EGLN2

egl-9 family hypoxia inducible factor 2

Basic information

Region (hg38): 19:40798996-40808434

Links

ENSG00000269858NCBI:112398OMIM:606424HGNC:14660Uniprot:Q96KS0AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the EGLN2 gene.

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.

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
261
clinvar
2
clinvar
263
missense
276
clinvar
3
clinvar
1
clinvar
280
nonsense
0
start loss
0
frameshift
0
inframe indel
0
splice donor/acceptor (+/-2bp)
0
splice region
3
3
non coding
14
clinvar
14
Total 0 0 276 264 17

Variants in EGLN2

This is a list of pathogenic ClinVar variants found in the EGLN2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position Type Phenotype Significance ClinVar
19-40799342-T-TG Benign (Oct 03, 2018)1260928
19-40799346-G-A Benign (Jun 23, 2018)1253009
19-40799402-G-T Benign (Jun 23, 2018)1283406
19-40799835-A-G Benign (Jun 22, 2018)1228041
19-40799888-CTCTG-C Benign (Jun 23, 2018)1228205
19-40799920-ACT-A Benign (Jun 23, 2018)1252635
19-40800164-C-T Benign (Jun 23, 2018)1291782
19-40800316-CT-C Benign (Aug 30, 2019)1297762
19-40800329-C-T Benign (Jun 22, 2018)1182618
19-40800457-G-A Benign (Jun 22, 2018)1283246
19-40800577-A-G not specified Uncertain significance (Oct 22, 2023)1750977
19-40800578-C-T not specified Likely benign (Jun 01, 2022)1756599
19-40800579-A-G not specified Uncertain significance (May 27, 2024)3274831
19-40800581-C-T not specified Likely benign (Aug 21, 2020)1768922
19-40800582-C-A not specified Uncertain significance (Nov 25, 2022)2449355
19-40800583-C-G not specified Uncertain significance (Oct 27, 2022)1747053
19-40800583-C-T Neoplasm - (-)3257799
19-40800584-G-A not specified Likely benign (Apr 07, 2022)1769368
19-40800584-G-C not specified Likely benign (May 25, 2022)1769372
19-40800584-G-T not specified Likely benign (Nov 08, 2023)3228984
19-40800587-C-G not specified Uncertain significance (Nov 05, 2023)1776133
19-40800591-C-G not specified Uncertain significance (May 22, 2022)1784153
19-40800592-C-T not specified Uncertain significance (May 14, 2023)2560617
19-40800593-G-A not specified Likely benign (Jun 25, 2022)1787599
19-40800593-G-C not specified Likely benign (Jul 08, 2023)2626067

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
EGLN2protein_codingprotein_codingENST00000593726 59438
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.7220.278125741071257480.0000278
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense1.452082760.7550.00001922589
Missense in Polyphen5597.8640.56201935
Synonymous-2.121461171.250.00000829875
Loss of Function3.19317.30.1739.79e-7167

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0001530.000153
Ashkenazi Jewish0.000.00
East Asian0.000.00
Finnish0.000.00
European (Non-Finnish)0.00003630.0000352
Middle Eastern0.000.00
South Asian0.000.00
Other0.000.00

dbNSFP

Source: dbNSFP

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

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