TNK2

Chr 3

tyrosine kinase non receptor 2

Also known as: ACK, ACK-1, ACK1, p21cdc42Hs

The protein is a non-receptor tyrosine kinase that regulates cell migration, survival, and proliferation through phosphorylation of multiple targets including AKT1 and plays roles in synaptic function and brain development. Mutations cause autosomal dominant developmental delays with or without dysmorphic facies and behavioral abnormalities. The gene is highly constrained against loss-of-function variants, suggesting intolerance to protein-disrupting mutations.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.80
Clinical SummaryTNK2
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
0.80LOEUF
pLI 0.000
Z-score 2.61
OE 0.57 (0.420.80)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.20Z-score
OE missense 1.02 (0.961.09)
710 obs / 695.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.57 (0.420.80)
00.351.4
Missense OE1.02 (0.961.09)
00.61.4
Synonymous OE1.36
01.21.6
LoF obs/exp: 25 / 43.6Missense obs/exp: 710 / 695.0Syn Z: -4.89
DN
0.7229th %ile
GOF
0.77top 25%
LOF
0.3358th %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

TNK2 · 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 →