Published in Sciencethe study shows how very different mutations can disrupt the same biological “crossroads”. A particularly important advance for the most severe forms of autism, even if no medication has yet resulted.
A huge list of genes, but how do they work?
For families faced with the most severe forms of autism, research is moving forward with the hope of one day better understanding the mechanisms at the origin of the disorder. But the immense genetic diversity of autism complicates this quest: hundreds of genes may be involved.
Researchers from the Quantitative Biosciences Institute (QBI) at the University of California, San Francisco (UCSF), with more than 70 scientists and clinicians, therefore chose to look beyond genes.
Published on August 27, 2026 in Sciencetheir study connects
100 genes at high risk for autism with more than 1,800 protein interactions. Even more spectacular:
87% of these interactions had never been described.
The proteins produced from genes interact with each other to ensure functions essential to brain development. Understanding these interactions therefore allows us to move from a simple list of mutations to a representation of the mechanisms they disrupt.
“When you have the genes and the mutations, it’s just a list. This is a parts list. What you need is a wiring diagram of this parts list”explains Nevan J. Krogan, professor at UCSF and director of the QBI.
Different mutations, the same biological “crossroads”
To establish this map, the researchers analyzed the interactions between the proteins produced by risk genes and studied 54 variants observed in patients.
They used AlphaFoldan artificial intelligence capable of predicting the structure of proteins, then studied certain interactions in neurons grown in the laboratory and human brain organoids.
The observation is essential: different mutations can disrupt the same protein complexes and the same biological pathways. Several genetic anomalies thus converge towards a few common mechanisms.
An example concerns FOXP1 : several variants associated with autism disrupt its interaction with
FOXP4. In the models studied, this disruption accelerates the maturation of certain neurons in the cortex and modifies the activity of neuronal circuits.
This convergence could make it possible to consider treatments targeting these common mechanisms rather than each mutation individually.
From the map to the drug: a long road still
“For the first time, we can point to the precise molecular mechanisms that cause autism — not just the genes associated with the disorder, but the interactions between proteins that malfunction and the specific interfaces that we can target with drugs“, says Nevan J. Krogan.
In particular, the researchers plan to stabilize weakened protein complexes or to block interactions that have become abnormal.
Fikri Birey of the Emory University School of Medicine, who was not involved in the study, told CNN that it could ultimately be possible.to identify drugs that stabilize disrupted protein complexes or block pathological interactions, rather than trying to correct each individual mutation responsible for autism”
But this prospect is still distant. The study mainly concerns people with profound autismwho represent approximately 30% of people with ASD and may require permanent assistance.
Andy Shih, scientific director of Autism Speaks, sums up this caution: “Translating these types of discoveries into treatments is a lengthy process. This study provides valuable information on potential targets, but much more research is needed before these results can lead to clinical applications.”. (Source: CNN)
The molecular map of autism is therefore not yet a treatment. But it perhaps changes the question posed to researchers. It’s no longer just about knowing which genes are involvedbut to understand how their anomalies connect and where to act.
For families, this nuance is essential. The hope is not that of an imminent cure, but that of a search that begins to see more clearly the path to follow.