TNKS2

tankyrase 2, the group of Sterile alpha motif domain containing|Poly(ADP-ribose) polymerases|Ankyrin repeat domain containing

Basic information

Region (hg38): 10:91798425-91865475

Links

ENSG00000107854 ∙ NCBI:80351 ∙ OMIM:607128 ∙ HGNC:15677 ∙ Uniprot:Q9H2K2 ∙ 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 TNKS2 gene.

• Inborn genetic diseases (28 variants)
• not provided (4 variants)
• not specified (1 variants)
• CIC-DUX Sarcoma (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TNKS2 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	1
missense			28		1	29
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					3	3
Total	0	0	28	0	5

Variants in TNKS2

This is a list of pathogenic ClinVar variants found in the TNKS2 region.

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

Position	Type	Phenotype	Significance	ClinVar
10-91798715-G-A		not specified	Uncertain significance (Feb 06, 2023)
10-91798761-C-T		not specified	Uncertain significance (Sep 29, 2023)
10-91798764-C-T		not specified	Uncertain significance (Apr 21, 2022)
10-91798767-G-C			Uncertain significance (Nov 08, 2023)
10-91813016-T-A		not specified	Uncertain significance (Dec 17, 2023)
10-91813054-G-A		not specified	Uncertain significance (Sep 09, 2021)
10-91813060-A-G		not specified	Uncertain significance (Nov 27, 2023)
10-91813137-T-A		not specified	Uncertain significance (Jul 27, 2021)
10-91813162-C-T		not specified	Uncertain significance (Jun 29, 2023)
10-91813227-C-T			Benign (Jan 06, 2022)
10-91819285-A-G		not specified	Uncertain significance (Jun 03, 2022)
10-91819544-G-T		not specified	Uncertain significance (Sep 20, 2023)
10-91827038-A-G		not specified	Uncertain significance (Jun 21, 2022)
10-91827200-G-A		not specified	Uncertain significance (Mar 03, 2023)
10-91828378-A-G		not specified	Uncertain significance (Oct 25, 2022)
10-91834033-T-G			Benign (Apr 04, 2018)
10-91836961-T-G		not specified	Uncertain significance (Oct 03, 2022)
10-91836963-G-A		not specified	Uncertain significance (Feb 12, 2024)
10-91840597-A-C		not specified	Uncertain significance (Apr 25, 2023)
10-91840654-G-A		not specified	Uncertain significance (Dec 16, 2023)
10-91840657-G-A		not specified	Uncertain significance (May 04, 2022)
10-91840660-G-C		not specified	Uncertain significance (Oct 05, 2023)
10-91840723-G-A			Benign (Jan 21, 2022)
10-91842188-C-CA		CIC-DUX Sarcoma	not provided (-)
10-91842212-C-T		not specified	Conflicting classifications of pathogenicity (Dec 19, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TNKS2	protein_coding	protein_coding	ENST00000371627	27	66965

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000367	1.00	125709	0	39	125748	0.000155

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.12	368	580	0.635	0.0000281	7581
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000276	0.000273
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.00	0.00
Finnish	0.000278	0.000277
European (Non-Finnish)	0.000188	0.000185
Middle Eastern	0.00	0.00
South Asian	0.000134	0.000131
Other	0.000163	0.000163

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 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}.
• Pathway: NAD+ biosynthetic pathways;Disease;Signaling by WNT;Signal Transduction;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;TCF dependent signaling in response to WNT;Degradation of AXIN;XAV939 inhibits tankyrase, stabilizing AXIN (Consensus)

Recessive Scores

• pRec: 0.125

Intolerance Scores

• loftool: 0.519
• rvis_EVS: -1.29
• rvis_percentile_EVS: 5.08

Haploinsufficiency Scores

• pHI: 0.633
• hipred: Y
• hipred_score: 0.648
• ghis: 0.653

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.677

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tnks2
• 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); embryo 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

Gene ontology

• Biological process: protein polyubiquitination;protein ADP-ribosylation;Wnt signaling pathway;positive regulation of telomere maintenance via telomerase;multicellular organism growth;regulation of multicellular organism growth;protein localization to chromosome, telomeric region;protein auto-ADP-ribosylation;positive regulation of canonical Wnt signaling pathway;positive regulation of telomere capping;negative regulation of telomere maintenance via telomere lengthening
• Cellular component: Golgi membrane;pericentriolar material;nuclear chromosome, telomeric region;nucleus;nuclear envelope;cytoplasm;cytosol;perinuclear region of cytoplasm
• Molecular function: NAD+ ADP-ribosyltransferase activity;protein binding;enzyme binding;metal ion binding