Congenital heart defects, multiple types, 2

Summary

Congenital heart defects, multiple types, 2 (MONDO:0014000) is a disease caused by TAB2 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: TAB2 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 57

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital heart defects, multiple types, 2
Mondo ID	MONDO:0014000
OMIM	614980
UMLS	C3554279
MedGen	767193
GARD	0024964
Is cancer (heuristic)	no

Also known as: CHTD2 · congenital heart defects, multiple types, 2 · congenital heart malformation caused by mutation in TAB2 · TAB2 congenital heart malformation · TAB2-related syndromic congenital heart disease

Data availability: 57 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › heart disorder › congenital heart disease › congenital heart defects, multiple types › congenital heart defects, multiple types, 2

Related subtypes (7): congenital heart defects, multiple types, 6, congenital heart defects, multiple types, 3, congenital heart defects, multiple types, 4, congenital heart defects, multiple types, 5, MYH-6 related congenital heart defects, congenital heart defects, multiple types, 8, with or without heterotaxy, congenital heart defects, multiple types, 9

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

57 retrieved; paginated sample, class counts are floors:

19 pathogenic, 17 likely pathogenic, 15 uncertain significance, 5 pathogenic/likely pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1328249	NM_001292034.3(TAB2):c.1340_1341del (p.Ser447fs)	LOC126859827	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1454884	NM_001292034.3(TAB2):c.1354C>T (p.Arg452Ter)	LOC126859827	Pathogenic	criteria provided, multiple submitters, no conflicts
1686244	NM_001292034.3(TAB2):c.1491T>G (p.Tyr497Ter)	LOC126859827	Pathogenic	criteria provided, single submitter
1805200	NM_001292034.3(TAB2):c.1462dup (p.Thr488fs)	LOC126859827	Pathogenic	criteria provided, single submitter
2443078	NM_001292034.3(TAB2):c.1056del (p.Ser353fs)	LOC126859827	Pathogenic	no assertion criteria provided
2505202	NM_001292034.3(TAB2):c.1572del (p.Ser524fs)	LOC126859827	Pathogenic	criteria provided, single submitter
2506347	NM_001292034.3(TAB2):c.1105dup (p.Ile369fs)	LOC126859827	Pathogenic	criteria provided, single submitter
2627254	NM_001292034.3(TAB2):c.1547_1551del (p.Arg516fs)	LOC126859827	Pathogenic	criteria provided, single submitter
3068516	NM_001292034.3(TAB2):c.1020_1021del (p.Lys340fs)	LOC126859827	Pathogenic	criteria provided, single submitter
3390788	NM_001292034.3(TAB2):c.1121dup (p.Asn375fs)	LOC126859827	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
373443	NM_001292034.3(TAB2):c.1039C>T (p.Arg347Ter)	LOC126859827	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
488615	NM_001292034.3(TAB2):c.1321C>T (p.Arg441Ter)	LOC126859827	Pathogenic	criteria provided, multiple submitters, no conflicts
561123	NM_001292034.3(TAB2):c.1491T>A (p.Tyr497Ter)	LOC126859827	Pathogenic	criteria provided, single submitter
561124	NM_001292034.3(TAB2):c.679C>T (p.Arg227Ter)	LOC126859827	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
996746	NM_001292034.3(TAB2):c.1398dup (p.Thr467fs)	LOC126859827	Pathogenic	criteria provided, single submitter
1030404	NM_001292034.3(TAB2):c.1764+1G>A	TAB2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1048629	NM_001292034.3(TAB2):c.446C>G (p.Ser149Ter)	TAB2	Pathogenic	no assertion criteria provided
2441831	NM_001292034.3(TAB2):c.473_474del (p.His158fs)	TAB2	Pathogenic	criteria provided, single submitter
3254807	NM_001292034.3(TAB2):c.379C>T (p.Gln127Ter)	TAB2	Pathogenic	criteria provided, single submitter
3255071	NM_001292034.3(TAB2):c.363_364insGTTA (p.Phe122fs)	TAB2	Pathogenic	criteria provided, single submitter
3255073	NM_001292034.3(TAB2):c.1813_1814delinsC (p.Asp605fs)	TAB2	Pathogenic	criteria provided, single submitter
4081888	NM_001292034.3(TAB2):c.24del (p.Ile8fs)	TAB2	Pathogenic	no assertion criteria provided
5211	NM_001292034.3(TAB2):c.622C>T (p.Pro208Ser)	TAB2	Pathogenic	no assertion criteria provided
976750	NM_001292034.3(TAB2):c.622_626del (p.Pro208fs)	TAB2	Pathogenic	criteria provided, single submitter
1325168	NM_001292034.3(TAB2):c.814C>T (p.Gln272Ter)	LOC126859827	Likely pathogenic	criteria provided, single submitter
1683671	NM_001292034.3(TAB2):c.1104C>G (p.Tyr368Ter)	LOC126859827	Likely pathogenic	criteria provided, single submitter
2431471	NM_001292034.3(TAB2):c.1433_1448del (p.Pro478fs)	LOC126859827	Likely pathogenic	criteria provided, single submitter
2444290	NM_001292034.3(TAB2):c.1501G>T (p.Glu501Ter)	LOC126859827	Likely pathogenic	criteria provided, single submitter
2627070	NM_001292034.3(TAB2):c.1522del (p.Asp508fs)	LOC126859827	Likely pathogenic	no assertion criteria provided
3024330	NM_001292034.3(TAB2):c.1591_1593delinsTTTT (p.Ala531fs)	LOC126859827	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
TAB2	Definitive	Autosomal dominant	congenital heart defects, multiple types, 2	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TAB2	Orphanet:664401	Cardiac anomalies-short stature-joint hypermobility-facial dysmorphism syndrome due to TAB2 mutation
TAB2	Orphanet:664404	6q25.1 microdeletion syndrome

