TAOK1

Chr 17AD

TAO kinase 1

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

NCBI Gene: 57551ENSG00000160551UniProt: Q7L7X3

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]

Primary Disease Associations & Inheritance

Developmental delay with or without intellectual impairment or behavioral abnormalitiesMIM #619575
AD
311
ClinVar variants
81
Pathogenic / LP
1.00
pLI score· haploinsufficient
1
Active trials
Clinical Summary— TAOK1
🧬
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.
📋
ClinVar Variants
81 Pathogenic / Likely Pathogenic· 191 VUS of 311 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
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?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.17 (0.10–0.27)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.42 (0.38–0.47)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.91
0≤1.21.6
LoF obs/exp: 11 / 66.5Missense obs/exp: 234 / 552.8Syn Z: 0.92

ClinVar Variant Classifications

311 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic36
Likely Pathogenic45
VUS191
Likely Benign25
Benign11
Conflicting3
36
Pathogenic
45
Likely Pathogenic
191
VUS
25
Likely Benign
11
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
14
1
21
0
36
Likely Pathogenic
18
13
14
0
45
VUS
3
165
19
4
191
Likely Benign
0
8
7
10
25
Benign
0
0
3
8
11
Conflicting
—3
Total351876422311

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

View 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.

Gene2Phenotype Curations

TAOK1-related intellectual disability

definitive
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
TAO KINASE 1; TAOK1
MIM #610266 · *

Developmental delay with or without intellectual impairment or behavioral abnormalities

MIM #619575

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Expanding the phenotype and genotype spectrum of TAOK1 neurodevelopmental disorder and delineating TAOK2 neurodevelopmental disorder.
Elkhateeb N et al.·Genet Med
2025
TAOK1 promotes filament formation in HR repair through phosphorylating USP7.
Zhu TC et al.·Proc Natl Acad Sci U S A
2025
Heterozygous truncating variant of TAOK1 in a boy with periventricular nodular heterotopia: a case report and literature review of TAOK1-related neurodevelopmental disorders.
Cavalli A et al.·BMC Med Genomics
2024Review
Research progress on anti-tumor mechanism of TAOK kinases.
Li J et al.·Cell Signal
2024Review
Pan-cancer genetic profiles of mitotic DNA integrity checkpoint protein kinases.
Rasteh AM et al.·Cancer Biomark
2024
Inherited and de novo variants extend the etiology of TAOK1-associated neurodevelopmental disorder.
Hunter JM et al.·Cold Spring Harb Mol Case Stud
2022
Taok1 haploinsufficiency leads to autistic-like behaviors in mice via the dorsal raphe nucleus.
Wang J et al.·Cell Rep
2023
ZNF142 mutation causes sex-dependent neurologic disorder.
Proskorovski-Ohayon R et al.·J Med Genet
2024
Ste20-Like Kinase TAOK1 Positively Regulates Antiviral Responses by Controlling the TBK1-IRF3 Signaling Axis.
Luo X et al.·J Innate Immun
2023
Targeting TAOK1 with resveratrol inhibits esophageal squamous cell carcinoma growth in vitro and in vivo.
Song M et al.·Mol Carcinog
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Discovery of VU6083859, a TAOK1 Selective Inhibitor, and VU6080195, a pan-TAOK Activator.
Schultz DC et al.·ACS Chem Neurosci
2026🔓 Open Access
PAD4+ neutrophils promote hepatic stellate cell activation and accelerate MASH fibrosis progression viaNET-DNA/TAOK1/MAPK pathways.
Shen J et al.·JCI Insight
2026🔓 Open Access
LncRNA C9orf139 Promotes Acute Myeloid Leukemia Cell Proliferation by Sponging miR-24-3p to Upregulate TAOK1.
Qin W et al.·Curr Med Sci
2025
LINC01198 activates Hippo signaling to stimulate IL-1β autocrine for driving vemurafenib resistance by associating with TAOK1/2 in melanoma.
Liu J et al.·Cell Death Discov
2025🔓 Open Access
Corylifol A ameliorates pancreatic cancer-associated cachexia by targeting TAOK3 in pancreatic cancer cells and targeting TAOK1 in skeletal muscle cells.
Yu K et al.·Toxicol Appl Pharmacol
2025
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
16P11.2 Deletion Syndrome16p11.2 Duplications1Q21.1 Deletion

Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight

RECRUITING
NCT01238250Simons SearchlightStarted 2010-10

External Resources

Links to major genomics databases and tools