GJA4 Gene - Gap Junction Protein Alpha 4
Connexin 37 (Cx37) - Vascular Homeostasis and Disease
Gene Information Card
| Symbol | GJA4 |
|---|---|
| Full Name | Gap Junction Protein Alpha 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 1p34.3 |
| NCBI Gene ID | 2701 ncbi.nlm.nih.gov/gene/2701 |
| Ensembl ID | ENSG00000187513 |
| UniProt ID | P48165 |
| OMIM ID | 121012 |
| HGNC ID | 4276 |
| Aliases | CX37, connexin 37 |
Description
GJA4 encodes connexin 37 (Cx37), a member of the connexin family that forms gap junction channels mediating intercellular communication. Cx37 is highly expressed in vascular endothelium and plays a critical role in vascular homeostasis, including regulation of blood pressure, atherosclerosis susceptibility, and endothelial cell function.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Atherosclerosis | Loss of Cx37 function increases monocyte adhesion and foam cell formation, promoting plaque development | NCBI Gene, OMIM |
| Hypertension | Cx37 variants alter endothelial gap junction coupling, affecting vascular tone and blood pressure regulation | ClinVar, OMIM |
| Myocardial infarction | Polymorphisms in GJA4 are associated with increased risk of MI, likely through altered endothelial communication | NCBI Gene, OMIM |
| Coronary artery disease | Reduced Cx37 expression correlates with endothelial dysfunction and CAD progression | ClinVar, NCBI Gene |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 7.2 | Medium |
| Heart | 5.8 | Medium |
| Artery | 6.1 | Medium |
| Spleen | 4.3 | Low |
| Liver | 1.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HUVEC (endothelial) | 8.5 | High expression |
| Aortic smooth muscle cells | 2.1 | Low expression |
| THP-1 monocytes | 0.8 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1019C>T (p.Pro340Leu) | Missense | <0.01% | Alters channel conductance; associated with hypertension |
| c.319G>A (p.Gly107Ser) | Missense | <0.01% | Reduced gap junction coupling; linked to atherosclerosis |
| c.44C>T (p.Pro15Leu) | Missense | <0.01% | Unknown functional effect; rare population variant |
Mutation functional classification
Loss of Function (LOF)
p.Gly107Ser reduces channel permeability and intercellular communication.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported.
Dominant Negative (DN)
p.Pro340Leu may exert dominant-negative effects on wild-type connexin 37 channels.
View complete mutation data：
Gene Ontology (GO)
| • gap junction channel activity (GO:0005243) | • connexin complex (GO:0005922) |
| • cell communication (GO:0007154) | • cell-cell signaling (GO:0007267) |
| • death receptor activity (GO:0016265) |
Pathways
• Gap junction trafficking and regulation (Reactome: R-HSA-190828)
• Cell-cell communication via gap junctions (KEGG: hsa04540)
Protein Summary
Connexin 37 is a 333-amino acid transmembrane protein that assembles into hexameric connexons (hemichannels) and forms gap junction channels between adjacent cells. It is predominantly expressed in vascular endothelium and mediates the transfer of ions and small molecules. Cx37 channels are voltage-sensitive and regulated by phosphorylation. The protein is critical for endothelial function, vascular tone, and inflammatory responses.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GJA4 Knockout HEK293 Cell Line | EDJ-KQ4708 | Human | 2701 | Details Get a Quote |
| GJA4 Knockout HeLa Cell Line | EDJ-KQ53345 | Human | 2701 | Details Get a Quote |
| GJA4 Knockout A-549 Cell Line | EDJ-KQ61824 | Human | 2701 | Details Get a Quote |
| GJA4 Knockout HCT 116 Cell Line | EDJ-KQ70311 | Human | 2701 | Details Get a Quote |
