TAB2

TGF-beta activated kinase 1 (MAP3K7) binding protein 2, the group of Zinc fingers RANBP2-type

Basic information

Region (hg38): 6:149218640-149411613

Previous symbols: [ "MAP3K7IP2" ]

Links

ENSG00000055208 ∙ NCBI:23118 ∙ OMIM:605101 ∙ HGNC:17075 ∙ Uniprot:Q9NYJ8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• chromosome 6q24-q25 deletion syndrome (Definitive), mode of inheritance: AD
• congenital heart defects, multiple types, 2 (Strong), mode of inheritance: AD
• polyvalvular heart disease syndrome (Supportive), mode of inheritance: AD
• congenital heart defects, multiple types, 2 (Moderate), mode of inheritance: AD
• congenital heart defects, multiple types, 2 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Congenital heart defects, nonsyndromic, 2	AD	Cardiovascular	While some reported cardiac malformations may be readily clinically ascertained, other reported types may be more subtle, and targeted surveillance (eg, with echocardiography and electrocardiography) for findings that have been reported as including bicuspid aortic valve and aortic dilatation, left ventricular outflow obstruction, subaortic stenosis, and atrial fibrillation, may allow early medical and/or surgical management, which may decrease morbidity and mortality	Cardiovascular	20493459; 26139517; 27452334; 28386937; 31250519; 31959127

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TAB2 gene.

• not provided (184 variants)
• Congenital heart defects, multiple types, 2 (31 variants)
• Inborn genetic diseases (21 variants)
• TAB2-related condition (6 variants)
• not specified (5 variants)
• TAB2-related disorder (1 variants)
• Encephalopathy (1 variants)
• Bicuspid aortic valve;Rectal prolapse;Stress urinary incontinence;Migraine;Atrial septal defect, ostium secundum type (1 variants)
• Primary dilated cardiomyopathy (1 variants)
• Type 1 diabetes mellitus 5 (1 variants)
• Congenital heart defects, multiple types, 2;Polyvalvular heart disease syndrome (1 variants)
• TAB2-related syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TAB2 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			3	31	5	39
missense		1	98	2		101
nonsense	6	9				15
start loss						0
frameshift	21	5				26
inframe indel			1			1
splice donor/acceptor (+/-2bp)		2				2
splice region			1		1	2
non coding			5	20	16	41
Total	27	17	107	53	21

Variants in TAB2

This is a list of pathogenic ClinVar variants found in the TAB2 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-149342836-ATG-A			Uncertain significance (Apr 03, 2023)
6-149369589-A-C			Benign (Sep 04, 2018)
6-149369601-A-G			Benign (May 22, 2020)
6-149369671-G-A			Likely benign (Sep 01, 2020)
6-149369892-T-TTTTC			Benign (Apr 28, 2021)
6-149370007-G-A			Uncertain significance (Aug 21, 2022)
6-149370014-A-G		Congenital heart defects, multiple types, 2	Uncertain significance (Jan 26, 2023)
6-149370015-C-T			Likely benign (Nov 01, 2022)
6-149370018-A-G		Congenital heart defects, multiple types, 2	Benign/Likely benign (Dec 19, 2023)
6-149370019-A-G		Inborn genetic diseases	Uncertain significance (Sep 07, 2022)
6-149370022-G-A			Uncertain significance (Nov 13, 2023)
6-149370047-G-A			Uncertain significance (Apr 14, 2023)
6-149370077-TTGTA-AGG		TAB2-related disorder	Likely pathogenic (Aug 02, 2023)
6-149370079-G-A			Uncertain significance (Apr 15, 2022)
6-149370086-G-A			Uncertain significance (Nov 02, 2023)
6-149370108-TC-T			Likely benign (Oct 02, 2023)
6-149370111-A-G			Likely benign (Oct 19, 2022)
6-149370113-G-A			Likely benign (Nov 01, 2022)
6-149370116-T-C			Likely benign (May 01, 2023)
6-149370116-T-G			Likely benign (Nov 01, 2022)
6-149370155-AT-A			Benign (Sep 06, 2018)
6-149370219-T-G			Benign (Sep 04, 2018)
6-149377766-G-T			Benign (Sep 04, 2018)
6-149377814-TAGTC-T			Benign (Nov 09, 2019)
6-149377880-A-T			Benign (Sep 04, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TAB2	protein_coding	protein_coding	ENST00000367456	6	192973

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.0000205	125742	0	3	125745	0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.61	272	358	0.760	0.0000190	4555
Missense in Polyphen		82	147.34	0.55655		1787
Synonymous	-0.934	136	123	1.11	0.00000611	1381
Loss of Function	5.11	0	30.4	0.00	0.00000216	308

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.00000879	0.00000879
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Adapter linking MAP3K7/TAK1 and TRAF6. Promotes MAP3K7 activation in the IL1 signaling pathway. The binding of 'Lys-63'- linked polyubiquitin chains to TAB2 promotes autophosphorylation of MAP3K7 at 'Thr-187'. Involved in heart development. {ECO:0000269|PubMed:10882101, ECO:0000269|PubMed:11460167, ECO:0000269|PubMed:20493459}.
• Disease: DISEASE: Congenital heart defects, multiple types, 2 (CHTD2) [MIM:614980]: A disease characterized by congenital developmental abnormalities involving structures of the heart. CHTD2 patients have left ventricular outflow tract obstruction, subaortic stenosis, residual aortic regurgitation, atrial fibrillation, bicuspid aortic valve and aortic dilation. {ECO:0000269|PubMed:20493459}. Note=The disease is caused by mutations affecting the gene represented in this entry. A chromosomal aberration involving TAB2 has been found in a family with congenital heart disease. Translocation t(2;6)(q21;q25).
• Pathway: TNF signaling pathway - Homo sapiens (human);Toll-like receptor signaling pathway - Homo sapiens (human);NOD-like receptor signaling pathway - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Leishmaniasis - Homo sapiens (human);IL-17 signaling pathway - Homo sapiens (human);Toxoplasmosis - Homo sapiens (human);Measles - Homo sapiens (human);Osteoclast differentiation - Homo sapiens (human);NF-kappa B signaling pathway - Homo sapiens (human);Epstein-Barr virus infection - Homo sapiens (human);Herpes simplex infection - Homo sapiens (human);EGF-Ncore;Regulation of toll-like receptor signaling pathway;IL-1 signaling pathway;RANKL-RANK (Receptor activator of NFKB (ligand)) Signaling Pathway;TNF alpha Signaling Pathway;Structural Pathway of Interleukin 1 (IL-1);MAPK Signaling Pathway;TLR4 Signaling and Tolerance;Exercise-induced Circadian Regulation;Toll-like Receptor Signaling Pathway;TLR NFkB;Toll Like Receptor 7/8 (TLR7/8) Cascade;Interleukin-17 signaling;Signal Transduction;Signaling by Interleukins;signal transduction through il1r;toll-like receptor pathway;Cytokine Signaling in Immune system;Toll Like Receptor 9 (TLR9) Cascade;MyD88 cascade initiated on plasma membrane;Toll Like Receptor 10 (TLR10) Cascade;Toll Like Receptor 3 (TLR3) Cascade;Toll Like Receptor 5 (TLR5) Cascade;B cell receptor signaling;Toll-Like Receptors Cascades;Downstream TCR signaling;TCR signaling;NOD1/2 Signaling Pathway;Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways;Interleukin-1 signaling;CLEC7A (Dectin-1) signaling;C-type lectin receptors (CLRs);Fc epsilon receptor (FCERI) signaling;Innate Immune System;Immune System;Adaptive Immune System;IL-1 NFkB;IL-1 p38;IL-1 JNK;ErbB4 signaling events;IL1;TLR p38;IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation;TAK1 activates NFkB by phosphorylation and activation of IKKs complex;JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1;activated TAK1 mediates p38 MAPK activation;TNFR1-induced NFkappaB signaling pathway;BMP receptor signaling;MAP kinase activation;TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation;TNF signaling;MyD88 dependent cascade initiated on endosome;Noncanonical Wnt signaling pathway;Death Receptor Signalling;C-MYB transcription factor network;FCERI mediated NF-kB activation;Nuclear signaling by ERBB4;Signaling by ERBB4;TNFalpha;TLR JNK;TRAF6-mediated induction of TAK1 complex within TLR4 complex;TRIF(TICAM1)-mediated TLR4 signaling ;MyD88-independent TLR4 cascade ;Toll Like Receptor 4 (TLR4) Cascade;Signaling by Receptor Tyrosine Kinases;IRAK2 mediated activation of TAK1 complex;MyD88:Mal cascade initiated on plasma membrane;Toll Like Receptor TLR1:TLR2 Cascade;RANKL;Toll Like Receptor TLR6:TLR2 Cascade;Toll Like Receptor 2 (TLR2) Cascade;TNF receptor signaling pathway ;p38 MAPK signaling pathway;IL1-mediated signaling events;TGF-beta receptor signaling;Interleukin-1 family signaling;CD4 T cell receptor signaling-NFkB cascade;TICAM1,TRAF6-dependent induction of TAK1 complex;CD4 T cell receptor signaling (Consensus)

Recessive Scores

• pRec: 0.227

Intolerance Scores

• loftool: 0.123
• rvis_EVS: -1.11
• rvis_percentile_EVS: 6.72

Haploinsufficiency Scores

• pHI: 0.419
• hipred: Y
• hipred_score: 0.591
• ghis: 0.665

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.539

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tab2
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; 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); embryo phenotype; immune system 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); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); liver/biliary system phenotype

Zebrafish Information Network

• Gene name: tab2
• Affected structure: pericardial cavity
• Phenotype tag: abnormal
• Phenotype quality: increased size

Gene ontology

• Biological process: activation of MAPK activity;stimulatory C-type lectin receptor signaling pathway;MyD88-dependent toll-like receptor signaling pathway;I-kappaB kinase/NF-kappaB signaling;JNK cascade;heart development;negative regulation of autophagy;Fc-epsilon receptor signaling pathway;positive regulation of I-kappaB kinase/NF-kappaB signaling;positive regulation of protein kinase activity;T cell receptor signaling pathway;positive regulation of NF-kappaB transcription factor activity;nucleotide-binding oligomerization domain containing signaling pathway;interleukin-1-mediated signaling pathway
• Cellular component: nucleoplasm;cytosol;plasma membrane;endosome membrane
• Molecular function: protein binding;metal ion binding;K63-linked polyubiquitin modification-dependent protein binding