TAOK1

Chr 17AD

TAO kinase 1

Also known as: DDIB, KFC-B, MAP3K16, MARKK, PSK-2, PSK2, TAO1, hKFC-B

NCBI Gene: 57551 ENSG00000160551 UniProt: Q7L7X3 OMIM: 610266

TAOK1 encodes a serine/threonine kinase that regulates the p38/MAPK14 stress response pathway, DNA damage checkpoints, and cytoskeleton stability, playing essential roles in neuronal development and migration in the central nervous system. Mutations cause autosomal dominant developmental delay with or without intellectual impairment or behavioral abnormalities. The gene is highly constrained against loss-of-function variants (pLI 0.998, LOEUF 0.274), indicating that even single functional copies are critical for normal development.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Enables alpha-tubulin binding activity; beta-tubulin binding activity; and kinase activity. Involved in several processes, including mitotic G2 DNA damage checkpoint signaling; negative regulation of microtubule depolymerization; and positive regulation of MAPK cascade. Located in several cellular components, including microtubule cytoskeleton; nuclear body; and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOFmechanismADLOEUF 0.271 OMIM phenotype

Clinical Summary— TAOK1

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Gene-Disease Validity (ClinGen)

syndromic intellectual disability · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.27LOEUF

pLI 0.998

Z-score 6.31

OE 0.17 (0.10–0.27)

Highly constrained

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

Missense Constraint?

4.82Z-score

OE missense 0.42 (0.38–0.47)

234 obs / 552.8 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.17 (0.10–0.27)

0≤0.351.4

Missense OE?0.42 (0.38–0.47)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 11 / 66.5Missense obs/exp: 234 / 552.8Syn Z: 0.92

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveTAOK1-related intellectual disabilityLOFAD

This gene — mechanism propensity

0.4982th %ile

GOF

0.5366th %ile

LOF

0.66top 25%

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOFprediction above median · LOEUF 0.27 · ClinGen HI: Sufficient evidence for dosage pathogenicity

DN1 literature citation

Literature Evidence

DNThe molecular spectrum of the identified TAOK1 variants comprises largely truncating and nonsense variants, but also missense variants, for which we provide evidence that they can have a loss of function or dominant-negative effect on TAOK1, expanding the potential underlying causative mechanisms re1

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

References