EIF2AK4 Gene (Protein Coding)

Eukaryotic Translation Initiation Factor 2 Alpha Kinase 4

GC15P039934
GIFtS:
45
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 hav... See more...

Aliases for EIF2AK4 Gene

Aliases for EIF2AK4 Gene

  • Eukaryotic Translation Initiation Factor 2 Alpha Kinase 4 2 3 5
  • GCN2 2 3 4
  • EIF-2-Alpha Kinase GCN2 3 4
  • GCN2-Like Protein 3 4
  • KIAA1338 2 4
  • Eukaryotic Translation Initiation Factor 2-Alpha Kinase 4 4
  • General Control Nonderepressible 2 3
  • GCN2 EIF2alpha Kinase 3
  • EC 2.7.11.1 4
  • EIF2AK4 5
  • 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 Venoocclusive Disease 2, Autosomal Recessive and Pulmonary Venoocclusive Disease 1, Autosomal Dominant. Among its related pathways are Nanog in Mammalian ESC Pluripotency and Apoptotic Pathways in Synovial Fibroblasts. Gene Ontology (GO) annotations related to this gene include protein homodimerization activity and protein kinase activity. An important paralog of this gene is EIF2AK3.

UniProtKB/Swiss-Prot Summary for EIF2AK4 Gene

  • Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) in response to low amino acid availability (PubMed:25329545). Plays a role as an activator of the integrated stress response (ISR) required for adaptation to amino acid starvation (By similarity). EIF2S1/eIF-2-alpha phosphorylation in response to stress converts EIF2S1/eIF-2-alpha in a global protein synthesis inhibitor, leading to a global attenuation of cap-dependent translation, and thus to a reduced overall utilization of amino acids, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activator ATF4, and hence allowing ATF4-mediated reprogramming of amino acid biosynthetic gene expression to alleviate nutrient depletion (By similarity). Binds uncharged tRNAs (By similarity). Involved in cell cycle arrest by promoting cyclin D1 mRNA translation repression after the unfolded protein response pathway (UPR) activation or cell cycle inhibitor CDKN1A/p21 mRNA translation activation in response to amino acid deprivation (PubMed:26102367). Plays a role in the consolidation of synaptic plasticity, learning as well as formation of long-term memory (By similarity). Plays a role in neurite outgrowth inhibition (By similarity). Plays a proapoptotic role in response to glucose deprivation (By similarity). Promotes global cellular protein synthesis repression in response to UV irradiation independently of the stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) and p38 MAPK signaling pathways (By similarity). Plays a role in the antiviral response against alphavirus infection; impairs early viral mRNA translation of the incoming genomic virus RNA, thus preventing alphavirus replication (By similarity).
  • (Microbial infection) Plays a role in modulating the adaptive immune response to yellow fever virus infection; promotes dendritic cells to initiate autophagy and antigene presentation to both CD4(+) and CD8(+) T-cells under amino acid starvation (PubMed:24310610).

Gene Wiki entry for EIF2AK4 Gene

Additional gene information for EIF2AK4 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for EIF2AK4 Gene

Genomics for EIF2AK4 Gene

GeneHancer (GH) Regulatory Elements Pubs

Download GeneHancer 2017 data
Promoters and enhancers for EIF2AK4 Gene
GeneHancer (GH) Identifier GH Type GH
Score		 GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites		 Gene Targets
GH15J039932 Promoter/Enhancer 2 EPDnew Ensembl ENCODE CraniofacialAtlas 261.8 +0.4 440 3.8 BCLAF1 SP1 ZNF207 MYC ZNF600 IKZF1 ZNF592 POLR2A NFIC YY1 EIF2AK4 FSIP1 C15orf62 SNODB1087 SRP14
GH15J039933 Enhancer 0.3 Ensembl 263 -1.9 -1914 0.4 RAD21 EIF2AK4 ENSG00000200305 GPR176
GH15J040090 Promoter/Enhancer 3.1 VISTA EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 19.8 +166.3 166285 19.2 BCLAF1 SP1 ZNF207 MYC NCOR1 ZNF600 IKZF1 SSRP1 JUND ZNF580 BMF ENSG00000259211 DNAJC17 RAD51-AS1 BAHD1 CHST14 BUB1B SRP14-AS1 EIF2AK4 ENSG00000259536
GH15J040037 Promoter/Enhancer 2.4 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 22.7 +105.1 105073 3.6 SP1 ZNF207 MYC ZNF592 ATF2 POLR2A CEBPA ATF3 NFIC ZIC2 SRP14-AS1 SRP14 lnc-BMF-3 EIF2AK4 BMF
GH15J039976 Promoter/Enhancer 1.7 Ensembl ENCODE CraniofacialAtlas 16.6 +42.6 42641 1.5 ZNF600 ZNF341 CTCF CTBP1 ZNF610 GABPB1 SIN3A RAD21 ZNF2 ZNF512B HSALNG0105184 HSALNG0105185 SRP14 ENSG00000259211 EIF2AK4 BAHD1 RAD51-AS1 DNAJC17 SRP14-AS1
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around EIF2AK4 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for EIF2AK4

