TNKS2
protein-codingtankyrase 2, the group of Sterile alpha motif domain containing|Poly(ADP-ribose) polymerases|Ankyrin repeat domain containing
Gene summary
Enables NAD+ poly-ADP-ribosyltransferase activity; NAD+-protein mono-ADP-ribosyltransferase activity; and enzyme binding activity. Involved in several processes, including positive regulation of canonical Wnt signaling pathway; post-translational protein modification; and regulation of telomere maintenance. Located in nuclear envelope; pericentriolar material; and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~67.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to TNKS2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_025235.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | 1 | 3 | ||
| missense | 107 | 2 | 109 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 111 | 3 | 1 | 115 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_079511.1 | 27 | MANE Select | |
| Ensembl | ENSP00000360689.4 | 27 | MANE Select | |
| Ensembl | ENSP00000518237.1 | 27 | Standard | |
| Ensembl | ENSP00000518237.1 | 27 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- NAD+ biosynthetic pathways
- Disease
- Signaling by WNT
- Signal Transduction
- Regulation of PTEN stability and activity
Biological Process
- protein polyubiquitination
- protein ADP-ribosylation
- Wnt signaling pathway
- positive regulation of telomere maintenance via telomerase
- multicellular organism growth
Molecular Function
- NAD+ ADP-ribosyltransferase activity
- protein binding
- enzyme binding
- metal ion binding
Cellular Component
- Golgi membrane
- pericentriolar material
- nuclear chromosome, telomeric region
- nucleus
- nuclear envelope
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000371627
- Coding exons
- 27
- Length
- 66965
- Individuals with no LoFs
- 125709
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 39
- Defined
- 125748
- p
- 0.000155
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.12 | 368 | 580 | 0.635 | 0.0000281 | 7581 |
| Missense (PolyPhen) | 170 | 313 | 0.54313 | 3988 | ||
| Synonymous | -0.0363 | 214 | 213 | 1.00 | 0.0000108 | 2290 |
| Loss of Function | 4.75 | 19 | 58.0 | 0.327 | 0.00000310 | 767 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00019 | 0.00018 | rare |
| Latino/Admixed American | 0.000088 | 0.000087 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.00028 | 0.00028 | rare |
| European (Non-Finnish) | 0.00019 | 0.00018 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Poly-ADP-ribosyltransferase involved in various processes such as Wnt signaling pathway, telomere length and vesicle trafficking. Acts as an activator of the Wnt signaling pathway by mediating poly-ADP-ribosylation of AXIN1 and AXIN2, 2 key components of the beta-catenin destruction complex: poly-ADP- ribosylated target proteins are recognized by RNF146, which mediates their ubiquitination and subsequent degradation. Also mediates poly-ADP-ribosylation of BLZF1 and CASC3, followed by recruitment of RNF146 and subsequent ubiquitination. Mediates poly-ADP-ribosylation of TERF1, thereby contributing to the regulation of telomere length. May also regulate vesicle trafficking and modulate the subcellular distribution of SLC2A4/GLUT4-vesicles. Stimulates 26S proteasome activity. {ECO:0000269|PubMed:11739745, ECO:0000269|PubMed:11802774, ECO:0000269|PubMed:19759537, ECO:0000269|PubMed:21478859, ECO:0000269|PubMed:23622245}.;
Recessive Scores
- pRec
- 0.125
Intolerance Scores
- LoFtool
- 0.519
- RVIS EVS
- -1.29
- RVIS percentile EVS
- 5.08
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.677
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |