C9ORF72
Chr 9ADC9orf72-SMCR8 complex subunit
Also known as: ALSFTD, DENND9, DENNL72, FTDALS, FTDALS1
The protein encoded by this gene plays an important role in the regulation of endosomal trafficking, and has been shown to interact with Rab proteins that are involved in autophagy and endocytic transport. Expansion of a GGGGCC repeat from 2-22 copies to 700-1600 copies in the intronic sequence between alternate 5' exons in transcripts from this gene is associated with 9p-linked ALS (amyotrophic lateral sclerosis) and FTD (frontotemporal dementia) (PMID: 21944778, 21944779). Studies suggest that hexanucleotide expansions could result in the selective stabilization of repeat-containing pre-mRNA, and the accumulation of insoluble dipeptide repeat protein aggregates that could be pathogenic in FTD-ALS patients (PMID: 23393093). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2016]
Primary Disease Associations & Inheritance
Clinical highlights
- C9orf72 ASO programs (e.g. BIIB078, WVE-004)ASODiscontinued
Lower the repeat-containing transcript.
Delivery: IntrathecalPhase 1 programs discontinued after not meeting endpoints — shown for transparency
Therapeutic landscape as of 2026-07. Educational only. Investigational ≠ available; not medical advice or eligibility. Approved entries are precise; investigational program names/phases are conservative and move fast. Curated from FDA/EMA approvals and the clinical-trial literature; verify against current labeling + ClinicalTrials.gov.
ClinicalTrials.govPopulation Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
C9ORF72 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
A Study Evaluating the Safety and Tolerability of QRL-201 in ALS
ACTIVE NOT RECRUITINGTracking and Predicting How Brain Damage Spreads in Neurodegenerative Diseases
ENROLLING BY INVITATIONNeuroinflammation in FTLD
ACTIVE NOT RECRUITINGNeurofilament Light Chain And Voice Acoustic Analyses In Dementia Diagnosis
RECRUITINGA Study of PBFT02 in Participants With FTD and Mutations in the Granulin Precursor (GRN) or C9ORF72 Genes
ACTIVE NOT RECRUITINGTRIAL READY (Clinical Trial Readiness)
ACTIVE NOT RECRUITINGNeurofilament Surveillance Project (NSP)
ACTIVE NOT RECRUITINGThe Benefits of Long-read High-throughput Genomic Sequencing for the Causal Diagnosis of Cerebellar Ataxias
RECRUITINGNeeds of ALS Patients With C9orf72 Mutation and Their Caregivers
RECRUITINGLongitudinal Assessment of Autonomic and Sensory Nervous System in ALS
RECRUITINGGENetic Fronto Temporal Dementia Initiative in Lille
RECRUITINGTesting Pulse Stimulation to Improve Motor Function in People With ALS: A Pilot Study
RECRUITINGExternal Resources
Links to major genomics databases and tools