gene

TGM2

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about TGM2: 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.

809Connections

2Hypotheses

2Analyses

50Outgoing

50Incoming

10Experiments

4Debates

Summary

Transglutaminase 2 (TGM2) is a calcium-dependent enzyme that catalyzes protein cross-linking, implicated in neurodegenerative diseases including Alzheimer's, Parkinson's, and Huntington's disease through promotion of protein aggregation.

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🧬 Gene Info

Gene Symbol	TGM2
Full Name	Transglutaminase 2
Protein Type	Enzyme
Target Class	Enzyme
Function	Small molecule inhibitors of transglutaminase enzymatic activity
Mechanism of Action	Small molecule inhibitors of transglutaminase enzymatic activity
Primary Expression	various tissues, including the central nervous system, where it is particularly abundant in neurons and glial cells
Druggability	Medium (0.49)
Clinical Stage	Phase II
Molecular Weight	77 kDa
Amino Acids	687 aa
Pathways	Autophagy, G Protein Signaling, Histone Modification, neuronal differentiation
UniProt ID	A2A2A0
Ensembl ID	ENSG00000198959
GeneCards	TGM2
Human Protein Atlas	TGM2
Associated Diseases	Aging, Als, Alzheimer, Alzheimer's disease
Known Drugs/Compounds	Cystamine Dihydrochloride, organophosphates, Urolithin A
Interactions	ACE2, Actin, Adiponectin, ADIPOQ, AGING, ALS
SciDEX Target	View Target Profile (5 clinical trials)
SciDEX Hypotheses	Transglutaminase-2 Cross-Linking Inhibition Strate Low Complexity Domain Cross-Linking Inhibition
KG Connections	807 knowledge graph edges
Databases	GeneCards NCBI Gene HPA STRING

🧬 3D Structure Comparison — TGM2 Experimental (PDB) vs Predicted (AlphaFold) — click to expand

📄 Experimental Structure

1KV3 — X-ray / Cryo-EM

🔮 AI Predicted Structure

A2A2A0 — 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

TGM2 — Transglutaminase 2

gene · 2103 words

→

TGM2 Protein

protein · 603 words

→

Pathway Diagram

flowchart TD
    TGM2["TGM2<br/>(Transglutaminase 2)"]
    
    %% Protective mechanisms
    TGM2 -->|"inhibits"| Inflammation["Inflammation"]
    TGM2 -->|"inhibits"| Neuroinflammation["Neuroinflammation"]
    TGM2 -->|"inhibits"| Senescence["Cellular<br/>Senescence"]
    TGM2 -->|"inhibits"| Aging["Aging<br/>Process"]
    
    %% Neurodegenerative diseases
    TGM2 -->|"regulates"| Neurodegeneration["Neurodegeneration"]
    TGM2 -->|"inhibits"| Alzheimer["Alzheimer's<br/>Disease"]
    TGM2 -->|"associated_with"| Dementia["Dementia"]
    TGM2 -->|"associated_with"| ALS["ALS"]
    TGM2 -->|"regulates"| MS["Multiple<br/>Sclerosis"]
    
    %% Psychiatric conditions
    TGM2 -->|"associated_with"| Schizophrenia["Schizophrenia"]
    TGM2 -->|"associated_with"| Depression["Depression"]
    TGM2 -->|"associated_with"| Anxiety["Anxiety"]
    TGM2 -->|"associated_with"| Autism["Autism"]
    
    %% Cancer pathways
    TGM2 -->|"regulates"| Cancer["Cancer"]
    TGM2 -->|"biomarker_for"| Glioblastoma["Glioblastoma<br/>Multiforme"]
    TGM2 -->|"promotes"| Radioresistance["Radioresistance"]
    
    %% Therapeutic implications
    Radioresistance -->|"reduces_efficacy"| Radiotherapy["Radiotherapy<br/>Treatment"]
    
    style TGM2 fill:#006494
    style Inflammation fill:#ef5350
    style Neuroinflammation fill:#ef5350
    style Senescence fill:#ef5350
    style Aging fill:#ef5350
    style Neurodegeneration fill:#ef5350
    style Alzheimer fill:#ef5350
    style Dementia fill:#ef5350
    style ALS fill:#ef5350
    style MS fill:#ef5350
    style Schizophrenia fill:#5d4400
    style Depression fill:#5d4400
    style Anxiety fill:#5d4400
    style Autism fill:#5d4400
    style Cancer fill:#ef5350
    style Glioblastoma fill:#ef5350
    style Radioresistance fill:#ef5350
    style Radiotherapy fill:#1b5e20

Outgoing (474)

Target	Relation	Type	Str
LC3	binds_to	entity	0.95
Autophagosome-Lysosome Fusion	regulates	process	0.95
Alternative Splicing	associated_with	process	0.95
MICROGLIA	expressed_in	entity	0.95
NFKB	activates	entity	0.95
H3Q5ser	modulates	phenotype	0.95
SEROTONYLATION	mediates	entity	0.95
hepatocellular carcinoma	promotes	disease	0.92
Radioresistance	contributes_to	phenotype	0.92
TRANSGLUTAMINASE CROSSLINKING	catalyzes	enzyme	0.90
Er-Mitochondria Contacts	modulates	process	0.90
LC3	binds	protein	0.90
POSTTRANSLATIONAL MODIFICATION	mediates	entity	0.90
MAP1LC3	binds	gene	0.90
IκBα	covalent_cross-linking	protein	0.90
Radiosensitivity	regulates	phenotype	0.90
Kinase Activity	mediates	mechanism	0.90
Transglutaminase Crosslinking	mediates	mechanism	0.90
ER-Mitochondria Contacts	regulates	process	0.90
IκBα	associated_with	protein	0.90
NFKB1	drives	protein	0.90
Senescent Microglia	upregulates	cell_type	0.90
THERAPEUTIC_TARGET	therapeutic_target	entity	0.90
NEUROINFLAMMATION	regulates	entity	0.90
MYC	interacts_with	gene	0.88
therapeutic_target	associated_with	pathway	0.85
SASP	drives	process	0.85
ALZHEIMER'S DISEASE	associated_with	entity	0.85
hepatocellular carcinoma	biomarker_for	disease	0.85
KINASE ACTIVITY	catalyzes	enzyme	0.85
G Protein Signaling	involved_in	pathway	0.85
radioresistance	promotes	phenotype	0.85
Senescence-Associated Secretory Phenotype	therapeutic_target	phenotype	0.80
NEURODEGENERATION	implicated_in	entity	0.80
oxidative stress response	participates_in	pathway	0.80
unfolded protein response	participates_in	pathway	0.80
IκBα	catalyzes_covalent_cross-linking_of	protein	0.80
inflammation	associated_with	biological_process	0.80
SASP	upregulates	process	0.80
protein_crosslinking_pathway	catalyzes	pathway	0.80
neurodegeneration	associated_with	disease	0.75
phagocytic capacity	downregulates	phenotype	0.75
Inflammation	associated_with	process	0.75
Cancer	associated_with	disease	0.75
Wound Healing	associated_with	process	0.75
radioresistance	associated_with	process	0.70
glioblastoma multiforme	biomarker_for	disease	0.70
radiotherapy	regulates	process	0.70
radioresistance	activates	process	0.70
glioblastoma multiforme	associated_with	disease	0.70

Incoming (335)

