TAOK3

protein-coding

TAO kinase 3, the group of Mitogen-activated protein kinase kinase kinases

Gene summary

The protein encoded by this gene is a serine/threonine protein kinase that activates the p38/MAPK14 stress-activated MAPK cascade but inhibits the basal activity of the MAPK8/JNK cascade. The encoded protein is a member of the GCK subfamily of STE20-like kinases. [provided by RefSeq, Oct 2016]

MANE transcript

NM_016281.4

Inheritance

—

ClinVar variants

U:98B:3

Top phenotype

Neurodevelopmental disorder

gnomAD constraint

pLI —, LoF o/e 0.13

Max pathogenic AF

—

Genomic locus

chr12:118,149,801-118,372,907

External References & Databases

Ensembl (ENSG00000135090)

Transcript & Mutation Effects

hg38 • Region Span ~223.1 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 TAOK3 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 80

not providedTotal: 5

Neurodevelopmental disorderTotal: 1

Prostate cancerTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_016281.4. 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					2 clinvar	2
missense			83 clinvar	1 clinvar		84
nonsense			1 clinvar			1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			13 clinvar			13
Total	0	0	98	1	2	101

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 61 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_016281.4	RefSeq	NP_057365.3	19	MANE Select
ENST00000392533.8	Ensembl	ENSP00000376317.3	19	MANE Select
NM_001346487.2	RefSeq	NP_001333416.1	19	Standard
NM_001346488.2	RefSeq	NP_001333417.1	19	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

MAPK signaling pathway - Homo sapiens (human)
EGF-Core
MAPK Signaling Pathway
p38 MAPK signaling pathway

Biological Process

MAPK cascade
activation of MAPKK activity
DNA repair
protein phosphorylation
negative regulation of protein kinase activity

Molecular Function

protein serine/threonine kinase activity
MAP kinase kinase kinase activity
protein kinase inhibitor activity
protein binding
ATP binding

Cellular Component

nucleus
cytoplasm
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000392533
Coding exons: 19
Length: 223145
Individuals with no LoFs: 125734
Homozygous LoFs: 0
Heterozygous LoFs: 14
Defined: 125748
p: 0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.03	313	505	0.620	0.0000293	6009
Missense (PolyPhen)		47	119.48	0.39339		1425
Synonymous	0.767	169	182	0.928	0.0000106	1566
Loss of Function	5.97	7	54.6	0.128	0.00000302	623

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000039	0.000029	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000098	0.000097	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Serine/threonine-protein kinase that acts as a regulator of the p38/MAPK14 stress-activated MAPK cascade and of the MAPK8/JNK cascade. Acts as an activator of the p38/MAPK14 stress- activated MAPK cascade. In response to DNA damage, involved in the G2/M transition DNA damage checkpoint by activating the p38/MAPK14 stress-activated MAPK cascade, probably by mediating phosphorylation of upstream MAP2K3 and MAP2K6 kinases. Inhibits basal activity of MAPK8/JNK cascade and diminishes its activation in response epidermal growth factor (EGF). {ECO:0000269|PubMed:10559204, ECO:0000269|PubMed:10924369, ECO:0000269|PubMed:17396146}.;

Recessive Scores

pRec: 0.112

Intolerance Scores

LoFtool: 0.177
RVIS EVS: -0.8
RVIS percentile EVS: 12.46

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.988

Gene Damage Prediction

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