gene

GNAL

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about GNAL: 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.

145Connections

30Hypotheses

0Analyses

50Outgoing

50Incoming

6Experiments

0Debates

Summary

GNAL encodes the Gαolf protein, which couples dopamine D1 and adenosine A2A receptors to cAMP signaling in the striatum, with roles in dystonia and Parkinson's disease.

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🧬 Gene Info

Gene Symbol	GNAL
Full Name	Gαolf Subunit
Chromosome	18p11.21
Function	encodes the Gαolf protein (Guanine nucleotide-binding protein subunit alpha L), a member of the Gαs family of heterotrimeric G proteins
Primary Expression	Neuron-specific (olfactory epithelium, striatum)
Molecular Weight	44 kDa
Exons	12
UniProt ID	[P38405](https://www.uniprot.org/uniprot/P38405)
Ensembl ID	ENSG00000141449
GeneCards	GNAL
Human Protein Atlas	GNAL
Chromosomal location	18p11.21
Genomic span	~67 kb, 12 exons
Associated Diseases	Als
Interactions	CAMKII, CCND1, CYTOKINES, IL1B, IL3, IL8
KG Connections	145 knowledge graph edges
Databases	GeneCards NCBI Gene HPA STRING

Wiki Pages (1)

Knowledge base pages for this entity

Canonical Page

GNAL — Gαolf Subunit

gene · 1593 words

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Pathway Diagram

graph TD
    GNAL["GNAL"]
    VAMP7["VAMP7"]
    GNAL -->|"expressed in"| VAMP7
    MMP9["MMP9"]
    GNAL -->|"expressed in"| MMP9
    PI3K["PI3K"]
    GNAL -->|"inhibits"| PI3K
    AKT["AKT"]
    GNAL -->|"associated with"| AKT
    AKT1["AKT1"]
    GNAL -->|"associated with"| AKT1
    NF__B["NF-KappaB"]
    GNAL -->|"inhibits"| NF__B
    MCC["MCC"]
    GNAL -->|"expressed in"| MCC
    AUTOPHAGY["AUTOPHAGY"]
    GNAL -->|"expressed in"| AUTOPHAGY
    CXCR4["CXCR4"]
    GNAL -->|"expressed in"| CXCR4
    ALDH1A3["ALDH1A3"]
    GNAL -->|"associated with"| ALDH1A3
    Autophagy(["Autophagy"])
    GNAL -->|"expressed in"| Autophagy
    Glycolysis(["Glycolysis"])
    GNAL -->|"expressed in"| Glycolysis
    style GNAL fill:#1a3a4a,stroke:#4fc3f7,stroke-width:3px,color:#e0e0e0

Outgoing (77)

Target	Relation	Type	Str
Als	associated_with	disease	0.65
Anxiety	contributes_to	disease	0.65
Als	inhibits	disease	0.65
DEPRESSION	contributes_to	gene	0.60
Actin	contributes_to	protein	0.60
IL8	inhibits	gene	0.60
VAMP7	expressed_in	gene	0.60
MMP9	expressed_in	gene	0.60
PI3K	inhibits	gene	0.60
AKT	associated_with	gene	0.60
AKT1	associated_with	gene	0.60
MCC	expressed_in	gene	0.60
CXCR4	expressed_in	gene	0.60
ALDH1A3	associated_with	gene	0.60
TOR1A	associated_with	gene	0.60
Rb	inhibits	protein	0.60
NF-ΚB	inhibits	gene	0.60
AUTOPHAGY	expressed_in	gene	0.60
Autophagy	expressed_in	pathway	0.60
Glycolysis	expressed_in	pathway	0.60
Akt	associated_with	pathway	0.60
Nf-Κb	inhibits	pathway	0.60
Pi3K	inhibits	pathway	0.60
FRONTOTEMPORAL DEMENTIA	co_discussed	disease	0.40
LC3B	co_discussed	protein	0.40
NLR	co_discussed	gene	0.40
PARKINSON	co_discussed	gene	0.40
PRESENILIN	co_discussed	protein	0.40
RAS	co_discussed	protein	0.40
REACTIVE OXYGEN SPECIES	co_discussed	process	0.40
INTERFERON	co_discussed	protein	0.40
MICROGLIA	co_discussed	cell_type	0.40
MACROPHAGES	co_discussed	cell_type	0.40
SQSTM1	co_discussed	gene	0.40
P62	co_discussed	protein	0.40
TAX1BP1	co_discussed	gene	0.40
TOLLIP	co_discussed	gene	0.40
UBIQUITIN	co_discussed	protein	0.40
ULK1	co_discussed	gene	0.40
SYNA	co_discussed	gene	0.40
APOE	co_discussed	gene	0.40
RELA	co_discussed	gene	0.40
C1QA	co_discussed	gene	0.40
C1QC	co_discussed	protein	0.40
FUNDC1	co_discussed	gene	0.40
GBA	co_discussed	gene	0.40
HIF1A	co_discussed	protein	0.40
LGALS3	co_discussed	gene	0.40
LMNA	co_discussed	gene	0.40
MAPK8	co_discussed	gene	0.40

