gene

SETX

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about SETX: 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.

396Connections

1Hypotheses

1Analyses

50Outgoing

50Incoming

10Experiments

2Debates

Summary

SETX is a gene implicated in neurodegeneration research. Key relationships include: associated with, activates, inhibits. Associated with ALS, Als, Als4. Connected to 128 entities in the SciDEX knowledge graph.

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🧬 Gene Info

Gene Symbol	SETX
Full Name	Senataxin
Aliases	SETX gene
Chromosome	9q34.13
Protein Type	Enzyme
Target Class	Enzyme
Function	The SETX gene encodes a protein belonging to the superfamily 1 helicases with both ATP-dependent DNA and RNA helicase activity[@suraweera2009].
Mechanism of Action	Therapeutic agents targeting SETX would likely enhance RNA helicase activity or stabilize protein function to improve transcriptional regulation and DNA repair, or alternatively inhibit aberrant signaling pathways triggered by SETX dysfunction in neuronal tissues. Small molecule stabilizers or gene therapy approaches could restore deficient helicase activity in ataxia-causing mutations.
Primary Expression	Brain, Spinal cord, Testis, Liver
Druggability	Low (0.28)
Clinical Stage	Approved
Molecular Weight	303 kDa
Amino Acids	2678 aa
Pathways	Autophagy, Dna Damage Response, Haploinsufficiency, Rna/Dna Helicase Activity
UniProt ID	Q9UH73
NCBI Gene ID	23067
Ensembl ID	ENSG00000112297
OMIM	604465
GeneCards	SETX
Human Protein Atlas	SETX
Associated Diseases	Als, Als4, Amyotrophic Lateral Sclerosis, Amyotrophic Lateral Sclerosis 4
Known Drugs/Compounds	Dna, rapamycin, R-loop, Rna, siRNA, Sirna
Interactions	ALS, ALS4, amyotrophic lateral sclerosis, AMYOTROPHIC LATERAL SCLEROSIS, AND, App
SciDEX Target	View Target Profile (2 clinical trials)
SciDEX Hypotheses	R-Loop Resolution Enhancement Therapy
KG Connections	396 knowledge graph edges
Databases	GeneCards HPA STRING

🔮 Predicted Structure: SETX — AlphaFold Q9UH73 Click to expand

AI-predicted structure from AlphaFold | Powered by Mol*

Wiki Pages (2)

Knowledge base pages for this entity

Canonical Page

SETX Gene

gene · 984 words

→

SETX Protein

protein · 780 words

→

Pathway Diagram

graph TD
    SETX["SETX"]
    SETX -->|"activates"| Cancer["Cancer"]
    SETX -->|"activates"| Als["Als"]
    SETX -->|"expressed in"| Ms["Ms"]
    SETX -->|"inhibits"| Amyotrophic_Lateral_Sclerosis["Amyotrophic Lateral Sclerosis"]
    SETX -->|"target for"| Stroke["Stroke"]
    SETX -->|"activates"| ALS["ALS"]
    h_c463d225["h-c463d225"] -->|"target for"| SETX
    XPG["XPG"] -->|"activates"| SETX
    ALS4["ALS4"] -->|"inhibits"| SETX
    XPF["XPF"] -->|"activates"| SETX
    PNKP["PNKP"] -->|"activates"| SETX
    TDP1["TDP1"] -->|"activates"| SETX
    FEN1["FEN1"] -->|"activates"| SETX
    DNA["DNA"] -->|"activates"| SETX

Outgoing (244)

Target	Relation	Type	Str
Amyotrophic Lateral Sclerosis Type 4	causes	disease	0.95
R-Loop	regulates	process	0.95
R-Loops	mediates	compound	0.95
ALS4	causes	disease	0.95
Ataxia With Oculomotor Apraxia Type 2	causes	disease	0.95
Als4	causes	disease	0.95
Amyotrophic Lateral Sclerosis 4	causes	disease	0.95
AOA2	causes	disease	0.95
Macroautophagy	regulates	pathway	0.95
Rna/Dna Helicase Activity	involved_in	mechanism	0.93
Rna/Dna Helicase Activity	mediates	process	0.93
Amyotrophic Lateral Sclerosis	associated_with	disease	0.92
m6A modification	activates	process	0.92
AOA2	associated_with	disease	0.90
Motor Neuron Degeneration	involved_in	phenotype	0.90
M6A Regulators	activates	protein	0.90
amyotrophic lateral sclerosis type 4	implicated_in	disease	0.90
R-Loop	interacts_with	mechanism	0.90
dominant mutation	causes	mutation	0.90
AUTOPHAGY GENES	upregulates	gene	0.90
R-loop	involved_in	process	0.90
Dna	binds	compound	0.90
R-Loop Structures	involved_in	mechanism	0.90
Rna	binds	compound	0.90
RNA/DNA Helicase Activity	mediates	process	0.88
HPV replication	suppresses	process	0.88
Motor Neuron Function	involved_in	process	0.88
Autosomal Recessive Ataxia	causes	disease	0.85
R-loop	biomarker_for	biomarker	0.85
Neurodegeneration	associated_with	disease	0.85
Dna Damage Response	involved_in	pathway	0.85
DNA Damage Response	involved_in	process	0.85
transcription	regulates	process	0.85
Transcriptional Regulation	involved_in	process	0.85
Hpv Replication	regulates	process	0.85
RNA/DNA Helicase Activity	involved_in	process	0.85
neurodegeneration	associated_with	disease	0.85
Haploinsufficiency	involved_in	mechanism	0.80
familial amyotrophic lateral sclerosis type 4	implicated_in	disease	0.80
Transcriptional Regulation	regulates	process	0.80
autophagy regulation	functions_in	process	0.80
R-loop	binds	compound	0.80
RNA processing	regulates	process	0.80
R-loop	regulates	biological_process	0.80
R-loop_resolution	catalyzes	pathway	0.80
motor neuron	expressed_in	cell_type	0.75
neural stem cells	regulates	cell_type	0.70
ALS	causes	disease	0.70
oxidative stress response	participates_in	pathway	0.70
neurons	expressed_in	cell_type	0.70

