HIF1A Gene: Hypoxia-Inducible Factor 1 Alpha Subunit
Master regulator of cellular oxygen homeostasis and hypoxic response
Gene Information Card
| Symbol | HIF1A |
|---|---|
| Full Name | Hypoxia Inducible Factor 1 Subunit Alpha |
| Gene Type | protein-coding |
| Chromosomal Location | 14q23.2 |
| NCBI Gene ID | 3091 ncbi.nlm.nih.gov/gene/3091 |
| Ensembl ID | ENSG00000100644 |
| UniProt ID | Q16665 |
| OMIM ID | 603348 |
| HGNC ID | 4910 |
| Aliases | HIF-1-alpha, HIF1, MOP1, PASD8, bHLHe78 |
Description
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Clear cell renal cell carcinoma | Loss of VHL function leads to HIF1A stabilization and constitutive activation of hypoxic gene programs | ClinVar, COSMIC |
| Hereditary erythrocytosis | Gain-of-function mutations in HIF1A impair prolyl hydroxylation, causing increased erythropoietin production | OMIM #603348 |
| Breast cancer | HIF1A overexpression correlates with poor prognosis and promotes metastasis via VEGF and glycolytic enzymes | NCBI Gene, COSMIC |
| Colorectal cancer | HIF1A upregulation drives angiogenesis and metabolic reprogramming under tumor hypoxia | COSMIC, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 12.5 | Medium |
| Liver | 8.3 | Medium |
| Heart | 6.1 | Low |
| Brain | 5.4 | Low |
| Lung | 4.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.2 | Embryonic kidney cells; moderate expression |
| HeLa | 10.7 | Cervical carcinoma; induced under hypoxia |
| MCF7 | 9.1 | Breast cancer; upregulated in hypoxic conditions |
| A549 | 8.5 | Lung carcinoma; responsive to oxygen levels |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2062C>T (p.Pro688Ser) | Missense | 0.01% | Reduced prolyl hydroxylation; gain-of-function in erythrocytosis |
| c.2074G>A (p.Gly692Arg) | Missense | 0.005% | Impaired VHL binding; associated with erythrocytosis |
| c.85G>A (p.Glu29Lys) | Missense | 0.02% | Unknown functional effect; reported in cancer |
Mutation functional classification
Loss of Function (LOF)
Rare; complete loss is embryonic lethal in mice; partial loss may impair hypoxic response.
Gain of Function (GOF)
Common in tumors and erythrocytosis; stabilizes HIF1A under normoxia, leading to constitutive activation.
Dominant Negative (DN)
Not well characterized; some missense variants may interfere with dimerization or DNA binding.
View complete mutation data：
Gene Ontology (GO)
| • DNA-binding transcription factor activity (GO:0003700) | • Protein heterodimerization activity (GO:0046982) |
| • Response to hypoxia (GO:0001666) | • Positive regulation of angiogenesis (GO:0045766) |
| • Positive regulation of glycolytic process (GO:0045821) |
Pathways
• HIF1A encodes the alpha subunit of the hypoxia-inducible factor 1 (HIF-1)
• a heterodimeric transcription factor that regulates cellular responses to reduced oxygen levels. Under normoxia
• HIF1A is hydroxylated by prolyl hydroxylases and targeted for proteasomal degradation via the von Hippel-Lindau (VHL) E3 ubiquitin ligase complex. Under hypoxia
• degradation is suppressed
• allowing HIF1A to accumulate
• dimerize with ARNT (HIF1B)
• and activate transcription of genes involved in angiogenesis
• erythropoiesis
• glycolysis
• and cell survival.
• HIF-1 signaling pathway (KEGG: hsa04066)
• Renal cell carcinoma (KEGG: hsa05211)
• Central carbon metabolism in cancer (KEGG: hsa05230)
• VEGF signaling pathway (KEGG: hsa04370)
• HIF1A is a 826-amino acid protein containing a basic helix-loop-helix (bHLH) domain
• a PAS domain
• and an oxygen-dependent degradation domain (ODD). Under normoxia
• hydroxylation at proline residues 402 and 564 by PHD enzymes targets HIF1A for VHL-mediated ubiquitination and proteasomal degradation. Under hypoxia
• hydroxylation is inhibited
• leading to stabilization
• nuclear translocation
• and transcriptional activation of target genes such as VEGFA
• EPO
• and GLUT1. HIF1A is overexpressed in many solid tumors and is a key therapeutic target.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HIF1A Knockout HEK293 Cell Line | EDJ-KQ1494 | Human | 3091 | Details Get a Quote |
| HIF1AN Knockout HEK293 Cell Line | EDJ-KQ11192 | Human | 55662 | Details Get a Quote |
| HIF1A Knockout A-549 Cell Line | EDJ-KQ21098 | Human | 3091 | Details Get a Quote |
| HIF1A Knockout HCT 116 Cell Line | EDJ-KQ21099 | Human | 3091 | Details Get a Quote |
| HIF1A Knockout HeLa Cell Line | EDJ-KQ21100 | Human | 3091 | Details Get a Quote |
| HIF1AN Knockout A-549 Cell Line | EDJ-KQ40490 | Human | 55662 | Details Get a Quote |
| HIF1AN Knockout HCT 116 Cell Line | EDJ-KQ40492 | Human | 55662 | Details Get a Quote |
| HIF1AN Knockout HeLa Cell Line | EDJ-KQ40493 | Human | 55662 | Details Get a Quote |
| HIF1A Knockout Hep-G2 Cell Line | EDJ-KZ281 | Human | 3091 | Details Get a Quote |
| Hif1a Knockout Hepa 1-6 Cell Line | EDJ-KZ282 | Mouse | 15251 | Details Get a Quote |
| HIF1A Knockout RAW 264.7 Cell Line | EDJ-KZ283 | Mouse | 15251 | Details Get a Quote |
| HIF1A Knockout HaCaT Cell Line | EDC07921 | Human | 3091 | Details Get a Quote |
| HIF1A Knockout HEK293T Cell Line | EDC08315 | Human | 3091 | Details Get a Quote |
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