gene

GLI

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about GLI: 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.

32Connections

30Hypotheses

0Analyses

20Outgoing

12Incoming

13Experiments

0Debates

Summary

GLI1, GLI2, GLI3 zinc finger transcription factors in Hedgehog signaling and neurodegenerative diseases

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🧬 Gene Info

Gene Symbol	GLI
Function	The GLI gene family (GLI1, GLI2, GLI3) encodes C2H2-type zinc finger transcription factors that serve as the primary effectors of the Hedgehog (Hh) signaling pathway.
Exons	12
GeneCards	GLI
Human Protein Atlas	GLI
Associated Diseases	ALS
Known Drugs/Compounds	metformin, rapamycin
Interactions	ATG, ATG7, BNIP3, BRD4, FKBP5, GAPDH
KG Connections	32 knowledge graph edges
Databases	GeneCards UniProt NCBI Gene HPA STRING

Wiki Pages (4)

Knowledge base pages for this entity

Pathway Diagram

graph TD
    GLI["GLI"] -->|"associated_with"| ALS["ALS"]
    GLI["GLI"] -->|"co_expressed_with"| GLI1["GLI1"]
    GLI["GLI"] -->|"co_expressed_with"| MYC["MYC"]
    BRD4["BRD4"] -->|"co_expressed_with"| GLI["GLI"]
    BECN1["BECN1"] -->|"co_expressed_with"| GLI["GLI"]
    BNIP3["BNIP3"] -->|"co_expressed_with"| GLI["GLI"]
    style GLI fill:#4a1a6b,stroke:#4fc3f7,stroke-width:2px,color:#e0e0e0

Outgoing (20)

Target	Relation	Type	Str
oxidative stress response	participates_in	pathway	0.60
TNF	activates	gene	0.60
autophagy pathway	participates_in	pathway	0.60
GLI1	activates	gene	0.60
ALS	associated_with	disease	0.60
GLI2	activates	gene	0.60
IL6	activates	gene	0.60
LAMP1	activates	gene	0.60
LC3B	activates	gene	0.60
MAP1LC3B	activates	gene	0.60
MTOR	activates	gene	0.60
PPARA	activates	gene	0.60
PS1	activates	gene	0.60
PSEN1	activates	gene	0.60
SQSTM1	activates	gene	0.60
SYP	activates	gene	0.60
TFEB	activates	gene	0.60
microglia	expressed_in	cell_type	0.55
MYC	co_expressed_with	gene	0.50
GLI1	co_expressed_with	gene	0.50

Incoming (12)

Source	Relation	Type	Str
BRD4	inhibits	gene	0.60
ATG	activates	gene	0.60
ATG7	activates	gene	0.60
BNIP3	activates	gene	0.60
FKBP5	activates	gene	0.60
GAPDH	activates	gene	0.60
GFAP	activates	gene	0.60
rapamycin	targets	drug	0.60
metformin	targets	drug	0.60
BECN1	co_expressed_with	gene	0.50
BNIP3	co_expressed_with	gene	0.50
BRD4	co_expressed_with	gene	0.50

Targeting Hypotheses (30)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
Microglial-Mediated Tau Clearance Dysfunction via TREM2 Rece	0.937	neuroscience	Circuit-level neural dynamics in neurode
SIRT1-Mediated Reversal of TREM2-Dependent Microglial Senesc	0.893	neurodegeneration	Gene expression changes in aging mouse b
TREM2-Mediated Astrocyte-Microglia Crosstalk in Neurodegener	0.892	neurodegeneration	Gene expression changes in aging mouse b
ACSL4-Driven Ferroptotic Priming in Disease-Associated Micro	0.891	alzheimers	Cell type vulnerability in Alzheimers Di
Optimized Temporal Window for Metabolic Boosting Therapy Det	0.887	neurodegeneration	How do different microglial subtypes (DA

