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Published on: October 17, 2025

Rare Variants in Purinergic P2X Receptor Genes (P2RX4, P2RX5, P2RX7) in Individuals With Autism Spectrum Disorder: An

Gül Ünsel-Bolat1, Hilmi Bolat2

  • 1Department of Child and Adolescent Psychiatry, Faculty of Medicine, Balıkesir University, Balıkesir, Türkiye, balikesir.edu.tr.

Human Mutation
|July 19, 2026
PubMed
Abstract

Insights

Rare variants in Purinergic P2X receptors (P2RX) genes are explored for their potential link to autism spectrum disorder (ASD). While preliminary, these P2RX gene variants may offer insights into ASD-related neuroinflammatory pathways.

Area of Science:

  • Neuroscience
  • Genetics
  • Biochemistry

Background:

  • Purinergic P2X receptors (P2RX) mediate ATP-gated ion channel signaling crucial for neuroinflammation.
  • P2RX dysregulation is linked to maternal immune activation, mitochondrial dysfunction, oxidative stress, and synaptic abnormalities in autism spectrum disorder (ASD).
  • The specific contribution of P2RX gene variants to ASD pathogenesis remains largely uncharacterized.

Purpose of the Study:

  • To investigate the presence and potential role of P2RX gene variants in individuals diagnosed with ASD.
  • To analyze clinical, genetic, and in silico data for identified P2RX variants.

Main Methods:

  • Retrospective analysis of whole-exome sequencing (WES) data from individuals with ASD.
  • Identification of variants within the P2RX1-P2RX7 gene family.
  • Classification of variants using ACMG/AMP guidelines and in silico pathogenicity predictions.

Main Results:

  • Eleven individuals with heterozygous P2RX variants were identified, predominantly in P2RX7 (54.5%), P2RX5 (27.3%), and P2RX4 (18.2%).
  • Core clinical features included ASD, intellectual disability (ID), and epilepsy.
  • In silico analyses suggested moderate to high functional impact for several variants, though functional validation data were limited.

Conclusions:

  • Rare P2RX variants represent preliminary, hypothesis-generating findings potentially relevant to ASD pathways.
  • Further large-scale genetic studies and functional investigations are required to validate any association or causality between P2RX variants and ASD.
Keywords:
P2X receptorsautism spectrum disordergenetic variantsmaternal immune activationneuroinflammationpurinergic signalingwhole-exome sequencing

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