GJA5 (Gap Junction Protein Alpha 5)
A key cardiac connexin gene associated with atrial fibrillation and congenital heart defects
Gene Information Card
| Symbol | GJA5 |
|---|---|
| Full Name | Gap Junction Protein Alpha 5 |
| Gene Type | Protein coding |
| Chromosomal Location | 1q21.2 |
| NCBI Gene ID | 2702 ncbi.nlm.nih.gov/gene/2702 |
| Ensembl ID | ENSG00000152977 |
| UniProt ID | P36382 |
| OMIM ID | 121013 |
| HGNC ID | 4279 |
| Aliases | CX40, MGC11132, connexin 40 |
Description
GJA5 encodes connexin 40 (Cx40), a member of the connexin family that forms gap junction channels in cardiac myocytes, particularly in the atria and conduction system. These channels mediate electrical coupling and impulse propagation. Mutations in GJA5 are associated with atrial fibrillation and congenital heart defects.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Atrial fibrillation, familial, 11 | Loss-of-function mutations impair gap junction conductance, disrupting atrial electrical synchronization | ClinVar, OMIM #614049 |
| Atrial standstill | Homozygous or compound heterozygous mutations abolish Cx40 function, leading to atrial inexcitability | ClinVar, OMIM #108770 |
| Congenital heart defects, multiple types | GJA5 variants disrupt cardiac development, associated with tetralogy of Fallot and septal defects | OMIM #121013, PubMed 20034092 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 12.3 | High |
| Lung | 1.2 | Low |
| Kidney | 0.8 | Low |
| Spleen | 0.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HL-1 atrial myocytes | 15.0 | Cardiac cell line |
| HEK293 | 0.1 | Low endogenous expression |
| H9c2 cardiomyoblasts | 2.5 | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.44G>A (p.Arg15Gln) | Missense | Rare | Reduced gap junction conductance; associated with atrial fibrillation |
| c.113G>A (p.Gly38Asp) | Missense | Rare | Dominant-negative effect; impaired trafficking to cell membrane |
| c.556C>T (p.Arg186*) | Nonsense | Very rare | Loss of function; truncation of C-terminal domain |
Mutation functional classification
Loss of Function (LOF)
Missense and nonsense mutations that reduce or abolish channel conductance (e.g., p.Arg15Gln, p.Arg186*)
Gain of Function (GOF)
Not reported for GJA5
Dominant Negative (DN)
Mutations such as p.Gly38Asp that interfere with wild-type connexin assembly and trafficking
View complete mutation data：
Gene Ontology (GO)
| • gap junction channel activity | • cell-cell signaling |
| • cardiac conduction | • protein homooligomerization |
| • transmembrane transport |
Pathways
• Gap junction trafficking and regulation
• Cardiac conduction
• Cell-cell communication
Protein Summary
Connexin 40 is a 40 kDa transmembrane protein that assembles into hexameric connexons (hemichannels) at the plasma membrane. Two connexons from adjacent cells dock to form a gap junction channel, allowing direct electrical and chemical communication. In the heart, Cx40 is predominantly expressed in atrial myocytes and the His-Purkinje system, where it ensures rapid impulse propagation. Mutations in GJA5 impair channel function, leading to arrhythmias and developmental defects.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GJA5 Knockout HEK293 Cell Line | EDJ-KQ2494 | Human | 2702 | Details Get a Quote |
| GJA5 Knockout HeLa Cell Line | EDJ-KQ53346 | Human | 2702 | Details Get a Quote |
| GJA5 Knockout A-549 Cell Line | EDJ-KQ61825 | Human | 2702 | Details Get a Quote |
| GJA5 Knockout HCT 116 Cell Line | EDJ-KQ70312 | Human | 2702 | Details Get a Quote |
