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Aliases for EIF2AK4 Gene

Aliases for EIF2AK4 Gene

  • Eukaryotic Translation Initiation Factor 2 Alpha Kinase 4 2 3
  • GCN2-Like Protein 3 4
  • GCN2 3 4
  • General Control Nonderepressible 2 3
  • GCN2 EIF2alpha Kinase 3
  • EC 4
  • KIAA1338 4
  • PVOD2 3

External Ids for EIF2AK4 Gene

Previous GeneCards Identifiers for EIF2AK4 Gene

  • GC15P033123
  • GC15P037805
  • GC15P037942
  • GC15P037962
  • GC15P038033
  • GC15P038014
  • GC15P040226
  • GC15P017070

Summaries for EIF2AK4 Gene

Entrez Gene Summary for EIF2AK4 Gene

  • This gene encodes a member of a family of kinases that phosphorylate the alpha subunit of eukaryotic translation initiation factor-2 (EIF2), resulting in the downregulaton of protein synthesis. The encoded protein responds to amino acid deprivation by binding uncharged transfer RNAs. It may also be activated by glucose deprivation and viral infection. Mutations in this gene have been found in individuals suffering from autosomal recessive pulmonary venoocclusive-disease-2. [provided by RefSeq, Mar 2014]

GeneCards Summary for EIF2AK4 Gene

EIF2AK4 (Eukaryotic Translation Initiation Factor 2 Alpha Kinase 4) is a Protein Coding gene. Diseases associated with EIF2AK4 include pulmonary capillary hemangiomatosis and pulmonary venoocclusive disease. Among its related pathways are Apoptotic Pathways in Synovial Fibroblasts and Nanog in Mammalian ESC Pluripotency. GO annotations related to this gene include protein homodimerization activity and protein kinase activity. An important paralog of this gene is EIF2AK1.

UniProtKB/Swiss-Prot for EIF2AK4 Gene

  • Can phosphorylate the alpha subunit of EIF2 and may mediate translational control.

Gene Wiki entry for EIF2AK4 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for EIF2AK4 Gene

Genomics for EIF2AK4 Gene

Regulatory Elements for EIF2AK4 Gene

Epigenetics Products

  • DNA Methylation CpG Assay Predesigned for Pyrosequencing in human,mouse,rat

Genomic Location for EIF2AK4 Gene

39,934,124 bp from pter
40,035,596 bp from pter
101,473 bases
Plus strand

Genomic View for EIF2AK4 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for EIF2AK4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for EIF2AK4 Gene

Proteins for EIF2AK4 Gene

  • Protein details for EIF2AK4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Eukaryotic translation initiation factor 2-alpha kinase 4
    Protein Accession:
    Secondary Accessions:
    • C9JEC4
    • Q69YL7
    • Q6DC97
    • Q96GN6
    • Q9H5K1
    • Q9NSQ3
    • Q9NSZ5
    • Q9UJ56

    Protein attributes for EIF2AK4 Gene

    1649 amino acids
    Molecular mass:
    186911 Da
    Quaternary structure:
    No Data Available
    • Sequence=BAA92576.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the N-terminal part.; Evidence={ECO:0000305}; Sequence=BAB15625.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};

    Alternative splice isoforms for EIF2AK4 Gene


neXtProt entry for EIF2AK4 Gene

Proteomics data for EIF2AK4 Gene at MOPED

Post-translational modifications for EIF2AK4 Gene

Other Protein References for EIF2AK4 Gene

Antibody Products

  • Cell Signaling Technology (CST) Antibodies for EIF2AK4 (GCN2)

No data available for DME Specific Peptides for EIF2AK4 Gene

Domains & Families for EIF2AK4 Gene

Gene Families for EIF2AK4 Gene

Suggested Antigen Peptide Sequences for EIF2AK4 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry



  • Kinase domain 1 is a degenerate kinase domain
  • Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. GCN2 subfamily.
  • Kinase domain 1 is a degenerate kinase domain
  • RWD domain is reported to interact with GCN1L1
  • Contains 2 protein kinase domains.
  • Contains 1 RWD domain.
  • Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. GCN2 subfamily.
genes like me logo Genes that share domains with EIF2AK4: view

Function for EIF2AK4 Gene

Molecular function for EIF2AK4 Gene

UniProtKB/Swiss-Prot CatalyticActivity:
ATP + a protein = ADP + a phosphoprotein
UniProtKB/Swiss-Prot Function:
Can phosphorylate the alpha subunit of EIF2 and may mediate translational control.

