gene

GJA1

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

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.

676Connections
3Hypotheses
3Analyses
50Outgoing
50Incoming
10Experiments
4Debates

Summary

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 Info
Gene SymbolGJA1
Full NameGap Junction Protein Alpha 1
Chromosome6q22.31
Protein FamilyConnexin family (21 members in humans)
Protein TypeChannel
Target ClassIon Channel
FunctionConnexin-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 ActionSmall molecule modulator of gap junction channel activity
DruggabilityLow (0.36)
Clinical StagePhase II
Molecular Weight43 kDa
PathwaysAutophagy, Blood-brain barrier function, Nf-Κb, Oxidative Stress, Proteasome
UniProt IDP17302
NCBI Gene ID2697
Ensembl IDENSG00000152661
OMIM121014
GeneCardsGJA1
Human Protein AtlasGJA1
Associated DiseasesAlzheimer, Alzheimer's Disease, Amyloidosis, Cardiac
Known Drugs/CompoundsBleomycin, Gap26
InteractionsABCA1, ACTB, Actin, ACTR2, ACTR3, AKT
SciDEX TargetView Target Profile (2 clinical trials)
SciDEX HypothesesAstroglial Gap Junction Coordination via Connexin-
CX43 hemichannel engineering enables size-selectiv
Astrocytic Connexin-43 Upregulation Enhances Neuro
KG Connections676 knowledge graph edges
DatabasesGeneCardsHPASTRING
🧬 3D Structure Comparison — GJA1 Experimental (PDB) vs Predicted (AlphaFold) — click to expand

📄 Experimental Structure

7F94 — X-ray / Cryo-EM

🔮 AI Predicted Structure

P17302 — AlphaFold

Left: Experimental structure from RCSB PDB | Right: AI-predicted structure from AlphaFold | Powered by Mol*

Wiki Pages (2)

Knowledge base pages for this entity

Canonical Page

GJA1 Protein

protein · 774 words

GJA1

gene · 711 words

Pathway Diagram

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

Outgoing (474)

TargetRelationTypeStr
exocytosispromotesprocess0.95
Connexin-43encodesprotein0.95
Cardiac Electrical Conductionmediatesprocess0.95
Ventricular Arrhythmiascausesdisease0.95
CONNEXIN 43encodesprotein0.95

Incoming (202)

SourceRelationTypeStr
genes-gja1linked_towiki1.00
ALZHEIMERassociated_withdisease0.95
h-13ef5927targetshypothesis0.90
h-16ee87a4targetshypothesis0.90
h-3a901ec3targetshypothesis0.90

Targeting Hypotheses (3)

Hypotheses where this entity is a therapeutic target

HypothesisScoreDiseaseAnalysis
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

Mentioning Analyses (3)

Scientific analyses that reference this entity

Mitochondrial transfer between astrocytes and neurons

neurodegeneration | 2026-04-01 | 7 hypotheses Top: 0.822

Perivascular spaces and glymphatic clearance failure in AD

neurodegeneration | 2026-04-01 | 7 hypotheses Top: 0.860

Mitochondrial transfer between neurons and glia

neurodegeneration | 2026-04-01 | 1 hypotheses Top: 0.380

Experiments (10)

Experimental studies targeting or related to this entity

ExperimentTypeDiseaseScoreFeasibilityModelStatusEst. 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

Related Papers (20)

Scientific publications cited in analyses involving this entity

Title & PMIDAuthorsJournalYearCitations
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

Debates (4)

Multi-agent debates referencing this entity

Mitochondrial transfer between neurons and glia?

closed · Rounds: 4 · Score: 0.71 · 2026-04-12

Analysis question not specified

closed · Rounds: 4 · Score: 0.81 · 2026-04-06

Mitochondrial transfer between astrocytes and neurons

closed · Rounds: 4 · Score: 0.95 · 2026-04-06

Perivascular spaces and glymphatic clearance failure in AD

closed · Rounds: 4 · Score: 0.95 · 2026-04-06

Related Research

Hypotheses and analyses mentioning GJA1 in their description or question text

No additional research found