Source	Relation	Type	Str
SDC1	interacts_with	protein	0.95
h-d4f71a6b	targets_gene	hypothesis	0.90
Alternative Splicing	regulates	biological_process	0.90
h-69d383ea	targets_gene	hypothesis	0.90
alternative splicing	modulates	process	0.90
Cystamine Dihydrochloride	inhibits	drug	0.85
Urolithin A	modulates	compound	0.85
h-69d383ea	targets	hypothesis	0.80
C-terminal truncated TGM2	interacts_with	protein	0.80
SDC1	binds	gene	0.80
GAPDH	interacts_with	gene	0.80
SDC1	transported_by	gene	0.70
EPG5	mediates	entity	0.60
SDC1	mediates	entity	0.60
SDC1	expressed_in	entity	0.60
GBM	activates	entity	0.60
SDC1	activates	entity	0.60
EPG5	interacts_with	entity	0.60
LC3	interacts_with	entity	0.60
SNAP29	interacts_with	entity	0.60
STX17	interacts_with	entity	0.60
GBM	inhibits	entity	0.60
EPG5	therapeutic_target	entity	0.60
GBM	therapeutic_target	entity	0.60
SDC1	therapeutic_target	entity	0.60
EPG5	regulates	entity	0.60
GBM	regulates	entity	0.60
PROGRANULIN	biomarker_for	gene	0.60
LC3	regulates	entity	0.60
P62	regulates	entity	0.60
SDC1	regulates	entity	0.60
SNAP29	regulates	entity	0.60
SQSTM1	regulates	entity	0.60
STX17	regulates	entity	0.60
LAMP2	regulates	entity	0.60
HMGB1	activates	gene	0.60
ALZHEIMER	inhibits	gene	0.60
AGING	inhibits	gene	0.60
ALZHEIMER	associated_with	gene	0.60
AGING	associated_with	gene	0.60
DEMENTIA	associated_with	gene	0.60
AND	expressed_in	gene	0.60
RNA	regulates	gene	0.60
ANXIETY	activates	gene	0.60
GENES	regulates	gene	0.60
SYNAPTIC PRUNING	activates	gene	0.60
MAP1LC3	regulates	gene	0.60
MAP1LC3	interacts_with	gene	0.60
SNARE	interacts_with	gene	0.60
NR1D2	expressed_in	gene	0.60

Targeting Hypotheses (2)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
Transglutaminase-2 Cross-Linking Inhibition Strategy	0.701	neurodegeneration	Protein aggregation cross-seeding across
Low Complexity Domain Cross-Linking Inhibition	0.617	neurodegeneration	TDP-43 phase separation therapeutics for

Mentioning Analyses (2)

Scientific analyses that reference this entity

TDP-43 phase separation therapeutics for ALS-FTD

neurodegeneration | 2026-04-01 | 7 hypotheses Top: 0.738

Protein aggregation cross-seeding across neurodegenerative diseases

neurodegeneration | 2026-04-01 | 7 hypotheses Top: 0.701

Experiments (10)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Feasibility	Model	Status	Est. Cost
Proposed experiment from debate on TDP-43 undergoes liquid-liquid phas	falsification	Neurodegeneration	0.400	0.50	cell_line	proposed	$80,000
s:** - Dose-response studies showing therapeutic window without toxici	falsification	Neurodegeneration	0.400	0.50	cell_line	proposed	$80,000
Alpha-Synuclein Spreading Mechanism — Prion-Like Propagation and Neuro	exploratory	Parkinson's Disease	0.400	0.50	human	proposed	$2,070,000
Mechanism: C9orf72 Hexanucleotide Repeat Expansion in ALS/FTD	validation	ALS	0.400	0.50	human	proposed	$2,730,000
C9orf72 Phenotype Divergence: ALS vs FTD Mechanism Study	clinical	ALS	0.400	0.50	human	proposed	$6,550,000
Multiscale Computational Modeling of Protein Aggregation Kinetics	validation	Parkinson's Disease	0.400	0.50	human	proposed	$2,280,000
Prion Strain Diversity and Selective Vulnerability in CJD	clinical	Neurodegeneration	0.400	0.50	human	proposed	$5,460,000
Prion Strain Diversity and Selective Vulnerability	clinical	Alzheimer's Disease	0.400	0.50	mouse	proposed	$400,000
Proteasome-Ubiquitin System Dysfunction Validation in Parkinson's Dise	clinical	Parkinson's Disease	0.400	0.50	human	proposed	$6,550,000
Protein Aggregation Kinetic Validation Results	validation	Neurodegeneration	0.400	0.50	in_silico	proposed	$120,000

