Details for: EDEM1

Gene ID: 9695

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: EDEM1

Ensembl ID: ENSG00000134109

Description: ER degradation enhancing alpha-mannosidase like protein 1

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • pro-B cell CL0000826
    CSI 32.37
    rCSI 26.81%
    PRS 62.3
  • CD14-positive, CD16-positive monocyte CL0002397
    CSI 15.66
    rCSI 20.52%
    PRS 73.91
  • effector memory CD8-positive, alpha-beta T cell CL0000913
    CSI 8.94
    rCSI 8.15%
    PRS 75.03
  • central memory CD4-positive, alpha-beta T cell CL0000904
    CSI 7.72
    rCSI 4.56%
    PRS 77.65
  • plasmablast CL0000980
    CSI 6.51
    rCSI 5.12%
    PRS 66.95
  • class switched memory B cell CL0000972
    CSI 6.17
    rCSI 4.61%
    PRS 77.03
  • lymphoid lineage restricted progenitor cell CL0000838
    CSI 5.24
    rCSI 20.39%
    PRS 80.29
  • kidney connecting tubule epithelial cell CL1000768
    CSI 5.01
    rCSI 12.71%
    PRS 49.73
  • epithelial cell of lung CL0000082
    CSI 4.12
    rCSI 3.42%
    PRS 59.25
  • CD4-positive, alpha-beta thymocyte CL0000810
    CSI 3.81
    rCSI 3.05%
    PRS 80.71
  • myeloid dendritic cell CL0000782
    CSI 3.57
    rCSI 5.18%
    PRS 76.26
  • IgG plasma cell CL0000985
    CSI 3.25
    rCSI 3.89%
    PRS 77.18
  • early lymphoid progenitor CL0000936
    CSI 3.08
    rCSI 2.71%
    PRS 65.71
  • T follicular helper cell CL0002038
    CSI 3
    rCSI 2.24%
    PRS 75.48
  • hepatic stellate cell CL0000632
    CSI 2.9
    rCSI 10.85%
    PRS 52.37
  • melanocyte CL0000148
    CSI 2.73
    rCSI 2.02%
    PRS 52.88
  • midzonal region hepatocyte CL0019028
    CSI 2.64
    rCSI 6.19%
    PRS 65.34
  • mucus secreting cell CL0000319
    CSI 2.63
    rCSI 4.18%
    PRS 71.3
  • epithelial cell of lower respiratory tract CL0002632
    CSI 2.59
    rCSI 2.01%
    PRS 61.89
  • plasmacytoid dendritic cell, human CL0001058
    CSI 2.58
    rCSI 1.8%
    PRS 62.94
  • common myeloid progenitor CL0000049
    CSI 2.55
    rCSI 2.06%
    PRS 61.57
  • retinal blood vessel endothelial cell CL0002585
    CSI 2.54
    rCSI 4.06%
    PRS 64.31
  • CD4-positive, alpha-beta memory T cell CL0000897
    CSI 2.53
    rCSI 1.81%
    PRS 74.71
  • mucosal invariant T cell CL0000940
    CSI 2.5
    rCSI 2.02%
    PRS 70.87
  • inflammatory macrophage CL0000863
    CSI 2.4
    rCSI 4.11%
    PRS 83.28
  • centrilobular region hepatocyte CL0019029
    CSI 2.38
    rCSI 6.2%
    PRS 64.44
  • precursor B cell CL0000817
    CSI 2.33
    rCSI 2.05%
    PRS 70.09
  • double-positive, alpha-beta thymocyte CL0000809
    CSI 2.31
    rCSI 2.36%
    PRS 73.44
  • alpha-beta T cell CL0000789
    CSI 2.31
    rCSI 2.71%
    PRS 76.77
  • naive T cell CL0000898
    CSI 2.31
    rCSI 1.6%
    PRS 75.5
  • lung secretory cell CL1000272
    CSI 2.3
    rCSI 5.7%
    PRS 58.59
  • hepatocyte CL0000182
    CSI 2.28
    rCSI 4.07%
    PRS 59.34
  • CD4-positive helper T cell CL0000492
    CSI 2.24
    rCSI 1.69%
    PRS 74.16
  • mature B cell CL0000785
    CSI 2.1
    rCSI 1.83%
    PRS 71.01
  • CD1c-positive myeloid dendritic cell CL0002399
    CSI 2.09
    rCSI 2.53%
    PRS 69.04
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 2.08
    rCSI 1.6%
    PRS 60.62
  • IgA plasma cell CL0000987
    CSI 2.06
    rCSI 2.11%
    PRS 75.11
  • central memory CD8-positive, alpha-beta T cell CL0000907
    CSI 2.02
    rCSI 1.36%
    PRS 73.43
  • colonocyte CL1000347
    CSI 1.96
    rCSI 2.8%
    PRS 64.29
  • goblet cell CL0000160
    CSI 1.94
    rCSI 1.83%
    PRS 59.73
  • lung ciliated cell CL1000271
    CSI 1.94
    rCSI 2.24%
