TESK2

Chr 1

testis associated actin remodelling kinase 2

This gene encodes a dual specificity protein kinase that phosphorylates cofilin and plays an important role in spermatogenesis, with predominant expression in testis and prostate. Mutations in TESK2 cause neurodevelopmental disorder with seizures and nonepileptic hyperkinetic movements, following an autosomal dominant inheritance pattern. The gene is not highly constrained against loss-of-function variants.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.81
Clinical SummaryTESK2
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.81LOEUF
pLI 0.000
Z-score 2.36
OE 0.52 (0.350.81)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.49Z-score
OE missense 0.92 (0.841.01)
318 obs / 343.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.52 (0.350.81)
00.351.4
Missense OE0.92 (0.841.01)
00.61.4
Synonymous OE1.01
01.21.6
LoF obs/exp: 15 / 28.6Missense obs/exp: 318 / 343.8Syn Z: -0.10
DN
0.7228th %ile
GOF
0.79top 25%
LOF
0.3550th %ile

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

GOFprediction above median
DNprediction 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.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

TESK2 · 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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