Incoming (68)

Source	Relation	Type	Str
CAMKII	inhibits	gene	0.60
CCND1	inhibits	gene	0.60
CYTOKINES	inhibits	gene	0.60
ANXIETY	contributes_to	gene	0.60
GCH1	associated_with	gene	0.60
THAP1	associated_with	gene	0.60
ANO3	associated_with	gene	0.60
TNF	inhibits	gene	0.60
IL3	inhibits	gene	0.60
IL1B	inhibits	gene	0.60
AUTOPHAGY	co_discussed	process	0.40
LATE	co_discussed	disease	0.40
ACTIN	co_discussed	protein	0.40
ALS	co_discussed	disease	0.40
AMYOTROPHIC LATERAL SCLEROSIS	co_discussed	gene	0.40
FTD	co_discussed	disease	0.40
DEMENTIA	co_discussed	gene	0.40
RNA	co_discussed	gene	0.40
MAP1LC3	co_discussed	gene	0.40
NES	co_discussed	protein	0.40
COMPLEMENT	co_discussed	pathway	0.40
ALZHEIMER DISEASE	co_discussed	gene	0.40
CALCOCO2	co_discussed	gene	0.40
NDP52	co_discussed	gene	0.40
FUS	co_discussed	protein	0.40
G3BP1	co_discussed	gene	0.40
LC3	co_discussed	protein	0.40
NBR1	co_discussed	gene	0.40
ABCD3	co_discussed	gene	0.40
MYOT	co_discussed	gene	0.40
AMBRA1	co_discussed	protein	0.40
ATM	co_discussed	protein	0.40
BCL2	co_discussed	gene	0.40
BCL2L11	co_discussed	gene	0.40
BCL2L13	co_discussed	gene	0.40
BNIP3	co_discussed	gene	0.40
BNIP3L	co_discussed	protein	0.40
CANX	co_discussed	gene	0.40
CAT	co_discussed	gene	0.40
CTSD	co_discussed	gene	0.40
HEPSIN	co_discussed	protein	0.40
DDIT3	co_discussed	gene	0.40
CHOP	co_discussed	gene	0.40
DISC1	co_discussed	gene	0.40
DNM1L	co_discussed	gene	0.40
DRP1	co_discussed	protein	0.40
EIF2AK3	co_discussed	gene	0.40
IRE1	co_discussed	protein	0.40
EIF2S1	co_discussed	gene	0.40
EMD	co_discussed	gene	0.40

Targeting Hypotheses (30)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
Beta-Hydroxybutyrate Receptor (HCAR2) Signaling Links Ketone	0.808	neurodegeneration	What are the precise temporal dynamics o
IL-6 Trans-Signaling Blockade at the Oligodendrocyte-Microgl	0.806	neuroinflammation	How do oligodendrocytes initiate neuroin
Hypothesis 1: MANF/CDNF Signaling as Primary Neuroprotective	0.798	neurodegeneration	View
Microglial-Mediated Tau Clearance Dysfunction via TREM2 Sign	0.792	neuroscience	Circuit-level neural dynamics in neurode
Therapeutic Window Exists Because Amplified Signals (Not Bas	0.780	neurodegeneration	Do pathogenic LRRK2 mutations amplify vo

