The protein encoded by this gene acts at the level of translation initiation to downregulate protein synthesis in response to stress. The encoded protein is a kinase that can be inactivated by hemin. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008] See more...

Aliases for EIF2AK1 Gene

Aliases for EIF2AK1 Gene

  • Eukaryotic Translation Initiation Factor 2 Alpha Kinase 1 2 3 5
  • HRI 2 3 4
  • Heme-Regulated Eukaryotic Initiation Factor EIF-2-Alpha Kinase 3 4
  • Eukaryotic Translation Initiation Factor 2-Alpha Kinase 1 3 4
  • Hemin-Sensitive Initiation Factor 2-Alpha Kinase 3 4
  • Heme Regulated Initiation Factor 2 Alpha Kinase 2 3
  • Heme-Controlled Repressor 3 4
  • Heme-Regulated Inhibitor 3 4
  • EC 2.7.11.1 4 51
  • KIAA1369 2 4
  • HHRI 3 4
  • HCR 3 4
  • Heme Sensitive Initiation Factor 2a Kinase 3
  • Heme-Regulated Repressor 3
  • EC 2.7.11 51
  • LEMSPAD 3
  • EIF2AK1 5

External Ids for EIF2AK1 Gene

Previous GeneCards Identifiers for EIF2AK1 Gene

  • GC07M005836
  • GC07M006028
  • GC07M006029
  • GC07M006061

Summaries for EIF2AK1 Gene

Entrez Gene Summary for EIF2AK1 Gene

  • The protein encoded by this gene acts at the level of translation initiation to downregulate protein synthesis in response to stress. The encoded protein is a kinase that can be inactivated by hemin. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]

GeneCards Summary for EIF2AK1 Gene

EIF2AK1 (Eukaryotic Translation Initiation Factor 2 Alpha Kinase 1) is a Protein Coding gene. Diseases associated with EIF2AK1 include Leukoencephalopathy, Motor Delay, Spasticity, And Dysarthria Syndrome and Pyriform Sinus Cancer. Among its related pathways are Toll-like Receptor Signaling Pathway and Regulation of lipid metabolism Insulin signaling-generic cascades. Gene Ontology (GO) annotations related to this gene include protein homodimerization activity and protein kinase activity. An important paralog of this gene is EIF2AK4.

UniProtKB/Swiss-Prot Summary for EIF2AK1 Gene

  • Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) in response to various stress conditions (PubMed:32132706, PubMed:32132707). Key activator of the integrated stress response (ISR) required for adaptation to various stress, such as heme deficiency, oxidative stress, osmotic shock, mitochondrial dysfunction and heat shock (PubMed:32132706, PubMed:32132707). 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, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activator ATF4, and hence allowing ATF4-mediated reprogramming (PubMed:32132706, PubMed:32132707). Acts as a key sensor of heme-deficiency: in normal conditions, binds hemin via a cysteine thiolate and histidine nitrogenous coordination, leading to inhibit the protein kinase activity (By similarity). This binding occurs with moderate affinity, allowing it to sense the heme concentration within the cell: heme depletion relieves inhibition and stimulates kinase activity, activating the ISR (By similarity). Thanks to this unique heme-sensing capacity, plays a crucial role to shut off protein synthesis during acute heme-deficient conditions (By similarity). In red blood cells (RBCs), controls hemoglobin synthesis ensuring a coordinated regulation of the synthesis of its heme and globin moieties (By similarity). It thereby plays an essential protective role for RBC survival in anemias of iron deficiency (By similarity). Similarly, in hepatocytes, involved in heme-mediated translational control of CYP2B and CYP3A and possibly other hepatic P450 cytochromes (By similarity). May also regulate endoplasmic reticulum (ER) stress during acute heme-deficient conditions (By similarity). Also activates the ISR in response to mitochondrial dysfunction: HRI/EIF2AK1 protein kinase activity is activated upon binding to the processed form of DELE1 (S-DELE1), thereby promoting the ATF4-mediated reprogramming (PubMed:32132706, PubMed:32132707).