Enzyme Numbers (IUBMB) for EIF2AK4 Gene

Gene Ontology (GO) - Molecular Function for EIF2AK4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004672 protein kinase activity --
GO:0004674 protein serine/threonine kinase activity ISS --
GO:0004694 eukaryotic translation initiation factor 2alpha kinase activity ISS 10504407
GO:0005515 protein binding --
GO:0005524 ATP binding IEA --
genes like me logo Genes that share ontologies with EIF2AK4: view
genes like me logo Genes that share phenotypes with EIF2AK4: view

Animal Models for EIF2AK4 Gene

MGI Knock Outs for EIF2AK4:

Animal Model Products

CRISPR Products

No data available for Transcription Factor Targets and HOMER Transcription for EIF2AK4 Gene

Localization for EIF2AK4 Gene

Subcellular locations from

Jensen Localization Image for EIF2AK4 Gene COMPARTMENTS Subcellular localization image for EIF2AK4 gene
Compartment Confidence
cytosol 4
endoplasmic reticulum 2
nucleus 1
vacuole 1

Gene Ontology (GO) - Cellular Components for EIF2AK4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005622 intracellular --
GO:0005844 polysome ISS --
GO:0022626 cytosolic ribosome ISS --
genes like me logo Genes that share ontologies with EIF2AK4: view

No data available for Subcellular locations from UniProtKB/Swiss-Prot for EIF2AK4 Gene

Pathways & Interactions for EIF2AK4 Gene

genes like me logo Genes that share pathways with EIF2AK4: view

Pathways by source for EIF2AK4 Gene

2 Qiagen pathways for EIF2AK4 Gene
1 Cell Signaling Technology pathway for EIF2AK4 Gene

SIGNOR curated interactions for EIF2AK4 Gene


Gene Ontology (GO) - Biological Process for EIF2AK4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006446 regulation of translational initiation ISS --
GO:0006468 protein phosphorylation ISS --
GO:0009267 cellular response to starvation --
GO:0010998 regulation of translational initiation by eIF2 alpha phosphorylation ISS 10504407
GO:0017148 negative regulation of translation IEA --
genes like me logo Genes that share ontologies with EIF2AK4: view

Drugs & Compounds for EIF2AK4 Gene

(7) Drugs for EIF2AK4 Gene - From: HMDB, PharmGKB, and NovoSeek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Haloperidol Approved Pharma Antagonist Antipsychotic drug 134
Olanzapine Approved, Investigational Pharma Antagonist 369
Quetiapine Approved Pharma Antagonist 400
Risperidone Approved, Investigational Pharma Antagonist SR-2A inhibitor 579
Ziprasidone Approved Pharma Antagonist 139

(2) Additional Compounds for EIF2AK4 Gene - From: HMDB and NovoSeek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
  • Adenosindiphosphorsaeure
  • Adenosine 5'-pyrophosphate
  • Adenosine diphosphate
  • Adenosine pyrophosphate
  • Adenosine-5'-diphosphate
Antagonist, Gating inhibitor 58-64-0
genes like me logo Genes that share compounds with EIF2AK4: view

Transcripts for EIF2AK4 Gene

Unigene Clusters for EIF2AK4 Gene

Eukaryotic translation initiation factor 2 alpha kinase 4:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for EIF2AK4

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for EIF2AK4 Gene

ExUns: 1a · 1b ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7a · 7b ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14a · 14b ^ 15 ^ 16 ^ 17 ^ 18a · 18b ^ 19 ^ 20a · 20b ^ 21 ^
SP1: - - -
SP2: -

