TAB1

protein-coding

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

Gene summary

The protein encoded by this gene was identified as a regulator of the MAP kinase kinase kinase MAP3K7/TAK1, which is known to mediate various intracellular signaling pathways, such as those induced by TGF beta, interleukin 1, and WNT-1. This protein interacts and thus activates TAK1 kinase. It has been shown that the C-terminal portion of this protein is sufficient for binding and activation of TAK1, while a portion of the N-terminus acts as a dominant-negative inhibitor of TGF beta, suggesting that this protein may function as a mediator between TGF beta receptors and TAK1. This protein can also interact with and activate the mitogen-activated protein kinase 14 (MAPK14/p38alpha), and thus represents an alternative activation pathway, in addition to the MAPKK pathways, which contributes to the biological responses of MAPK14 to various stimuli. Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

Previous symbols:

MAP3K7IP1

MANE transcript

NM_006116.3

Inheritance

—

ClinVar variants

U:77B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.6

Max pathogenic AF

—

Genomic locus

chr22:39,399,778-39,437,060

External References & Databases

Ensembl (ENSG00000100324)

Transcript & Mutation Effects

hg38 • Region Span ~37.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TAB1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 72

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006116.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	1 clinvar	1 clinvar	3
missense			74 clinvar	1 clinvar		75
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	77	2	1	80

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 18 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006116.3	RefSeq	NP_006107.1	11	MANE Select
ENST00000216160.11	Ensembl	ENSP00000216160.6	11	MANE Select
NM_153497.3	RefSeq	NP_705717.1	11	Standard
ENST00000331454.3	Ensembl	ENSP00000333049.3	11	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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)

Biological Process

activation of MAPKKK activity
activation of MAPK activity
in utero embryonic development
stimulatory C-type lectin receptor signaling pathway
MyD88-dependent toll-like receptor signaling pathway

Molecular Function

protein serine/threonine phosphatase activity
magnesium-dependent protein serine/threonine phosphatase activity
protein binding
enzyme activator activity
kinase activator activity

Cellular Component

nucleus
cytosol
endosome membrane
nuclear speck
protein-containing complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000216160
Coding exons: 11
Length: 37320
Individuals with no LoFs: 125714
Homozygous LoFs: 0
Heterozygous LoFs: 33
Defined: 125747
p: 0.000131

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.75	239	328	0.728	0.0000216	3274
Missense (PolyPhen)		80	137.23	0.58295		1412
Synonymous	0.254	143	147	0.973	0.0000108	1021
Loss of Function	1.81	14	23.5	0.596	0.00000118	259

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00049	0.00049	rare
Finnish	0.000093	0.000092	rare
European (Non-Finnish)	0.00015	0.00015	rare
South Asian	0	0.0	absent
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May be an important signaling intermediate between TGFB receptors and MAP3K7/TAK1. May play an important role in mammalian embryogenesis.;

Recessive Scores

pRec: 0.303

Intolerance Scores

LoFtool: 0.666
RVIS EVS: -1.22
RVIS percentile EVS: 5.64

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.322

Gene Damage Prediction

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