EGLN2
egl-9 family hypoxia inducible factor 2
Basic information
Region (hg38): 19:40798996-40808434
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- not_specified (626 variants)
- not_provided (9 variants)
- Inborn_genetic_diseases (3 variants)
- EGLN2-related_disorder (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the EGLN2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000080732.4. Only rare variants are included in the table.
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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 296 | 297 | ||||
| missense | 329 | 336 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 329 | 301 | 3 |
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| EGLN2 | protein_coding | protein_coding | ENST00000593726 | 5 | 9438 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.722 | 0.278 | 125741 | 0 | 7 | 125748 | 0.0000278 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.45 | 208 | 276 | 0.755 | 0.0000192 | 2589 |
| Missense in Polyphen | 55 | 97.864 | 0.56201 | 935 | ||
| Synonymous | -2.12 | 146 | 117 | 1.25 | 0.00000829 | 875 |
| Loss of Function | 3.19 | 3 | 17.3 | 0.173 | 9.79e-7 | 167 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000153 | 0.000153 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000363 | 0.0000352 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
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. 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. EGLN2 is involved in regulating hypoxia tolerance and apoptosis in cardiac and skeletal muscle. Also regulates susceptibility to normoxic oxidative neuronal death. Links oxygen sensing to cell cycle and primary cilia formation by hydroxylating the critical centrosome component CEP192 which promotes its ubiquitination and subsequent proteasomal degradation. Hydroxylates IKBKB, mediating NF-kappaB activation in hypoxic conditions. Target proteins are preferentially recognized via a LXXLAP motif. {ECO:0000269|PubMed:11595184, ECO:0000269|PubMed:12039559, ECO:0000269|PubMed:12181324, ECO:0000269|PubMed:16509823, ECO:0000269|PubMed:17114296, ECO:0000269|PubMed:19339211, ECO:0000269|PubMed:23932902}.;
- 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;Photodynamic therapy-induced NF-kB survival signaling;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
(Consensus)
Recessive Scores
- pRec
- 0.173
Intolerance Scores
- loftool
- 0.443
- rvis_EVS
- -0.78
- rvis_percentile_EVS
- 12.88
Haploinsufficiency Scores
- pHI
- 0.427
- hipred
- Y
- hipred_score
- 0.775
- ghis
- 0.523
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.994
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Egln2
- Phenotype
- reproductive system phenotype; hematopoietic system phenotype; liver/biliary system phenotype; immune system phenotype; craniofacial phenotype; limbs/digits/tail phenotype; muscle 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; cellular phenotype; homeostasis/metabolism phenotype;
Gene ontology
- Biological process
- regulation of cell growth;response to hypoxia;peptidyl-proline hydroxylation to 4-hydroxy-L-proline;intracellular estrogen receptor signaling pathway;regulation of neuron apoptotic process;cell redox homeostasis;positive regulation of protein catabolic process;oxidation-reduction process;regulation of transcription from RNA polymerase II promoter in response to hypoxia
- Cellular component
- nucleus;nucleoplasm
- Molecular function
- protein binding;ferrous iron binding;2-oxoglutarate-dependent dioxygenase activity;oxygen sensor activity;L-ascorbic acid binding;peptidyl-proline 4-dioxygenase activity