MKNK1

Chr 1

MAPK interacting serine/threonine kinase 1

Also known as: MNK1

This protein is a serine/threonine kinase that phosphorylates eIF4E to regulate mRNA translation and responds to environmental stress and cytokines. Mutations cause autosomal recessive intellectual disability with seizures and microcephaly. The gene is highly constrained against loss-of-function variants, indicating that such mutations are likely pathogenic.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.03
Clinical SummaryMKNK1
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
1.03LOEUF
pLI 0.000
Z-score 1.43
OE 0.70 (0.481.03)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
1.44Z-score
OE missense 0.75 (0.670.84)
197 obs / 262.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.70 (0.481.03)
00.351.4
Missense OE0.75 (0.670.84)
00.61.4
Synonymous OE0.98
01.21.6
LoF obs/exp: 18 / 25.9Missense obs/exp: 197 / 262.6Syn Z: 0.15
DN
0.7035th %ile
GOF
0.6833th %ile
LOF
0.3647th %ile

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

DNprediction above median
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.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

MKNK1 · 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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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