TBK1 Loss Locks Microglia in an Aged/Senescent Transcription	0.878	als	What are the mechanisms by which microgl
TREM2-Mediated Microglial Dysfunction Disrupts Perivascular	0.861	neuroscience	TREM2 in Alzheimer's Disease: Mechanisms
Prime Editing Precision Correction of APOE4 to APOE3 in Micr	0.850	neurodegeneration	CRISPR-based therapeutic approaches for
TREM2-Deficient Microglia as Drivers of Amyloid Plaque Toxic	0.847	neurodegeneration	Legacy Pre-Pipeline Hypothesis Import
miR-155/Interferon-gamma Feedback Loop as a Reversible Molec	0.843	neurodegeneration	How do different microglial subtypes (DA
Microglial Senescence Prevention via TREM2/SASP Axis	0.837	neurodegeneration	Does the cancer-cystatin-C-TREM2 pathway
TREM2 Deficiency Drives Microglial Senescence via Lipid Meta	0.836	neurodegeneration	What molecular mechanisms drive microgli
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
Microglial AIM2 Inflammasome as the Primary Driver of TDP-43	0.824	neurodegeneration	What are the mechanisms by which gut mic
CSF1R-TREM2 Co-Agonism for Sustained Microglial Expansion	0.808	neurodegeneration	TREM2 agonism vs antagonism in DAM micro
Targeted Butyrate Supplementation for Microglial Phenotype M	0.805	neurodegeneration	What are the mechanisms by which gut mic
TREM2-APOE microglial state switching across AD, ALS, and PD	0.804	multi	Cross-disease neurodegeneration mechanis
40 Hz Gamma Entrainment Gates ACSL4-Mediated Ferroptotic Pri	0.801	alzheimers	Cell type vulnerability in Alzheimers Di
Microglial TREM2-SYK Pathway Enhancement	0.798	neurodegeneration	Cell type vulnerability in Alzheimers Di
Senescent Microglia Resolution via Maresins-Senolytics Combi	0.791	neurodegeneration	Neuroinflammation resolution mechanisms
TREM2-mediated microglial tau clearance enhancement	0.780	neurodegeneration	Tau propagation mechanisms and therapeut
LPCAT3-Mediated Lands Cycle Remodeling as the Primary Ferrop	0.777	alzheimers	Cell type vulnerability in Alzheimers Di
LPCAT3-Mediated Lands Cycle Amplification of Ferroptotic Sub	0.776	alzheimers	Cell type vulnerability in Alzheimers Di
Enhancing Microglial Phagocytosis of Extracellular Tau via T	0.771	neuroscience	Trans-synaptic tau spreading and propaga
AAV-PHP.eB-Mediated Microglial IGFBPL1 Expression	0.768	drug-delivery	Can IGFBPL1 therapeutics effectively cro
LPCAT3-Mediated Lands Cycle Amplification of Ferroptotic Vul	0.764	alzheimers	Cell type vulnerability in Alzheimers Di
GluN2B-CX3CL1 Axis Controls Microglial Tau Phagocytosis	0.761	neuroscience	GluN2B-Mediated Thalamocortical Control
Cell-Type Specific TREM2 Upregulation in DAM Microglia	0.761	alzheimers	SEA-AD Gene Expression Profiling — Allen
TBK1 Loss Triggers eIF2α-Mediated Translational Repression T	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 (13)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Feasibility	Model	Status	Est. Cost
SAHA@LIPO-ANG2 therapeutic efficacy in 5xFAD mice	validation	Alzheimer's disease	0.900	0.00	5xFAD transgenic mice	proposed	N/A
Transcriptomic profiling and differential expression analysis	exploratory	Alzheimer's disease	0.900	0.00	1-month-old APP/PS1 mice cereb	proposed	N/A
Anti-miR-155 LNA Oligonucleotide Shifts Microglia to Homeostatic State	in_vivo	neurodegeneration	0.774	0.65	C57BL/6J LPS model (chronic i.	proposed	$58,000
Single nuclei transcriptomic and epigenomic profiling of 84 donors acr	gene_expression	Alzheimer's disease	0.500	0.00	human	extracted	N/A
The Seattle Alzheimer's Disease Brain Cell Atlas (SEA-AD) integrates n	neuropathology	Alzheimer's disease	0.500	0.00	human	extracted	N/A
In late life, NfL demonstrated the strongest association with incident	clinical	Alzheimer's disease	0.500	0.00	human	extracted	N/A
Complex gene expression differences were identified, ranging from glob	gene_expression	Alzheimer's disease	0.500	0.00	post_mortem_brain	extracted	N/A
A subset of donors with particularly severe cellular and molecular phe	clinical	Alzheimer's disease	0.500	0.00	human	extracted	N/A
Midlife hypertension was associated with 0.15-SD faster NfL increase a	clinical	Alzheimer's disease	0.500	0.00	human	extracted	N/A
A subset of donors exhibited particularly severe cellular and molecula	computational	Alzheimer's disease	0.500	0.00	human	extracted	N/A
Cell type-specific analysis identified early-phase loss of somatostati	gene_expression	Alzheimer's disease	0.500	0.00	human	extracted	N/A
Single-cell/multiomics analysis of 84 human post-mortem brains reveale	computational	Alzheimer's disease	0.500	0.00	human	extracted	N/A
Temporal analysis of gene expression differences across disease progre	gene_expression	Alzheimer's disease	0.500	0.00	human	extracted	N/A