    PRS 50.3
  • intestine goblet cell CL0019031
    CSI 1.92
    rCSI 1.71%
    PRS 58.3
  • Kupffer cell CL0000091
    CSI 1.82
    rCSI 4.17%
    PRS 60.09
  • extravillous trophoblast CL0008036
    CSI 1.77
    rCSI 2.19%
    PRS 56.6
  • mononuclear phagocyte CL0000113
    CSI 1.76
    rCSI 3.87%
    PRS 64.53
  • periportal region hepatocyte CL0019026
    CSI 1.74
    rCSI 6.76%
    PRS 65.51
  • CD8-positive, CD28-negative, alpha-beta regulatory T cell CL0000920
    CSI 1.74
    rCSI 3.46%
    PRS 77.91
  • promyelocyte CL0000836
    CSI 1.7
    rCSI 2.45%
    PRS 69.79
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 1.7
    rCSI 6.12%
    PRS 40.57
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 1.65
    rCSI 2.06%
    PRS 40.21
  • elicited macrophage CL0000861
    CSI 1.63
    rCSI 1.5%
    PRS 69.09
  • common dendritic progenitor CL0001029
    CSI 1.63
    rCSI 2.04%
    PRS 70.75
  • dendritic cell, human CL0001056
    CSI 1.57
    rCSI 2.42%
    PRS 69.28
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.52
    rCSI 2.68%
    PRS 41.17
  • sst GABAergic cortical interneuron CL4023017
    CSI 1.5
    rCSI 1.93%
    PRS 43.35
  • promonocyte CL0000559
    CSI 1.48
    rCSI 2.53%
    PRS 69.12
  • granulocyte CL0000094
    CSI 1.47
    rCSI 2.25%
    PRS 69.73
  • alveolar macrophage CL0000583
    CSI 1.47
    rCSI 2.42%
    PRS 65.64
  • group 3 innate lymphoid cell CL0001071
    CSI 1.46
    rCSI 1.1%
    PRS 65.71
  • vascular leptomeningeal cell CL4023051
    CSI 1.45
    rCSI 2.55%
    PRS 52.21
  • pulmonary alveolar type 2 cell CL0002063
    CSI 1.43
    rCSI 2.21%
    PRS 67.94
  • granulocyte monocyte progenitor cell CL0000557
    CSI 1.37
    rCSI 1.19%
    PRS 65.21
  • Langerhans cell CL0000453
    CSI 1.34
    rCSI 2.05%
    PRS 75.99
  • pancreatic acinar cell CL0002064
    CSI 1.3
    rCSI 1.73%
    PRS 66.7
  • activated CD8-positive, alpha-beta T cell, human CL0001049
    CSI 1.3
    rCSI 2.22%
    PRS 78.45
  • lung macrophage CL1001603
    CSI 1.23
    rCSI 2.74%
    PRS 68.04
  • placental villous trophoblast CL2000060
    CSI 1.22
    rCSI 1.89%
    PRS 58.3
  • conjunctival epithelial cell CL1000432
    CSI 1.22
    rCSI 1.86%
    PRS 60.85
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.11
    rCSI 1.86%
    PRS 42.12
  • intermediate monocyte CL0002393
    CSI 1.03
    rCSI 1.55%
    PRS 64.33
  • type B pancreatic cell CL0000169
    CSI 1.02
    rCSI 2.25%
    PRS 58.12
  • colon goblet cell CL0009039
    CSI 0.99
    rCSI 2.36%
    PRS 69.39
  • fraction A pre-pro B cell CL0002045
    CSI 0.98
    rCSI 1.12%
    PRS 79.11
  • germinal center B cell CL0000844
    CSI 0.92
    rCSI 2.73%
    PRS 77.94
  • mature alpha-beta T cell CL0000791
    CSI 0.89
    rCSI 3.24%
    PRS 79.91
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 0.79
    rCSI 1.91%
    PRS 40.75
  • colon macrophage CL0009038
    CSI 0.73
    rCSI 3.38%
    PRS 79.04
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.68
    rCSI 2.12%
    PRS 43.69
  • endothelial cell of placenta CL0009092
    CSI 0.55
    rCSI 2.69%
    PRS 71.39
  • antibody secreting cell CL0000946
    CSI 0.53
    rCSI 2.37%
    PRS 91.29
  • myeloid dendritic cell, human CL0001057
    CSI 0.52
    rCSI 2.9%
    PRS 83.73
  • late pro-B cell CL0002048
    CSI 0.49
    rCSI 1.22%
    PRS 84.32
  • direct pathway medium spiny neuron CL4023026
    CSI 0.41
    rCSI 9.93%
    PRS 41.24
  • indirect pathway medium spiny neuron CL4023029
    CSI 0.27
    rCSI 6.61%
    PRS 42.16
  • cytotoxic T cell CL0000910
    CSI 0.16
    rCSI 0.89%
    PRS 69.83

