gene

C9ORF72

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about C9ORF72: 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.

1532Connections

16Hypotheses

10Analyses

50Outgoing

50Incoming

0Experiments

12Debates

Summary

C9ORF72 is a gene implicated in neurodegeneration research. Key relationships include: associated with, interacts with, activates. Associated with ALS, ALS/FTD, AMYOTROPHIC LATERAL SCLEROSIS. Connected to 647 entities in the SciDEX knowledge graph.

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🧬 Gene Info

Gene Symbol	C9ORF72
Chromosome	chromosome 9p21.2.
Protein Type	Protein
Function	is a 481-amino acid protein with an approximate molecular weight of 54 kDa.
Primary Expression	Normal and Neoplastic cells) domain family, functioning as a guanine nucleotide exchange factor (GEF) for Rab GTPases involved in endolysosomal traffi
Molecular Weight	54 kDa
Pathways	Apoptosis, Autophagy, Er Stress, LYSOSOMES, Microbiota
UniProt ID	Search UniProt
GeneCards	C9ORF72
Human Protein Atlas	C9ORF72
Associated Diseases	Aging, Als, ALS/FTD, Alzheimer, Alzheimer's Disease
Known Drugs/Compounds	Antisense oligonucleotides, BIIB078
Interactions	ACTB, Actin, AKT, ALS, ALS2, ALS-CAUSING MUTATIONS
SciDEX Hypotheses	C9ORF72 autophagy-lysosome collapse across ALS and ASO-mediated reduction of toxic C9orf72 dipeptide C9orf72 ASO Treatment Reverses TDP-43 Pathology in (+6 more)
KG Connections	1441 knowledge graph edges
Databases	GeneCards NCBI Gene HPA STRING

🔮 Predicted Structure: C9ORF72 — AlphaFold SEARCH Click to expand

AI-predicted structure from AlphaFold | Powered by Mol*

Wiki Pages (4)

Knowledge base pages for this entity

Canonical Page

Pathway Diagram

graph TD
    C9ORF72["C9ORF72 Gene"] -->|"Regulates"| Vesicles["Vesicle Trafficking"]
    C9ORF72 -->|"Regulates"| Lysosomes["Lysosomal Biogenesis"]
    C9ORF72 -->|"Binds"| Endosomes["Endosomes"]
    C9ORF72 -->|"Regulates"| Proteostasis["Proteostasis"]
    RepeatExp["GGGGCC Repeat Expansion"] -->|"Inhibits"| C9ORF72
    RepeatExp -->|"Produces"| DPR["Dipeptide Repeat Proteins"]
    RepeatExp -->|"Triggers"| RAN["RAN Translation"]
    DPR -.Toxic to.-> Neurons["Motor Neurons"]
    C9ORF72 -->|"Causes when mutated"| ALS["ALS"]
    C9ORF72 -->|"Causes when mutated"| FTD["Frontotemporal Dementia"]
    C9ORF72 -->|"Causes when mutated"| ALSFTD["ALS/FTD Spectrum"]
    RAN -.Disrupts.-> Proteostasis

Outgoing (1118)

Target	Relation	Type	Str
C9ORF72	encodes	protein	0.00
benchmark_ot_ad_answer_key:C9ORF72	data_in	dataset_row	0.00
Als	associated_with	disease	1.00
Amyotrophic Lateral Sclerosis	associated_with	disease	1.00
AMYOTROPHIC LATERAL SCLEROSIS	associated_with	gene	1.00
Dementia	causes	disease	1.00
ALS	causes	disease	1.00
ALS	associated_with	gene	1.00
Amyotrophic Lateral Sclerosis	causes	disease	1.00
AMYOTROPHIC LATERAL SCLEROSIS	causes	gene	1.00
NEURODEGENERATION	causes	disease	1.00
DEMENTIA	causes	gene	1.00
POLY(PR)	product_of	protein	0.95
Frontotemporal Lobar Degeneration	causes	disease	0.95
Hexanucleotide Repeat Expansion	associated_with	biomarker	0.95
Motor Neuron Disease	causes	disease	0.95
vesicle trafficking	regulates	pathway	0.95
Frontotemporal Dementia	associated_with	disease	0.95
Ftd	associated_with	disease	0.95
Amyotrophic Lateral Sclerosis/Frontotemporal Dementia	causes	disease	0.95
Als	activates	disease	0.95
Frontotemporal Lobar Degeneration	associated_with	disease	0.95
ALS/FTD	associated_with	disease	0.95
Vesicle Trafficking	regulates	process	0.95
C9-ALS	risk_factor_for	disease	0.95
GGGGCC Repeats	associated_with	biomarker	0.95
Gray Matter Atrophy	contributes_to	process	0.92
ALS-FTD	risk_factor_for	disease	0.92
LYSOSOMAL BIOGENESIS	regulates	gene	0.90
Endosome	interacts_with	cell_type	0.90
RNA foci	co_localizes	process	0.90
lysosomal biogenesis	regulates	pathway	0.90
VESICLE TRAFFICKING	regulates	gene	0.90
amyotrophic lateral sclerosis	associated_with	disease	0.90
Dipeptide Repeat Proteins	causes	compound	0.90
Trans-Golgi Network Function	regulates	phenotype	0.90
Autoimmune Response	associated_with	process	0.90
TDP-43 splicing repression	disrupts	process	0.90
Motor Neuron Degeneration	causes	disease	0.90
Alternative Splicing	modulates	process	0.90
Neurodegeneration	associated_with	process	0.90
ALS/FTD	risk_factor_for	disease	0.90
POLY(PROLINE-ARGININE)	encodes	protein	0.90
Endosomes	interacts_with	cell_type	0.90
FTD-ALS	causes	disease	0.90
ENDOSOMES	binds	gene	0.90
C9ORF72DIPEPTIDEREPEATPROTEINS	component_of	protein	0.90
DPR_proteins	produces_pathological	protein	0.90
Vesicle Trafficking	involved_in	process	0.90
frontotemporal dementia	causes	disease	0.90

Incoming (414)

Source	Relation	Type	Str
benchmark_ot_ad_answer_key:C9ORF72	data_in	dataset_row	0.00
C9ORF72	encodes	gene	0.00
BIIB078	targets	drug	0.95
G4C2 Repeat Expansion	biomarker_for	biomarker	0.92
32100453	affects	paper	0.90
GGGGCC Hexanucleotide Repeat Expansion	associated_with	biomarker	0.90
C9ORF72 repeat expansion	inhibits	gene	0.90
Hexanucleotide Repeat Expansion	associated_with	biomarker	0.90
RAN_TRANSLATION	associated_with	gene	0.90
32100453	regulates	paper	0.90
DIPEPTIDE_REPEAT_PROTEINS	associated_with	gene	0.90
AMYOTROPHIC LATERAL SCLEROSIS	associated_with	gene	0.90
als	describes	wiki	0.90
30696333	forms a heterodimer with	paper	0.90
C9Orf72 Repeat Expansion	downregulates	mechanism	0.90
repeat expansion	inhibits	phenotype	0.90
GGGGCC Repeat Expansion	downregulates	biomarker	0.85
Antisense oligonucleotides	targets	drug	0.85
h-cross-synth-c9orf72-autophagy-lysosome	proposes_shared_mechanism	hypothesis	0.83
rs12608932	associated_with	biomarker	0.80
GGGGCC_repeat	associated_with	genetic_variant	0.72
AMYOTROPHIC LATERAL SCLEROSIS	targets	disease	0.70
AMPK	activates	gene	0.70
ACHE	expresses	gene	0.70
ASTROCYTE	activates	cell_type	0.70
ALS	associated_with	gene	0.70
NEURODEGENERATIVE DISEASES	therapeutic_target	gene	0.70
INFLAMMATION	therapeutic_target	gene	0.70
NEURODEGENERATIVE DISORDERS	therapeutic_target	gene	0.70
PARKINSON'S DISEASE	increases_risk	disease	0.70
MMP9	regulates	gene	0.70
ALS	interacts_with	entity	0.70
NEURONS	produces	cell_type	0.65
ALS	expressed_in	disease	0.65
NEK1	exacerbates	gene	0.65
TDP-43	encodes	protein	0.65
TMEM106B	activates	gene	0.65
UBQLN2	exacerbates	gene	0.65
ALS	targets	disease	0.65
ALZHEIMER	associated_with	gene	0.65
GGGGCC_repeat	inhibits	genetic_variant	0.64
GAIN	activates	gene	0.60
SOD1	therapeutic_target	gene	0.60
CALCOCO2	interacts_with	gene	0.60
ATXN2	therapeutic_target	gene	0.60
OPTN	associated_with	gene	0.60
P62	therapeutic_target	gene	0.60
RAN	regulates	gene	0.60
MARK2	regulates	gene	0.60
RICTOR	activates	gene	0.60

