Features include always present findings: Exaggerated startle response, Hypertonia, Loss of previously acquired skills (developmental regression), and Global developmental delay and others; and common findings: Bilateral tonic-clonic seizure, Trigonocephaly, Focal impaired awareness seizure, and Overgrowth and others.

ARHGEF9 encodes Cdc42 guanine nucleotide exchange factor 9 (516 aa). Acts as a guanine nucleotide exchange factor (GEF) for CDC42. Promotes formation of GPHN clusters Highest expression in Brain Frontal Cortex BA9 (36.4 TPM) and Brain Cerebellar Hemisphere (32.1 TPM).

Developmental and epileptic encephalopathy, 8 is associated with mutations in the ARHGEF9 gene on chromosome X.

The ARHGEF9 protein participates in RHOJ GEFs activate RHOJ, RHOQ GEFs activate RHOQ, and RHOC GEFs activate RHOC pathways.

ARHGEF9 is classified as a druggable target with score 0.0.

Genetic testing for ARHGEF9 is available. Testing is considered confirmatory for diagnosis.

Phenotype severity distribution: 7 always present features, 6 common features.

Estimated prevalence: <1 in 1,000,000 (VERY_RARE).

No clinical trials have been registered for developmental and epileptic encephalopathy, 8.

4 publications have been identified in PubMed for developmental and epileptic encephalopathy, 8. Research spans Review / Meta-Analysis (50%) and Basic Science / Preclinical (50%).

Recent Publications

• Medyanik AD (2025). [PMID: 39858526](https://pubmed.ncbi.nlm.nih.gov/39858526/). *Biomolecules*. [Review / Meta-Analysis]

• Akter H (2025). [PMID: 40671880](https://pubmed.ncbi.nlm.nih.gov/40671880/). *Genetics in medicine open*. [Basic Science / Preclinical]

• Wang W (2024). [PMID: 39374387](https://pubmed.ncbi.nlm.nih.gov/39374387/). *Proceedings of the National Academy of Sciences of the United States of America*. [Basic Science / Preclinical]

• Bernardo P (2024). [PMID: 38612920](https://pubmed.ncbi.nlm.nih.gov/38612920/). *International journal of molecular sciences*. [Review / Meta-Analysis]