Direct Toxicity Hypothesis: β-Amyloid Directly Impairs Choli	0.769	-	Do β-amyloid plaques and neurofibrillary
Astrocyte C3aR Signaling as Bifurcation Point for A1/A2 Fate	0.750	Alzheimer's disease, Parkinson's disease	-
Autophagic Receptor Sequestration via K63-Ub 'Signalone' Rec	0.720	neurodegeneration	How does TRIM21-mediated K63 ubiquitinat
TREM2-DAP12 Signalosome Enhancement — Boosting PI3K-AKT-mTOR	0.718	Alzheimer's disease	TREM2 agonism vs antagonism in DAM micro
Purinergic Signaling Polarization Control	0.713	neurodegeneration	Astrocyte reactivity subtypes in neurode
RAB29 Is the Critical Molecular Switch That Determines Wheth	0.710	neurodegeneration	Do pathogenic LRRK2 mutations amplify vo
TREM2-Dependent Switch Hypothesis: TREM2 Agonism Redirects S	0.708	synaptic biology	Does SPP1-mediated synaptic engulfment r
Calcium-Dependent S100B Release from Astrocyte End-Feet as a	0.700	-	What blood-brain barrier permeability ch
Astrocytic-Mediated Tau Clearance Dysfunction via TREM2 Sign	0.672	neuroscience	Circuit-level neural dynamics in neurode
Fyn-anchored dendritic tau/NMDAR signaling persists after tr	0.670	neurodegeneration	Does tau dendritic missorting persist in
Leaky Gut LPS Translocation Activates Systemic TLR4/MyD88 Si	0.670	neurodegeneration	How does gut microbiome dysbiosis contri
Dissociating SCFA's Dual Signaling Through GPR43/GPR41 Biase	0.670	neurodegeneration	Do SCFAs directly modulate α-synuclein a
Enhancing Vagal Cholinergic Signaling to Restore Gut-Brain A	0.669	neurodegeneration	What are the mechanisms by which gut mic
Chronic cGAS/STING Hyperactivation Drives Progressive Neurod	0.660	neuroinflammation	How does chronic cGAS/STING activation d
Age-Dependent TREM2 Signaling Disrupts Astrocyte-Microglia C	0.649	neurodegeneration	Gene expression changes in aging mouse b
S100B as Active Pathogenic BBB-Disrupting Signal via RAGE/NF	0.647	-	Blood-brain barrier permeability changes
Parthenolide reduces tonic ADORA2A signaling by lowering inf	0.640	neuropharmacology	How does parthenolide specifically modul
Layer V excitatory neurons show selectively enhanced vulnera	0.632	Alzheimer's disease	SEA-AD Single-Cell Analysis: Cell-Type V
C1q has spatially distinct functions, with synapse-bound C1q	0.630	neurodegeneration	Does C1q function differ based on subcel
APOE4-microglial complement signaling causes cholinergic-enr	0.630	neurodegeneration	What determines the temporal sequence of
ATF4-DDIT3 stress signaling indirectly represses MAPT transc	0.624	neurodegeneration	Which specific transcription factors med
Vagal Afferent Microbial Signal Modulation	0.621	neurodegeneration	What are the mechanisms by which gut mic
Retromer-dependent retrograde endosomal signaling compartmen	0.620	neuroscience	How can subcellular compartmentalization
PDGF-BB/PDGFRβ/STAT3 Paracrine Signaling Axis Mediates Aβ-In	0.618	neurodegeneration	How do perivascular cells specifically r
Blocking AGE-RAGE Signaling in Enteric Glia to Prevent Neuro	0.613	neurodegeneration	What are the mechanisms by which gut mic

Mentioning Analyses (0)