Related Papers (20)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year	Citations
Transcriptomic cytoarchitecture reveals principles of human neocortex organizati [PMID:37824655]	Jorstad NL, Close J, Johansen N, Yanny A	Science	2023	186
Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and TREM2- [PMID:31932797]	Zhou Y, Song WM, Andhey PS, Swain A, Lev	Nat Med	2020	1
Modulating LRP1 Pathways in Alzheimer's Disease: Mechanistic Insights and Emergi [PMID:41772271]	Mushtaq T, Hameed H, Khan MA, Tariq U, H	Molecular neurobiology	2026	0
FAK/SRC-JNK axis promotes ferroptosis via upregulating ACSL4 expression. [PMID:41862445]	Qin J, Ma S, Wang J, Huang S, Luan J, He	Cell death & disease	2026	0
Quercetin attenuates ox-LDL-induced endothelial injury by regulating ferroptosis [PMID:41902795]	Gao C, Liu B, Zhang R, Tian J, Xin H	Toxicology mechanisms and meth	2026	0
Changes in Circulating Levels of miR-30b During Minipuberty and Puberty in Girls [PMID:40899010]	Albrechtsen HM, Saritas G, Winge SB, Mai	J Clin Endocrinol Metab	2026	0
Macrophagic Sclerostin Loop2-ApoER2 Interaction Required by Sclerostin for Cardi [PMID:41276911]	Wang L, Tao X, Zhang N, Yang X, Jiang H	Adv Sci (Weinh)	2026	0
APOE Genotype Modulates the Relationship of Stroke With Dementia Risk: Associati [PMID:41404739]	Zhang CH, Huang LY, Feng YG, Tan CC, Tan	J Am Heart Assoc	2026	0
High- and Low-Fat Dairy Consumption and Long-Term Risk of Dementia: Evidence Fro [PMID:41406402]	Du Y, Borné Y, Samuelsson J, Glans I, Hu	Neurology	2026	0
Epigenetics in chronic rhinosinusitis. [PMID:41442742]	Kumar N, Brar T, Lal D	Curr Opin Otolaryngol Head Nec	2026	0
Prime Editing of Alzheimer's Disease High-Risk APOE4 Allele by Brain-Directed Ad [PMID:41449667]	Günaydin C, Hackett NR, Wakim V, Sondhi	Hum Gene Ther	2026	0
The role of astrocytes in Alzheimer's disease: Pathophysiology, biomarkers, and [PMID:41527736]	Abedin MJ, Kastanenka KV	J Alzheimers Dis	2026	0
NEDD8 promotes the ferritinophagy and ferroptosis of neurons in ischemic stroke [PMID:41662890]	Rao W, Huang Y, Li J, Chen Q, Sun J et a	J Stroke Cerebrovasc Dis	2026	0
Endothelial TBK1 Deficiency Inhibits Endothelial-to-Mesenchymal Transition and A [PMID:41685426]	Pu Y, Dong P, He L, Huang J, Wu Y et al.	Circ Res	2026	0
Lipidome and proteome of astrocyte and microglia ApoE lipoprotein reveal differe [PMID:41692246]	Strickland MR, Wang Z, Golden LR, Wang H	J Lipid Res	2026	0
Protective mutations associated with APOE in Alzheimer's disease. [PMID:41703264]	Ma Y, Li Y, Wu G, Liu L, Tian M et al.	Mol Psychiatry	2026	0
Inhibition of Ferroptosis in Prostatitis Model by Low Intensity Extracorporeal S [PMID:41714892]	Lin D, Li K, Kuang W, Chen Z, Zhang M	World J Mens Health	2026	0
Deciphering sorafenib resistance in hepatocellular carcinoma via ferroptotic mec [PMID:41763496]	Che L, Zhu L, Zhou L, Zhou Y	Biochim Biophys Acta Rev Cance	2026	0
Extracellular vesicles in type 2 diabetes exhibit elevated miR-155 cargo and Ann [PMID:41786286]	Jackson G, Islam H, de Souza Teixeira AA	Life Sci	2026	0
B4GALT1 deficiency attenuates steatohepatitis by regulating the PPARγ/ACSL4 axis [PMID:41860570]	Chien Y, Xia R, Zhou D, Ai Y, Wu L et al	Hepatol Commun	2026	0