ExUns: 22 ^ 23 ^ 24 ^ 25 ^ 26 ^ 27a · 27b ^ 28a · 28b ^ 29 ^ 30 ^ 31a · 31b ^ 32 ^ 33 ^ 34
SP1: -
SP2: -
SP3: - -
SP4: - - -
SP7: - -

Relevant External Links for EIF2AK4 Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for EIF2AK4 Gene

mRNA expression in normal human tissues for EIF2AK4 Gene

Protein differential expression in normal tissues from HIPED for EIF2AK4 Gene

This gene is overexpressed in NK cells (44.2) and Breast (11.3).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MOPED, and MaxQB for EIF2AK4 Gene

SOURCE GeneReport for Unigene cluster for EIF2AK4 Gene Hs.656673

mRNA Expression by UniProt/SwissProt for EIF2AK4 Gene

Tissue specificity: Widely expressed. Expressed in the lung in smooth muscle cells of the pulmonary vessel wall, interstitial tissue and macrophages.
genes like me logo Genes that share expression patterns with EIF2AK4: view

Protein tissue co-expression partners for EIF2AK4 Gene

Primer Products

In Situ Assay Products

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and mRNA differential expression in normal tissues for EIF2AK4 Gene

Orthologs for EIF2AK4 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for EIF2AK4 Gene

Organism Taxonomy Gene Similarity Type Details
(Bos Taurus)
Mammalia EIF2AK4 35
  • 91.55 (n)
  • 93.88 (a)
EIF2AK4 36
  • 94 (a)
(Canis familiaris)
Mammalia EIF2AK4 35
  • 90.06 (n)
  • 91 (a)
EIF2AK4 36
  • 90 (a)
(Mus musculus)
Mammalia Eif2ak4 35
  • 86.82 (n)
  • 90.51 (a)
Eif2ak4 16
Eif2ak4 36
  • 90 (a)
(Pan troglodytes)
Mammalia EIF2AK4 35
  • 99.72 (n)
  • 99.88 (a)
EIF2AK4 36
  • 100 (a)
(Rattus norvegicus)
Mammalia Eif2ak4 35
  • 86.56 (n)
  • 90.58 (a)
(Monodelphis domestica)
Mammalia EIF2AK4 36
  • 83 (a)
(Ornithorhynchus anatinus)
Mammalia EIF2AK4 36
  • 76 (a)
(Gallus gallus)
Aves EIF2AK4 35
  • 71.58 (n)
  • 73.51 (a)
EIF2AK4 36
  • 72 (a)
(Anolis carolinensis)
Reptilia EIF2AK4 36
  • 74 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia eif2ak4 35
  • 68.61 (n)
  • 69.27 (a)
(Danio rerio)
Actinopterygii eif2ak4 35
  • 63.01 (n)
  • 62.94 (a)
eif2ak4 36
  • 64 (a)
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP012368 35
  • 24.31 (n)
  • 6.4 (a)
fruit fly
(Drosophila melanogaster)
Insecta Gcn2 35
  • 45.78 (n)
  • 35.67 (a)
Gcn2 36
  • 33 (a)
(Caenorhabditis elegans)
Secernentea gcn-2 35
  • 44.87 (n)
  • 31.79 (a)
A. gosspyii yeast
(Ashbya gossypii)
Saccharomycetes AGOS_AAL083W 35
  • 45.53 (n)
  • 33.98 (a)
K. lactis yeast
(Kluyveromyces lactis)
Saccharomycetes KLLA0C10802g 35
  • 44.06 (n)
  • 32.02 (a)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes GCN2 35
  • 43.75 (n)
  • 31.83 (a)
GCN2 36
  • 24 (a)
GCN2 38
bread mold
(Neurospora crassa)
Ascomycetes NCU01187 35
  • 44.52 (n)
  • 32.52 (a)
fission yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes gcn2 35
  • 43.18 (n)
  • 32.4 (a)
Species with no ortholog for EIF2AK4:
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for EIF2AK4 Gene