Incoming (152)

Source	Relation	Type	Str
Sirna Treatment	downregulates	drug	0.95
Sirna	targets	drug	0.92
Cell Differentiation	upregulates	process	0.90
h-c463d225	targets	hypothesis	0.90
siRNA	targets	drug	0.85
cell differentiation	upregulates	process	0.85
RNA	accumulates_in	gene	0.70
LC3	activates	gene	0.60
AND	associated_with	gene	0.60
AMYOTROPHIC LATERAL SCLEROSIS	associated_with	gene	0.60
ACTB	regulates	gene	0.60
ATG7	regulates	gene	0.60
BECN1	regulates	gene	0.60
DNMT1	regulates	gene	0.60
HTT	regulates	gene	0.60
LC3	regulates	gene	0.60
ALS4	interacts_with	gene	0.60
XRCC1	activates	gene	0.60
FIG4	causes	gene	0.60
XPF	encodes	gene	0.60
XPG	encodes	gene	0.60
FEN1	encodes	gene	0.60
FTD	activates	entity	0.60
STROKE	therapeutic_target	gene	0.60
AND	inhibits	gene	0.60
RNF216	associated_with	gene	0.60
GENES	associated_with	gene	0.60
ALS	causes	entity	0.60
ALS2	associated_with	gene	0.60
CNTN4	associated_with	gene	0.60
RAD52	causes	gene	0.60
RAD52	targets	gene	0.60
AFG3L2	associated_with	gene	0.60
DNA	activates	gene	0.60
MAP1LC3	associated_with	gene	0.60
AND	regulates	gene	0.60
XPF	activates	gene	0.60
PNKP	activates	gene	0.60
TDP1	activates	gene	0.60
FEN1	activates	gene	0.60
SQSTM1	associated_with	gene	0.60
SMN1	associated_with	gene	0.60
DNMT1	associated_with	gene	0.60
P62	associated_with	gene	0.60
TFEB	associated_with	gene	0.60
ALS4	associated_with	gene	0.60
ALS4	regulates	gene	0.60
WFS1	associated_with	gene	0.60
HARS	associated_with	gene	0.60
ATM	associated_with	gene	0.60

Targeting Hypotheses (1)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
R-Loop Resolution Enhancement Therapy	0.680	neurodegeneration	RNA binding protein dysregulation across

Mentioning Analyses (1)

Scientific analyses that reference this entity

RNA binding protein dysregulation across ALS FTD and AD

neurodegeneration | 2026-04-01 | 7 hypotheses Top: 0.720

Experiments (10)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Feasibility	Model	Status	Est. Cost
s:** - Temporal analysis showing mitochondrial defects precede other p	falsification	Neurodegeneration	0.400	0.50	cell_line	proposed	$80,000
Proposed experiment from debate on TDP-43 undergoes liquid-liquid phas	falsification	Neurodegeneration	0.400	0.50	cell_line	proposed	$80,000
s:** - Single-cell RNA-seq to measure editing efficiency across differ	falsification	ALS	0.400	0.50	cell_line	proposed	$150,000
ALS Progression Rate Heterogeneity — mechanism and biomarker predictor	clinical	ALS	0.400	0.50	human	proposed	$6,550,000
ALS Regional Onset and Spread: Network-Level Staging Model	clinical	ALS	0.400	0.50	human	proposed	$7,500,000
Sporadic ALS Initiation Biology: Deep Phenotyping of At-Risk Cohorts	clinical	ALS	0.400	0.50	human	proposed	$6,550,000
DNA Damage Repair Deficiency Validation Study in Parkinson's Disease	clinical	Parkinson's Disease	0.400	0.50	human	proposed	$7,500,000
Environmental Exposure Causal Attribution in ALS — Experiment Design	validation	ALS	0.400	0.50	human	proposed	$3,000,000
Frontal and Temporal Lobe Selective Vulnerability in FTD — Mechanisms	validation	Neurodegeneration	0.400	0.50	human	proposed	$3,000,000
FXTAS Phenotypic Penetrance: Why Only 40% of FMR1 Premutation Carriers	validation	ALS	0.400	0.50	human	proposed	$3,000,000

