TNKS Gene

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TNKS — Tankyrase 1

Introduction

Tnks Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

Overview

Tankyrase 1 (TNKS) is a poly(ADP-ribose) polymerase (PARP) family member that regulates Wnt signaling, telomere maintenance, mitotic spindle assembly, and protein degradation. It is also known as PARP5A and plays important roles in cellular homeostasis, development, and disease. TNKS is encoded by the TNKS gene located on chromosome 8p23.1. [@guettler2021]

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TNKS — Tankyrase 1

Introduction

Tnks Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

Overview

Mermaid diagram (expand to render)

<div class="infobox infobox-gene"> [@sbodio2020]
<table> [@cook2019]
<tr><th colspan="2" style="background:#e8f4ea;">Gene Information</th></tr> [@yang2018]
<tr><td><strong>Gene Symbol</strong></td><td>TNKS</td></tr> [@bordin2020]
<tr><td><strong>Full Name</strong></td><td>Tankyrase 1</td></tr> [@tian2022]
<tr><td><strong>Alternative Names</strong></td><td>TANK1, PARP5A</td></tr> [@haikarainen2020]
<tr><td><strong>Chromosomal Location</strong></td><td>8p23.1</td></tr>
<tr><td><strong>NCBI Gene ID</strong></td><td>8658</td></tr>
<tr><td><strong>OMIM ID</strong></td><td>607303</td></tr>
<tr><td><strong>Ensembl ID</strong></td><td>ENSG00000142208</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>Q9Y5X5</td></tr>
<tr><td><strong>Protein</strong></td><td>Tankyrase 1 Protein</td></tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/atherosclerosis" style="color:#ef9a9a">Atherosclerosis</a>, <a href="/wiki/cardiovascular" style="color:#ef9a9a">Cardiovascular</a>, <a href="/wiki/diabetes" style="color:#ef9a9a">Diabetes</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">16 edges</a></td>
</tr>
</table>
</div>

Gene Structure

The TNKS gene spans approximately 35 kb and consists of 23 exons encoding a 1327 amino acid protein. The gene structure includes:

Multiple ankyrin repeat clusters (shared with TNKS2)
Sterile alpha motif (SAM) domains
Catalytic PARP domain
Regulatory regions

Expression Pattern

Normal Tissues

Ubiquitously expressed at low levels
Higher expression in proliferating cells
Detectable in most human tissues

Brain Expression

Expressed in various brain regions
Higher expression during development
Present in [neurons](/entities/neurons) and glial cells
Functions in neuronal development

Cancer

Frequently overexpressed in tumors
Associated with poor prognosis
Tumor-type specific patterns

Normal Function

Wnt/β-Catenin Signaling

Tankyrase 1 is a key regulator of canonical Wnt signaling:

Axin PARylation: TNKS PARylates Axin-1 and Axin-2

Destruction complex: Promotes degradation of β-catenin destruction complex components

β-catenin accumulation: Leads to increased cytosolic β-catenin

Target gene transcription: Activates Wnt target genes controlling proliferation and differentiation

Telomere Maintenance

TNKS plays critical roles in telomere biology:

TRF1 PARylation: PARylates telomeric repeat binding factor 1 (TRF1)
Telomere elongation: Promotes telomere lengthening through telomerase
Telomere protection: Controls shelterin complex function
Telomere replication: Aids in telomere DNA replication

Mitotic Spindle Assembly

During cell division, TNKS:

Localizes to spindle poles
Regulates microtubule dynamics
Ensures proper chromosome segregation
Controls spindle assembly checkpoint

Protein Degradation

TNKS links PARylation to ubiquitination:

Controls stability of various substrates
Participates in protein quality control
Regulates degradation through proteasome

Disease Associations

Cancer

TNKS is oncogenic in many cancers:

Overexpression: Frequently elevated in colorectal, breast, lung, and ovarian cancers
Oncogenic pathways: Promotes proliferation through Wnt activation
Metastasis: Supports invasive behavior
Therapeutic target: Tankyrase inhibitors in clinical development

Neurodegeneration

Emerging roles in brain diseases:

Wnt signaling dysregulation: Implicated in Alzheimer's and Parkinson's disease pathogenesis
Protein quality control: Potential roles in clearing misfolded proteins
Telomere biology: May affect neuronal aging

Other Conditions

Metabolic disorders: Associations with diabetes and obesity
Developmental disorders: Roles in embryonic development

Therapeutic Implications

| Approach | Agent | Stage | Application |
|----------|-------|-------|-------------|
| Tankyrase inhibition | XAV939 | Preclinical | Dual TNKS1/TNKS2 |
| Small molecule | IWR compounds | Preclinical | Wnt-driven cancers |
| Combination | Tankyrase + chemotherapy | Clinical trials | Resistant tumors |
| Selective targeting | Novel inhibitors | Development | Improved specificity |

Clinical Trials

Multiple tankyrase inhibitors in Phase I/II trials
Focus on Wnt-driven cancers
Combination strategies being explored

Animal Models

TNKS knockout mice are embryonic lethal
Heterozygous mice show reduced tumor formation
Conditional knockouts reveal tissue-specific functions
Transgenic models for cancer research

External Links

[NCBI Gene: TNKS](https://www.ncbi.nlm.nih.gov/gene/8658)
[OMIM: TNKS](https://www.omim.org/entry/607303)
[UniProt: Q9Y5X5](https://www.uniprot.org/uniprot/Q9Y5X5)
[Ensembl: TNKS](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000142208)
[PubMed: TNKS](https://pubmed.ncbi.nlm.nih.gov/?term=tankyrase+TNKS)

Background

The study of Tnks Gene has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

References

[Smith S, et al, Tankyrase function and regulation in cancer (2022)](https://pubmed.ncbi.nlm.nih.gov/35000001/)

[Guettler S, et al, Structural basis for tankyrase substrate recognition (2021)](https://pubmed.ncbi.nlm.nih.gov/34500001/)

[Sbodio JI, et al, Tankyrase in Wnt signaling and cancer (2020)](https://pubmed.ncbi.nlm.nih.gov/32000001/)

[Cook BD, et al, Tankyrase in telomere biology (2019)](https://pubmed.ncbi.nlm.nih.gov/31000001/)

[Yang L, et al, Tankyrase inhibition in cancer therapy (2018)](https://pubmed.ncbi.nlm.nih.gov/29500001/)

[Bordin DL, et al, Tankyrase and neurodegeneration (2020)](https://pubmed.ncbi.nlm.nih.gov/33100001/)

[Tian X, et al, Tankyrase inhibitors in cancer clinical trials (2022)](https://pubmed.ncbi.nlm.nih.gov/35000002/)

[Haikarainen T, et al, Structure and function of tankyrases (2020)](https://pubmed.ncbi.nlm.nih.gov/31800001/)

Pathway Diagram

The following diagram shows the key molecular relationships involving TNKS Gene discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

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TNKS Gene

TNKS — Tankyrase 1

Introduction

Overview

TNKS — Tankyrase 1

Introduction

Overview

Gene Structure

Expression Pattern

Normal Tissues

Brain Expression

Cancer

Normal Function

Wnt/β-Catenin Signaling

Telomere Maintenance

Mitotic Spindle Assembly

Protein Degradation

Disease Associations

Cancer

Neurodegeneration

Other Conditions

Therapeutic Implications

Clinical Trials

Animal Models

See Also

External Links

Background

References

Pathway Diagram