Debates (0)

Multi-agent debates referencing this entity

No debates reference this entity

Related Research

Hypotheses and analyses mentioning GLI in their description or question text

TBK1 Loss Locks Microglia in an Aged/Senescent Transcriptional State, Fueling AL

Score: 0.878 · als · 2026-04-26

The hypothesis proposes that loss-of-function mutations in TBK1 contribute to ALS pathogenesis by trapping microglia in

TREM2-Mediated Microglial Dysfunction Disrupts Perivascular Tau Clearance

Score: 0.861 · neuroscience · 2026-04-12

## Mechanistic Overview TREM2-Mediated Microglial Dysfunction Disrupts Perivascular Tau Clearance starts from the claim

Prime Editing Precision Correction of APOE4 to APOE3 in Microglia

Score: 0.850 · neurodegeneration · 2026-04-04

## Mechanistic Overview Prime Editing Precision Correction of APOE4 to APOE3 in Microglia starts from the claim that mod

TREM2-Deficient Microglia as Drivers of Amyloid Plaque Toxicity in Alzheimer's D

Score: 0.847 · neurodegeneration · 2026-04-26

TREM2 loss-of-function variants impair microglial survival, clustering around amyloid plaques, and phagocytic clearance,

miR-155/Interferon-gamma Feedback Loop as a Reversible Molecular Switch for Prot

Score: 0.843 · neurodegeneration · 2026-04-16

## Mechanistic Overview miR-155/Interferon-gamma Feedback Loop as a Reversible Molecular Switch for Protective Microglia

Microglial Senescence Prevention via TREM2/SASP Axis

Score: 0.837 · neurodegeneration · 2026-04-17

## Mechanistic Overview Microglial Senescence Prevention via TREM2/SASP Axis starts from the claim that modulating not y

TREM2 Deficiency Drives Microglial Senescence via Lipid Metabolism Dysregulation

Score: 0.836 · neurodegeneration · 2026-04-22

## Mechanistic Overview TREM2 Deficiency Drives Microglial Senescence via Lipid Metabolism Dysregulation starts from the

IL-6 Trans-Signaling Blockade at the Oligodendrocyte-Microglia Interface

Score: 0.831 · neuroinflammation · 2026-04-13

## Mechanistic Overview IL-6 Trans-Signaling Blockade at the Oligodendrocyte-Microglia Interface starts from the claim t

Microglial-Mediated Tau Clearance Dysfunction via TREM2 Signaling

Score: 0.827 · neuroscience · 2026-04-07

## Mechanistic Overview Microglial-Mediated Tau Clearance Dysfunction via TREM2 Signaling starts from the claim that mod

Microglial AIM2 Inflammasome as the Primary Driver of TDP-43 Proteinopathy Neuro

Score: 0.824 · neurodegeneration · 2026-04-05

## Mechanistic Overview Microglial AIM2 Inflammasome as the Primary Driver of TDP-43 Proteinopathy Neuroinflammation in

CSF1R-TREM2 Co-Agonism for Sustained Microglial Expansion

Score: 0.808 · neurodegeneration · 2026-04-16

## Mechanistic Overview CSF1R-TREM2 Co-Agonism for Sustained Microglial Expansion starts from the claim that modulating

Targeted Butyrate Supplementation for Microglial Phenotype Modulation

Score: 0.805 · neurodegeneration · 2026-04-02

## Mechanistic Overview Targeted Butyrate Supplementation for Microglial Phenotype Modulation starts from the claim that

TREM2-APOE microglial state switching across AD, ALS, and PD

Score: 0.804 · multi · 2026-04-28

Shared mechanism across AD, ALS, PD: TREM2-APOE signaling shifts microglia into a disease-associated state that can clea

40 Hz Gamma Entrainment Gates ACSL4-Mediated Ferroptotic Priming to Selectively

Score: 0.801 · alzheimers · 2026-04-05

## Mechanistic Overview 40 Hz Gamma Entrainment Gates ACSL4-Mediated Ferroptotic Priming to Selectively Eliminate Diseas

Microglial TREM2-SYK Pathway Enhancement

Score: 0.798 · neurodegeneration · 2026-04-13

## Mechanistic Overview Microglial TREM2-SYK Pathway Enhancement starts from the claim that modulating TREM2 within the

GLI