Top Transcription factor binding sites by QIAGEN in the EIF2AK4 gene promoter:
  • CREB
  • deltaCREB
  • NF-kappaB1
  • p53

Genomic Locations for EIF2AK4 Gene

Latest Assembly
chr15:39,934,115-40,035,591
(GRCh38/hg38)
Size:
101,477 bases
Orientation:
Plus strand

Previous Assembly
chr15:40,226,316-40,327,792
(GRCh37/hg19 by Entrez Gene)
Size:
101,477 bases
Orientation:
Plus strand

chr15:40,226,347-40,327,797
(GRCh37/hg19 by Ensembl)
Size:
101,451 bases
Orientation:
Plus strand

Genomic View for EIF2AK4 Gene

Genes around EIF2AK4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
EIF2AK4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for EIF2AK4 Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for EIF2AK4 Gene

Proteins for EIF2AK4 Gene

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

    Protein Symbol:
    Q9P2K8-E2AK4_HUMAN
    Recommended name:
    eIF-2-alpha kinase GCN2
    Protein Accession:
    Q9P2K8
    Secondary Accessions:
    • C9JEC4
    • Q69YL7
    • Q6DC97
    • Q96GN6
    • Q9H5K1
    • Q9NSQ3
    • Q9NSZ5
    • Q9UJ56

    Protein attributes for EIF2AK4 Gene

    Size:
    1649 amino acids
    Molecular mass:
    186911 Da
    Quaternary structure:
    • Homodimer; homodimerization is important for kinase activation by uncharged tRNAs. Interacts with GCN1; this interaction stimulates EIF2AK4/GCN2 kinase activity and is impaired by IMPACT upon a variety of stress conditions, such as amino acid depletion, UV-C irradiation, proteasome inhibitor treatment and glucose deprivation. Interacts with DNAJC3; this interaction inhibits EIF2AK4/GCN2 kinase activity during endoplasmic reticulum (ER), hypothermic and amino acid-starving stress conditions.
    SequenceCaution:
    • 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=Truncated N-terminus.; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for EIF2AK4 Gene

    Alternative splice isoforms for EIF2AK4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for EIF2AK4 Gene

Protein Expression for EIF2AK4 Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Post-translational modifications for EIF2AK4 Gene

  • Autophosphorylated; autophosphorylation on Thr-899 is increased upon amino acid starvation and in UV irradiation cells and inhibited in presence of IMPACT.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for EIF2AK4 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for EIF2AK4 Gene

Domains & Families for EIF2AK4 Gene

Gene Families for EIF2AK4 Gene

IUPHAR :
Human Protein Atlas (HPA):
  • Disease related genes
  • Enzymes
  • Potential drug targets
  • Predicted intracellular proteins

Protein Domains for EIF2AK4 Gene

InterPro:
Blocks:
  • Ubiquitin-conjugating enzymes
  • RWD

Suggested Antigen Peptide Sequences for EIF2AK4 Gene

GenScript: Design optimal peptide antigens:
  • GCN2-like protein (E2AK4_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9P2K8

UniProtKB/Swiss-Prot:

E2AK4_HUMAN :
  • The histidyl-tRNA synthetase-like region and protein kinase domains are necessary for eIF-2-alpha kinase activity and eIF-2-alpha-mediated translational control. The histidyl-tRNA synthetase-like domain is necessary for binding to uncharged tRNAs. Kinase domain 1 is a degenerate kinase domain.
  • Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. GCN2 subfamily.
Domain:
  • The histidyl-tRNA synthetase-like region and protein kinase domains are necessary for eIF-2-alpha kinase activity and eIF-2-alpha-mediated translational control. The histidyl-tRNA synthetase-like domain is necessary for binding to uncharged tRNAs. Kinase domain 1 is a degenerate kinase domain.
Family:
  • 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

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  6. Cell Lines for research

Molecular function for EIF2AK4 Gene

UniProtKB/Swiss-Prot Function:
Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) in response to low amino acid availability (PubMed:25329545). Plays a role as an activator of the integrated stress response (ISR) required for adaptation to amino acid starvation (By similarity). EIF2S1/eIF-2-alpha phosphorylation in response to stress converts EIF2S1/eIF-2-alpha in a global protein synthesis inhibitor, leading to a global attenuation of cap-dependent translation, and thus to a reduced overall utilization of amino acids, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activator ATF4, and hence allowing ATF4-mediated reprogramming of amino acid biosynthetic gene expression to alleviate nutrient depletion (By similarity). Binds uncharged tRNAs (By similarity). Involved in cell cycle arrest by promoting cyclin D1 mRNA translation repression after the unfolded protein response pathway (UPR) activation or cell cycle inhibitor CDKN1A/p21 mRNA translation activation in response to amino acid deprivation (PubMed:26102367). Plays a role in the consolidation of synaptic plasticity, learning as well as formation of long-term memory (By similarity). Plays a role in neurite outgrowth inhibition (By similarity). Plays a proapoptotic role in response to glucose deprivation (By similarity). Promotes global cellular protein synthesis repression in response to UV irradiation independently of the stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) and p38 MAPK signaling pathways (By similarity). Plays a role in the antiviral response against alphavirus infection; impairs early viral mRNA translation of the incoming genomic virus RNA, thus preventing alphavirus replication (By similarity).
UniProtKB/Swiss-Prot Function:
(Microbial infection) Plays a role in modulating the adaptive immune response to yellow fever virus infection; promotes dendritic cells to initiate autophagy and antigene presentation to both CD4(+) and CD8(+) T-cells under amino acid starvation (PubMed:24310610).
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1; Evidence={ECO:0000250|UniProtKB:Q9QZ05};.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.1; Evidence={ECO:0000250|UniProtKB:Q9QZ05};.

Enzyme Numbers (IUBMB) for EIF2AK4 Gene

Phenotypes From GWAS Catalog for EIF2AK4 Gene

Gene Ontology (GO) - Molecular Function for EIF2AK4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000049 tRNA binding ISS --
GO:0000166 nucleotide binding IEA --
GO:0003723 RNA binding IEA --
GO:0004672 protein kinase activity IEA,IBA 21873635
GO:0004674 protein serine/threonine kinase activity IEA,ISS --
genes like me logo Genes that share ontologies with EIF2AK4: view
genes like me logo Genes that share phenotypes with EIF2AK4: view

Human Phenotype Ontology for EIF2AK4 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for EIF2AK4 Gene

MGI Knock Outs for EIF2AK4:

Animal Models for research

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for EIF2AK4

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

Localization for EIF2AK4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for EIF2AK4 Gene

Cytoplasm.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for EIF2AK4 gene
Compartment Confidence
cytosol 5
nucleus 4
endoplasmic reticulum 3
plasma membrane 2
extracellular 2
cytoskeleton 2
mitochondrion 2
peroxisome 2
endosome 2
lysosome 2
golgi apparatus 2

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for EIF2AK4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IEA --
GO:0005829 cytosol IBA 21873635
GO:0005844 polysome ISS --
GO:0022626 cytosolic ribosome IBA,ISS --
genes like me logo Genes that share ontologies with EIF2AK4: view

Pathways & Interactions for EIF2AK4 Gene

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

Pathways by source for EIF2AK4 Gene

1 GeneGo (Thomson Reuters) pathway for EIF2AK4 Gene
  • Translation Regulation of EIF2 activity
2 Qiagen pathways for EIF2AK4 Gene
  • eIF2 Pathway
  • GSK3 Signaling
1 Cell Signaling Technology pathway for EIF2AK4 Gene

SIGNOR curated interactions for EIF2AK4 Gene

Inactivates:
Is inactivated by:

Gene Ontology (GO) - Biological Process for EIF2AK4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000077 DNA damage checkpoint IEA --
GO:0002230 positive regulation of defense response to virus by host ISS --
GO:0002250 adaptive immune response IEA --
GO:0002286 T cell activation involved in immune response ISS --
GO:0002376 immune system process IEA --
genes like me logo Genes that share ontologies with EIF2AK4: view

Drugs & Compounds for EIF2AK4 Gene

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(8) Drugs for EIF2AK4 Gene - From: DrugBank, PharmGKB, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
fostamatinib Approved, Investigational Pharma Target, inhibitor Kinase Inhibitors 0
Haloperidol Approved Pharma Antipsychotic drug 174
Olanzapine Approved, Investigational Pharma 455
Quetiapine Approved Pharma 0
Risperidone Approved, Investigational Pharma SR-2A inhibitor 545

