C9ORF72 (Q96LT7) variants and mutations

C9ORF72 (also known as Q96LT7) is a human protein-coding gene encoding a guanine nucleotide exchange factor protein. It participates in endolysosomal trafficking, autophagy, and immune regulation through complexes with SMCR8 and WDR41. A large GGGGCC repeat expansion causes the most common inherited form of amyotrophic lateral sclerosis and frontotemporal dementia. This analysis covers 668 C9ORF72 variants and mutations. Of these, 75% have computational variant effect predictions. Disease context includes amyotrophic lateral sclerosis, frontotemporal dementia and/or amyotrophic lateral sclerosis 1, and frontotemporal dementia with motor neuron disease. Example C9ORF72 variants include S2A, S2L, and S2W.

Variant analysis overview

Variant and mutation evidence

Clinical, disease, and population context

Protein structure and variant hotspots

Data sources

Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.

Notable C9ORF72 variants

Examples include S2A, S2L, S2W, L4F, P6S, P7L, P7S, P8L. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.