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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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EDEM1
ER degradation enhancing alpha-mannosidase like protein 1
Chromosome 3 · 3p26.1
NCBI Gene: 9695Ensembl: ENSG00000134109.11HGNC: HGNC:18967UniProt: Q92611
56PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
mannosyl-oligosaccharide 1,2-alpha-mannosidase activityERAD pathwayprotein targeting to ERpositive regulation of retrograde protein transport, ER to cytosolhypertrophic cardiomyopathysmoking initiationankylosing spondylitissmoking behavior
✦AI Summary

EDEM1 (ER degradation enhancing alpha-mannosidase like protein 1) is a glycosyl hydrolase 47 family member that serves as a critical quality control factor in endoplasmic reticulum-associated degradation (ERAD) 1. Its primary function is extracting misfolded N-glycosylated proteins from the calnexin chaperone cycle for proteasomal degradation, while permitting productive protein folding to proceed 2. Mechanistically, EDEM1 catalyzes α1,2-mannose trimming of N-glycans, converting Man8GlcNAc2 to Man7GlcNAc2 and generating oligosaccharide structures (M7, M6, M5) that mark proteins for degradation 3. This mannose-trimming activity operates in both ERAD-dependent and independent pathways, often coordinating with the SEL1L/Hrd1 complex 4. EDEM1 protein levels are dynamically regulated through both ERAD and autophagy during ER stress 4. Disease relevance extends to conditions involving ER stress and protein misfolding; notably, EDEM1 alterations enhance ATF6 pro-survival signaling in hepatocellular carcinoma cells 5, and EDEM1 expression is upregulated in response to chemical stressors like PFAS-induced toxicity 6. Clinically, understanding EDEM1 function informs therapeutic strategies targeting ER stress-related pathologies and may have implications for viral infections that manipulate ER quality control mechanisms.

Sources cited
1
EDEM1 role in glycoprotein quality control and routing misfolded glycoproteins to ERAD through N-glycan handling
PMID: 27803995
2
EDEM1 as a glycosyl hydrolase 47 family member that extracts folding-incompetent glycoproteins from calnexin cycle
PMID: 17499246
3
EDEM1 catalyzes α1,2-mannose trimming producing M7, M6, and M5 oligosaccharide structures for ERAD
PMID: 34698634
4
EDEM1 degradation is mediated by both ERAD and autophagy through mannose-trimming dependent and independent mechanisms
PMID: 38682256
5
EDEM1 alterations enhance ATF6 pro-survival signaling; somatic EDEM1 variant N198I found in hepatocellular carcinoma
PMID: 30281916
6
EDEM1 gene expression is upregulated as inflammatory response marker in PFAS-mediated hepatic toxicity and steatosis
PMID: 37806615
Disease Associationsⓘ20
hypertrophic cardiomyopathyOpen Targets
0.31Weak
smoking initiationOpen Targets
0.28Weak
ankylosing spondylitisOpen Targets
0.27Weak
attention deficit hyperactivity disorderOpen Targets
0.20Weak
smoking behaviorOpen Targets
0.20Weak
substance abuseOpen Targets
0.20Weak
Precordial painOpen Targets
0.20Weak
Abruptio PlacentaeOpen Targets
0.20Weak
preeclampsiaOpen Targets
0.19Weak
brain injuryOpen Targets
0.18Weak
vascular diseaseOpen Targets
0.18Weak
placenta praeviaOpen Targets
0.16Weak
placental retentionOpen Targets
0.16Weak
ThrombocytopeniaOpen Targets
0.08Suggestive
breast cancerOpen Targets
0.07Suggestive
macrothrombocytopenia, isolated, 2, autosomal dominantOpen Targets
0.07Suggestive
triple-negative breast cancerOpen Targets
0.07Suggestive
strictureOpen Targets
0.07Suggestive
thrombocytopenia 4Open Targets
0.07Suggestive
autosomal dominant macrothrombocytopeniaOpen Targets
0.07Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
OS9Protein interaction100%ATF6Protein interaction100%FAF2Protein interaction100%VCPProtein interaction99%ERLEC1Protein interaction99%DERL1Protein interaction99%
Tissue Expression6 tissues
Liver
100%
Bone Marrow
92%
Lung
52%
Ovary
23%
Heart
13%
Brain
8%
Gene Interaction Network
Click a node to explore
EDEM1OS9ATF6FAF2VCPERLEC1DERL1
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q92611
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.11LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.90 [0.73–1.11]
RankingsWhere EDEM1 stands among ~20K protein-coding genes
  • #8,060of 20,598
    Most Researched56
  • #11,451of 17,882
    Most Constrained (LOEUF)1.11
Genes detectedEDEM1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Coronavirus interactions with the cellular autophagy machinery.
PMID: 32964796
Autophagy · 2020
1.00
2
Pathogenicity and virulence of Japanese encephalitis virus: Neuroinflammation and neuronal cell damage.
PMID: 33724154
Virulence · 2021
0.90
3
Quality control of glycoprotein folding and ERAD: the role of N-glycan handling, EDEM1 and OS-9.
PMID: 27803995
Histochem Cell Biol · 2017
0.80
4
Alterations of EDEM1 functions enhance ATF6 pro-survival signaling.
PMID: 30281916
FEBS J · 2018
0.70
5
Glycoprotein folding and the role of EDEM1, EDEM2 and EDEM3 in degradation of folding-defective glycoproteins.
PMID: 17499246
FEBS Lett · 2007
0.60