TESK1

Chr 9

testis associated actin remodelling kinase 1

This dual specificity protein kinase regulates the cellular cytoskeleton by phosphorylating cofilin to enhance actin stress fiber formation and by inhibiting microtubule breakdown, and also suppresses ciliogenesis through multiple pathways including cofilin phosphorylation and regulation of ciliary trafficking. TESK1 is highly constrained against loss-of-function variants, but no definitive human disease associations have been established in the provided data. The inheritance pattern for potential TESK1-related disorders has not been determined.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.28
Clinical SummaryTESK1
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.28LOEUF
pLI 0.993
Z-score 4.36
OE 0.11 (0.050.28)
Highly constrained

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

Missense Constraint
1.61Z-score
OE missense 0.77 (0.700.85)
291 obs / 379.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.11 (0.050.28)
00.351.4
Missense OE0.77 (0.700.85)
00.61.4
Synonymous OE0.92
01.21.6
LoF obs/exp: 3 / 27.9Missense obs/exp: 291 / 379.0Syn Z: 0.82
DN
0.4389th %ile
GOF
0.6832th %ile
LOF
0.71top 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 0.28
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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

TESK1 · 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.

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Clinical Literature
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