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [EDEM1](/details-gene/9695) (ER degradation enhancing alpha-mannosidase like protein 1) is a protein-coding gene located on chromosome 3p26.1. It functions as a key component of the endoplasmic reticulum (ER) quality control system. Specifically, [EDEM1](/details-gene/9695) is involved in the ER-associated degradation (ERAD) pathway, where it recognizes, binds, and targets terminally misfolded glycoproteins for retrotranslocation to the cytosol and subsequent proteasomal degradation ([Link](https://doi.org/10.1126/science.1079474), [Link](https://doi.org/10.1016/j.molcel.2009.05.018)). Its molecular function involves mannosidase activity, which trims mannose residues from N-linked glycans on misfolded proteins, a crucial step that signals them for destruction. Expression data indicate that [EDEM1](/details-gene/9695) is of paramount significance in immune cells undergoing development and differentiation, particularly in the B-cell lineage, suggesting a critical role in managing the high protein synthesis load required for immune function. ## Cellular Roles and Expression Landscape The expression profile of [EDEM1](/details-gene/9695) highlights its specialized role in cells with high secretory capacity and active protein quality control needs, particularly within the hematopoietic system. **Overall**, the gene's significance is highest in immune cells, especially those of the B-lymphocyte lineage. It is the most significant marker in [pro-B cell](/details-cell/CL0000826) (CSI: 32.37), a stage characterized by the assembly and quality control of the B-cell receptor. Its importance extends to more mature B-cell types such as [plasmablast](/details-cell/CL0000980) (CSI: 6.51) and [class switched memory B cell](/details-cell/CL0000972) (CSI: 6.17), which are responsible for massive antibody production. This pattern suggests that [EDEM1](/details-gene/9695) is fundamental for ensuring the fidelity of immunoglobulin synthesis. Beyond the B-cell lineage, [EDEM1](/details-gene/9695) also shows high significance in myeloid cells, such as [CD14-positive, CD16-positive monocyte](/details-cell/CL0002397) (CSI: 15.66), and various T-cell subsets, including [effector memory CD8-positive, alpha-beta T cell](/details-cell/CL0000913) (CSI: 8.94) and [central memory CD4-positive, alpha-beta T cell](/details-cell/CL0000904) (CSI: 7.72). This broad expression across professional secretory cells of the immune system underscores its general importance in managing the unfolded protein response during immune cell activation and function. Moderate significance in non-immune secretory cells like [kidney connecting tubule epithelial cell](/details-cell/CL1000768) (CSI: 5.01) and [epithelial cell of lung](/details-cell/CL0000082) (CSI: 4.12) further supports its role as a key component of the ER quality control machinery in diverse cellular contexts. ## Pathways and Molecular Function The functional annotations for [EDEM1](/details-gene/9695) firmly place it within the cellular machinery for protein quality control. Its primary molecular functions include '[Misfolded protein binding](/details-ontology/GO:0051787)', '[Mannosyl-oligosaccharide 1,2-alpha-mannosidase activity](/details-ontology/GO:0004571)', and '[Calcium ion binding](/details-ontology/GO:0005509)'. These activities are central to its role in the '[Erad pathway](/details-ontology/GO:0036503)', a biological process that identifies