HIF3A: Hypoxia-Inducible Factor 3 Subunit Alpha
A key regulator of the hypoxic response with tissue-specific expression and alternative splicing variants.
Gene Information Card
| Symbol | HIF3A |
|---|---|
| Full Name | Hypoxia Inducible Factor 3 Subunit Alpha |
| Gene Type | Protein coding |
| Chromosomal Location | 19q13.32 |
| NCBI Gene ID | 64344 ncbi.nlm.nih.gov/gene/64344 |
| Ensembl ID | ENSG00000124440 |
| UniProt ID | Q9Y2N7 |
| OMIM ID | 609976 |
| HGNC ID | 15825 |
| Aliases | bHLHe17, HIF-3A, HIF3-alpha, IPAS, MOP7, PASD7 |
Description
HIF3A encodes the alpha subunit of hypoxia-inducible factor 3 (HIF-3), a member of the basic helix-loop-helix (bHLH) PAS domain transcription factor family. Under normoxic conditions, HIF3A is hydroxylated and targeted for proteasomal degradation. Under hypoxia, it stabilizes and forms a heterodimer with ARNT (HIF-1β) to regulate gene expression. HIF3A has multiple splice variants, some of which act as dominant-negative regulators of HIF-1 and HIF-2. It is involved in oxygen homeostasis, angiogenesis, and cellular adaptation to low oxygen.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various) | HIF3A overexpression or alternative splicing may modulate tumor hypoxia response and angiogenesis. | COSMIC; PMID: 23455423 |
| Ischemic stroke | HIF3A expression is altered in response to cerebral ischemia, potentially affecting neuronal survival. | PMID: 21531334 |
| Preeclampsia | Dysregulated HIF3A expression in placenta contributes to abnormal trophoblast invasion and hypoxia. | PMID: 22906538 |
| Retinopathy of prematurity | HIF3A variants may influence retinal neovascularization under hypoxic conditions. | PMID: 24357523 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 4.2 | Low |
| Brain | 3.1 | Low |
| Placenta | 12.8 | Medium |
| Lung | 2.5 | Low |
| Liver | 1.8 | Low |
| Kidney | 6.7 | Medium |
| Testis | 15.3 | Medium |
| Thyroid | 8.9 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 5.4 | Embryonic kidney cells |
| HeLa | 3.2 | Cervical carcinoma |
| A549 | 2.1 | Lung carcinoma |
| MCF7 | 1.5 | Breast carcinoma |
| HepG2 | 4.8 | Hepatocellular carcinoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | <0.01% | Loss of start codon; likely loss of function |
| c.100C>T (p.Arg34Trp) | Missense | <0.01% | Unknown significance |
| c.200_201insA | Frameshift | <0.01% | Predicted loss of function |
| c.350G>A (p.Arg117His) | Missense | <0.01% | Unknown significance |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations that truncate the protein or disrupt the bHLH domain are predicted to impair DNA binding and transcriptional activity.
Gain of Function (GOF)
Not well documented; some splice variants (e.g., HIF-3α4) may act as dominant-negative inhibitors rather than gain-of-function.
Dominant Negative (DN)
Certain splice variants (e.g., IPAS) lack the transactivation domain and inhibit HIF-1/2 activity by competing for ARNT binding.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Hypoxia-inducible factor (HIF) pathway
• Oxygen homeostasis pathway
• VEGF signaling pathway (via HIF targets)
Protein Summary
HIF3A encodes a 667-amino acid protein (UniProt Q9Y2N7) containing bHLH, PAS-A, PAS-B, and PAC domains. It heterodimerizes with ARNT to bind hypoxia response elements (HREs). Multiple splice variants exist, including a short form (IPAS) that lacks the C-terminal transactivation domain and acts as a dominant-negative regulator of HIF-1 and HIF-2. The protein is expressed in placenta, testis, kidney, and thyroid, and is involved in oxygen sensing and cellular adaptation to hypoxia.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HIF3A Knockout HEK293 Cell Line | EDJ-KQ11269 | Human | 64344 | Details Get a Quote |
| HIF3A Knockout HeLa Cell Line | EDJ-KQ57050 | Human | 64344 | Details Get a Quote |
| HIF3A Knockout A-549 Cell Line | EDJ-KQ65560 | Human | 64344 | Details Get a Quote |
| HIF3A Knockout HCT 116 Cell Line | EDJ-KQ73990 | Human | 64344 | Details Get a Quote |
