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This gene encodes the alpha subunit of transcription factor hypoxia-inducible factor-1 (HIF-1), which is a heterodimer composed of an alpha and a beta subunit. HIF-1 functions as a master regulator of cellular and systemic homeostatic response to hypoxia by activating transcription of many genes, including those involved in energy metabolism, angiogenesis, apoptosis, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia. HIF-1 thus plays an essential role in embryonic vascularization, tumor angiogenesis and pathophysiology of ischemic disease. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jul 2011]
HIF1A (Hypoxia Inducible Factor 1 Subunit Alpha) is a Protein Coding gene. Diseases associated with HIF1A include Hypoxia and Retinal Ischemia. Among its related pathways are Notch-mediated HES/HEY network and Signaling by GPCR. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and protein heterodimerization activity. An important paralog of this gene is EPAS1.
Hypoxia Inducible Factors (HIFs) are transcription factors that are activated in response to decreased oxygen availability in the cellular environment. They influence cell metabolism, cell survival and angiogenesis to maintain biological homeostasis.
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000977 | RNA polymerase II regulatory region sequence-specific DNA binding | IDA | 19782034 |
GO:0000978 | RNA polymerase II proximal promoter sequence-specific DNA binding | IEA | -- |
GO:0000981 | DNA-binding transcription factor activity, RNA polymerase II-specific | IEA,ISA | -- |
GO:0001228 | DNA-binding transcription activator activity, RNA polymerase II-specific | IEA,IMP | 24983504 |
GO:0002039 | p53 binding | IPI | 15629713 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000785 | chromatin | IDA,ISA | -- |
GO:0005634 | nucleus | IDA | 8089148 |
GO:0005654 | nucleoplasm | TAS | -- |
GO:0005667 | transcription factor complex | IPI | 9576906 |
GO:0005737 | cytoplasm | IEA,IDA | 19651758 |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | CDK-mediated phosphorylation and removal of Cdc6 | ||
2 | HIF Repressor Pathways | ||
3 | Signaling by NOTCH1 | ||
4 | Signaling by PTK6 |
.01
|
|
5 | Notch Signaling Pathway (WikiPathways) |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000302 | response to reactive oxygen species | IDA | 32697943 |
GO:0001525 | angiogenesis | IEA | -- |
GO:0001568 | blood vessel development | IEA | -- |
GO:0001666 | response to hypoxia | IEA,IMP | 12411310 |
GO:0001755 | neural crest cell migration | IEA | -- |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Nitroglycerin | Approved, Investigational | Pharma | inhibitor, stimulator | 242 | ||
Carvedilol | Approved, Investigational | Pharma | Target, modulator | 204 | ||
Hydralazine | Approved | Pharma | Target, inducer | 58 | ||
Axitinib | Approved, Investigational | Pharma | Kinase Inhibitors, Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) inhibitors | 160 | ||
Sorafenib | Approved, Investigational | Pharma | Raf kinases and tyrosine kinases inhibitor, RAF, VEGFR2, and PDGFR-beta inhibitors, Kinase Inhibitors, Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) inhibitors | 795 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs | |
---|---|---|---|---|---|---|
TC-S 7009 |
|
1422955-31-4 |
|
|
Compound | Action | Cas Number |
---|---|---|
Echinomycin | Highly potent and selective HIF-1alpha inhibitor | 512-64-1 |