Related Papers (20)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year	Citations
Allele-specific silencing of a dominant SETX mutation in familial amyotrophic la [PMID:40200577]	Winkelsas A, Apfel A, Johnson B, Harmiso	HGG Adv	2025	1
SETX (senataxin), the helicase mutated in AOA2 and ALS4, functions in autophagy [PMID:32686621]	Richard P, Feng S, Tsai YL, Li W, Rinche	Autophagy	2021	1
Dual Processing of R-Loops and Topoisomerase I Induces Transcription-Dependent D [PMID:31533039]	Cristini A, Ricci G, Britton S, Salimben	Cell Rep	2019	1
Molecular characterization of recessively inherited ataxic and neuropathic disor [PMID:41606223]	["Aslam F", "Wajid M", "Butt A", "Wohler	Scientific reports	2026	0
Deciphering ALS-linked genetic variants in indian patients using targeted and ex [PMID:41137727]	["Reza S", "Handique J", "Sharma P", "Ma	Amyotrophic lateral sclerosis	2026	0
Genetic commonalities between rare subtypes of ALS and CMT: insights into molecu [PMID:41621017]	Aynaashe A, Kursula P	Amino Acids	2026	0
Genetic commonalities between rare subtypes of ALS and CMT: insights into molecu [PMID:41621017]	Aynaashe A, Kursula P	Amino acids	2026	0
N(6)-methyladenosine modification of RNA is regulated by senataxin and E6 to con [PMID:41518615]	["Templeton C", "Laimins L"]	Cell reports	2026	0
The SMC5/SMC6 complex is critical for resolving R-loop-induced transcription-rep [PMID:41533569]	Wu T, Li Y, Zhao Y, Bournique E, Ortega	Nucleic acids research	2026	0
Resolution of R-loops and transcription-replication conflicts by SETX-BRCA1-BARD [PMID:41917467]	Dutta A, Ji JH, Syed S, Fang Q, Mukhopad	Nature structural & molecular	2026	0
Ataxia and oculomotor apraxia caused by a large-scale deletion in the senataxin [PMID:40830689]	["Rusecka J", "Kierdaszuk B", "St\u0119p	Journal of applied genetics	2025	0
Unraveling the genetic landscape of ALS in Greece: identification of known and n [PMID:41196070]	["Kartanou C", "Kontogeorgiou Z", "Loupi	Amyotrophic lateral sclerosis	2025	0
Break-induced replication is activated to repair R-loop-associated double-strand [PMID:40475435]	["Wu T", "Li Y", "Shi L", "Wu X"]	bioRxiv : the preprint server	2025	0
A role for human senataxin in contending with pausing and backtracking during tr [PMID:41232527]	Han Z, Fu S, Johansen JV, Lopez Martinez	Molecular cell	2025	0
Break-induced replication is activated to repair R-loop-associated double-strand [PMID:41037402]	Wu T, Li Y, Zhao Y, Shah SB, Shi LZ, Wu	Cell reports	2025	0
Unveiling ten novel SETX mutations: implications for ALS pathogenesis and clinic [PMID:40338003]	["Chen X", "Chen X", "Lin X", "Zhou W",	Somatosensory & motor research	2025	0
ZPR1 Is Dispensable for HPV R-Loop Resolution but Regulates Host R-Loop Dynamics [PMID:41305523]	Moffitt R, Brooks S, Androphy EJ, DeSmet	Viruses	2025	0
Senataxin: A key actor in RNA metabolism, genome integrity and neurodegeneration [PMID:37558082]	["Giannini M", "Porrua O"]	Biochimie	2024	0
Role of senataxin in R-loop-mediated neurodegeneration. [PMID:39070547]	Kannan A, Gangadharan Leela S, Branzei D	Brain communications	2024	0
Helicases in R-loop Formation and Resolution. [PMID:37778731]	Yang S, Winstone L, Mondal S, Wu Y	The Journal of biological chem	2023	0

Debates (2)

Multi-agent debates referencing this entity

RNA binding protein dysregulation across ALS FTD and AD

closed · Rounds: 4 · Score: 0.72 · 2026-04-12

RNA binding protein dysregulation across ALS FTD and AD

closed · Rounds: 4 · Score: 0.88 · 2026-04-06