TAOK2

Chr 16

TAO kinase 2

Also known as: MAP3K17, PSK, PSK1, PSK1-BETA, TAO1, TAO2, Tao2beta

NCBI Gene: 9344 ENSG00000149930 UniProt: Q9UL54 OMIM: 613199

TAOK2 encodes a serine/threonine kinase that activates p38 MAPK signaling pathways, regulates microtubule organization, and controls cellular responses to DNA damage and osmotic stress. Mutations cause autosomal dominant neurodevelopmental disorders with intellectual disability, autism spectrum disorder, and developmental delay. This gene is highly constrained against loss-of-function variants, indicating that TAOK2 is essential for normal human development.

OMIM ResearchSummary from RefSeq, UniProt

Enables mitogen-activated protein kinase kinase binding activity; neuropilin binding activity; and protein serine/threonine kinase activity. Involved in several processes, including focal adhesion assembly; intracellular signal transduction; and positive regulation of MAPK cascade. Located in cytoplasmic vesicle; nucleolus; and nucleoplasm. Part of signaling receptor complex. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.24

LOEUF· LoF intol.

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.24LOEUF

pLI 1.000

Z-score 5.97

OE 0.13 (0.07–0.24)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

3.21Z-score

OE missense 0.67 (0.63–0.72)

518 obs / 768.4 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.13 (0.07–0.24)

0≤0.351.4

Missense OE?0.67 (0.63–0.72)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 7 / 54.7Missense obs/exp: 518 / 768.4Syn Z: -1.09

Background carrier burden — how many people carry a rare variant somewhere in TAOK2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 38

1,832 rare PASS variants

Rare truncating (LoF)

1 in 1,500

163 rare PASS variants

Rare synonymous (reference)

1 in 48

978 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TAOK2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 48	1 in 1,600
South Asian	~43k	1 in 34	1 in 2,700
Remaining (unassigned)	~30k	1 in 41	1 in 2,700
European (Finnish)	~27k	1 in 79	1 in 480
Admixed American	~22k	1 in 35	1 in 1,200
African / African American	~21k	1 in 36	1 in 1,400
East Asian	~20k	1 in 32	1 in 1,900
Ashkenazi Jewish	~13k	1 in 97	1 in 2,300
Middle Eastern	~2,884	1 in 35	≈ 1 in 1,300

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 15 coding exons well covered in gnomAD exomes and genomes.? see exons ↓