TAOK1

Chr 17AD

TAO kinase 1

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

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.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.271 OMIM phenotype
Clinical SummaryTAOK1
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Gene-Disease Validity (ClinGen)
syndromic intellectual disability · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.27LOEUF
pLI 0.998
Z-score 6.31
OE 0.17 (0.100.27)
Highly constrained

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

Missense Constraint
4.82Z-score
OE missense 0.42 (0.380.47)
234 obs / 552.8 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.17 (0.100.27)
00.351.4
Missense OE0.42 (0.380.47)
00.61.4
Synonymous OE0.91
01.21.6
LoF obs/exp: 11 / 66.5Missense obs/exp: 234 / 552.8Syn Z: 0.92
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveTAOK1-related intellectual disabilityLOFAD
DN
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
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 rePMID:33565190

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

TAOK1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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