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.

412Connections

1Hypotheses

1Analyses

50Outgoing

50Incoming

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, AOA2, Amyotrophic Lateral Sclerosis
Known Drugs/Compounds	Rna, Dna, R-loop, siRNA, Sirna, rapamycin
Interactions	TDP1, PNKP, FEN1, XPF, XRCC1, ALS4
SciDEX Target	View Target Profile (2 clinical trials)
SciDEX Hypotheses	R-Loop Resolution Enhancement Therapy
KG Connections	412 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 (21)

Knowledge base pages for this entity

Canonical Page

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 (253)

Target	Relation	Type	Str
Amyotrophic Lateral Sclerosis Type 4	causes	disease	0.95
Als4	causes	disease	0.95
Ataxia With Oculomotor Apraxia Type 2	causes	disease	0.95
ALS4	causes	disease	0.95
R-Loops	mediates	compound	0.95
AOA2	causes	disease	0.95
R-Loop	regulates	process	0.95
Macroautophagy	regulates	pathway	0.95
Amyotrophic Lateral Sclerosis 4	causes	disease	0.95
Rna/Dna Helicase Activity	involved_in	mechanism	0.93
Rna/Dna Helicase Activity	mediates	process	0.93
m6A modification	activates	process	0.92
Amyotrophic Lateral Sclerosis	implicated_in	disease	0.92
R-loop	involved_in	process	0.90
Rna	binds	compound	0.90
Dna	binds	compound	0.90
AOA2	associated_with	disease	0.90
Motor Neuron Degeneration	involved_in	phenotype	0.90
R-Loop Structures	involved_in	mechanism	0.90
amyotrophic lateral sclerosis type 4	implicated_in	disease	0.90
R-Loop	interacts_with	mechanism	0.90
AUTOPHAGY GENES	upregulates	gene	0.90
dominant mutation	causes	mutation	0.90
M6A Regulators	activates	protein	0.90
RNA/DNA Helicase Activity	mediates	process	0.88
Motor Neuron Function	involved_in	process	0.88
HPV replication	suppresses	process	0.88
RNA/DNA Helicase Activity	involved_in	process	0.85
DNA Damage Response	involved_in	process	0.85
Transcriptional Regulation	involved_in	process	0.85
R-loop	biomarker_for	biomarker	0.85
transcription	regulates	process	0.85
Autosomal Recessive Ataxia	causes	disease	0.85
Hpv Replication	regulates	process	0.85
Neurodegeneration	associated_with	disease	0.85
Dna Damage Response	involved_in	pathway	0.85
Haploinsufficiency	involved_in	mechanism	0.80
R-loop	regulates	biological_process	0.80
Transcriptional Regulation	regulates	process	0.80
autophagy regulation	functions_in	process	0.80
familial amyotrophic lateral sclerosis type 4	implicated_in	disease	0.80
R-loop	binds	compound	0.80
RNA processing	regulates	process	0.80
R-loop_resolution	catalyzes	pathway	0.80
motor neuron	expressed_in	cell_type	0.75
ALS	causes	disease	0.70
oxidative stress response	participates_in	pathway	0.70
neurons	expressed_in	cell_type	0.70
neural stem cells	regulates	cell_type	0.70
Spinal Muscular Atrophy	associated_with	disease	0.65

Incoming (159)

Source	Relation	Type	Str
Sirna Treatment	downregulates	drug	0.95
Sirna	targets	drug	0.92
Cell Differentiation	upregulates	process	0.90
h-c463d225	targets_gene	hypothesis	0.90
siRNA	targets	drug	0.85
cell differentiation	upregulates	process	0.85
h-c463d225	targets	hypothesis	0.80
RNA	accumulates_in	gene	0.70
XPG	activates	gene	0.60
ACTB	associated_with	gene	0.60
GABARAP	associated_with	gene	0.60
ULK1	associated_with	gene	0.60
WIPI2	associated_with	gene	0.60
LC3	associated_with	gene	0.60
BECN1	associated_with	gene	0.60
HTT	associated_with	gene	0.60
ATG7	associated_with	gene	0.60
ALS4	inhibits	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
CLPP	associated_with	gene	0.60
XRCC1	activates	gene	0.60
ALS4	causes	entity	0.60
ACTB	activates	entity	0.60
ALS4	activates	entity	0.60
ATG7	activates	entity	0.60
BECN1	activates	entity	0.60
DNMT1	activates	entity	0.60
GABARAP	activates	entity	0.60
HTT	activates	entity	0.60
HUNTINGTIN	activates	entity	0.60
P62	activates	entity	0.60
ALS4	treats	entity	0.60
HUNTINGTIN	associated_with	gene	0.60
PNPLA6	associated_with	gene	0.60
POLG	associated_with	gene	0.60
TWNK	associated_with	gene	0.60
LARS2	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	0.428	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: 0.490

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
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
R-loop-derived cytoplasmic RNA-DNA hybrids activate an immune response. [PMID:36544021]	Crossley MP, Song C, Bocek MJ, Choi JH,	Nature	2023	0

SETX

Understanding Entity Pages

Summary

Wiki Pages (21)

SETX Gene

LARS2 — Leucyl-tRNA Synthetase 2, Mitochondrial

ALS-FTD-Parkinsonism Comparison Matrix

Gene Page: ALS4 (SENATAXIN)

PNPLA6 Gene — Neuropathy Target Esterase (NTE) in Neurodegeneration

FEN1 — Flap Endonuclease 1

ERCC5 (XPG) Gene — Excision Repair Cross-Complementation Group 5

siRNA Therapy for Parkinson's Disease

GDAP1 — Ganglioside-Induced Differentiation-Associated Protein 1

Alsin Protein

HARS1 — Histidyl-tRNA Synthetase 1

FANCM Protein

R-Loop Stress in Neurodegeneration

XPF Gene

Ataxia with Oculomotor Apraxia Type 2 (AOA2)

AFG3L2 Gene

ALS7 - Amyotrophic Lateral Sclerosis 7

MFSD8 — Major Facilitator Superfamily Domain Containing 8

Presubiculum

SETX Protein