Gene Wiki entry for EIF2AK1 Gene

Additional gene information for EIF2AK1 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for EIF2AK1 Gene

Genomics for EIF2AK1 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for EIF2AK1 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around EIF2AK1 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for EIF2AK1

Top Transcription factor binding sites by QIAGEN in the EIF2AK1 gene promoter:
  • Bach1
  • c-Myc
  • Max1
  • NF-1
  • Sp1
  • SREBP-1a
  • SREBP-1b
  • SREBP-1c

Genomic Locations for EIF2AK1 Gene

Genomic Locations for EIF2AK1 Gene
chr7:6,022,247-6,059,229
(GRCh38/hg38)
Size:
36,983 bases
Orientation:
Minus strand
chr7:6,061,878-6,098,861
(GRCh37/hg19)
Size:
36,984 bases
Orientation:
Minus strand

Genomic View for EIF2AK1 Gene

Genes around EIF2AK1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
EIF2AK1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for EIF2AK1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for EIF2AK1 Gene

Proteins for EIF2AK1 Gene

  • Protein details for EIF2AK1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9BQI3-E2AK1_HUMAN
    Recommended name:
    Eukaryotic translation initiation factor 2-alpha kinase 1
    Protein Accession:
    Q9BQI3
    Secondary Accessions:
    • A8K2R2
    • Q549K6
    • Q8NBW3
    • Q9HC02
    • Q9NYE0
    • Q9P0V6
    • Q9P1J5
    • Q9P2H8
    • Q9UHG4

    Protein attributes for EIF2AK1 Gene

    Size:
    630 amino acids
    Molecular mass:
    71106 Da
    Quaternary structure:
    • Synthesized in an inactive form that binds to the N-terminal domain of CDC37 (PubMed:11036079). Has to be associated with a multiprotein complex containing Hsp90, CDC37 and PPP5C for maturation and activation by autophosphorylation (PubMed:11036079). The phosphatase PPP5C modulates this activation (PubMed:11036079). Homodimer; homodimerizes in presence of heme, forming a disulfide-linked inactive homodimer (By similarity). Interacts with DELE1; binds to the processed form of DELE1 (S-DELE1) in response to mitochondrial stress, leading to activate its protein kinase activity and trigger the integrated stress response (ISR) (PubMed:32132706, PubMed:32132707).
    SequenceCaution:
    • Sequence=AAF70289.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=AAF71057.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=BAA92607.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};

    Alternative splice isoforms for EIF2AK1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for EIF2AK1 Gene

Selected DME Specific Peptides for EIF2AK1 Gene

Q9BQI3:
  • YHLMLHIQMQLCELSLWDWI
  • CMKVLREVKVLAGLQHPNIVGYHTAWIEHVHV
  • VANQLLLVSLLEHLSHVHEPNPL
  • VATKIFQELVEGVFYIHNMGIVHRDLKPRNIFLHGPDQQV
  • KVRNKLDG
  • THTSRVGTCLYASPEQLEGS
  • YDESDVPAE
  • EAQTSRYLNEFEE
  • LGKGGYG
  • ERVRQDPC
  • VHRDLKP
  • QKIRSRE
  • IVHRDLK

Post-translational modifications for EIF2AK1 Gene

  • Activated by autophosphorylation; phosphorylated predominantly on serine and threonine residues, but also on tyrosine residues. Autophosphorylation at Thr-488 is required for kinase activation. The active autophosphorylated form apparently is largely refractory to cellular heme fluctuations.
  • Ubiquitination at Lys472
  • Modification sites at PhosphoSitePlus

Other Protein References for EIF2AK1 Gene

Domains & Families for EIF2AK1 Gene

Gene Families for EIF2AK1 Gene

IUPHAR :
Human Protein Atlas (HPA):
  • Enzymes
  • Predicted intracellular proteins

Protein Domains for EIF2AK1 Gene

Suggested Antigen Peptide Sequences for EIF2AK1 Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ58724, highly similar to Eukaryotic translation initiation factor2-alpha kinase 1 (EC 2.7.11.1) (B4DIP4_HUMAN)
  • Hemin-sensitive initiation factor 2-alpha kinase (E2AK1_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9BQI3

UniProtKB/Swiss-Prot:

E2AK1_HUMAN :
  • Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. GCN2 subfamily.
Family:
  • Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. GCN2 subfamily.
genes like me logo Genes that share domains with EIF2AK1: view