KC7F2 | HIF-1alpha inhibitor; down-regulates HIF-1alpha protein synthesis | 927822-86-4 |
ML 228 | HIF pathway activator | 1357171-62-0 |
TC-S 7009 | High affinity and selective HIF-2alpha inhibitor | 1422955-31-4 |
Compound | Action | Cas Number |
---|---|---|
BAY 87-2243 | HIF-1 inhibitor,potent and selective | 1227158-85-1 |
Chetomin | A4505 inhibitor | 1403-36-7 |
DMOG | Competitive HIF-PH inhibitor, cell-permeable | 89464-63-1 |
FG-4592 (ASP1517) | HIF prolyl-hydroxylase inhibitor | 808118-40-3 |
IOX2(Glycine) | HIF-1α prolyl hydroxylase-2 (PHD2) inhibitor | 931398-72-0 |
KC7F2 | HIF-1α inhibitor | 927822-86-4 |
ML 228 | HIF pathway activator | 1357171-62-0 |
Molidustat (BAY85-3934) | Novel HIF-PH inhibitor | 1154028-82-6 |
PX 12 | Trx-1 inhibitor | 141400-58-0 |
PX-478 2HCl | HIF-1α inhibitor | 685898-44-6 |
YC 1 | inhibitor of HIF-1α | 170632-47-0 |
ExUns: | 1a | · | 1b | · | 1c | ^ | 2 | ^ | 3 | ^ | 4 | ^ | 5a | · | 5b | ^ | 6 | ^ | 7 | ^ | 8 | ^ | 9 | ^ | 10 | ^ | 11 | ^ | 12 | ^ | 13 | ^ | 14 | ^ | 15 |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
SP1: | - | ||||||||||||||||||||||||||||||||||
SP2: | - | ||||||||||||||||||||||||||||||||||
SP3: | - | - | |||||||||||||||||||||||||||||||||
SP4: |
This gene was present in the common ancestor of animals.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | HIF1A 30 31 |
|
OneToOne | |
Dog (Canis familiaris) |
Mammalia | HIF1A 30 31 |
|
OneToOne | |
Cow (Bos Taurus) |
Mammalia | HIF1A 30 31 |
|
OneToOne | |
Mouse (Mus musculus) |
Mammalia | Hif1a 30 17 31 |
|
OneToOne | |
Rat (Rattus norvegicus) |
Mammalia | Hif1a 30 |
|
||
Oppossum (Monodelphis domestica) |
Mammalia | HIF1A 31 |
|
OneToOne | |
Platypus (Ornithorhynchus anatinus) |
Mammalia | HIF1A 31 |
|
OneToOne | |
Chicken (Gallus gallus) |
Aves | HIF1A 30 31 |
|
OneToOne | |
Lizard (Anolis carolinensis) |
Reptilia | HIF1A 31 |
|
OneToOne | |
African clawed frog (Xenopus laevis) |
Amphibia | hif1a-prov 30 |
|
||
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | Str.10694 30 |
|
||
Zebrafish (Danio rerio) |
Actinopterygii | hif1ab 30 31 |
|
OneToOne | |
zgc55405 30 |
|
||||
Rainbow Trout (Oncorhynchus mykiss) |
Actinopterygii | Omy.8039 30 |
|
||
Fruit Fly (Drosophila melanogaster) |
Insecta | sima 31 32 |
|
OneToMany | |
Worm (Caenorhabditis elegans) |
Secernentea | hif-1 31 |
|
OneToMany | |
Sea Squirt (Ciona savignyi) |
Ascidiacea | -- 31 |
|
OneToMany |
SNP ID | Clinical significance and condition | Chr 14 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
988324 | Pathogenic: not provided | 61,721,575(+) |
G/A NM_001530.4(HIF1A):c.293G>A (p.Gly98Asp) |
MISSENSE | |
rs112401635 | Benign: not provided | 61,734,128(+) |
T/TC NM_001530.4(HIF1A):c.881-4dup |
INTRON | |
rs113805602 | Benign: not provided | 61,727,650(+) |
T/C NM_001530.4(HIF1A):c.768T>C (p.Asp256=) |
SYNONYMOUS | |
rs141997782 | Benign: not provided | 61,732,424(+) |
C/T NM_001530.4(HIF1A):c.780C>T (p.Thr260=) |
SYNONYMOUS | |
rs142179458 | Benign: not provided | 61,736,905(+) |
G/A NM_001530.4(HIF1A):c.1045G>A (p.Asp349Asn) |
MISSENSE |
Variant ID | Type | Subtype | PubMed ID |
---|---|---|---|
dgv3721n54 | CNV | loss | 21841781 |
nsv1131145 | CNV | deletion | 24896259 |
nsv1300 | CNV | deletion | 18451855 |
nsv564884 | CNV | loss | 21841781 |
nsv952848 | CNV | duplication | 24416366 |
Disorder | Aliases | PubMed IDs |
---|---|---|
hypoxia |
|
|
retinal ischemia |
|
|
polycythemia |
|
|
ischemia |
|
|
aging |
|
|