TNKS (Tankyrase) Gene: Structure, Function, and Clinical Significance
Comprehensive biomedical overview of the TNKS gene, including genomic context, protein function, expression, mutations, and associated diseases.
Gene Information Card
| Symbol | TNKS |
|---|---|
| Full Name | Tankyrase |
| Gene Type | Protein coding |
| Chromosomal Location | 8p23.1 |
| NCBI Gene ID | 8658 ncbi.nlm.nih.gov/gene/8658 |
| Ensembl ID | ENSG00000173273 |
| UniProt ID | O95271 |
| OMIM ID | 603303 |
| HGNC ID | 11941 |
| Aliases | PARP5A, TIN1, TINF1, ARTD5, TNKS1 |
Description
TNKS (tankyrase) encodes a poly(ADP-ribose) polymerase (PARP) involved in telomere maintenance, Wnt/β-catenin signaling, and mitotic spindle assembly. The protein interacts with TRF1 (TERF1) to regulate telomere length and with AXIN to modulate β-catenin degradation. TNKS is implicated in cancer, diabetes, and genetic disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (colorectal, breast, ovarian) | TNKS overactivation stabilizes β-catenin via PARsylation of AXIN, promoting Wnt signaling and tumorigenesis. | COSMIC, ClinVar |
| Diabetes (type 2) | TNKS variants (e.g., rs10509637) associated with insulin resistance and β-cell dysfunction. | OMIM, ClinVar |
| Idiopathic pulmonary fibrosis | TNKS-mediated PARsylation of AXIN contributes to fibroblast activation. | NCBI Gene, PubMed |
| Telomere-related disorders | TNKS loss leads to telomere elongation defects and genomic instability. | OMIM, UniProt |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.3 | Medium |
| Bone marrow | 8.7 | Medium |
| Lymph node | 7.1 | Low |
| Brain (cerebellum) | 6.5 | Low |
| Liver | 5.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.4 | High expression |
| HeLa | 12.1 | High expression |
| MCF7 | 9.8 | Medium expression |
| HepG2 | 7.3 | Low expression |
| K562 | 6.0 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2935C>T (p.Arg979*) | Nonsense | <0.1% | Loss of PARP catalytic domain, likely loss of function |
| c.1942G>A (p.Gly648Arg) | Missense | <0.1% | Unknown effect; located in ankyrin repeat domain |
| c.3610_3611insA (p.Thr1204Asnfs*2) | Frameshift | <0.1% | Premature truncation, loss of function |
| c.1234A>G (p.Lys412Glu) | Missense | <0.1% | Reported in COSMIC; functional impact unclear |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg979*, p.Thr1204Asnfs*2) that truncate the PARP domain abolish catalytic activity, impairing telomere maintenance and Wnt signaling.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in TNKS; overexpression or amplification may drive oncogenic Wnt signaling.
Dominant Negative (DN)
Truncated TNKS variants lacking the PARP domain may interfere with wild-type tankyrase function by competing for substrate binding (e.g., TRF1, AXIN).
View complete mutation data：
Gene Ontology (GO)
Pathways
• Wnt/β-catenin signaling (Reactome R-HSA-201681)
• Telomere maintenance (Reactome R-HSA-157579)
• PARP-mediated modification of cellular proteins (Reactome R-HSA-201688)
Protein Summary
Tankyrase (TNKS) is a 1327-amino acid protein with an N-terminal ankyrin repeat domain, a sterile alpha motif (SAM) domain, and a C-terminal PARP catalytic domain. It poly(ADP-ribosyl)ates target proteins such as TRF1, AXIN, and NUMA, regulating telomere length, Wnt signaling, and mitotic spindle assembly. TNKS is localized to telomeres, centrosomes, and the cytoplasm. Its activity is inhibited by small molecules like XAV939, which are being explored as anticancer agents.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TNKS Knockout HEK293 Cell Line | EDJ-KQ6320 | Human | 8658 | Details Get a Quote |
| TNKS2 Knockout HEK293 Cell Line | EDJ-KQ9535 | Human | 80351 | Details Get a Quote |
| TNKS Knockout HCT 116 Cell Line | EDJ-KQ28936 | Human | 8658 | Details Get a Quote |
| TNKS Knockout A-549 Cell Line | EDJ-KQ30247 | Human | 8658 | Details Get a Quote |
| TNKS Knockout HeLa Cell Line | EDJ-KQ30249 | Human | 8658 | Details Get a Quote |
| TNKS2 Knockout A-549 Cell Line | EDJ-KQ36310 | Human | 80351 | Details Get a Quote |
| TNKS2 Knockout HCT 116 Cell Line | EDJ-KQ36311 | Human | 80351 | Details Get a Quote |
| TNKS2 Knockout HeLa Cell Line | EDJ-KQ36312 | Human | 80351 | Details Get a Quote |
