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Research

Scientists Map Key Protein Interactions Linked to Profound Autism

UC San Francisco scientists have mapped over 1,000 protein interactions tied to profound autism, a step toward turning genetic discoveries into drug treatments.

AI News Feed · 2026-09-05 04:44

The study is the result of a collaboration between Matthew State, a clinical psychiatrist and geneticist at UCSF, and Nevan Krogan, director of UCSF's Quantitative Biosciences Institute. “It's an unprecedented resource for the field,” said Daniel Geschwind, a UCLA professor not involved in the research. “A lot of people interested in understanding autism and drug development are going to be using this.”

For families affected by profound autism, the new findings bring hope for eventual drug therapies. Alison Singer, president of the nonprofit Autism Science Foundation, who has a daughter with severe cognitive impairment, said, “This is the kind of scientific advance we have been waiting for and praying for. There's still a lot of work ahead, [but] this paper makes the path from genetic discovery to treatment much clearer.”

People with profound autism often live with severe intellectual disability and require around-the-clock care. They are nonverbal or minimally verbal, and often have serious medical conditions like epilepsy. In the past decade or so, researchers have discovered several hundred genes and corresponding mutations prevalent in a subset of people with profound autism. But as Krogan put it, scientists “kind of hit a wall” because those discoveries had not led to many treatments.

Krogan said scientists lacked the mechanistic understanding needed to make use of those genetic findings: “What we've been missing is the mechanistic understanding of how these mutations [on the genes] are seemingly resulting in autism. In order to understand that, you need to go to the proteins.” State put it this way: “What makes an eye cell an eye cell, and a muscle a muscle, are the proteins and how they work together. They are the machinery of life.”

To create the map, the researchers went on a “fishing expedition” for protein interactions. They selected 100 proteins from autism-risk genes, placed them into lab-grown cells, and then pulled them out with the additional proteins that had attached to them. They used Google DeepMind's AlphaFold, an AI system, to predict which proteins in the clumps were directly touching. “Where AI is playing an important role is being predictive about who's talking to who,” Krogan said. Although imperfect, the system has worked well enough to save significant time and money.

Finally, the researchers introduced mutations seen in patients with profound autism into the genes and observed what changed in the protein interactions. “We broke the proteins in the way that they're broken in autism,” State said. “That allows us ultimately to answer the question of, when they're going wrong.”