TNKS

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

Basic information

Region (hg38): 8:9555911-9782346

Links

ENSG00000173273 ∙ NCBI:8658 ∙ OMIM:603303 ∙ HGNC:11941 ∙ Uniprot:O95271 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TNKS gene.

• Inborn genetic diseases (44 variants)
• not provided (8 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TNKS gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1	4	5
missense			45			45
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					2	2
non coding						0
Total	0	0	45	1	4

Variants in TNKS

This is a list of pathogenic ClinVar variants found in the TNKS region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
8-9555947-C-A		not specified	Uncertain significance (Feb 23, 2023)
8-9555966-T-A		not specified	Uncertain significance (Nov 18, 2023)
8-9555970-C-T		not specified	Uncertain significance (Jun 02, 2023)
8-9555997-C-G		not specified	Uncertain significance (Apr 13, 2022)
8-9556006-G-C		not specified	Uncertain significance (Jan 02, 2024)
8-9556010-C-T			Uncertain significance (Dec 19, 2023)
8-9556042-C-G		not specified	Uncertain significance (May 31, 2023)
8-9556061-C-T		not specified	Uncertain significance (Dec 16, 2022)
8-9556063-G-C		not specified	Uncertain significance (Nov 17, 2022)
8-9556105-T-G		not specified	Uncertain significance (Mar 29, 2022)
8-9556112-C-G		not specified	Uncertain significance (Oct 24, 2023)
8-9556145-A-G		not specified	Uncertain significance (Dec 02, 2021)
8-9556169-G-A		not specified	Uncertain significance (Aug 13, 2021)
8-9556178-C-T		not specified	Uncertain significance (Jan 23, 2024)
8-9556210-A-G		not specified	Uncertain significance (Apr 04, 2023)
8-9556213-A-G		not specified	Uncertain significance (May 23, 2023)
8-9556224-A-T			Benign (Jun 26, 2018)
8-9556235-T-G		not specified	Uncertain significance (Dec 19, 2023)
8-9556297-C-G		not specified	Uncertain significance (May 27, 2022)
8-9556363-T-C		not specified	Uncertain significance (Dec 13, 2022)
8-9556366-C-G		not specified	Uncertain significance (Oct 19, 2021)
8-9556383-G-A			Benign (Jul 16, 2018)
8-9556386-C-G		not specified	Uncertain significance (Oct 05, 2023)
8-9556397-G-A		not specified	Uncertain significance (Jul 25, 2023)
8-9556526-C-G		not specified	Uncertain significance (Nov 09, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TNKS	protein_coding	protein_coding	ENST00000310430	27	226433

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0114	0.989	125720	0	28	125748	0.000111

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.825	678	741	0.915	0.0000386	8593
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000356	0.000337
Ashkenazi Jewish	0.00	0.00
East Asian	0.000218	0.000163
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000134	0.000132
Middle Eastern	0.000218	0.000163
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

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}.
• Pathway: NAD+ biosynthetic pathways;Regulation of Wnt-B-catenin Signaling by Small Molecule Compounds;Disease;Signaling by WNT;Signal Transduction;telomeres telomerase cellular aging and immortality;Regulation of PTEN stability and activity;Post-translational protein modification;Metabolism of proteins;Ub-specific processing proteases;PTEN Regulation;PIP3 activates AKT signaling;Deubiquitination;Signaling by WNT in cancer;Intracellular signaling by second messengers;Diseases of signal transduction;Regulation of Telomerase;TCF dependent signaling in response to WNT;Degradation of AXIN;XAV939 inhibits tankyrase, stabilizing AXIN (Consensus)

Recessive Scores

• pRec: 0.152

Intolerance Scores

• loftool: 0.410
• rvis_EVS: -2.45
• rvis_percentile_EVS: 1.01

Haploinsufficiency Scores

• pHI: 0.741
• hipred: Y
• hipred_score: 0.706
• ghis: 0.651

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.749

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tnks
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype; cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype

Zebrafish Information Network

• Gene name: tnksb
• Affected structure: whole organism
• Phenotype tag: abnormal
• Phenotype quality: decreased length

Gene ontology

• Biological process: protein polyubiquitination;protein ADP-ribosylation;mitotic spindle organization;protein transport;Wnt signaling pathway;peptidyl-serine phosphorylation;peptidyl-threonine phosphorylation;cellular response to nutrient;regulation of telomere maintenance via telomerase;positive regulation of telomere maintenance via telomerase;positive regulation of transcription by RNA polymerase II;mRNA transport;spindle assembly;cell division;positive regulation of telomerase activity;protein localization to chromosome, telomeric region;protein poly-ADP-ribosylation;protein auto-ADP-ribosylation;positive regulation of canonical Wnt signaling pathway;positive regulation of telomere capping;negative regulation of telomere maintenance via telomere lengthening;negative regulation of telomeric DNA binding;negative regulation of maintenance of mitotic sister chromatid cohesion, telomeric
• Cellular component: Golgi membrane;pericentriolar material;chromosome, centromeric region;chromosome, telomeric region;nuclear chromosome, telomeric region;nucleus;nuclear pore;nucleoplasm;cytoplasm;Golgi apparatus;cytosol;nuclear body;nuclear membrane;mitotic spindle pole
• Molecular function: NAD+ ADP-ribosyltransferase activity;protein binding;zinc ion binding;histone binding