense | <1% | Reduced telomerase inhibition |
| c.784_785del (p.Lys262Glufs*5) | Frameshift | <1% | Loss of function |
| c.1A>G (p.Met1?) | Start loss | <1% | No protein production |
Mutation functional classification
Loss of Function (LOF)
Most reported PINX1 mutations (nonsense, frameshift, start loss) result in loss of telomerase inhibitory activity, leading to telomere elongation and increased cancer risk.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in PINX1.
Dominant Negative (DN)
Some missense mutations (e.g., p.Arg211Gln) may act in a dominant-negative manner by competing with wild-type PINX1 for TRF1 binding, reducing overall telomerase inhibition.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Telomere maintenance (Reactome: R-HSA-157579)
• Senescence and autophagy (KEGG: hsa04218)
• Cellular senescence (WikiPathways: WP2449)
Protein Summary
The PINX1 protein (UniProt Q96BK5) is a 328-amino acid nuclear protein that contains a G-patch domain and a TRF1-binding domain. It localizes to telomeres and directly inhibits telomerase activity by binding to the TERT subunit. PINX1 also interacts with TRF1, modulating telomere length homeostasis. Loss of PINX1 function leads to telomerase reactivation, telomere elongation, and is implicated in multiple cancers.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PINX1 Knockout HEK293 Cell Line | EDJ-KQ12095 | Human | 54984 | Details Get a Quote |
| PINX1 Knockout A-549 Cell Line | EDJ-KQ40764 | Human | 54984 | Details Get a Quote |
| PINX1 Knockout HCT 116 Cell Line | EDJ-KQ40765 | Human | 54984 | Details Get a Quote |
| PINX1 Knockout HeLa Cell Line | EDJ-KQ40766 | Human | 54984 | Details Get a Quote |