Gene Tree for EIF2AK4 (if available)
Gene Tree for EIF2AK4 (if available)

Paralogs for EIF2AK4 Gene

Paralogs for EIF2AK4 Gene

(1) SIMAP similar genes for EIF2AK4 Gene using alignment to 4 proteins:

genes like me logo Genes that share paralogs with EIF2AK4: view

Variants for EIF2AK4 Gene

Sequence variations from dbSNP and Humsavar for EIF2AK4 Gene

SNP ID Clin Chr 15 pos Sequence Context AA Info Type MAF
rs472027 -- 39,965,414(-) AGGCG(C/T)GGTGG intron-variant
rs473191 -- 39,956,515(-) TTCCT(A/G)CTCTC intron-variant
rs479500 -- 39,963,061(-) TGCTG(C/G)CTGCT intron-variant
rs480095 -- 39,942,715(+) CAGAG(G/T)TGCAG intron-variant
rs480321 -- 39,942,801(+) GGGAT(A/G)CAGCA intron-variant

Structural Variations from Database of Genomic Variants (DGV) for EIF2AK4 Gene

Variant ID Type Subtype PubMed ID
nsv832983 CNV Gain 17160897
nsv1503 CNV Insertion 18451855
nsv516913 CNV Loss 19592680

Variation tolerance for EIF2AK4 Gene

Residual Variation Intolerance Score: 39.01% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 10.09; 90.21% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for EIF2AK4 Gene

HapMap Linkage Disequilibrium report
Human Gene Mutation Database (HGMD)

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for EIF2AK4 Gene

Disorders for EIF2AK4 Gene

MalaCards: The human disease database

(6) MalaCards diseases for EIF2AK4 Gene - From: OMIM, ClinVar, GeneTests, Orphanet, Swiss-Prot, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
pulmonary capillary hemangiomatosis
pulmonary venoocclusive disease
  • pulmonary veno-occlusive disease
pulmonary venoocclusive disease 2
  • hemangiomatosis, familial pulmonary capillary
yellow fever
  • sylvatic yellow fever
skin papilloma
  • skin papilloma nos
- elite association


  • Pulmonary venoocclusive disease 2, autosomal recessive (PVOD2) [MIM:234810]: A disease characterized by widespread fibrous obstruction and intimal thickening of septal veins and preseptal venules, a low diffusing capacity for carbon monoxide, occult alveolar hemorrhage, and nodular ground-glass opacities, septal lines and lymph node enlargement showed by high-resolution computed tomography of the chest. It is frequently associated with pulmonary capillary dilatation and proliferation, and is a rare and devastating cause of pulmonary hypertension. {ECO:0000269 PubMed:24135949, ECO:0000269 PubMed:24292273}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Relevant External Links for EIF2AK4

Atlas of Genetics and Cytogenetics in Oncology and Haematology:
genes like me logo Genes that share disorders with EIF2AK4: view

No data available for Genatlas for EIF2AK4 Gene

Publications for EIF2AK4 Gene

  1. Characterization of a mammalian homolog of the GCN2 eukaryotic initiation factor 2alpha kinase. (PMID: 10504407) Berlanga J.J. … de Haro C. (Eur. J. Biochem. 1999) 2 23 67
  2. The interface between metabolic and stress signalling. (PMID: 20007158) Hey S.J. … Halford N.G. (Ann. Bot. 2010) 23 67
  3. The roles of nitric oxide synthase and eIF2alpha kinases in regulation of cell cycle upon UVB-irradiation. (PMID: 20016280) Wang L. … Wu S. (Cell Cycle 2010) 23 67
  4. Regulation of G(1) arrest and apoptosis in hypoxia by PERK and GCN2-mediated eIF2alpha phosphorylation. (PMID: 20072654) Liu Y. … Wu S. (Neoplasia 2010) 23 67
  5. Autophagy impairment stimulates PS1 expression and gamma-secretase activity. (PMID: 20168091) Ohta K. … Nakagawa T. (Autophagy 2010) 23 67

Products for EIF2AK4 Gene

Sources for EIF2AK4 Gene

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