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

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
ADP
  • 5'-Adenylphosphoric acid
  • Adenosine 5'-diphosphate
  • ADENOSINE-5'-diphosphATE
  • H3ADP
  • 5'-Adenylphosphate
 58-64-0
genes like me logo Genes that share compounds with EIF2AK4: view

Transcripts for EIF2AK4 Gene

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mRNA/cDNA for EIF2AK4 Gene

1 REFSEQ mRNAs :
15 NCBI additional mRNA sequence :
11 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for EIF2AK4

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: -
SP3:
SP4:
SP5:
SP6:
SP7:

ExUns: 22 ^ 23 ^ 24 ^ 25 ^ 26 ^ 27a · 27b ^ 28a · 28b ^ 29 ^ 30 ^ 31a · 31b ^ 32 ^ 33 ^ 34
SP1: -
SP2: -
SP3: - -
SP4: - - -
SP5:
SP6:
SP7: - -

Relevant External Links for EIF2AK4 Gene

GeneLoc Exon Structure for
EIF2AK4

Expression for EIF2AK4 Gene

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mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for EIF2AK4 Gene

mRNA expression in normal human tissues for EIF2AK4 Gene
mRNA expression by BioGPS for EIF2AK4 GenemRNA expression by GTEx 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, MaxQB, and MOPED for EIF2AK4 Gene



Protein tissue co-expression partners for EIF2AK4 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for EIF2AK4

SOURCE GeneReport for Unigene cluster for EIF2AK4 Gene:

Hs.656673

mRNA Expression by UniProt/SwissProt for EIF2AK4 Gene:

Q9P2K8-E2AK4_HUMAN
Tissue specificity: Widely expressed (PubMed:10504407). Expressed in lung, smooth muscle cells and macrophages (PubMed:24292273).

Evidence on tissue expression from TISSUES for EIF2AK4 Gene

  • Nervous system(4.6)
  • Muscle(4.5)
  • Liver(2.6)
  • Spleen(2.5)
  • Kidney(2.5)
  • Lymph node(2.5)
  • Blood(2.4)
  • Heart(2.4)
  • Intestine(2.3)
  • Skin(2.2)
  • Lung(2.1)
  • Pancreas(2.1)
  • Bone marrow(2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for EIF2AK4 Gene

Germ Layers:
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • nervous
  • respiratory
Regions:
Head and neck:
  • ear
  • epiglottis
  • larynx
  • neck
Thorax:
  • heart
  • lung
General:
  • blood
  • blood vessel
genes like me logo Genes that share expression patterns with EIF2AK4: view

Primer products for research

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
Chimpanzee
(Pan troglodytes)
 Mammalia EIF2AK4 29 30
  • 99.72 (n)
 OneToOne
Cow
(Bos Taurus)
 Mammalia EIF2AK4 29 30
  • 91.55 (n)
 OneToOne
Dog
(Canis familiaris)
 Mammalia EIF2AK4 29 30
  • 90.06 (n)
 OneToOne
Mouse
(Mus musculus)
 Mammalia Eif2ak4 29 16 30
  • 86.82 (n)
 OneToOne
Rat
(Rattus norvegicus)
 Mammalia Eif2ak4 29
  • 86.56 (n)
Oppossum
(Monodelphis domestica)
 Mammalia EIF2AK4 30
  • 83 (a)
 OneToOne
Platypus
(Ornithorhynchus anatinus)
 Mammalia EIF2AK4 30
  • 76 (a)
 OneToOne
Chicken
(Gallus gallus)
 Aves EIF2AK4 29 30
  • 71.58 (n)
 OneToOne
Lizard
(Anolis carolinensis)
 Reptilia EIF2AK4 30
  • 74 (a)
 OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
 Amphibia eif2ak4 29
  • 68.61 (n)
Zebrafish
(Danio rerio)
 Actinopterygii eif2ak4 29 30
  • 63.01 (n)
 OneToOne
Fruit Fly
(Drosophila melanogaster)
 Insecta Gcn2 29 30
  • 45.78 (n)
 OneToOne
African malaria mosquito
(Anopheles gambiae)
 Insecta AgaP_AGAP012368 29
  • 24.31 (n)
Worm
(Caenorhabditis elegans)
 Secernentea gcn-2 29
  • 44.87 (n)
A. gosspyii yeast
(Eremothecium gossypii)
 Saccharomycetes AGOS_AAL083W 29
  • 45.53 (n)
K. Lactis Yeast
(Kluyveromyces lactis)
 Saccharomycetes KLLA0C10802g 29
  • 44.06 (n)
Baker's yeast
(Saccharomyces cerevisiae)
 Saccharomycetes GCN2 29 30 32
  • 43.75 (n)
 OneToMany
Bread mold
(Neurospora crassa)
 Ascomycetes NCU01187 29
  • 44.52 (n)
Fission Yeast
(Schizosaccharomyces pombe)
 Schizosaccharomycetes gcn2 29
  • 43.18 (n)
Species where no ortholog for EIF2AK4 was found in the sources mined by GeneCards:
  • 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 Vase (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

