EEF2K

Chr 16

eukaryotic elongation factor 2 kinase

Also known as: CaMKIII, HSU93850, eEF-2K

NCBI Gene: 29904ENSG00000103319UniProt: O00418

This gene encodes a highly conserved protein kinase in the calmodulin-mediated signaling pathway that links activation of cell surface receptors to cell division. This kinase is involved in the regulation of protein synthesis. It phosphorylates eukaryotic elongation factor 2 (EEF2) and thus inhibits the EEF2 function. The activity of this kinase is increased in many cancers and may be a valid target for anti-cancer treatment. [provided by RefSeq, Jul 2008]

264
ClinVar variants
70
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— EEF2K
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
70 Pathogenic / Likely Pathogenic· 183 VUS of 264 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.
1.08LOEUF
pLI 0.000
Z-score 1.13
OE 0.81 (0.62–1.08)
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.
0.61Z-score
OE missense 0.92 (0.85–1.00)
432 obs / 469.4 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.0.81 (0.62–1.08)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.92 (0.85–1.00)
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.0.97
0≤1.21.6
LoF obs/exp: 34 / 41.9Missense obs/exp: 432 / 469.4Syn Z: 0.33

ClinVar Variant Classifications

264 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic55
Likely Pathogenic15
VUS183
Likely Benign6
Benign1
Conflicting4
55
Pathogenic
15
Likely Pathogenic
183
VUS
6
Likely Benign
1
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
55
0
55
Likely Pathogenic
0
0
15
0
15
VUS
0
137
46
0
183
Likely Benign
0
1
4
1
6
Benign
0
0
1
0
1
Conflicting
—4
Total01381211264

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

View in ClinVar →

Protein Context — Lollipop Plot

EEF2K · 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
📖
GeneReview available — EEF2K
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Pharmacologic targeting of eEF2K in cardiovascular diseases: Mechanisms and potential clinical applications.
Rezabakhsh A et al.·Eur J Pharmacol
2025Review
Eukaryotic elongation factor-2 kinase (eEF2K) signaling in tumor and microenvironment as a novel molecular target.
Karakas D et al.·J Mol Med (Berl)
2020Review
Transcriptional-translational conflict is a barrier to cellular transformation and cancer progression.
Jana S et al.·Cancer Cell
2023
Duhuo Jisheng Decoction mitigates postmenopausal rheumatoid arthritis by suppressing eEF2K-mediated cellular senescence.
Chen D et al.·Pharmacol Res
2025
eEF2K promotes PD-L1 stabilization through inactivating GSK3β in melanoma.
Chen X et al.·J Immunother Cancer
2022
eEF2K as an important kinase associated with cancer survival and prognosis.
Wang N et al.·Sci Rep
2024
Can endocan serve as a molecular "hepatostat" in liver regeneration?
Yazici SE et al.·Mol Med
2023
eEF2K as a novel metastatic and prognostic biomarker in gastric cancer patients.
Jiang M et al.·Pathol Res Pract
2021Cohort
eEF2K enhances expression of PD-L1 by promoting the translation of its mRNA.
Wu Y et al.·Biochem J
2020
AMPK Activation Downregulates TXNIP, Rab5, and Rab7 Within Minutes, Thereby Inhibiting the Endocytosis-Mediated Entry of Human Pathogenic Viruses.
Diesendorf V et al.·Cells
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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