TNKS

protein-coding

tankyrase, the group of Sterile alpha motif domain containing|Poly(ADP-ribose) polymerases|Ankyrin repeat domain containing|MicroRNA protein coding host genes

Gene summary

Enables several functions, including pentosyltransferase activity; telomerase inhibitor activity; and zinc ion binding activity. Involved in several processes, including positive regulation of canonical Wnt signaling pathway; post-translational protein modification; and regulation of chromosome organization. Acts upstream of or within peptidyl-serine phosphorylation and peptidyl-threonine phosphorylation. Located in Golgi apparatus; chromosome, telomeric region; and mitotic spindle pole. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_003747.3

Inheritance

—

ClinVar variants

U:171B:9

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.27

Max pathogenic AF

—

Genomic locus

chr8:9,555,912-9,782,346

External References & Databases

Ensembl (ENSG00000173273)

Transcript & Mutation Effects

hg38 • Region Span ~226.4 kb

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GenCC 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 TNKS variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 168

not providedTotal: 8

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003747.3. 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			2 clinvar	3 clinvar	4 clinvar	9
missense			167 clinvar	2 clinvar		169
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	171	5	4	180

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 20 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003747.3	RefSeq	NP_003738.2	27	MANE Select
ENST00000310430.11	Ensembl	ENSP00000311579.6	27	MANE Select
ENST00000517770.2	Ensembl	ENSP00000428185.2	27	Standard
ENST00000518281.5	Ensembl	ENSP00000429890.1	26	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
tnksb	Danio rerio	Structure: whole organism Quality: decreased length abnormal

Gene / Model

Organism

Observed Phenotype

tnksb

Danio rerio

Structure: whole organism

Quality: decreased length

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

NAD+ biosynthetic pathways
Regulation of Wnt-B-catenin Signaling by Small Molecule Compounds
Disease
Signaling by WNT
Signal Transduction

Biological Process

protein polyubiquitination
protein ADP-ribosylation
mitotic spindle organization
protein transport
Wnt signaling pathway

Molecular Function

NAD+ ADP-ribosyltransferase activity
protein binding
zinc ion binding
histone binding

Cellular Component

Golgi membrane
pericentriolar material
chromosome, centromeric region
chromosome, telomeric region
nuclear chromosome, telomeric region

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000310430
Coding exons: 27
Length: 226433
Individuals with no LoFs: 125720
Homozygous LoFs: 0
Heterozygous LoFs: 28
Defined: 125748
p: 0.000111

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.825	678	741	0.915	0.0000386	8593
Missense (PolyPhen)		265	383.91	0.69027		4558
Synonymous	-5.06	409	298	1.37	0.0000170	2722
Loss of Function	5.28	16	60.2	0.266	0.00000307	753

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00033	0.00031	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00022	0.00016	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00013	0.00013	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

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 (PARsylation) 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 PARsylation of BLZF1 and CASC3, followed by recruitment of RNF146 and subsequent ubiquitination. Mediates PARsylation of TERF1, thereby contributing to the regulation of telomere length. Involved in centrosome maturation during prometaphase by mediating PARsylation of HEPACAM2/MIKI. May also regulate vesicle trafficking and modulate the subcellular distribution of SLC2A4/GLUT4-vesicles. May be involved in spindle pole assembly through PARsylation of NUMA1. Stimulates 26S proteasome activity. {ECO:0000269|PubMed:10988299, ECO:0000269|PubMed:11739745, ECO:0000269|PubMed:16076287, ECO:0000269|PubMed:19759537, ECO:0000269|PubMed:21478859, ECO:0000269|PubMed:22864114, ECO:0000269|PubMed:23622245}.;

Recessive Scores

pRec: 0.152

Intolerance Scores

LoFtool: 0.410
RVIS EVS: -2.45
RVIS percentile EVS: 1.01

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): H
Indispensability pred.: E
Indispensability score: 0.749

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium