EGLN2

egl-9 family hypoxia inducible factor 2

Basic information

Region (hg38): 19:40798996-40808434

Links

ENSG00000269858 ∙ NCBI:112398 ∙ OMIM:606424 ∙ HGNC:14660 ∙ Uniprot:Q96KS0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

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	2	263
missense			276	3	1	280
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				3		3
non coding					14	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)
19-40799346-G-A			Benign (Jun 23, 2018)
19-40799402-G-T			Benign (Jun 23, 2018)
19-40799835-A-G			Benign (Jun 22, 2018)
19-40799888-CTCTG-C			Benign (Jun 23, 2018)
19-40799920-ACT-A			Benign (Jun 23, 2018)
19-40800164-C-T			Benign (Jun 23, 2018)
19-40800316-CT-C			Benign (Aug 30, 2019)
19-40800329-C-T			Benign (Jun 22, 2018)
19-40800457-G-A			Benign (Jun 22, 2018)
19-40800577-A-G		not specified	Uncertain significance (Oct 22, 2023)
19-40800578-C-T		not specified	Likely benign (Jun 01, 2022)
19-40800579-A-G		not specified	Uncertain significance (May 27, 2024)
19-40800581-C-T		not specified	Likely benign (Aug 21, 2020)
19-40800582-C-A		not specified	Uncertain significance (Nov 25, 2022)
19-40800583-C-G		not specified	Uncertain significance (Oct 27, 2022)
19-40800583-C-T		Neoplasm	- (-)
19-40800584-G-A		not specified	Likely benign (Apr 07, 2022)
19-40800584-G-C		not specified	Likely benign (May 25, 2022)
19-40800584-G-T		not specified	Likely benign (Nov 08, 2023)
19-40800587-C-G		not specified	Uncertain significance (Nov 05, 2023)
19-40800591-C-G		not specified	Uncertain significance (May 22, 2022)
19-40800592-C-T		not specified	Uncertain significance (May 14, 2023)
19-40800593-G-A		not specified	Likely benign (Jun 25, 2022)
19-40800593-G-C		not specified	Likely benign (Jul 08, 2023)

GnomAD

Source: gnomAD

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: 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

	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