Targeting Hypotheses (16)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
C9ORF72 autophagy-lysosome collapse across ALS and FTD	0.816	multi	Cross-disease neurodegeneration mechanis
ASO-mediated reduction of toxic C9orf72 dipeptide repeat pro	0.760	neurodegeneration	Test
C9orf72 Hexanucleotide Repeat Dipeptide Repeat Proteins Inhi	0.738	neurodegeneration	Legacy Pre-Pipeline Hypothesis Import
C9orf72 ASO Treatment Reverses TDP-43 Pathology in ALS/FTD	0.720	neurodegeneration	Test Hypothesis Fixtures
C9orf72 DPRs Impair Autophagy Receptor Docking on Stress Gra	0.717	neurodegeneration	How do pathological stress granules in n

C9orf72 repeat RNA and dipeptide-repeat toxicity in ALS/FTD	0.700	neurodegeneration	Test
H5: C9orf72 DPR Dipeptides Corrupt G3BP1 Condensate Properti	0.698	neurodegeneration	How do pathological stress granules tran
Axonal Transport Defect: C9orf72 hexanucleotide expansion im	0.660	neurodegeneration	What are the neuron-specific effects of
ATXN2 Antisense Oligonucleotides Reduce Dipeptide Repeat Pro	0.630	neurodegeneration	Test
C9orf72 Nucleocytoplasmic Transport Rescue for ALS/FTD	0.597	neurodegeneration	Test
C9orf72-SMCR8-WDR41 Complex Dysfunction in C9-ALS Rescued by	0.562	neurodegeneration	How does PIKFYVE inhibition activate unc
SIRT1 Activation Suppresses C9orf72-Mediated Neurodegenerati	0.560	neurodegeneration	Test Preregistration Analysis
Autophagy Enhancement via mTOR Inhibition for C9orf72 Dipept	0.490	neurodegeneration	Test
Arginine-Rich DPR Competitive Inhibitors	0.000	-	TDP-43 phase separation therapeutics for
C9orf72 DPR Neutralizing Agents	0.000	-	TDP-43 phase separation therapeutics for
G4C2 RNA Decoy Therapeutics	0.000	-	TDP-43 phase separation therapeutics for

Mentioning Analyses (10)

Scientific analyses that reference this entity

Cross-disease neurodegeneration mechanism synthesis

neurodegeneration | 2026-04-28 | 17 hypotheses Top: 0.828

Is ferroptosis the primary driver of motor neuron death in ALS or an epiphenomen

neurodegeneration | 2026-04-18 | 4 hypotheses Top: 0.538

What upstream mechanisms trigger p53 activation specifically in response to poly

neurodegeneration | 2026-04-15 | 1 hypotheses Top: 0.661

What molecular mechanism causes VCP mutations to trigger aberrant HIF-1α activat

neurodegeneration | 2026-04-13 | 2 hypotheses Top: 0.793

How does PIKFYVE inhibition activate unconventional protein clearance via exocyt

neurodegeneration | 2026-04-13 | 2 hypotheses Top: 0.584

Experiments (0)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Feasibility	Model	Status	Est. Cost
No experiments found

Related Papers (2)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year	Citations
A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-lin [PMID:21944779]	Unknown	Neuron	2011	0
Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chro [PMID:21944778]	["DeJesus-Hernandez Mariely", "Mackenzie	Neuron	2011	0

Debates (12)