Related Papers (20)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year	Citations
Tgm2-Catalyzed Covalent Cross-Linking of IκBα Drives NF-κB Nuclear Translocation [PMID:39749582]	Li Z, Wang T, Du S, Miao Z, Zhao Y, Tang	Aging Cell	2025	1
Role of Serotonylation and SERT Posttranslational Modifications in Alzheimer's D [PMID:39254383]	Reddy AP, Rawat P, Rohr N, Alvir R, Bish	Aging Dis	2024	1
SDC1-dependent TGM2 determines radiosensitivity in glioblastoma by coordinating [PMID:35913916]	Zheng W, Chen Q, Liu H, Zeng L, Zhou Y,	Autophagy	2023	1
How autophagy controls the intestinal epithelial barrier. [PMID:33906557]	Foerster EG, Mukherjee T, Cabral-Fernand	Autophagy	2022	1
TGM2 and implications for human disease: role of alternative splicing. [PMID:23276939]	Lai TS, Greenberg CS	Front Biosci (Landmark Ed)	2013	1
Transglutaminase 2 modulates inflammatory angiogenesis via vascular endothelial [PMID:40619121]	Zhou G, Zhang M, Zheng S, Yang G, Li L e	J Adv Res	2026	0
Combining bulk and scRNA-seq to explore the molecular mechanisms governing the d [PMID:38501838]	Zhu S, Cheng Q, Zou M, Li C, Tang Y, Xia	Journal of cellular and molecu	2024	0
The Search for a Universal Treatment for Defined and Mixed Pathology Neurodegene [PMID:39769187]	O'Day DH	International journal of molec	2024	0
Allosteric Activation of Transglutaminase 2 via Inducing an "Open" Conformation [PMID:37088726]	Yang Z, Zhang XW, Zhuo FF, Liu TT, Luo Q	Advanced science (Weinheim, Ba	2023	0
[WALANT - Wide Awake Local Anaesthesia No Tourniquet: Complications in elective [PMID:35168268]	Wieschollek S, Forster S, Megerle K	Handchirurgie, Mikrochirurgie,	2022	0
Calmodulin Binding Domains in Critical Risk Proteins Involved in Neurodegenerati [PMID:36421678]	["O'Day D"]	Current issues in molecular bi	2022	0
Urolithin A suppresses high glucose-induced neuronal amyloidogenesis by modulati [PMID:32704090]	Lee HJ, Jung YH, Choi GE	Cell Death Differ	2021	0
Engineering complex communities by directed evolution. [PMID:33986540]	Chang CY, Vila JCC, Bender M, Li R, Mank	Nature ecology & evolution	2021	0
Successful Nonoperative Treatment of Osteochondritis Dissecans of the Humeral Ca [PMID:34825100]	Tajika T, Kuboi T, Endo F, Hatori Y, Sai	Progress in rehabilitation med	2021	0
A Consensus-Developed Morphological Re-Evaluation of 196 High-Grade Gastroentero [PMID:33002892]	["Elvebakken H", "Perren A", "Scoazec J"	Neuroendocrinology	2021	0
Development of Ligand-Drug Conjugates Targeting Melanoma through the Overexpress [PMID:33073191]	["Zhou Y", "Mowlazadeh Haghighi S", "Liu	ACS pharmacology & translation	2020	0
Dietary Gluten and Neurodegeneration: A Case for Preclinical Studies. [PMID:32751379]	Mohan M, Okeoma CM, Sestak K	International journal of molec	2020	0
Trainee doctor is suspended for 12 months for faking signatures over competencie [PMID:30389657]	["Clare Dyer"]	BMJ (Clinical research ed.)	2019	0
An in vitro model maintaining taxon-specific functional activities of the gut mi [PMID:31515476]	["Li L", "Abou-Samra E", "Ning Z", "Zhan	Nature communications	2019	0
Human and mouse albumin bind their respective neonatal Fc receptors differently. [PMID:30279529]	["Nilsen J", "Bern M", "Sand K", "Grevys	Scientific reports	2018	0

Debates (4)

Multi-agent debates referencing this entity

TGM2

Understanding Entity Pages

Summary

Wiki Pages (2)

TGM2 — Transglutaminase 2

TGM2 Protein

Pathway Diagram

Outgoing (474)

Incoming (335)

Targeting Hypotheses (2)

Mentioning Analyses (2)

TDP-43 phase separation therapeutics for ALS-FTD

Protein aggregation cross-seeding across neurodegenerative diseases

Experiments (10)

Related Papers (20)

Debates (4)

Protein aggregation cross-seeding across neurodegenerative diseases?

TDP-43 undergoes liquid-liquid phase separation that becomes pathological. Small

TDP-43 phase separation therapeutics for ALS-FTD

Analysis question not specified