Function for EIF2AK1 Gene

Molecular function for EIF2AK1 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 various stress conditions (PubMed:32132706, PubMed:32132707). Key activator of the integrated stress response (ISR) required for adaptation to various stress, such as heme deficiency, oxidative stress, osmotic shock, mitochondrial dysfunction and heat shock (PubMed:32132706, PubMed:32132707). 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, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activator ATF4, and hence allowing ATF4-mediated reprogramming (PubMed:32132706, PubMed:32132707). Acts as a key sensor of heme-deficiency: in normal conditions, binds hemin via a cysteine thiolate and histidine nitrogenous coordination, leading to inhibit the protein kinase activity (By similarity). This binding occurs with moderate affinity, allowing it to sense the heme concentration within the cell: heme depletion relieves inhibition and stimulates kinase activity, activating the ISR (By similarity). Thanks to this unique heme-sensing capacity, plays a crucial role to shut off protein synthesis during acute heme-deficient conditions (By similarity). In red blood cells (RBCs), controls hemoglobin synthesis ensuring a coordinated regulation of the synthesis of its heme and globin moieties (By similarity). It thereby plays an essential protective role for RBC survival in anemias of iron deficiency (By similarity). Similarly, in hepatocytes, involved in heme-mediated translational control of CYP2B and CYP3A and possibly other hepatic P450 cytochromes (By similarity). May also regulate endoplasmic reticulum (ER) stress during acute heme-deficient conditions (By similarity). Also activates the ISR in response to mitochondrial dysfunction: HRI/EIF2AK1 protein kinase activity is activated upon binding to the processed form of DELE1 (S-DELE1), thereby promoting the ATF4-mediated reprogramming (PubMed:32132706, PubMed:32132707).
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:0000269|PubMed:32132707};.
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:Q9Z2R9};.
UniProtKB/Swiss-Prot BiophysicochemicalProperties:
Kinetic parameters: KM=3.88 uM for eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) (in absence of DELE1 and in absence of hemin) {ECO:0000269|PubMed:32132707}; KM=1.13 uM for eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) (in presence of DELE1 and in absence of hemin) {ECO:0000269|PubMed:32132707}; KM=71.91 uM for eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) (in absence of DELE1 and in presence of hemin) {ECO:0000269|PubMed:32132707}; KM=6.56 uM for eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) (in presence of DELE1 and in presence of hemin) {ECO:0000269|PubMed:32132707};
UniProtKB/Swiss-Prot EnzymeRegulation:
In normal conditions, the protein kinase activity is inhibited; inhibition is relieved by various stress conditions (By similarity). Inhibited by heme: in presence of heme, forms a disulfide-linked inactive homodimer (By similarity). Heme depletion relieves inhibition and stimulates kinase activity by autophosphorylation. Inhibited by the heme metabolites biliverdin and bilirubin (By similarity). Induced by oxidative stress generated by arsenite treatment. Binding of nitric oxide (NO) to the heme iron in the N-terminal heme-binding domain activates the kinase activity, while binding of carbon monoxide (CO) suppresses kinase activity (By similarity). Protein kinase activity is also activated upon binding to the processed form of DELE1 (S-DELE1): interaction with S-DELE1 takes place in response to mitochondrial stress and triggers the integrated stress response (ISR) (PubMed:32132706, PubMed:32132707).

Enzyme Numbers (IUBMB) for EIF2AK1 Gene

Phenotypes From GWAS Catalog for EIF2AK1 Gene

Gene Ontology (GO) - Molecular Function for EIF2AK1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000166 nucleotide binding IEA --
GO:0003743 translation initiation factor activity IEA --
GO:0004672 protein kinase activity IBA 21873635
GO:0004674 protein serine/threonine kinase activity IEA --
GO:0004694 eukaryotic translation initiation factor 2alpha kinase activity IDA 11036079
genes like me logo Genes that share ontologies with EIF2AK1: view
genes like me logo Genes that share phenotypes with EIF2AK1: view

Animal Models for EIF2AK1 Gene

MGI Knock Outs for EIF2AK1:

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for EIF2AK1

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for EIF2AK1 Gene

Localization for EIF2AK1 Gene

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 EIF2AK1 gene
Compartment Confidence
nucleus 3
cytosol 3
mitochondrion 2
endoplasmic reticulum 2
plasma membrane 1
extracellular 1
cytoskeleton 1
peroxisome 1
endosome 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (3)
  • Nucleoplasm (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for EIF2AK1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IEA --
genes like me logo Genes that share ontologies with EIF2AK1: view

No data available for Subcellular locations from UniProtKB/Swiss-Prot for EIF2AK1 Gene

Pathways & Interactions for EIF2AK1 Gene

genes like me logo Genes that share pathways with EIF2AK1: view

Pathways by source for EIF2AK1 Gene

1 BioSystems pathway for EIF2AK1 Gene
1 GeneGo (Thomson Reuters) pathway for EIF2AK1 Gene
  • Translation Regulation of EIF2 activity
1 Qiagen pathway for EIF2AK1 Gene
  • eIF2 Pathway

SIGNOR curated interactions for EIF2AK1 Gene

Activates:
Inactivates:

Gene Ontology (GO) - Biological Process for EIF2AK1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002526 acute inflammatory response IEA --
GO:0006413 translational initiation IEA --
GO:0006417 regulation of translation IEA --
GO:0006468 protein phosphorylation IEA --
GO:0006909 phagocytosis IEA --
genes like me logo Genes that share ontologies with EIF2AK1: view

Drugs & Compounds for EIF2AK1 Gene

(10) Drugs for EIF2AK1 Gene - From: DrugBank, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
fostamatinib Approved, Investigational Pharma Target, inhibitor Kinase Inhibitors 0
Carbon monoxide Approved, Investigational Pharma 171
Hemin Approved, Investigational Pharma 0
Iron Approved, Experimental Pharma 1560
ATP Investigational Nutra Agonist, Activator, Partial agonist, Antagonist, Full agonist, Gating inhibitor, Pore Blocker, Potentiation 0

(2) Additional Compounds for EIF2AK1 Gene - From: HMDB and Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
ADP
  • 5'-Adenylphosphoric acid
  • Adenosine 5'-diphosphate
  • ADENOSINE-5'-diphosphATE
  • H3ADP
  • 5'-Adenylphosphate
Agonist, Full agonist, Partial agonist, Gating inhibitor, Antagonist 58-64-0
genes like me logo Genes that share compounds with EIF2AK1: view

Transcripts for EIF2AK1 Gene

mRNA/cDNA for EIF2AK1 Gene

2 REFSEQ mRNAs :
14 NCBI additional mRNA sequence :
10 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for EIF2AK1

Alternative Splicing Database (ASD) splice patterns (SP) for EIF2AK1 Gene

ExUns: 1a · 1b · 1c · 1d ^ 2 ^ 3a · 3b ^ 4a · 4b ^ 5 ^ 6 ^ 7 ^ 8a · 8b ^ 9a · 9b ^ 10 ^ 11 ^ 12 ^ 13a · 13b ^ 14a · 14b ^ 15 ^ 16a · 16b ^
SP1: - -
SP2: - -
SP3: -
SP4: -
SP5: - -
SP6: - - -
SP7: - -
SP8: - - - -
SP9: - -
SP10: - - - -
SP11: -
SP12:
SP13:

ExUns: 17a · 17b ^ 18a · 18b
SP1:
SP2:
SP3:
SP4:
SP5:
SP6:
SP7:
SP8:
SP9:
SP10:
SP11:
SP12:
SP13:

Relevant External Links for EIF2AK1 Gene

GeneLoc Exon Structure for
EIF2AK1

Expression for EIF2AK1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for EIF2AK1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for EIF2AK1 Gene

This gene is overexpressed in Peripheral blood mononuclear cells (57.2) and Fetal Liver (8.6).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for EIF2AK1 Gene



Protein tissue co-expression partners for EIF2AK1 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for EIF2AK1

SOURCE GeneReport for Unigene cluster for EIF2AK1 Gene:

Hs.520205

mRNA Expression by UniProt/SwissProt for EIF2AK1 Gene:

Q9BQI3-E2AK1_HUMAN
Tissue specificity: Expressed predominantly in erythroid cells (PubMed:20071449). Expressed at much lower levels in hepatocytes (at protein level) (PubMed:20071449).

Evidence on tissue expression from TISSUES for EIF2AK1 Gene

  • Nervous system(4.9)
  • Skin(4.6)
  • Bone marrow(4.5)
  • Lung(4)
  • Intestine(3.9)
  • Pancreas(3.3)
  • Kidney(3.3)
  • Liver(3.2)
  • Blood(2.9)
  • Eye(2.7)
  • Heart(2.5)
  • Muscle(2.3)
  • Stomach(2.3)
  • Spleen(2.1)
genes like me logo Genes that share expression patterns with EIF2AK1: view

No data available for mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for EIF2AK1 Gene

Orthologs for EIF2AK1 Gene

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

Orthologs for EIF2AK1 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia EIF2AK1 30 31
  • 99.31 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia EIF2AK1 30 31
  • 87.06 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia EIF2AK1 30 31
  • 84 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Eif2ak1 30 17 31
  • 83.44 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Eif2ak1 30
  • 82.18 (n)
Oppossum
(Monodelphis domestica)
Mammalia EIF2AK1 31
  • 68 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia EIF2AK1 31
  • 59 (a)
OneToOne
Chicken
(Gallus gallus)
Aves EIF2AK1 30 31
  • 63.1 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia EIF2AK1 31
  • 48 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia eif2ak1 30
  • 58.19 (n)
Zebrafish
(Danio rerio)
Actinopterygii eif2ak1 30 31
  • 54.79 (n)
OneToOne
Worm
(Caenorhabditis elegans)
Secernentea gcn-2 31
  • 8 (a)
ManyToMany
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes GCN2 31
  • 9 (a)
OneToMany
Fission Yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes hri1 30
  • 45.79 (n)
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 30 (a)
OneToOne
Species where no ortholog for EIF2AK1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • 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 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 EIF2AK1 Gene

