# Boston Children's Hospital team links ZFX gene to autism sex gap in cell cultures and organoids

- Published: 2026-11-05 10:13 UTC
- Section: Life & Health › Neurotechnology
- Tags: autism sex difference, ZFX gene, X chromosome, female protective effect, brain organoids, neuronal progenitor cells, autism-associated genes, ZFY gene, Boston Children's Hospital, transcription factor
- URL: https://realtech.media/news/rt-247fb17cc89610582b4502e9_boston_children_s/

**In lab-grown neuronal progenitors, disrupting autism-linked genes lowered activity of a shared gene network. ZFX, active on both X copies, may buffer this in females, the authors say.**

![Boston Children's Hospital team links ZFX gene to autism sex gap in cell cultures and organoids](https://sgzwpqqelzmajkcubgkl.supabase.co/storage/v1/object/public/rt-media/2026/11/439bab0e161b3c03.jpg)
*NASA Kennedy Space Center / NASA/Tony Gray and Kenny Allen, Wikimedia Commons, Public domain*

A team led by Boston Children's Hospital in the US reports that a single X-linked gene, ZFX, may help explain why autism is diagnosed in boys about three to four times as often as in girls, New Atlas writes. The work was done in lab-grown cells and brain organoids and published in Nature. [1]

The researchers wanted to understand how hundreds of genes, each a relatively rare factor on its own, contribute to overlapping sets of autism characteristics. [1]

## Shared gene network and ZFX

Using cultures of progenitor cells that precede neurons, the team reduced the activity of a number of individual autism-associated genes. Different disruptions repeatedly lowered the activity of other autism-associated genes. Twenty-seven genes became quieter in at least 10 experiments after the initial change. [1] Experiments on brain organoids, clumps of lab-grown tissue, supported this convergence. [1]

Mapping the regulatory relationships pointed to ZFX, a zinc finger transcription factor gene on the X chromosome. It encodes a protein that helps activate other genes, including many associated with autism. [1]

In most cases, genes on one of the two X chromosomes in each cell are switched off. ZFX is an exception and typically stays active on both copies. According to the study, this higher baseline expression in female brains could help maintain activity across the network when other genes are disrupted. [1] The Y chromosome carries a similar gene, ZFY, but it is a weaker activator of other genes. [1]

The team also reanalyzed existing gene-expression data from donated brain tissue and found evidence of reduced ZFX activity in excitatory neurons from autistic males. [1] The results fit the female protective effect hypothesis. A 2014 genetic study found that autistic women carried more autism genes than autistic men. [1]

## Limits of the study

The results do not show that ZFX alone is responsible for the protection. The experiments used a single male-derived stem-cell line, and comparing cells from men and women is needed to test whether the extra ZFX protects. [1]

The diagnostic gap may also partly reflect recognition. A 2012 population study found that girls with high autistic-trait scores were less likely to meet diagnostic criteria unless they also had intellectual or behavioral difficulties. Differences in presentation and camouflaging of traits could further complicate identification. [1]

Other biological explanations have not been ruled out. A study of amniotic fluid from male fetuses later diagnosed with autism found relatively higher steroid hormone activity. Other studies describe exposure to hormone-mimicking pollutants. [1]

## Sources

1. [New Atlas](https://newatlas.com/mental-health/one-gene-autism-affect-boys-more-than-girls)

---

Source: RealTech, realtech.media — https://realtech.media/news/rt-247fb17cc89610582b4502e9_boston_children_s/