Scientific analyses that reference this entity

No analyses mention this entity

Experiments (6)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Feasibility	Model	Status	Est. Cost
iPSC-derived astrocyte-neuron co-culture mitochondrial transfer in PD	exploratory	Parkinson's disease	0.900	0.00	iPSC-derived dopaminergic neur	proposed	N/A
Single-cell RNA sequencing of microglial states in AD hippocampus	exploratory	Alzheimer's disease	0.850	0.00	AD mouse hippocampus	proposed	N/A
s:** - GPR32 knockout in microglia should worsen neuroinflammation if	falsification	Neuroinflammation	0.400	0.50	cell_line	proposed	$80,000
Proposed experiment from debate on Synaptic pruning by microglia in ea	falsification	Neuroinflammation	0.400	0.50	mouse	proposed	$240,000
Endocannabinoid System Dysfunction Validation in Parkinson's Disease	clinical	Parkinson's Disease	0.400	0.50	human	proposed	$6,550,000
Purinergic Signaling Dysfunction Validation in Parkinson's Disease	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 & PMID	Authors	Journal	Year	Citations
Oligodendrocytes drive neuroinflammation and neurodegeneration in Parkinson's di [PMID:39913287]	Ma Q, Tian JL, Lou Y, Guo R, Ma XR, Wu J	Cell Rep	2025	1
Purinergic signaling elements are correlated with coagulation players in periphe [PMID:35091759]	Schultz IC, Bertoni APS, Wink MR	J Mol Med (Berl)	2022	1
Purinergic Receptors in the Airways: Potential Therapeutic Targets for Asthma? [PMID:35386996]	Thompson RJ, Sayers I, Kuokkanen K, Hall	Front Allergy	2021	1
Variation in glucose homeostasis traits associated with P2RX7 polymorphisms in m [PMID:25719930]	Todd JN, Poon W, Lyssenko V, Groop L, Ni	J Clin Endocrinol Metab	2015	1
Targeting Microglial Phagocytosis for Alzheimer's Disease Management: Natural, P [PMID:40641018]	Raghuvanshi S, Mazumder A, Das S	CNS & neurological disorders d	2026	0
Enhancing TREM2 expression activates microglia and modestly mitigates tau pathol [PMID:40122810]	["Chen Kai", "Li Fuyao", "Zhang Shuwen",	Journal of neuroinflammation	2025	0
The APOE-Microglia Axis in Alzheimer's Disease: Functional Divergence and Therap [PMID:40722268]	Unknown	Brain sciences	2025	0
Enhancing TREM2 expression activates microglia and modestly mitigates tau pathol [PMID:40122810]	["Chen Kai", "Li Fuyao", "Zhang Shuwen",	Journal of neuroinflammation	2025	0
Axonal injury is a targetable driver of glioblastoma progression. [PMID:40836081]	Clements M, Tang W, Florjanic Baronik Z,	Nature	2025	0
Soluble CSF1R promotes microglial activation and amyloid clearance in alzheimer' [PMID:41152873]	Zhang L, Chen K, Zeng R	J Neuroinflammation	2025	0
CSF ATP levels correlate with Alzheimer's disease severity and predict progressi [PMID:synthetic_4]	Unknown	JAMA Neurol	2024	0
Delivery of CDNF by AAV-mediated gene transfer protects dopamine neurons and reg [PMID:39019902]	Nam J, Richie CT, Harvey BK	Sci Rep	2024	0
Astrocyte phenotype switching controlled by purinergic receptor balance regulate [PMID:synthetic_1]	Unknown	Nature Neuroscience	2023	0
α7nAChR activation in AT2 cells promotes alveolar regeneration through WNT7B sig [PMID:37410546]	Unknown	JCI Insight	2023	0
P2Y1 agonist enhances astrocyte-mediated neuroprotection via BDNF upregulation [PMID:synthetic_3]	Unknown	Glia	2023	0
Astrocyte phenotype heterogeneity may not fit simple A1/A2 binary classification [PMID:synthetic_8]	Unknown	Cell	2023	0
Untangling the Role of TREM2 in Conjugation with Microglia in Neuronal Dysfuncti [PMID:36683512]	Basha SC, Ramaiah MJ, Kosagisharaf JR	J Alzheimers Dis	2023	0
P2X7 antagonists failed to show efficacy in depression trials despite target eng [PMID:synthetic_6]	Unknown	Mol Psychiatry	2022	0
P2X7 antagonist reduces amyloid pathology and preserves cognition in APP/PS1 mic [PMID:synthetic_2]	Unknown	Neurobiol Dis	2022	0
JNJ-47965567 P2X7 antagonist shows CNS penetration and safety in Phase 2 trial [PMID:synthetic_5]	Unknown	Lancet Psychiatry	2021	0

Debates (0)

