ALS Gene Library

C9orf72

Chromosome 9 Open Reading Frame 72

A pathogenic GGGGCC hexanucleotide repeat expansion in C9orf72 is a major genetic cause of ALS and frontotemporal dementia.

C9orf72-associated disease may present as ALS, FTD, ALS and FTD together, or other less common neurological presentations.

The phenotype and age of onset can vary substantially, including among members of the same family.

Sources: C9orf72 Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis · Evidence-Based Consensus Guidelines for ALS Genetic Testing and Counseling · Pre-fALS Study

Associated conditions

  • Amyotrophic lateral sclerosis
  • Frontotemporal dementia
  • ALS-FTD spectrum disease

Sources: C9orf72 Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis

ALS / FTD relationship

C9orf72 is particularly important because the same pathogenic repeat expansion can be associated with ALS, FTD, or a combined ALS-FTD phenotype.

This makes C9orf72 relevant to both motor-neuron and cognitive/behavioral disease research.

Sources: C9orf72 Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis

Typical inheritance pattern

Usually autosomal dominant.

Each biological child of a carrier generally has a 50% chance of inheriting the repeat expansion.

This is inheritance probability, not disease penetrance.

Sources: C9orf72 Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis

Penetrance

C9orf72 penetrance is age-dependent and incomplete.

Disease expression cannot be predicted precisely for an individual carrier.

Not every carrier will develop ALS or FTD.

GeneReviews notes substantial variability in age at onset and phenotype.

Sources: C9orf72 Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis

Clinical presentation

  • ALS
  • FTD
  • ALS-FTD
  • behavioral or cognitive symptoms
  • motor-neuron symptoms

Clinical presentation can differ even within the same family.

Sources: C9orf72 Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis

Genetic testing considerations

C9orf72 disease is caused by a repeat expansion.

Testing therefore requires an assay capable of detecting the repeat expansion.

Standard sequencing alone should not be assumed to be sufficient.

Expert ALS testing guidelines specifically recommend C9orf72 repeat expansion analysis.

Sources: Evidence-Based Consensus Guidelines for ALS Genetic Testing and Counseling

Biomarkers

Research is ongoing into biomarkers that may help characterize presymptomatic disease and phenoconversion.

There is not currently a validated biomarker that can precisely predict when an individual C9orf72 carrier will develop ALS or FTD.

Sources: Pre-fALS Study

Available treatments

There is currently no FDA-approved treatment specifically targeting the C9orf72 repeat expansion.

Standard ALS treatments and multidisciplinary care may still apply to people who develop ALS.

The absence of a gene-specific approval does not mean research activity has stopped.

Sources: Amyotrophic Lateral Sclerosis Overview

Clinical trials

Search C9orf72 ALS studies Search C9orf72 FTD studies

Sources: ClinicalTrials.gov: Amyotrophic Lateral Sclerosis studies

Presymptomatic research

Asymptomatic C9orf72 carriers are studied longitudinally to investigate:

  • biomarkers
  • brain changes
  • disease modifiers
  • phenoconversion
  • potential prevention strategies

Sources: Pre-fALS Study

Current research

Research areas include repeat-expansion biology, RNA toxicity, dipeptide-repeat proteins, loss of normal C9orf72 function, biomarkers, modifiers, and targeted therapeutic strategies.

Sources: C9orf72 Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis

Key research institutions / studies

  • Pre-fALS Study – University of Miami / collaborators
  • ClinicalTrials.gov C9orf72 studies
Open the Pre-fALS study

Sources: Pre-fALS Study

Sources & Further Reading

These source cards link directly to the original material. External websites open in a new tab.

This information is for education and does not replace individualized medical advice, genetic counseling, diagnosis, or treatment. Genetic risk, penetrance, and testing implications can differ by gene, variant, family, and individual.

Last reviewed: 09-30-2026

Medical information should be reviewed periodically as genetic research and clinical trials change.

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