ENSEMBL:
Gene Tree for EIF2AK4 (if available)
TreeFam:
Gene Tree for EIF2AK4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for EIF2AK4: view image
Alliance of Genome Resources:
Additional Orthologs for EIF2AK4

Paralogs for EIF2AK4 Gene

Paralogs for EIF2AK4 Gene

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

  • E2AK4_HUMAN
  • H0YME5_HUMAN
  • H0YND8_HUMAN
  • H0YNY9_HUMAN
genes like me logo Genes that share paralogs with EIF2AK4: view

Variants for EIF2AK4 Gene

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Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for EIF2AK4 Gene

SNP ID Clinical significance and condition Chr 15 pos Variation AA Info Type
1028446 Pathogenic: Pulmonary venoocclusive disease 2, autosomal recessive 40,007,013(+) CA/C
NM_001013703.4(EIF2AK4):c.3358-2del 		SPLICE_ACCEPTOR
993619 Uncertain Significance: Pulmonary venoocclusive disease 2, autosomal recessive 39,973,625(+) T/C
NM_001013703.4(EIF2AK4):c.1694T>C (p.Ile565Thr) 		MISSENSE
993740 Likely Benign: Pulmonary venoocclusive disease 2, autosomal recessive 39,949,175(+) C/T
NM_001013703.4(EIF2AK4):c.420C>T (p.Pro140=) 		SYNONYMOUS
993783 Benign: Pulmonary venoocclusive disease 2, autosomal recessive 39,934,184(+) C/A
NM_001013703.4(EIF2AK4):c.-12C>A 		FIVE_PRIME_UTR
994197 Uncertain Significance: Pulmonary venoocclusive disease 2, autosomal recessive 39,967,404(+) C/T
NM_001013703.4(EIF2AK4):c.1078C>T (p.Arg360Cys) 		MISSENSE

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for EIF2AK4 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

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

Variant ID Type Subtype PubMed ID
esv3581639 CNV loss 25503493
nsv1503 CNV insertion 18451855
nsv516913 CNV loss 19592680
nsv832983 CNV gain 17160897
nsv974559 CNV duplication 23825009
nsv974560 CNV duplication 23825009

Variation tolerance for EIF2AK4 Gene

Residual Variation Intolerance Score: 39% 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)

Additional Variant Information for EIF2AK4 Gene

Human Gene Mutation Database (HGMD)
EIF2AK4
SNPedia medical, phenotypic, and genealogical associations of SNPs for
EIF2AK4
Leiden Open Variation Database (LOVD)
EIF2AK4

SNP Genotyping and Copy Number Assays for research

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

Disorders for EIF2AK4 Gene

MalaCards: The human disease database

(10) MalaCards diseases for EIF2AK4 Gene - From: OMI, CVR, GTR, ORP, SWI, COP, and GCD

- elite association - COSMIC cancer census association via MalaCards

UniProtKB/Swiss-Prot

E2AK4_HUMAN
  • 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 variants affecting the gene represented in this entry.

Additional Disease Information for EIF2AK4

Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
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 JJ … De Haro C (European journal of biochemistry 1999) 2 3 4 22
  2. EIF2AK4 mutations cause pulmonary veno-occlusive disease, a recessive form of pulmonary hypertension. (PMID: 24292273) Eyries M … Soubrier F (Nature genetics 2014) 3 4 72
  3. EIF2AK4 mutations in pulmonary capillary hemangiomatosis. (PMID: 24135949) Best DH … Elliott CG (Chest 2014) 3 4 72
  4. p58IPK is an inhibitor of the eIF2α kinase GCN2 and its localization and expression underpin protein synthesis and ER processing capacity. (PMID: 25329545) Roobol A … Smales CM (The Biochemical journal 2015) 3 4
  5. A founder EIF2AK4 mutation causes an aggressive form of pulmonary arterial hypertension in Iberian Gypsies. (PMID: 25512148) Tenorio J … Lapunzina P (Clinical genetics 2015) 3 72

ExternalLinks

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Sources for EIF2AK4 Gene