EGLN3
egl-9 family hypoxia inducible factor 3
Basic information
Region (hg38): 14:33924227-34462774
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the EGLN3 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 | 1 | |||||
| missense | 5 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 0 | 4 | 0 | 2 |
Variants in EGLN3
This is a list of pathogenic ClinVar variants found in the EGLN3 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 14-33929099-T-C | Benign (Dec 31, 2019) | |||
| 14-33929149-T-C | not specified | Uncertain significance (Oct 16, 2023) | ||
| 14-33929173-A-G | not specified | Uncertain significance (May 23, 2023) | ||
| 14-33950541-C-T | Benign (Dec 31, 2019) | |||
| 14-33950611-T-C | not specified | Uncertain significance (Jan 08, 2024) | ||
| 14-33950730-C-T | not specified | Uncertain significance (Oct 10, 2023) | ||
| 14-34435209-C-T | not specified | Uncertain significance (Mar 15, 2024) | ||
| 14-34435244-TGG-T | Spastic paraplegia 90B, autosomal recessive | Pathogenic (Dec 07, 2023) | ||
| 14-34435265-G-A | SPTSSA-related disorder • Spastic paraplegia 90A, autosomal dominant | Conflicting classifications of pathogenicity (Dec 07, 2023) | ||
| 14-34462156-A-C | not specified | Uncertain significance (Oct 20, 2021) | ||
| 14-34462156-A-T | not specified | Uncertain significance (Jan 04, 2022) | ||
| 14-34462198-T-C | not specified | Uncertain significance (Aug 02, 2021) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| EGLN3 | protein_coding | protein_coding | ENST00000250457 | 5 | 538544 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.00948 | 0.945 | 125727 | 0 | 21 | 125748 | 0.0000835 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.72 | 86 | 144 | 0.598 | 0.00000734 | 1551 |
| Missense in Polyphen | 17 | 40.116 | 0.42377 | 422 | ||
| Synonymous | -0.804 | 69 | 61.0 | 1.13 | 0.00000319 | 479 |
| Loss of Function | 1.73 | 5 | 11.3 | 0.443 | 4.79e-7 | 129 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000623 | 0.0000615 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.000556 | 0.000554 |
| European (Non-Finnish) | 0.0000442 | 0.0000439 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000327 | 0.0000327 |
| Other | 0.000327 | 0.000326 |
dbNSFP
Source:
- Function
- FUNCTION: Cellular oxygen sensor that catalyzes, under normoxic conditions, the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. Hydroxylates a specific proline found in each of the oxygen-dependent degradation (ODD) domains (N-terminal, NODD, and C-terminal, CODD) of HIF1A. Also hydroxylates HIF2A. Has a preference for the CODD site for both HIF1A and HIF2A. Hydroxylation on the NODD site by EGLN3 appears to require prior hydroxylation on the CODD site. Hydroxylated HIFs are then targeted for proteasomal degradation via the von Hippel-Lindau ubiquitination complex. Under hypoxic conditions, the hydroxylation reaction is attenuated allowing HIFs to escape degradation resulting in their translocation to the nucleus, heterodimerization with HIF1B, and increased expression of hypoxy-inducible genes. EGLN3 is the most important isozyme in limiting physiological activation of HIFs (particularly HIF2A) in hypoxia. Also hydroxylates PKM in hypoxia, limiting glycolysis. Under normoxia, hydroxylates and regulates the stability of ADRB2. Regulator of cardiomyocyte and neuronal apoptosis. In cardiomyocytes, inhibits the anti-apoptotic effect of BCL2 by disrupting the BAX-BCL2 complex. In neurons, has a NGF-induced proapoptotic effect, probably through regulating CASP3 activity. Also essential for hypoxic regulation of neutrophilic inflammation. Plays a crucial role in DNA damage response (DDR) by hydroxylating TELO2, promoting its interaction with ATR which is required for activation of the ATR/CHK1/p53 pathway. Target proteins are preferentially recognized via a LXXLAP motif. {ECO:0000269|PubMed:11595184, ECO:0000269|PubMed:12181324, ECO:0000269|PubMed:16098468, ECO:0000269|PubMed:19584355, ECO:0000269|PubMed:20849813, ECO:0000269|PubMed:20978507, ECO:0000269|PubMed:21317538, ECO:0000269|PubMed:21483450, ECO:0000269|PubMed:21575608, ECO:0000269|PubMed:21620138, ECO:0000269|PubMed:22797300}.;
- Pathway
- Renal cell carcinoma - Homo sapiens (human);HIF-1 signaling pathway - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);The oncogenic action of Succinate;The oncogenic action of Fumarate;Type 2 papillary renal cell carcinoma;Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha;Regulation of Hypoxia-inducible Factor (HIF) by oxygen;Cellular response to hypoxia;Cellular responses to stress;HIF-2-alpha transcription factor network;Hypoxic and oxygen homeostasis regulation of HIF-1-alpha;Cellular responses to external stimuli;HIF-1-alpha transcription factor network
(Consensus)
Recessive Scores
- pRec
- 0.215
Intolerance Scores
- loftool
- 0.474
- rvis_EVS
- -0.07
- rvis_percentile_EVS
- 48.12
Haploinsufficiency Scores
- pHI
- 0.804
- hipred
- Y
- hipred_score
- 0.728
- ghis
- 0.479
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.940
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Egln3
- Phenotype
- cellular phenotype; homeostasis/metabolism phenotype; craniofacial phenotype; muscle phenotype; endocrine/exocrine gland 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); growth/size/body region phenotype; immune system phenotype; vision/eye 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; 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; reproductive system 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; liver/biliary system phenotype;
Gene ontology
- Biological process
- response to hypoxia;apoptotic process;activation of cysteine-type endopeptidase activity involved in apoptotic process;cellular response to DNA damage stimulus;protein hydroxylation;peptidyl-proline hydroxylation to 4-hydroxy-L-proline;regulation of cell population proliferation;regulation of neuron apoptotic process;oxidation-reduction process;regulation of transcription from RNA polymerase II promoter in response to hypoxia
- Cellular component
- nucleus;nucleoplasm;cytoplasm;cytosol
- Molecular function
- iron ion binding;protein binding;2-oxoglutarate-dependent dioxygenase activity;L-ascorbic acid binding;peptidyl-proline 4-dioxygenase activity