EIF2AK3 Gene - Eukaryotic Translation Initiation Factor 2 Alpha Kinase 3
Key regulator of the unfolded protein response and ER stress signaling
Gene Information Card
| Symbol | EIF2AK3 |
|---|---|
| Full Name | Eukaryotic Translation Initiation Factor 2 Alpha Kinase 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 2p11.2 |
| NCBI Gene ID | 9451 ncbi.nlm.nih.gov/gene/9451 |
| Ensembl ID | ENSG00000172071 |
| UniProt ID | Q9NZJ5 |
| OMIM ID | 604032 |
| HGNC ID | 3255 |
| Aliases | PERK, PEK, WRS |
Description
EIF2AK3 (also known as PERK) encodes a transmembrane protein kinase located in the endoplasmic reticulum (ER). It is a key sensor of ER stress and phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (eIF2α), leading to attenuation of global protein synthesis and activation of stress-responsive genes. This gene is essential for maintaining ER homeostasis and is implicated in the unfolded protein response (UPR).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Wolcott-Rallison syndrome | Loss-of-function mutations in EIF2AK3 impair eIF2α phosphorylation, leading to defective UPR and beta-cell apoptosis | Multiple homozygous/compound heterozygous mutations reported in patients (OMIM #226980) |
| Diabetes mellitus (neonatal) | ER stress-induced beta-cell dysfunction due to impaired PERK signaling | Case reports and functional studies (ClinVar) |
| Osteoporosis | PERK deficiency disrupts osteoblast differentiation and bone formation | Mouse models and human association studies (NCBI) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Pancreas | 12.5 | Medium |
| Liver | 8.3 | Medium |
| Kidney | 7.1 | Medium |
| Brain | 6.4 | Low |
| Heart | 5.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 10.1 | Cervical cancer cell line |
| HEK293 | 9.8 | Embryonic kidney cells |
| MCF7 | 8.5 | Breast cancer cells |
| HepG2 | 7.9 | Hepatocellular carcinoma cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1610G>A (p.Arg537Gln) | Missense | Rare | Loss of kinase activity, associated with Wolcott-Rallison syndrome |
| c.2056C>T (p.Arg686Trp) | Missense | Rare | Impaired eIF2α phosphorylation |
| c.1A>G (p.Met1Val) | Start loss | Very rare | Complete loss of protein function |
Mutation functional classification
Loss of Function (LOF)
Most EIF2AK3 mutations are loss-of-function, leading to reduced eIF2α phosphorylation and defective UPR.
Gain of Function (GOF)
Not reported in literature.
Dominant Negative (DN)
Not reported; disease inheritance is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004672 - protein kinase activity | • GO:0005524 - ATP binding |
| • GO:0006986 - response to unfolded protein | • GO:0034976 - response to endoplasmic reticulum stress |
| • GO:0006417 - regulation of translation | • GO:0005783 - endoplasmic reticulum |
Pathways
• Unfolded Protein Response (UPR) - Reactome R-HSA-381119
• PERK-mediated eIF2α phosphorylation - KEGG hsa04141
• ER stress signaling - WikiPathways WP3404
Protein Summary
EIF2AK3 (PERK) is a 1116-amino acid transmembrane protein with an N-terminal luminal domain that senses ER stress, a transmembrane domain, and a C-terminal cytoplasmic kinase domain. Upon ER stress, PERK dimerizes and autophosphorylates, then phosphorylates eIF2α at Ser51, reducing global translation while selectively upregulating stress-response genes like ATF4. This protein is critical for cell survival under ER stress and for normal function of secretory cells such as pancreatic beta cells.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| EIF2AK3 Knockout HEK293 Cell Line | EDJ-KQ1938 | Human | 9451 | Details Get a Quote |
| EIF2AK3 Knockout HeLa Cell Line | EDJ-KQ20578 | Human | 9451 | Details Get a Quote |
| EIF2AK3 Knockout A-549 Cell Line | EDJ-KQ21871 | Human | 9451 | Details Get a Quote |
| EIF2AK3 Knockout HCT 116 Cell Line | EDJ-KQ21872 | Human | 9451 | Details Get a Quote |
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