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

10Experiments

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	inhibits	disease	0.65
Anxiety	contributes_to	disease	0.65
Als	associated_with	disease	0.65
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
VAMP7	expressed_in	gene	0.60
MMP9	expressed_in	gene	0.60
PI3K	inhibits	gene	0.60
DEPRESSION	contributes_to	gene	0.60
Actin	contributes_to	protein	0.60
IL8	inhibits	gene	0.60
Rb	inhibits	protein	0.60
TOR1A	associated_with	gene	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
JNK	co_discussed	protein	0.40
MAP1LC3B	co_discussed	gene	0.40
MFN1	co_discussed	gene	0.40
DYSF	co_discussed	gene	0.40
MUL1	co_discussed	gene	0.40
NLRP3	co_discussed	protein	0.40
FMR1	co_discussed	gene	0.40
PARL	co_discussed	protein	0.40
PEX3	co_discussed	gene	0.40
PINK1	co_discussed	gene	0.40
PTEN	co_discussed	gene	0.40
PRKN	co_discussed	gene	0.40
PARKIN	co_discussed	gene	0.40
RB1CC1	co_discussed	gene	0.40
FIP200	co_discussed	gene	0.40
RB1	co_discussed	protein	0.40
FAM134B	co_discussed	gene	0.40
RHOT1	co_discussed	gene	0.40
MIRO1	co_discussed	protein	0.40
RIPK3	co_discussed	gene	0.40
RTN3	co_discussed	gene	0.40
SESN2	co_discussed	gene	0.40
SNCA	co_discussed	gene	0.40
SNCAIP	co_discussed	gene	0.40
STING1	co_discussed	protein	0.40
FUNDC1	co_discussed	gene	0.40
HIF1A	co_discussed	protein	0.40

Incoming (68)

Source	Relation	Type	Str
ANXIETY	contributes_to	gene	0.60
CAMKII	inhibits	gene	0.60
CCND1	inhibits	gene	0.60
CYTOKINES	inhibits	gene	0.60
TNF	inhibits	gene	0.60
IL3	inhibits	gene	0.60
IL1B	inhibits	gene	0.60
GCH1	associated_with	gene	0.60
THAP1	associated_with	gene	0.60
ANO3	associated_with	gene	0.60
IRE1	co_discussed	protein	0.40
TRIM2	co_discussed	gene	0.40
STING	co_discussed	gene	0.40
ACTB	co_discussed	gene	0.40
BECN1	co_discussed	gene	0.40
C9ORF72	co_discussed	gene	0.40
SMCR8	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
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
PERK	co_discussed	protein	0.40
EIF2S1	co_discussed	gene	0.40
EMD	co_discussed	gene	0.40
EPAS1	co_discussed	gene	0.40
ERN1	co_discussed	gene	0.40
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

Targeting Hypotheses (30)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
IL-6 Trans-Signaling Blockade at the Oligodendrocyte-Microgl	0.831	neuroinflammation	How do oligodendrocytes initiate neuroin
Microglial-Mediated Tau Clearance Dysfunction via TREM2 Sign	0.827	neuroscience	Circuit-level neural dynamics in neurode
TREM2-Dependent Switch Hypothesis: TREM2 Agonism Redirects S	0.813	synaptic-biology	Does SPP1-mediated synaptic engulfment r
Beta-Hydroxybutyrate Receptor (HCAR2) Signaling Links Ketone	0.808	neurodegeneration	What are the precise temporal dynamics o
Hypothesis 1: MANF/CDNF Signaling as Primary Neuroprotective	0.798	neurodegeneration	Which specific factors in conditioned me

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	0.749	alzheimers-disease-parkinsons	-
Calcium-Dependent S100B Release from Astrocyte End-Feet as a	0.725	-	What blood-brain barrier permeability ch
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	alzheimers	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
Gamma entrainment enhances TREM2-mediated microglial clearan	0.678	alzheimers	Gamma entrainment therapy to restore hip
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	0.661	neuroinflammation	How does chronic cGAS/STING activation d
Parthenolide reduces tonic ADORA2A signaling by lowering inf	0.659	neuropharmacology	How does parthenolide specifically modul
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
Activity-Dependent Synaptic Tagging via CREB-BDNF-TrkB Signa	0.646	synaptic-biology	What determines the selectivity of compl
Retromer-dependent retrograde endosomal signaling compartmen	0.645	neuroscience	How can subcellular compartmentalization
Layer V excitatory neurons show selectively enhanced vulnera	0.632	alzheimers	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
VEGF-family genetic control of vascular-neuronal coupling in	0.626	neurodegeneration	VEGF Family GWAS Signals and Cerebrovasc
TBK1 Loss Triggers Astrocyte-to-Neuron Senescence Propagatio	0.000	als	What are the mechanisms by which microgl

