EEF2K

protein-coding

eukaryotic elongation factor 2 kinase, the group of Calmodulin dependent protein kinases

Gene summary

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]

MANE transcript

NM_013302.5

Inheritance

—

ClinVar variants

U:152B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.81

Max pathogenic AF

—

Genomic locus

chr16:22,206,278-22,288,738

External References & Databases

Ensembl (ENSG00000103319)

Transcript & Mutation Effects

hg38 • Region Span ~82.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to EEF2K variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 140

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_013302.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	1 clinvar		4
missense			142 clinvar	1 clinvar		143
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	152	2	0	154

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 36 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_013302.5	RefSeq	NP_037434.2	17	MANE Select
ENST00000263026.10	Ensembl	ENSP00000263026.5	17	MANE Select
ENST00000568269.5	Ensembl	ENSP00000456243.1	9	Standard
ENST00000868084.1	Ensembl	ENSP00000538143.1	16	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Oxytocin signaling pathway - Homo sapiens (human)
AMPK signaling pathway - Homo sapiens (human)
Translation Factors
AMP-activated Protein Kinase (AMPK) Signaling
BDNF-TrkB Signaling

Biological Process

response to ischemia
translational elongation
regulation of protein autophosphorylation
cellular response to insulin stimulus
negative regulation of apoptotic process

Molecular Function

protein kinase activity
elongation factor-2 kinase activity
calcium ion binding
calmodulin binding
ATP binding

Cellular Component

cytoplasm
cytosol
postsynaptic density
dendritic spine

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000263026
Coding exons: 17
Length: 80952
Individuals with no LoFs: 125477
Homozygous LoFs: 0
Heterozygous LoFs: 270
Defined: 125747
p: 0.00107

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.613	432	469	0.920	0.0000303	4801
Missense (PolyPhen)		136	170.38	0.7982		1746
Synonymous	0.326	193	199	0.971	0.0000147	1347
Loss of Function	1.13	34	41.9	0.812	0.00000239	432

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00074	0.00074	rare
Latino/Admixed American	0.0012	0.0012	notable
Ashkenazi Jewish	0.0020	0.0020	notable
East Asian	0.00033	0.00033	rare
Finnish	0.00037	0.00037	rare
European (Non-Finnish)	0.0014	0.0014	notable
South Asian	0.00049	0.00049	rare
Other	0.0011	0.0011	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Threonine kinase that regulates protein synthesis by controlling the rate of peptide chain elongation. Upon activation by a variety of upstream kinases including AMPK or TRPM7, phosphorylates the elongation factor EEF2 at a single site, renders it unable to bind ribosomes and thus inactive. In turn, the rate of protein synthesis is reduced. {ECO:0000269|PubMed:14709557, ECO:0000269|PubMed:9144159}.;

Recessive Scores

pRec: 0.174

Intolerance Scores

LoFtool: 0.917
RVIS EVS: -1.48
RVIS percentile EVS: 3.7

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.977

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium