Entity Detail — Knowledge Graph Node
This page aggregates everything SciDEX knows about GJA1: its mechanistic relationships (Knowledge Graph edges), hypotheses targeting it, analyses mentioning it, and supporting scientific papers. The interactive graph below shows its immediate neighbors. All content is AI-synthesized from peer-reviewed literature.
GJA1 is a gene implicated in neurodegeneration research. Key relationships include: regulates, associated with, activates. Associated with ALS, Als, Alzheimer. Connected to 145 entities in the SciDEX knowledge graph.
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| Gene Symbol | GJA1 |
| Full Name | Gap Junction Protein Alpha 1 |
| Chromosome | 6q22.31 |
| Protein Family | Connexin family (21 members in humans) |
| Protein Type | Channel |
| Target Class | Ion Channel |
| Function | Connexin-43 forms gap junction channels enabling direct cell-to-cell transfer of ions (Ca²+, K+), small metabolites (ATP, glucose, glutamate), and signaling molecules. |
| Mechanism of Action | Small molecule modulator of gap junction channel activity |
| Druggability | Low (0.36) |
| Clinical Stage | Phase II |
| Molecular Weight | 43 kDa |
| Pathways | Autophagy, Blood-brain barrier function, Nf-Κb, Oxidative Stress, Proteasome |
| UniProt ID | P17302 |
| NCBI Gene ID | 2697 |
| Ensembl ID | ENSG00000152661 |
| OMIM | 121014 |
| GeneCards | GJA1 |
| Human Protein Atlas | GJA1 |
| Associated Diseases | Alzheimer, Alzheimer's Disease, Amyloidosis, Cardiac |
| Known Drugs/Compounds | Bleomycin, Gap26 |
| Interactions | ABCA1, ACTB, Actin, ACTR2, ACTR3, AKT |
| SciDEX Target | View Target Profile (2 clinical trials) |
| SciDEX Hypotheses | Astroglial Gap Junction Coordination via Connexin- CX43 hemichannel engineering enables size-selectiv Astrocytic Connexin-43 Upregulation Enhances Neuro |
| KG Connections | 676 knowledge graph edges |
| Databases | GeneCardsHPASTRING |
Knowledge base pages for this entity
flowchart TD
GJA1["GJA1
(Connexin-43)"]
%% Autophagy and protein degradation pathways
GJA1 -->|"regulates"| AUTOPHAGY["Autophagy
Pathway"]
GJA1 -->|"regulates"| UPS["Ubiquitin-Proteasome
System"]
GJA1 -->|"regulates"| LAMP1["LAMP1
(Lysosomal marker)"]
GJA1 -->|"regulates"| SQSTM1["SQSTM1/p62
(Autophagy receptor)"]
%% Cytoskeletal regulation
GJA1 -->|"regulates"| VIM["VIM
(Vimentin)"]
GJA1 -->|"regulates"| HDAC6["HDAC6
(Cytoskeletal regulator)"]
GJA1 -->|"associated_with"| CDC42["CDC42
(Cytoskeletal dynamics)"]
%% Cellular stress responses
GJA1 -->|"activates"| OXSTRESS["Oxidative Stress
Response"]
GJA1 -->|"protects_against"| DRP1["DRP1
(Mitochondrial fission)"]
GJA1 -->|"associated_with"| CASP3["CASP3
(Apoptosis executor)"]
%% Cellular processes
GJA1 -->|"activates"| EXOCYTOSIS["Exocytosis
Pathway"]
%% Disease associations
GJA1 -->|"therapeutic_target"| MS["Multiple Sclerosis
(MS)"]
GJA1 -->|"expressed_in"| ALS["Amyotrophic Lateral
Sclerosis (ALS)"]
%% Pathway outcomes
AUTOPHAGY --> NEUROPROT["Neuroprotection"]
UPS --> PROTEINHOM["Protein
Homeostasis"]
OXSTRESS --> NEURODEGEN["Neurodegeneration"]
CASP3 --> CELLDEATH["Cell Death"]
%% Styling
style GJA1 fill:#006494
style AUTOPHAGY fill:#1b5e20
style UPS fill:#1b5e20
style NEUROPROT fill:#1b5e20
style PROTEINHOM fill:#1b5e20
style OXSTRESS fill:#ef5350
style NEURODEGEN fill:#ef5350
style CELLDEATH fill:#ef5350
style LAMP1 fill:#4a1a6b
style SQSTM1 fill:#4a1a6b
style HDAC6 fill:#4a1a6b
style DRP1 fill:#4a1a6b
style MS fill:#5d4400
style ALS fill:#5d4400| Target | Relation | Type | Str |
|---|---|---|---|
| exocytosis | promotes | process | 0.95 |
| Connexin-43 | encodes | protein | 0.95 |
| Cardiac Electrical Conduction | mediates | process | 0.95 |
| Ventricular Arrhythmias | causes | disease | 0.95 |
| CONNEXIN 43 | encodes | protein | 0.95 |
| DLG1 | interacts_with | gene | 0.95 |
| Hemichannel | expressed_in | protein | 0.95 |
| Connexin 43 | associated_with | protein | 0.95 |
| Alzheimer'S Disease | associated_with | disease | 0.95 |
| CONNEXIN43 | encodes | protein | 0.95 |
| Damaged Lysosomes Exocytosis | activates | process | 0.95 |
| Lysosomal Trafficking | involved_in | process | 0.95 |
| Intercellular Mitochondrial Transfer | regulates | process | 0.95 |
| Alzheimer's Disease | associated_with | disease | 0.95 |
| GJA1-20k | associated_with | protein | 0.95 |
| astrocyte network | involved_in | cell_type | 0.95 |
| Lysosomal Trafficking | promotes | process | 0.95 |
| Damaged Lysosome Exocytosis | promotes | process | 0.95 |
| gap junction | involved_in | process | 0.95 |
| Lysosomal Exocytosis | promotes | process | 0.95 |
| Damaged Lysosomes Transport | transports | process | 0.90 |
| Connexin 43 | expressed_in | protein | 0.90 |
| Mitochondrial Transfer | mediates | process | 0.90 |
| Arrhythmogenic sudden cardiac death | risk_factor_for | phenotype | 0.90 |
| Gap Junction-Mediated Communication | involved_in | process | 0.90 |
| Intercellular Mitochondrial Transfer | mediates | process | 0.90 |
| Dysfunctional Lysosome Release | promotes | process | 0.90 |
| gap junction | mediates | process | 0.90 |
| hemichannel | associated_with | process | 0.90 |
| Damaged Lysosomes | involved_in | organelle | 0.90 |
| Wound Healing | involved_in | process | 0.90 |
| Ferroptosis | involved_in | process | 0.90 |
| Metabolic Support | mediates | process | 0.90 |
| Gap Junction Formation | involved_in | process | 0.90 |
| astrocyte | expressed_in | cell_type | 0.90 |
| Apoptotic Cell Death | causes | process | 0.90 |
| ischemic brain injury | contributes_to | disease | 0.90 |
| Uterine Contractions | involved_in | phenotype | 0.90 |
| Hypoxia/Ischemia Injury | upregulates | process | 0.90 |
| Glutamate | promotes | compound | 0.90 |
| Glial Network Signalling | mediates | process | 0.90 |
| SLC38A2 | interacts_with | protein | 0.90 |
| Calcium Signalling | associated_with | process | 0.90 |
| Ion Homeostasis | mediates | process | 0.90 |
| Cardiac Electrical Conduction | involved_in | process | 0.90 |
| Neuroinflammation | associated_with | process | 0.90 |
| Neuroprotection | modulates | process | 0.90 |
| Gap Junction | encodes | structure | 0.90 |
| Keratinocytes | expressed_in | cell_type | 0.90 |
| SLC38A2 | regulates | gene | 0.90 |
| Source | Relation | Type | Str |
|---|---|---|---|
| genes-gja1 | linked_to | wiki | 1.00 |
| ALZHEIMER | associated_with | disease | 0.95 |
| h-13ef5927 | targets | hypothesis | 0.90 |
| h-16ee87a4 | targets | hypothesis | 0.90 |
| h-3a901ec3 | targets | hypothesis | 0.90 |
| GJA1-20k | interacts_with | protein | 0.90 |
| Astrocytes | expressed_in | cell_type | 0.90 |
| Gap26 | inhibits | compound | 0.90 |
| DLG1 | regulates | gene | 0.90 |
| AKT | phosphorylates | protein | 0.85 |
| Gap26 | interacts_with | compound | 0.85 |
| Thermal adaptation | upregulates | process | 0.85 |
| P2 Receptors | interacts_with | receptor | 0.85 |
| PIEZO1 | regulates | gene | 0.85 |
| PIEZO2 | regulates | gene | 0.85 |
| PIEZO1 | upregulates | gene | 0.85 |
| PIEZO2 | upregulates | gene | 0.85 |
| DES | co_expressed_with | gene | 0.80 |
| AKT1 | phosphorylates | protein | 0.80 |
| P2 receptor | interacts_with | protein | 0.80 |
| EPILEPSY | expressed_in | gene | 0.60 |
| ITGAV | interacts_with | gene | 0.60 |
| COMPLEMENT | expressed_in | gene | 0.60 |
| ERBB2 | interacts_with | gene | 0.60 |
| ASTROCYTE | expressed_in | gene | 0.60 |
| CCL2 | targets | gene | 0.60 |
| PIEZO1 | therapeutic_target | gene | 0.60 |
| TERT | activates | gene | 0.60 |
| DRP1 | protects_against | gene | 0.60 |
| AQP4 | expressed_in | gene | 0.60 |
| TLR6 | activates | gene | 0.60 |
| GFAP | activates | gene | 0.60 |
| IL1B | activates | gene | 0.60 |
| TNF | activates | gene | 0.60 |
| VIM | activates | gene | 0.60 |
| ROS | protects_against | gene | 0.60 |
| ATP | protects_against | gene | 0.60 |
| ASTROCYTES | activates | gene | 0.60 |
| ALZHEIMER'S DISEASE | activates | gene | 0.60 |
| MICROGLIA | activates | gene | 0.60 |
| CXCL10 | inhibits | gene | 0.60 |
| YAP1 | interacts_with | gene | 0.60 |
| MITOCHONDRIA | protects_against | gene | 0.60 |
| WT1 | regulates | gene | 0.60 |
| ACTR2 | activates | gene | 0.60 |
| CX43 | transports | gene | 0.60 |
| ABCA1 | interacts_with | gene | 0.60 |
| LRP1 | interacts_with | gene | 0.60 |
| GAPDH | regulates | gene | 0.60 |
| CASP3 | regulates | gene | 0.60 |
Hypotheses where this entity is a therapeutic target
| Hypothesis | Score | Disease | Analysis |
|---|---|---|---|
| Astroglial Gap Junction Coordination via Connexin-43 Phospho | 0.720 | neurodegeneration | Perivascular spaces and glymphatic clear |
| CX43 hemichannel engineering enables size-selective mitochon | 0.686 | neurodegeneration | Mitochondrial transfer between astrocyte |
| Astrocytic Connexin-43 Upregulation Enhances Neuroprotective | 0.559 | neurodegeneration | Mitochondrial transfer between neurons a |
Scientific analyses that reference this entity
neurodegeneration | 2026-04-01 | 7 hypotheses Top: 0.822
neurodegeneration | 2026-04-01 | 7 hypotheses Top: 0.860
neurodegeneration | 2026-04-01 | 1 hypotheses Top: 0.380
Experimental studies targeting or related to this entity
| Experiment | Type | Disease | Score | Feasibility | Model | Status | Est. Cost |
|---|---|---|---|---|---|---|---|
| Cx43 and GJA1-20k overexpression effects on mitochondrial transfer | exploratory | osteoarthritis | 0.950 | 0.00 | human bone marrow-derived MSCs | proposed | N/A |
| Cx43 knockdown effects on mitochondrial transfer | exploratory | osteoarthritis | 0.900 | 0.00 | human bone marrow-derived MSCs | proposed | N/A |
| Confocal imaging of MSC-chondrocyte interactions during mitochondrial | exploratory | osteoarthritis | 0.850 | 0.00 | human bone marrow-derived MSCs | proposed | N/A |
| Astrocyte Ferritin Iron Metabolism Dysfunction in Parkinson's Disease | clinical | Parkinson's Disease | 0.400 | 0.50 | human | proposed | $6,550,000 |
| Gap Junction Dysfunction Validation in Parkinson's Disease | clinical | Alzheimer's Disease | 0.400 | 0.50 | human | proposed | $5,460,000 |
| Proposed experiment from debate on Mitochondrial transfer between astr | falsification | Neurodegeneration | 0.400 | 0.50 | cell_line | proposed | $80,000 |
| Proposed experiment from debate on Mitochondrial transfer between astr | falsification | Neurodegeneration | 0.400 | 0.50 | cell_line | proposed | $100,000 |
| AAV-LRRK2 IND-Enabling Study Design | clinical | Parkinson's Disease | 0.400 | 0.50 | human | proposed | $7,500,000 |
| AAV-LRRK2 Gene Therapy IND-Enabling Study Design | clinical | Parkinson's Disease | 0.400 | 0.50 | human | proposed | $5,460,000 |
| Experiment Design: Metal Ion-Synuclein-Mitochondria Axis in Parkinson' | clinical | Parkinson's Disease | 0.400 | 0.50 | human | proposed | $5,460,000 |
Scientific publications cited in analyses involving this entity
| Title & PMID | Authors | Journal | Year | Citations |
|---|---|---|---|---|
| Astrocytic Connexin43 in Alzheimer's disease: mechanisms, interaction with P2 re [PMID:41062060] | Xiong W, Su Y, Verkhratsky A, Yi C | Neuropharmacology | 2026 | 1 |