and eliminates misfolded proteins from the ER. [EDEM1](/details-gene/9695) operates within the '[Endoplasmic reticulum](/details-ontology/GO:0005783)' and is integral to the '[Endoplasmic reticulum quality control compartment](/details-ontology/GO:0044322)'. It plays a critical part in the '[Unfolded protein response (upr)](/details-pathway/R-HSA-381119)', a stress response pathway activated by an accumulation of unfolded or misfolded proteins. Reactome pathway analysis shows its involvement in '[Asparagine n-linked glycosylation](/details-pathway/R-HSA-446203)' and specifically in the '[Calnexin/calreticulin cycle](/details-pathway/R-HSA-901042)', where it helps extract terminally misfolded glycoproteins that fail to achieve their proper conformation ([Link](https://doi.org/10.1126/science.1079474)). By trimming mannose residues, [EDEM1](/details-gene/9695) creates a signal that targets the substrate for ubiquitination and degradation, thereby preventing proteotoxicity and maintaining cellular homeostasis. This function is particularly critical for the high-volume production of complex glycoproteins like antibodies in B-cells and plasma cells, which aligns perfectly with its observed expression pattern. ## Research Directions The central role of [EDEM1](/details-gene/9695) in managing proteotoxic stress, combined with its high significance in specific immune cell populations, presents several avenues for future investigation and potential therapeutic intervention. Based on the available data, the following hypotheses can be proposed: 1. **Hypothesis 1:** Loss-of-function mutations in [EDEM1](/details-gene/9695) may impair B-cell development at the [pro-B cell](/details-cell/CL0000826) stage due to an inability to resolve ER stress caused by B-cell receptor assembly, leading to apoptosis and resulting in specific forms of congenital B-cell immunodeficiency. 2. **Hypothesis 2:** In plasma cell malignancies such as multiple myeloma, which are characterized by the overproduction of monoclonal immunoglobulins and are highly dependent on the ERAD pathway for survival, [EDEM1](/details-gene/9695) may be a critical survival factor. Its inhibition could selectively induce lethal proteotoxicity in malignant plasma cells. To test the second hypothesis, a key experiment could be designed. * **Proposed Experiment:** CRISPR-Cas9 could be used to knock out [EDEM1](/details-gene/9695) in a panel of human multiple myeloma cell lines. The effects would be assessed by measuring markers of ER stress (e.g., phosphorylation of PERK and eIF2α, splicing of XBP1, and upregulation of CHOP) via western blot and RT-qPCR. Cell viability and apoptosis could be quantified using Annexin V/PI staining and flow cytometry. A significant increase in ER stress and apoptosis in [EDEM1](/details-gene/9695)-deficient myeloma cells compared to controls would support its role as a crucial survival factor. Given its intracellular localization within the ER, [EDEM1](/details-gene/9695) presents a challenging but potentially valuable therapeutic target. Small molecule inhibitors designed to block its mannosidase active site could be developed. The therapeutic strategy would be **inhibition**, aiming to overwhelm the protein quality control capacity of cancer cells like multiple myeloma that are already operating at the precipice of proteotoxic collapse. This approach could offer a targeted therapy that exploits a key vulnerability of these malignancies.