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TAB2	HGNC:17075	ENSG00000055208	Q9NYJ8	TGF-beta-activated kinase 1 and MAP3K7-binding protein 2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TAB2	TGF-beta-activated kinase 1 and MAP3K7-binding protein 2	Adapter required to activate the JNK and NF-kappa-B signaling pathways through the specific recognition of ‘Lys-63’-linked polyubiquitin chains by its RanBP2-type zinc finger (NZF).

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TAB2	Transcription factor	no		Znf_RanBP2, CUE, Znf_RanBP2_sf

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
colonic epithelium	1
parotid gland	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TAB2	293	ubiquitous	marker	parotid gland, ventricular zone, colonic epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TAB2	2,606

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TAB2	Q9NYJ8	6

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 55. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
IRAK2 mediated activation of TAK1 complex	1	1142.0×	0.010	TAB2
TICAM1,TRAF6-dependent induction of TAK1 complex	1	1038.2×	0.010	TAB2
Alpha-protein kinase 1 signaling pathway	1	1038.2×	0.010	TAB2
IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation	1	761.3×	0.010	TAB2
TRAF6-mediated induction of TAK1 complex within TLR4 complex	1	713.8×	0.010	TAB2
JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1	1	519.1×	0.010	TAB2
TCR signaling	1	496.5×	0.010	TAB2
activated TAK1 mediates p38 MAPK activation	1	496.5×	0.010	TAB2
TNF signaling	1	423.0×	0.010	TAB2
Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways	1	356.9×	0.010	TAB2
Nuclear signaling by ERBB4	1	346.1×	0.010	TAB2
TNFR1-induced NF-kappa-B signaling pathway	1	335.9×	0.010	TAB2
NOD1/2 Signaling Pathway	1	317.2×	0.010	TAB2
MAP kinase activation	1	308.6×	0.010	TAB2
TAK1-dependent IKK and NF-kappa-B activation	1	300.5×	0.010	TAB2
Signaling by ERBB4	1	271.9×	0.010	TAB2
Fc epsilon receptor (FCERI) signaling	1	271.9×	0.010	TAB2
Interleukin-1 family signaling	1	271.9×	0.010	TAB2
Interleukin-17 signaling	1	253.8×	0.010	TAB2
C-type lectin receptors (CLRs)	1	237.9×	0.010	TAB2
Toll Like Receptor 10 (TLR10) Cascade	1	215.5×	0.010	TAB2
Toll Like Receptor 5 (TLR5) Cascade	1	215.5×	0.010	TAB2
MyD88 cascade initiated on plasma membrane	1	203.9×	0.010	TAB2
Toll Like Receptor 3 (TLR3) Cascade	1	193.6×	0.010	TAB2
TRIF (TICAM1)-mediated TLR4 signaling	1	190.3×	0.010	TAB2
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation	1	190.3×	0.010	TAB2
MyD88 dependent cascade initiated on endosome	1	190.3×	0.010	TAB2
MyD88-independent TLR4 cascade	1	184.2×	0.010	TAB2
Toll Like Receptor 7/8 (TLR7/8) Cascade	1	184.2×	0.010	TAB2
Toll Like Receptor 9 (TLR9) Cascade	1	175.7×	0.010	TAB2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
non-canonical NF-kappaB signal transduction	1	842.6×	0.006	TAB2
positive regulation of protein kinase activity	1	674.1×	0.006	TAB2
negative regulation of autophagy	1	259.3×	0.010	TAB2
response to lipopolysaccharide	1	124.8×	0.015	TAB2
defense response to bacterium	1	108.0×	0.015	TAB2
heart development	1	78.8×	0.016	TAB2
positive regulation of canonical NF-kappaB signal transduction	1	72.6×	0.016	TAB2
inflammatory response	1	37.7×	0.027	TAB2

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TAB2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
TAB2	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	TAB2

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
TAB2	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.