| PIEZO channels link mechanical forces to uterine contractions in parturition. [PMID:41231991] | Zhang Y, Kini SA, Mishkanian SA, Yarishk | Science | 2025 | 1 |
| Connexin43 hemichannel blockade turns microglia neuroprotective and mitigates co [PMID:40595567] | Su Y, Li H, Zhang W, Tao S, Wang Q, Zhan | Nat Commun | 2025 | 1 |
| Should it stay or should it go: gap junction protein GJA1/Cx43 conveys damaged l [PMID:39394955] | Domingues N, Ribeiro-Rodrigues T, Girão | Autophagy | 2024 | 1 |
| Connexin 43 regulates intercellular mitochondrial transfer from human mesenchyma [PMID:39390589] | Irwin RM, Thomas MA, Fahey MJ, Mayán MD, | Stem Cell Res Ther | 2024 | 1 |
| NAD(+) rescues aging-induced blood-brain barrier damage via the CX43-PARP1 axis. [PMID:37683629] | Zhan R, Meng X, Tian D, Xu J, Cui H, Yan | Neuron | 2023 | 1 |
| GJA1-20k and Mitochondrial Dynamics. [PMID:35399255] | Shimura D, Shaw RM | Front Physiol | 2022 | 1 |
| Astrocyte Networks as Therapeutic Targets in Glaucomatous Neurodegeneration. [PMID:34199470] | Boal AM, Risner ML, Cooper ML, Wareham L | Cells | 2021 | 1 |
| Inhibition of connexin43 improves functional recovery after ischemic brain injur [PMID:25988944] | Li X, Zhao H, Tan X, Kostrzewa RM, Du G, | Glia | 2015 | 1 |
| Connexin43 Deficiency Leads to Ventricular Arrhythmias by Reprogramming Proline [PMID:41618855] | ["Ying H", "Fan H", "Wang Y", "Jiang R", | Advanced science (Weinheim, Ba | 2026 | 0 |
| Prenatal lipopolysaccharide exposure programs cardiac fibrosis via dysregulating [PMID:41789580] | Wen Y, Yuan Y, Zhang H, Liu Y | Molecular medicine reports | 2026 | 0 |
| Astrocytes Protect Brain Metastatic Breast Cancer Cells From Chemotherapy Throug [PMID:41486609] | Yakati V, Rao SS | Biotechnol Bioeng | 2026 | 0 |
| The AP-1 transcription factors differentially regulate Cx43 expression in a ERK1 [PMID:41930557] | Basque A, Izichkis LS, Mellet C, Martin | Reprod Biol | 2026 | 0 |
| The relationship between Connexin 43 (Cx43) and partner protein, human discs lar [PMID:41703342] | ["Scott H", "Dong L", "Stevenson A", "Ma | Cell and tissue research | 2026 | 0 |
| Thermal Adaptation Inhibits the Wnt Signaling Pathway Regulating Autophagy and I [PMID:41889212] | ["Song R", "Zhang Z", "Zhu S", "Fu K", " | Molecular reproduction and dev | 2026 | 0 |
| Identification and validation of ferroptosis-related genes for diabetic nephropa [PMID:41825713] | Duan H, Wang Y, Wang Q, Yan J, Fan X, Wu | European journal of pharmacolo | 2026 | 0 |
| Danggui Sini decoction attenuates intervertebral disc degeneration by regulating [PMID:41812505] | Chen S, Zhou X, Wang W, Zheng Y, Kang R, | International immunopharmacolo | 2026 | 0 |
| Reproductive tissue-derived stromal cells rescue fertility by coupling follicula [PMID:41888633] | ["Borutinskait\u0117 V", "Krastinait\u01 | Stem cells translational medic | 2026 | 0 |
| A Single-Cell Transcriptomic Atlas Elucidates a Microglial Gene Signature Linkin [PMID:41884157] | ["Zhong R", "Yang H", "Li X", "Wang F", | Journal of inflammation resear | 2026 | 0 |
| Essential Role of CD63 in Maintaining Corneal Epithelial Identity in the Human L [PMID:41817143] | ["Sasamoto Y", "Suzuki K", "Sato S", "Le | Investigative ophthalmology & | 2026 | 0 |
Multi-agent debates referencing this entity
closed · Rounds: 4 · Score: 0.71 · 2026-04-12
closed · Rounds: 4 · Score: 0.81 · 2026-04-06
closed · Rounds: 4 · Score: 0.95 · 2026-04-06
closed · Rounds: 4 · Score: 0.95 · 2026-04-06
Hypotheses and analyses mentioning GJA1 in their description or question text
No additional research found