ENSEMBL:
Gene Tree for EIF2AK1 (if available)
TreeFam:
Gene Tree for EIF2AK1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for EIF2AK1: view image

Paralogs for EIF2AK1 Gene

Paralogs for EIF2AK1 Gene

(3) SIMAP similar genes for EIF2AK1 Gene using alignment to 5 proteins:

  • E2AK1_HUMAN
  • B4DIP4_HUMAN
  • C9J7U7_HUMAN
  • F8WCM0_HUMAN
  • H7C033_HUMAN
genes like me logo Genes that share paralogs with EIF2AK1: view

Variants for EIF2AK1 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for EIF2AK1 Gene

SNP ID Clinical significance and condition Chr 07 pos Variation AA Info Type
711476 Benign: not provided 6,049,922(-) C/T MISSENSE_VARIANT
736718 Benign: not provided 6,038,600(-) C/T SYNONYMOUS_VARIANT
768139 Benign: not provided 6,038,617(-) A/G MISSENSE_VARIANT
804245 Uncertain Significance: EIF2AK1-related condition; LEUKOENCEPHALOPATHY, MOTOR DELAY, SPASTICITY, AND DYSARTHRIA SYNDROME 6,029,023(-) T/C MISSENSE_VARIANT
872212 Pathogenic: not provided 6,023,380(-) TTC/T FRAMESHIFT_VARIANT,THREE_PRIME_UTR_VARIANT

Additional dbSNP identifiers (rs#s) for EIF2AK1 Gene

Structural Variations from Database of Genomic Variants (DGV) for EIF2AK1 Gene

Variant ID Type Subtype PubMed ID
esv1385792 CNV deletion 17803354
esv1914954 OTHER inversion 16254605
esv2658842 CNV deletion 23128226
esv3891031 CNV loss 25118596
esv988101 CNV deletion 20482838
nsv1018388 CNV gain 25217958
nsv1034916 CNV gain 25217958
nsv1114913 CNV deletion 24896259
nsv1124167 CNV deletion 24896259
nsv1146112 CNV insertion 26484159
nsv436904 CNV insertion 17901297
nsv471823 CNV novel sequence insertion 20440878
nsv605998 CNV loss 21841781
nsv7392 OTHER inversion 18451855
nsv830894 CNV loss 17160897

Variation tolerance for EIF2AK1 Gene

Residual Variation Intolerance Score: 28.9% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 6.94; 79.77% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for EIF2AK1 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
EIF2AK1

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for EIF2AK1 Gene

Disorders for EIF2AK1 Gene

MalaCards: The human disease database

(5) MalaCards diseases for EIF2AK1 Gene - From: OMIM, DISEASES, and GeneCards

- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for EIF2AK1

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with EIF2AK1: view

No data available for UniProtKB/Swiss-Prot and Genatlas for EIF2AK1 Gene

Publications for EIF2AK1 Gene

  1. Hsp90 regulates p50(cdc37) function during the biogenesis of the activeconformation of the heme-regulated eIF2 alpha kinase. (PMID: 11036079) Shao J … Matts RL (The Journal of biological chemistry 2001) 3 4 23
  2. Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro. (PMID: 10718198) Nagase T … Ohara O (DNA research : an international journal for rapid publication of reports on genes and genomes 2000) 2 3 4
  3. Cloning of hHRI, human heme-regulated eukaryotic initiation factor 2alpha kinase: down-regulated in epithelial ovarian cancers. (PMID: 11101152) Hwang SY … Kim JC (Molecules and cells 2000) 3 4 23
  4. Regulation of protein synthesis by heme-regulated eIF-2 alpha kinase. (PMID: 7709427) Chen JJ … London IM (Trends in biochemical sciences 1995) 2 3 23
  5. Mitochondrial stress is relayed to the cytosol by an OMA1-DELE1-HRI pathway. (PMID: 32132707) Guo X … Kampmann M (Nature 2020) 3 4

Products for EIF2AK1 Gene

  • Signalway Proteins for EIF2AK1

Sources for EIF2AK1 Gene