EGLN1 (Egl-9 Family Hypoxia Inducible Factor 1)
Key regulator of the hypoxic response via HIF prolyl hydroxylation
Gene Information Card
| Symbol | EGLN1 |
|---|---|
| Full Name | Egl-9 Family Hypoxia Inducible Factor 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 1q42.2 |
| NCBI Gene ID | 54583 ncbi.nlm.nih.gov/gene/54583 |
| Ensembl ID | ENSG00000135766 |
| UniProt ID | Q9GZT9 |
| OMIM ID | 606425 |
| HGNC ID | 14659 |
| Aliases | PHD2, HPH-2, HIF-PH2, SM20, ECYT3 |
Description
EGLN1 encodes prolyl hydroxylase domain-containing protein 2 (PHD2), a key oxygen sensor that hydroxylates hypoxia-inducible factor (HIF) alpha subunits under normoxic conditions, targeting them for proteasomal degradation. This regulation is critical for cellular adaptation to low oxygen levels. Mutations in EGLN1 are associated with familial erythrocytosis and various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Erythrocytosis, familial, 3 (ECYT3) | Loss-of-function mutations reduce HIF degradation, leading to increased erythropoietin and red cell mass | OMIM #609820 |
| Renal cell carcinoma | Somatic mutations or downregulation promote HIF stabilization and tumor growth | COSMIC, ClinVar |
| Pheochromocytoma/paraganglioma | Germline mutations in EGLN1 predispose to these neuroendocrine tumors | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Kidney | 10.8 | Medium |
| Heart | 8.2 | Medium |
| Brain | 6.1 | Low |
| Lung | 7.5 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.3 | High expression |
| HeLa | 11.0 | Moderate expression |
| HepG2 | 9.8 | Moderate expression |
| A549 | 8.5 | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.950C>T (p.Pro317Leu) | Missense | <0.01% | Loss of function; associated with erythrocytosis |
| c.1119G>A (p.Trp373*) | Nonsense | <0.01% | Truncation; loss of function; erythrocytosis |
| c.1A>G (p.Met1Val) | Missense | <0.01% | Start codon loss; loss of function; erythrocytosis |
Mutation functional classification
Loss of Function (LOF)
Most EGLN1 mutations are loss-of-function, impairing HIF hydroxylation and leading to HIF stabilization and increased erythropoietin.
Gain of Function (GOF)
Rare; gain-of-function variants may enhance HIF degradation and are not well characterized.
Dominant Negative (DN)
Not commonly reported; some missense variants may exert dominant-negative effects by dimerizing with wild-type protein.
View complete mutation data：
Gene Ontology (GO)
| • oxygen sensor activity | • prolyl 4-hydroxylase activity |
| • iron ion binding | • hypoxia-inducible factor-alpha hydroxylase activity |
| • cellular response to hypoxia |
Pathways
• HIF-1-alpha transcription factor network
• Oxygen-dependent proline hydroxylation of HIF-alpha
• Cellular response to hypoxia
Protein Summary
EGLN1 encodes the prolyl hydroxylase domain-containing protein 2 (PHD2), which hydroxylates HIF-1α and HIF-2α on specific proline residues in an oxygen-dependent manner. This modification promotes binding to the von Hippel-Lindau (VHL) E3 ubiquitin ligase complex, leading to HIF degradation. Under hypoxia, PHD2 activity is reduced, allowing HIF to accumulate and activate genes involved in erythropoiesis, angiogenesis, and metabolism.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| EGLN1 Knockout HEK293 Cell Line | EDJ-KQ1495 | Human | 54583 | Details Get a Quote |
| EGLN1 Knockout A-549 Cell Line | EDJ-KQ21101 | Human | 54583 | Details Get a Quote |
| EGLN1 Knockout HCT 116 Cell Line | EDJ-KQ21102 | Human | 54583 | Details Get a Quote |
| EGLN1 Knockout HeLa Cell Line | EDJ-KQ19765 | Human | 54583 | Details Get a Quote |
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