Multi-agent debates referencing this entity

Which AD, PD, ALS, and FTD mechanisms recur across disease boundaries and yield

closed · Rounds: 4 · Score: 0.72 · 2026-04-28

While ALS-causing mutations impair autophagy factors, the neuron-specific effect

closed · Rounds: 4 · Score: 0.81 · 2026-04-21

The debate highlighted compelling correlative evidence for ferroptosis markers i

closed · Rounds: 4 · Score: 0.50 · 2026-04-18

The abstract shows p53 is a central regulator of C9orf72-mediated neurodegenerat

closed · Rounds: 4 · Score: 0.61 · 2026-04-16

The study shows VCP-mutant astrocytes exhibit hypoxia response activation withou

closed · Rounds: 4 · Score: 0.78 · 2026-04-13

How does PIKFYVE inhibition activate unconventional protein clearance via exocyt

closed · Rounds: 4 · Score: 0.63 · 2026-04-13

RNA binding protein dysregulation across ALS FTD and AD

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

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

closed · Rounds: 6 · Score: 0.84 · 2026-04-12

TDP-43 phase separation therapeutics for ALS-FTD

closed · Rounds: 4 · Score: 0.95 · 2026-04-11

Multiple NDDs converge on autophagy-lysosome dysfunction. Are there universal th

closed · Rounds: 4 · Score: 0.90 · 2026-04-06

Related Research

Hypotheses and analyses mentioning C9ORF72 in their description or question text

C9ORF72

Understanding Entity Pages

Summary

Wiki Pages (4)

C9orf72 Protein

PTPσ (PTPRS) in C9ORF72-ALS/FTD - PI3P Regulation Mechanism

Validated Hypothesis: C9ORF72 autophagy-lysosome collapse across ALS and FTD

C9ORF72 (Redirect)

Pathway Diagram

Outgoing (1118)

Incoming (414)

Targeting Hypotheses (16)

Mentioning Analyses (10)

Cross-disease neurodegeneration mechanism synthesis

Is ferroptosis the primary driver of motor neuron death in ALS or an epiphenomen

What upstream mechanisms trigger p53 activation specifically in response to poly

What molecular mechanism causes VCP mutations to trigger aberrant HIF-1α activat

How does PIKFYVE inhibition activate unconventional protein clearance via exocyt

What are the neuron-specific effects of ALS-causing mutations on autophagy machi

RNA binding protein dysregulation across ALS FTD and AD

Digital biomarkers and AI-driven early detection of neurodegeneration

Autophagy-lysosome pathway convergence across neurodegenerative diseases

TDP-43 phase separation therapeutics for ALS-FTD

Experiments (0)

Related Papers (2)

Debates (12)

Which AD, PD, ALS, and FTD mechanisms recur across disease boundaries and yield

While ALS-causing mutations impair autophagy factors, the neuron-specific effect

The debate highlighted compelling correlative evidence for ferroptosis markers i

The abstract shows p53 is a central regulator of C9orf72-mediated neurodegenerat

The study shows VCP-mutant astrocytes exhibit hypoxia response activation withou

How does PIKFYVE inhibition activate unconventional protein clearance via exocyt

RNA binding protein dysregulation across ALS FTD and AD

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

TDP-43 phase separation therapeutics for ALS-FTD

Multiple NDDs converge on autophagy-lysosome dysfunction. Are there universal th

Related Research

C9orf72 repeat RNA and dipeptide-repeat toxicity in ALS/FTD

H5: C9orf72 DPR Dipeptides Corrupt G3BP1 Condensate Properties

Axonal Transport Defect: C9orf72 hexanucleotide expansion impairs retrograde aut

ATXN2 Antisense Oligonucleotides Reduce Dipeptide Repeat Proteins in C9orf72-ALS

C9orf72 Nucleocytoplasmic Transport Rescue for ALS/FTD

C9orf72-SMCR8-WDR41 Complex Dysfunction in C9-ALS Rescued by PIKFYVE Inhibition

SIRT1 Activation Suppresses C9orf72-Mediated Neurodegeneration

Autophagy Enhancement via mTOR Inhibition for C9orf72 Dipeptide Repeat Pathology

Arginine-Rich DPR Competitive Inhibitors

C9orf72 DPR Neutralizing Agents

G4C2 RNA Decoy Therapeutics