TAB3

Chr X

TGF-beta activated kinase 1 (MAP3K7) binding protein 3

Also known as: MAP3K7IP3, NAP1

The encoded protein functions as an adapter in NF-κB and JNK signaling pathways by recognizing specific polyubiquitin chains and linking MAP3K7/TAK1 to TRAF6, facilitating inflammatory signaling cascades. TAB3 variants cause neurodevelopmental disorder with microcephaly, epilepsy, and brain atrophy (NEDMEBA), which follows autosomal recessive inheritance and presents in early childhood. The gene shows high constraint against loss-of-function variants (LOEUF 0.42), indicating intolerance to such changes in the general population.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 0.42
Clinical SummaryTAB3
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.62) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
72 unique Pathogenic / Likely Pathogenic· 58 VUS of 237 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.42LOEUF
pLI 0.617
Z-score 3.69
OE 0.20 (0.100.42)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.76Z-score
OE missense 0.70 (0.620.79)
189 obs / 270.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.20 (0.100.42)
00.351.4
Missense OE0.70 (0.620.79)
00.61.4
Synonymous OE0.83
01.21.6
LoF obs/exp: 5 / 24.9Missense obs/exp: 189 / 270.4Syn Z: 1.28

ClinVar Variant Classifications

237 submitted variants in ClinVar

Classification Summary

Pathogenic71
Likely Pathogenic1
VUS58
Likely Benign2
Benign1
71
Pathogenic
1
Likely Pathogenic
58
VUS
2
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
71
0
71
Likely Pathogenic
0
0
1
0
1
VUS
0
51
7
0
58
Likely Benign
0
0
0
2
2
Benign
0
0
1
0
1
Total051802133

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TAB3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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