TAOK2

Chr 16

TAO kinase 2

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

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.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.24
Clinical SummaryTAOK2
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.
📋
ClinVar Variants
22 unique Pathogenic / Likely Pathogenic· 275 VUS of 499 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.24LOEUF
pLI 1.000
Z-score 5.97
OE 0.13 (0.070.24)
Highly constrained

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

Missense Constraint
3.21Z-score
OE missense 0.67 (0.630.72)
518 obs / 768.4 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.13 (0.070.24)
00.351.4
Missense OE0.67 (0.630.72)
00.61.4
Synonymous OE1.08
01.21.6
LoF obs/exp: 7 / 54.7Missense obs/exp: 518 / 768.4Syn Z: -1.09
DN
0.4090th %ile
GOF
0.6735th %ile
LOF
0.69top 10%

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). 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 0.24
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

499 submitted variants in ClinVar

Classification Summary

Pathogenic22
VUS275
Likely Benign172
Benign5
Conflicting1
22
Pathogenic
275
VUS
172
Likely Benign
5
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
21
0
22
Likely Pathogenic
0
0
0
0
0
VUS
9
251
14
1
275
Likely Benign
0
5
46
121
172
Benign
0
2
1
2
5
Conflicting
1
Total1025882124475

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TAOK2 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