MKNK1

Chr 1

MAPK interacting serine/threonine kinase 1

Also known as: MNK1

NCBI Gene: 8569ENSG00000079277UniProt: Q9BUB5

This gene encodes a Ser/Thr protein kinase that interacts with, and is activated by ERK1 and p38 mitogen-activated protein kinases, and thus may play a role in the response to environmental stress and cytokines. This kinase may also regulate transcription by phosphorylating eIF4E via interaction with the C-terminal region of eIF4G. Alternatively spliced transcript variants have been noted for this gene. [provided by RefSeq, Jan 2012]

65
ClinVar variants
6
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— MKNK1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
6 Pathogenic / Likely Pathogenic· 55 VUS of 65 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
1.03LOEUF
pLI 0.000
Z-score 1.43
OE 0.70 (0.48–1.03)
Tolerant

Highly tolerant — LoF variants common in population

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.
1.44Z-score
OE missense 0.75 (0.67–0.84)
197 obs / 262.6 exp
Tolerant

Mild missense constraint

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.0.70 (0.48–1.03)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.75 (0.67–0.84)
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.0.98
0≤1.21.6
LoF obs/exp: 18 / 25.9Missense obs/exp: 197 / 262.6Syn Z: 0.15

ClinVar Variant Classifications

65 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4
Likely Pathogenic2
VUS55
Likely Benign4
4
Pathogenic
2
Likely Pathogenic
55
VUS
4
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
4
0
4
Likely Pathogenic
0
0
2
0
2
VUS
0
47
8
0
55
Likely Benign
0
2
1
1
4
Benign
0
0
0
0
0
Total04915165

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

View 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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
ephrin-B2 promotes nociceptive plasticity and hyperalgesic priming through EphB2-MNK-eIF4E signaling in both mice and humans.
David ET et al.·Pharmacol Res
2024
miR-483-5p Targets MKNK1 to Suppress Wilms' Tumor Cell Proliferation and Apoptosis In Vitro and In Vivo.
Liu K et al.·Med Sci Monit
2019
Diagnostic signature composed of seven genes in HIF-1 signaling pathway for preeclampsia.
Yang X et al.·BMC Pregnancy Childbirth
2023
miR-1227-3p participates in the development of fetal growth restriction via regulating trophoblast cell proliferation and apoptosis.
Cui J et al.·Sci Rep
2022
Genome-Wide Gene-Sodium Interaction Analyses on Blood Pressure: The Genetic Epidemiology Network of Salt-Sensitivity Study.
Li C et al.·Hypertension
2016
Myoglobin Protects Breast Cancer Cells Due to Its ROS and NO Scavenging Properties.
Quinting T et al.·Front Endocrinol (Lausanne)
2021
LY2801653 is an orally bioavailable multi-kinase inhibitor with potent activity against MET, MST1R, and other oncoproteins, and displays anti-tumor activities in mouse xenograft models.
Yan SB et al.·Invest New Drugs
2013Clinical trial
Stratifying Cumulus Cell Samples Based on Molecular Profiling to Help Resolve Biomarker Discrepancies and to Predict Oocyte Developmental Competence.
El-Maarri O et al.·Int J Mol Sci
2021
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Integrated bioinformatics and machine learning approaches reveal that Venenum bufonis acts against acute pharyngitis by inhibiting the p38 MAPK/ERK-MKNK1-eIF4E signaling pathway.
Chen D et al.·J Ethnopharmacol
2026
Endocrine-exocrine miR-503-322 drives aging-associated pancreatitis via targeting MKNK1 in acinar cells.
Liu K et al.·Nat Commun
2025🔓 Open Access
A tRF-5a fragment that regulates radiation resistance of colorectal cancer cells by targeting MKNK1.
Huang T et al.·J Cell Mol Med
2023🔓 Open Access
Identification of MKNK1 and TOP3A as ovarian endometriosis risk-associated genes using integrative genomic analyses and functional experiments.
Huang Y et al.·Comput Struct Biotechnol J
2023🔓 Open AccessFunctional
MAPK interacting serine/threonine kinase 1 (MKNK1), one target gene of miR-223-3p, correlates with neutrophils in sepsis based on bioinformatic analysis.
Fu M et al.·Bioengineered
2021🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools