HIF1A
hypoxia inducible factor 1 subunit alpha, the group of PAS domain containing|Basic helix-loop-helix proteins
Basic information
Region (hg38): 14:61695512-61748259
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- Inborn genetic diseases (18 variants)
- not provided (16 variants)
- Enchondromatosis (4 variants)
- Maffucci syndrome (3 variants)
- not specified (1 variants)
- Cholangiocarcinoma (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the HIF1A gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 8 | |||||
| missense | 22 | 31 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region ? | 1 | 1 | ||||
| non coding ? | 0 | |||||
| Total | 1 | 6 | 22 | 1 | 9 |
Highest pathogenic variant AF is 0.00213
Variants in HIF1A
This is a list of pathogenic ClinVar variants found in the HIF1A region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 14-61697832-AT-A | Benign (Sep 18, 2023) | |||
| 14-61720408-A-G | not specified | Uncertain significance (Feb 26, 2024) | ||
| 14-61720467-G-T | not specified | Uncertain significance (Jul 26, 2022) | ||
| 14-61720494-G-C | Maffucci syndrome | Likely pathogenic (-) | ||
| 14-61720501-C-T | not specified | Uncertain significance (Nov 10, 2022) | ||
| 14-61720526-G-A | not specified | Uncertain significance (Oct 04, 2022) | ||
| 14-61721514-T-A | not specified | Uncertain significance (Jun 06, 2023) | ||
| 14-61721575-G-A | Pathogenic (May 23, 2018) | |||
| 14-61721641-T-C | not specified | Uncertain significance (Jan 04, 2022) | ||
| 14-61727495-A-G | not specified | Uncertain significance (Jul 11, 2022) | ||
| 14-61727515-G-A | Benign (Apr 10, 2018) | |||
| 14-61727521-G-A | Benign (Nov 30, 2023) | |||
| 14-61727526-C-T | Enchondromatosis | Likely pathogenic (-) | ||
| 14-61727582-G-A | Malignant tumor of prostate | Uncertain significance (-) | ||
| 14-61727604-C-A | Uncertain significance (Jan 01, 2023) | |||
| 14-61727650-T-C | Benign (Jun 14, 2018) | |||
| 14-61732415-C-T | Likely benign (Mar 22, 2023) | |||
| 14-61732424-C-T | Benign (Apr 10, 2018) | |||
| 14-61732425-G-A | not specified | Uncertain significance (Nov 13, 2023) | ||
| 14-61732512-A-T | not specified | Uncertain significance (Feb 27, 2023) | ||
| 14-61732540-G-T | Likely benign (Apr 01, 2023) | |||
| 14-61734128-T-TC | Benign (Jun 14, 2018) | |||
| 14-61736905-G-A | Benign/Likely benign (Apr 01, 2023) | |||
| 14-61736925-A-T | not specified | Uncertain significance (Jul 14, 2021) | ||
| 14-61736951-T-C | not specified | Uncertain significance (Aug 02, 2021) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| HIF1A | protein_coding | protein_coding | ENST00000539097 | 15 | 52746 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.978 | 0.0223 | 125732 | 0 | 13 | 125745 | 0.0000517 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.22 | 317 | 450 | 0.705 | 0.0000226 | 5634 |
| Missense in Polyphen | 54 | 128.31 | 0.42084 | 1673 | ||
| Synonymous | 0.180 | 154 | 157 | 0.982 | 0.00000828 | 1561 |
| Loss of Function | 5.05 | 7 | 42.5 | 0.165 | 0.00000238 | 528 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000298 | 0.0000298 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.0000547 | 0.0000544 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000896 | 0.0000879 |
| Middle Eastern | 0.0000547 | 0.0000544 |
| South Asian | 0.0000327 | 0.0000327 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Functions as a master transcriptional regulator of the adaptive response to hypoxia. Under hypoxic conditions, activates the transcription of over 40 genes, including erythropoietin, glucose transporters, glycolytic enzymes, vascular endothelial growth factor, HILPDA, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia. Plays an essential role in embryonic vascularization, tumor angiogenesis and pathophysiology of ischemic disease. Heterodimerizes with ARNT; heterodimer binds to core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters (By similarity). Activation requires recruitment of transcriptional coactivators such as CREBBP and EP300. Activity is enhanced by interaction with both, NCOA1 or NCOA2. Interaction with redox regulatory protein APEX seems to activate CTAD and potentiates activation by NCOA1 and CREBBP. Involved in the axonal distribution and transport of mitochondria in neurons during hypoxia. {ECO:0000250|UniProtKB:Q61221, ECO:0000269|PubMed:11292861, ECO:0000269|PubMed:11566883, ECO:0000269|PubMed:15465032, ECO:0000269|PubMed:16543236, ECO:0000269|PubMed:16973622, ECO:0000269|PubMed:17610843, ECO:0000269|PubMed:19528298, ECO:0000269|PubMed:20624928, ECO:0000269|PubMed:22009797, ECO:0000269|PubMed:9887100}.;
- Pathway
- Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human);Renal cell carcinoma - Homo sapiens (human);Central carbon metabolism in cancer - Homo sapiens (human);Choline metabolism in cancer - Homo sapiens (human);HIF-1 signaling pathway - Homo sapiens (human);Autophagy - animal - Homo sapiens (human);Mitophagy - animal - Homo sapiens (human);Thyroid hormone signaling pathway - Homo sapiens (human);Th17 cell differentiation - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);The oncogenic action of Succinate;The oncogenic action of Fumarate;Angiogenesis;AGE-RAGE pathway;Adipogenesis;Oncostatin M Signaling Pathway;HIF1A and PPARG regulation of glycolysis;Vitamin D Receptor Pathway;miR-148a-miR-31-FIH1-HIF1α-Notch signaling in glioblastoma;Photodynamic therapy-induced HIF-1 survival signaling;NAD metabolism, sirtuins and aging;Hepatitis C and Hepatocellular Carcinoma;LncRNA-mediated mechanisms of therapeutic resistance;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;Pathways in clear cell renal cell carcinoma;Interleukin-4 and 13 signaling;Hereditary Leiomyomatosis and Renal Cell Carcinoma Pathway;EMT transition in Colorectal Cancer;Type 2 papillary renal cell carcinoma;Notch Signaling Pathway;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways;Oxygen-dependent asparagine hydroxylation of Hypoxia-inducible Factor Alpha;Signaling by PTK6;RAGE;Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha;Regulation of gene expression by Hypoxia-inducible Factor;Regulation of Hypoxia-inducible Factor (HIF) by oxygen;Cellular response to hypoxia;Signal Transduction;hypoxia-inducible factor in the cardivascular system;hypoxia and p53 in the cardiovascular system;erythropoietin mediated neuroprotection through nf-kb;vegf hypoxia and angiogenesis;Cellular responses to stress;Post-translational protein modification;Metabolism of proteins;Hypoxic and oxygen homeostasis regulation of HIF-1-alpha;Signaling by NOTCH1;PTK6 promotes HIF1A stabilization;PTK6 Expression;Signaling by NOTCH;Cellular responses to external stimuli;Neddylation;Ub-specific processing proteases;Signaling by Non-Receptor Tyrosine Kinases;Deubiquitination;Notch-mediated HES/HEY network;AP-1 transcription factor network;HIF-1-alpha transcription factor network;NOTCH1 Intracellular Domain Regulates Transcription;VEGFR1 specific signals
(Consensus)
Recessive Scores
- pRec
- 0.911
Intolerance Scores
- loftool
- 0.433
- rvis_EVS
- -0.2
- rvis_percentile_EVS
- 39.17
Haploinsufficiency Scores
- pHI
- 0.986
- hipred
- Y
- hipred_score
- 0.767
- ghis
- 0.488
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.988
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Hif1a
- Phenotype
- homeostasis/metabolism phenotype; cellular phenotype; muscle phenotype; craniofacial phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); endocrine/exocrine gland phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; liver/biliary system phenotype; immune system phenotype; skeleton phenotype; renal/urinary system phenotype; digestive/alimentary phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; vision/eye phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; neoplasm; embryo phenotype;
Zebrafish Information Network
- Gene name
- hif1ab
- Affected structure
- goblet cell
- Phenotype tag
- abnormal
- Phenotype quality
- disrupted
Gene ontology
- Biological process
- angiogenesis;response to hypoxia;neural crest cell migration;epithelial to mesenchymal transition;embryonic placenta development;B-1 B cell homeostasis;positive regulation of endothelial cell proliferation;heart looping;positive regulation of neuroblast proliferation;connective tissue replacement involved in inflammatory response wound healing;outflow tract morphogenesis;cardiac ventricle morphogenesis;lactate metabolic process;regulation of transcription, DNA-templated;regulation of transcription by RNA polymerase II;transcription by RNA polymerase II;cellular iron ion homeostasis;signal transduction;lactation;visual learning;response to iron ion;regulation of gene expression;vascular endothelial growth factor production;positive regulation of vascular endothelial growth factor production;positive regulation of gene expression;negative regulation of gene expression;positive regulation of epithelial cell migration;positive regulation of receptor biosynthetic process;response to muscle activity;positive regulation of macroautophagy;protein deubiquitination;cytokine-mediated signaling pathway;axonal transport of mitochondrion;neural fold elevation formation;cerebral cortex development;negative regulation of bone mineralization;positive regulation of vascular endothelial growth factor receptor signaling pathway;negative regulation of TOR signaling;oxygen homeostasis;positive regulation of chemokine production;regulation of transforming growth factor beta2 production;collagen metabolic process;embryonic hemopoiesis;positive regulation of insulin secretion involved in cellular response to glucose stimulus;hemoglobin biosynthetic process;glucose homeostasis;mRNA transcription by RNA polymerase II;positive regulation of blood vessel endothelial cell migration;regulation of transcription from RNA polymerase II promoter in response to oxidative stress;post-translational protein modification;positive regulation of erythrocyte differentiation;positive regulation of angiogenesis;positive regulation of glycolytic process;positive regulation of transcription, DNA-templated;negative regulation of growth;positive regulation of transcription by RNA polymerase II;muscle cell cellular homeostasis;positive regulation of hormone biosynthetic process;digestive tract morphogenesis;positive regulation of nitric-oxide synthase activity;cartilage development;elastin metabolic process;intestinal epithelial cell maturation;epithelial cell differentiation involved in mammary gland alveolus development;iris morphogenesis;retina vasculature development in camera-type eye;regulation of transcription from RNA polymerase II promoter in response to hypoxia;positive regulation of transcription from RNA polymerase II promoter in response to hypoxia;positive regulation of chemokine-mediated signaling pathway;negative regulation of thymocyte apoptotic process;cellular response to interleukin-1;cellular response to hypoxia;dopaminergic neuron differentiation;hypoxia-inducible factor-1alpha signaling pathway;positive regulation of pri-miRNA transcription by RNA polymerase II;negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway;positive regulation of autophagy of mitochondrion;regulation of aerobic respiration;negative regulation of reactive oxygen species metabolic process;negative regulation of mesenchymal cell apoptotic process
- Cellular component
- nucleus;nucleoplasm;transcription factor complex;cytoplasm;cytosol;nuclear body;nuclear speck;motile cilium;protein-containing complex;RNA polymerase II transcription factor complex;axon cytoplasm
- Molecular function
- DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;p53 binding;DNA-binding transcription factor activity;protein binding;transcription factor binding;enzyme binding;protein kinase binding;protein domain specific binding;ubiquitin protein ligase binding;histone acetyltransferase binding;nuclear hormone receptor binding;histone deacetylase binding;sequence-specific DNA binding;protein heterodimerization activity;Hsp90 protein binding;E-box binding