EGLN1

Chr 1AD

egl-9 family hypoxia inducible factor 1

Also known as: C1orf12, ECYT3, HALAH, HIF-PH2, HIFPH2, HPH-2, HPH2, PHD2

NCBI Gene: 54583ENSG00000135766UniProt: Q9GZT9OMIM: 606425

The protein encoded by this gene catalyzes the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. HIF is a transcriptional complex that plays a central role in mammalian oxygen homeostasis. This protein functions as a cellular oxygen sensor, and under normal oxygen concentration, modification by prolyl hydroxylation is a key regulatory event that targets HIF subunits for proteasomal destruction via the von Hippel-Lindau ubiquitylation complex. Mutations in this gene are associated with erythrocytosis familial type 3 (ECYT3). [provided by RefSeq, Nov 2009]

GeneReviewsOMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

[Hemoglobin, high altitude adaptation]MIM #609070
AD
Erythrocytosis, familial, 3MIM #609820
AD

Clinical highlights

Gene-disease validity (ClinGen)
EGLN1-related erythrocytosis and pheochromocytoma/paraganglioma predisposition · ADDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.
0
Active trials
60
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.30
LOEUF· LoF intol.
Multiple*
Mechanism· predicted
📖
GeneReview available — EGLN1
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?
0.30LOEUF
pLI 0.974
Z-score 3.43
OE 0.06 (0.02–0.30)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
2.15Z-score
OE missense 0.58 (0.50–0.67)
119 obs / 205.8 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?
LoF OE?0.06 (0.02–0.30)
0≤0.351.4
Missense OE?0.58 (0.50–0.67)
0≤0.61.4
Synonymous OE?1.29
0≤1.21.6
LoF obs/exp: 1 / 15.7Missense obs/exp: 119 / 205.8Syn Z: -2.09

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

EGLN1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients