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GeneE
10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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EMC4
ER membrane protein complex subunit 4
Chromosome 15 · 15q14
NCBI Gene: 51234Ensembl: ENSG00000128463.14HGNC: HGNC:28032UniProt: A0A024R9N3
60PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
membrane insertase activityprotein bindingprotein insertion into ER membrane by stop-transfer membrane-anchor sequencetail-anchored membrane protein insertion into ER membraneneurodegenerative diseaselysosomal storage diseasedengue diseaseAlzheimer disease
✦AI Summary

EMC4 (ER membrane protein complex subunit 4) is a crucial component of the endoplasmic reticulum membrane protein complex (EMC) that facilitates energy-independent insertion of newly synthesized membrane proteins into ER membranes, with particular preference for proteins containing weakly hydrophobic transmembrane domains or destabilizing features 123. The protein functions in both cotranslational insertion of multi-pass membrane proteins and post-translational insertion of tail-anchored proteins, controlling membrane protein topology including G protein-coupled receptors 23. Beyond its canonical role, EMC4 serves as a molecular tether between intracellular compartments, facilitating late endosome-to-ER transport by engaging Rab7 and syntaxin18 4. EMC4 also promotes viral membrane fusion during Dengue virus entry by mediating ER-to-endosome phosphatidylserine transfer 5. Disease relevance includes involvement in neuropathic pain, where decreased EMC4 expression was identified as a potential biomarker 6, and roles in α-synuclein aggregation relevant to Parkinson's disease, where EMC4 ablation enhanced autophagic clearance and reduced pathological aggregates 7. Additionally, EMC4 participates in eIF2B-mediated translation regulation and stress response in yeast 8.

⚠Limited data available — This gene has 0 indexed publications. Summary and analysis may be incomplete.
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.57Moderate
lysosomal storage diseaseOpen Targets
0.48Moderate
dengue diseaseOpen Targets
0.38Weak
Alzheimer diseaseOpen Targets
0.38Weak
multiple sclerosisOpen Targets
0.38Weak
Parkinson diseaseOpen Targets
0.38Weak
agenesis of the corpus callosum with peripheral neuropathyOpen Targets
0.17Weak
linear and whorled nevoid hypermelanosisOpen Targets
0.04Suggestive
Griscelli diseaseOpen Targets
0.04Suggestive
immunodeficiency 88Open Targets
0.04Suggestive
uncombable hair syndromeOpen Targets
0.04Suggestive
primary immunodeficiency syndrome due to p14 deficiencyOpen Targets
0.03Suggestive
Griscelli disease type 1Open Targets
0.03Suggestive
Griscelli syndrome type 1Open Targets
0.03Suggestive
chronic myeloproliferative disorderOpen Targets
0.03Suggestive
Griscelli disease type 3Open Targets
0.03Suggestive
Griscelli syndrome type 3Open Targets
0.03Suggestive
neutropenia, severe congenital, 1, autosomal dominantOpen Targets
0.03Suggestive
idiopathic hypereosinophilic syndromeOpen Targets
0.03Suggestive
Clouston syndromeOpen Targets
0.03Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
EMC2Protein interaction100%EMC8Protein interaction100%EMC1Protein interaction100%EMC9Protein interaction100%EMC7Protein interaction100%EMC3Protein interaction100%
Tissue Expression6 tissues
Brain
100%
Heart
63%
Ovary
51%
Lung
49%
Liver
49%
Bone Marrow
41%
Gene Interaction Network
Click a node to explore
EMC4EMC2EMC8EMC1EMC9EMC7EMC3
PROTEIN STRUCTURE
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PDB8J0O · 3.32 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.71LoF Tolerant
pLIⓘ
0.34Tolerant
Observed/Expected LoF0.41 [0.24–0.71]
RankingsWhere EMC4 stands among ~20K protein-coding genes
  • #7,657of 20,598
    Most Researched60
  • #5,410of 17,882
    Most Constrained (LOEUF)0.71
Genes detectedEMC4
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Analysis of Potential Hub Genes for Neuropathic Pain Based on Differential Expression in Rat Models.
PMID: 35281346
Pain Res Manag · 2022
1.00
2
Cloning and sequencing of a Porifera partial cDNA coding for a short-chain collagen.
PMID: 2163843
Eur J Biochem · 1990
0.90
3
Selective EMC subunits act as molecular tethers of intracellular organelles exploited during viral entry.
PMID: 32111841
Nat Commun · 2020
0.80
4
A specific EMC subunit supports Dengue virus infection by promoting virus membrane fusion essential for cytosolic genome delivery.
PMID: 35834589
PLoS Pathog · 2022
0.70
5
Large-scale bidirectional arrayed genetic screens identify OXR1 and EMC4 as modifiers of αSynuclein aggregation.
PMID: 41911287
FEBS Open Bio · 2026
0.60