Mentioning Analyses (0)

Scientific analyses that reference this entity

No analyses mention this entity

Experiments (10)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Model	Status	Est. Cost
PINK1 mutation carriers frequently report experiencing pain.	genetic_association	Parkinson's disease	0.500	human	extracted	N/A
Evidence regarding pain in DNAJC6 pathogenic variants is limited and i	genetic_association	Parkinson's disease	0.500	human	extracted	N/A
Identification of a vulnerable subtype of dopaminergic neurons co-expr	genetic_association	Parkinson's disease	0.500	mouse	extracted	N/A
Evidence regarding pain in SYNJ1 pathogenic variants is limited and in	genetic_association	Parkinson's disease	0.500	human	extracted	N/A
Anxa1+ DANs show selective earlier loss compared to other dopaminergic	neuropathology	Parkinson's disease	0.500	mouse	extracted	N/A
Released prosaposin (PSAP) was shown to induce interleukin-6 (IL-6) up	cell_biology	Parkinson's disease	0.500	cell_culture	extracted	N/A
Evidence regarding pain in FBXO7 pathogenic variants is limited and in	genetic_association	Parkinson's disease	0.500	human	extracted	N/A
Evidence regarding pain in ATP13A2 pathogenic variants is limited and	genetic_association	Parkinson's disease	0.500	human	extracted	N/A
Inhibition of transmitter release specifically in Anxa1+ neurons was s	animal_model	Parkinson's disease	0.500	mouse	extracted	N/A
Identified a subtype of Sox6+ Anxa1+ dopaminergic neurons that are sel	neuropathology	Parkinson's disease	0.500	mouse	extracted	N/A

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
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
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
α7nAChR activation in AT2 cells promotes alveolar regeneration through WNT7B sig [PMID:37410546]	Unknown	JCI Insight	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
CD38 in Neurodegeneration and Neuroinflammation. [PMID:32085567]	Guerreiro S, Privat AL, Bressac L, Toulo	Cells	2020	0
Neurodegeneration and Inflammation-An Interesting Interplay in Parkinson's Disea [PMID:33182554]	Marogianni C, Sokratous M, Dardiotis E,	International journal of molec	2020	0
CD38 in Neurodegeneration and Neuroinflammation. [PMID:32085567]	Guerreiro S, Privat AL, Bressac L, Toulo	Cells	2020	0
Neurodegeneration and Inflammation-An Interesting Interplay in Parkinson's Disea [PMID:33182554]	Marogianni C, Sokratous M, Dardiotis E,	International journal of molec	2020	0
Cholinergic Signaling via Muscarinic Receptors Directly and Indirectly Suppresse [PMID:30185628]	Unknown	Cancer discovery	2019	0
LC3-Associated Endocytosis Facilitates β-Amyloid Clearance and Mitigates Neurode [PMID:31257024]	["Heckmann Bradlee L", "Teubner Brett J	Cell	2019	0
Effects of Neurotrophic Factors in Glial Cells in the Central Nervous System: Ex [PMID:31105589]	Pöyhönen S, Er S, Domanskyi A, Airavaara	Frontiers in physiology	2019	0
Unconventional neurotrophic factors CDNF and MANF: Structure, physiological func [PMID:27425895]	Unknown	Neurobiology of disease	2018	0
Multiple Sclerosis Pathology. [PMID:29358320]	Lassmann H	Cold Spring Harbor perspective	2018	0
CHRNA7 Deletions are Enriched in Risperidone-Treated Children and Adolescents. [PMID:28817303]	Gillentine Madelyn A; White Janson J; Gr	Journal of child and adolescen	2017	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

Therapeutic Window Exists Because Amplified Signals (Not Baseline) Drive Pathoge

Score: 0.780 · neurodegeneration · 2026-04-26

G2019S basal RAB10 phosphorylation elevation may be secondary; true pathogenic driver is amplified stress-response signa

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

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

Score: 0.725 · unknown disease · 2026-04-26

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

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 · alzheimers · 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

Gamma entrainment enhances TREM2-mediated microglial clearance of Aβ plaques via

Score: 0.678 · alzheimers · 2026-04-28

40 Hz neural activity induces Ca2+ oscillations in microglia through P2X7 receptor activation, promoting TREM2 phosphory

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: 0.661 · neuroinflammation · 2026-04-21

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