Genular Protein ID: 1403086130

Symbol: EDEM1_HUMAN

Name: ER degradation-enhancing alpha-mannosidase-like protein 1

UniProtKB Accession Codes:

Q92611 A8K9C8 B4DXP3

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CAZy 1 CCDS 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 6 Ensembl 2 ExpressionAtlas 1 GO 15 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRINTS 1 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 Pumba 1 RNAct 1 Reactome 2 RefSeq 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 9039502

Title: Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain.

PubMed ID: 9039502

DOI: 10.1093/dnares/3.5.321

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16641997

Title: The DNA sequence, annotation and analysis of human chromosome 3.

PubMed ID: 16641997

DOI: 10.1038/nature04728

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 12610306

Title: Role of EDEM in the release of misfolded glycoproteins from the calnexin cycle.

PubMed ID: 12610306

DOI: 10.1126/science.1079474

PubMed ID: 16449189

Title: Derlin-2 and Derlin-3 are regulated by the mammalian unfolded protein response and are required for ER-associated degradation.

PubMed ID: 16449189

DOI: 10.1083/jcb.200507057

PubMed ID: 19934218

Title: A dual role for EDEM1 in the processing of rod opsin.

PubMed ID: 19934218

DOI: 10.1242/jcs.055228

PubMed ID: 19524542

Title: EDEM1 recognition and delivery of misfolded proteins to the SEL1L-containing ERAD complex.

PubMed ID: 19524542

DOI: 10.1016/j.molcel.2009.05.018

PubMed ID: 25092655

Title: EDEM2 initiates mammalian glycoprotein ERAD by catalyzing the first mannose trimming step.

PubMed ID: 25092655

DOI: 10.1083/jcb.201404075

Sequence Information:

  • Length: 657
  • Mass: 73768
  • Checksum: E0097901B3BF02FB
  • Sequence:
    • MQWRALVLGL VLLRLGLHGV LWLVFGLGPS MGFYQRFPLS FGFQRLRSPD GPASPTSGPV 
GRPGGVSGPS WLQPPGTGAA QSPRKAPRRP GPGMCGPANW GYVLGGRGRG PDEYEKRYSG 
AFPPQLRAQM RDLARGMFVF GYDNYMAHAF PQDELNPIHC RGRGPDRGDP SNLNINDVLG 
NYSLTLVDAL DTLAIMGNSS EFQKAVKLVI NTVSFDKDST VQVFEATIRV LGSLLSAHRI 
ITDSKQPFGD MTIKDYDNEL LYMAHDLAVR LLPAFENTKT GIPYPRVNLK TGVPPDTNNE 
TCTAGAGSLL VEFGILSRLL GDSTFEWVAR RAVKALWNLR SNDTGLLGNV VNIQTGHWVG 
KQSGLGAGLD SFYEYLLKSY ILFGEKEDLE MFNAAYQSIQ NYLRRGREAC NEGEGDPPLY 
VNVNMFSGQL MNTWIDSLQA FFPGLQVLIG DVEDAICLHA FYYAIWKRYG ALPERYNWQL 
QAPDVLFYPL RPELVESTYL LYQATKNPFY LHVGMDILQS LEKYTKVKCG YATLHHVIDK 
STEDRMESFF LSETCKYLYL LFDEDNPVHK SGTRYMFTTE GHIVSVDEHL RELPWKEFFS 
EEGGQDQGGK SVHRPKPHEL KVINSSSNCN RVPDERRYSL PLKSIYMRQI DQMVGLI