Multi-agent debates referencing this entity

No debates reference this entity

Related Research

Hypotheses and analyses mentioning GNAL in their description or question text

Direct Toxicity Hypothesis: β-Amyloid Directly Impairs Cholinergic Signaling

Score: 0.769 · unknown disease · 2026-04-12

## Mechanistic Overview Direct Toxicity Hypothesis: β-Amyloid Directly Impairs Cholinergic Signaling starts from the cla

Autophagic Receptor Sequestration via K63-Ub 'Signalone' Recognition

Score: 0.720 · neurodegeneration · 2026-04-21

**Molecular Mechanism and Rationale** The autophagic receptor sequestration mechanism centers on the dynamic regulation

TREM2-DAP12 Signalosome Enhancement — Boosting PI3K-AKT-mTOR Axis for Microglial

Score: 0.718 · Alzheimer's disease · 2026-04-04

## Mechanistic Overview TREM2-DAP12 Signalosome Enhancement — Boosting PI3K-AKT-mTOR Axis for Microglial Metabolic Fitne

Purinergic Signaling Polarization Control

Score: 0.713 · neurodegeneration · 2026-04-02

## Mechanistic Overview Purinergic Signaling Polarization Control starts from the claim that modulating P2RY1 and P2RX7

RAB29 Is the Critical Molecular Switch That Determines Whether LRRK2 Signal Ampl

Score: 0.710 · neurodegeneration · 2026-04-26

RAB29 functions as a gatekeeper—when lysosomes swell, RAB29-GTP increases, recruits LRRK2, and G2019S hyperphosphorylate

TREM2-Dependent Switch Hypothesis: TREM2 Agonism Redirects SPP1 Signaling from D

Score: 0.708 · synaptic biology · 2026-04-21

## Mechanistic Overview TREM2-Dependent Switch Hypothesis: TREM2 Agonism Redirects SPP1 Signaling from Destructive to Re

Calcium-Dependent S100B Release from Astrocyte End-Feet as an Early Signal of As

Score: 0.700 · unknown disease · 2026-04-26

S100B is released from astrocytes upon inflammatory activation or metabolic stress, causing pericyte dysfunction and end

Astrocytic-Mediated Tau Clearance Dysfunction via TREM2 Signaling

Score: 0.672 · neuroscience · 2026-04-12

## **Molecular Mechanism and Rationale** The astrocytic-mediated tau clearance dysfunction hypothesis centers on the pa

Fyn-anchored dendritic tau/NMDAR signaling persists after transient Aβ exposure

Score: 0.670 · neurodegeneration · 2026-04-25

Aβ drives tau into dendritic spines, where tau binds Fyn and stabilizes a PSD95-NMDAR-associated excitotoxic scaffold. O

Leaky Gut LPS Translocation Activates Systemic TLR4/MyD88 Signaling, Driving CNS

Score: 0.670 · neurodegeneration · 2026-04-26

Dysbiosis compromises intestinal tight junctions (occludin, claudin-1, ZO-1) and reduces α-defensin production, permitti

Dissociating SCFA's Dual Signaling Through GPR43/GPR41 Biased Agonism

Score: 0.670 · neurodegeneration · 2026-04-13

## Mechanistic Overview Dissociating SCFA's Dual Signaling Through GPR43/GPR41 Biased Agonism starts from the claim that

Enhancing Vagal Cholinergic Signaling to Restore Gut-Brain Anti-Inflammatory Com

Score: 0.669 · neurodegeneration · 2026-04-02

## Mechanistic Overview Enhancing Vagal Cholinergic Signaling to Restore Gut-Brain Anti-Inflammatory Communication start

Chronic cGAS/STING Hyperactivation Drives Progressive Neurodegeneration Through

Score: 0.660 · neuroinflammation · 2026-04-21

## Mechanistic Overview Chronic cGAS/STING Hyperactivation Drives Progressive Neurodegeneration Through Sustained Type I

Age-Dependent TREM2 Signaling Disrupts Astrocyte-Microglia Communication Leading

Score: 0.649 · neurodegeneration · 2026-04-17

**Molecular Mechanism and Rationale** The TREM2 (Triggering Receptor Expressed on Myeloid cells 2) signaling pathway re