protein
Homeobox protein ARX
Gene
ARX
Organism
Homo sapiens(9606)
Length
562 aa
Mass
58,160 Da
# Homeobox Protein ARX
Homeobox protein ARX (ARX) is a transcription factor that binds to specific DNA sequence motifs (5'-TAATTA-3') to regulate target genes, including histone demethylase KDM5C, which it activates both independently and synergistically with other regulatory proteins (UniProt: Q96QS3). ARX is a 562-amino acid protein essential for normal brain development, with documented roles in neuronal proliferation, interneuronal migration and differentiation in the embryonic forebrain, as well as potential involvement in axonal guidance.
ARX mutations cause severe neurodevelopmental disorders characterized by epilepsy, structural brain abnormalities, and intellectual disability. These include X-linked lissencephaly with abnormal genitalia (LISX2), developmental and epileptic encephalopathy 1 (DEE1) featuring suppression-burst EEG patterns and potential progression to West syndrome, Partington syndrome marked by dystonic movements and spasticity, and agenesis of the corpus callosum with intellectual disability and seizures (UniProt: Q96QS3). Additional associations include X-linked intellectual developmental disorder 29 (XLID29).
ARX is classified as SFARI Category S (syndromic) for autism spectrum disorder, reflecting its established role in neurodevelopmental pathology (SFARI Cat S). The protein's involvement in cortical patterning and neuronal development links its dysfunction to both autism and broader epileptic encephalopathies in affected individuals.
Generated from the curated entity record below. May contain errors — verify against source links.
Genetic Evidence · ASD
Source: SFARI Gene database · gene.sfari.org
Related Publications
Browse all →Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.
Ruzzo Elizabeth K et al.Cell2019PMID 31398340Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model.
Guo Hui et al.Molecular autism2018PMID 30564305Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder.
C Yuen Ryan K et al.Nature neuroscience2017PMID 28263302Identification of common genetic risk variants for autism spectrum disorder.
Grove Jakob et al.Nature genetics2019PMID 30804558Synaptic, transcriptional and chromatin genes disrupted in autism.
De Rubeis Silvia et al.Nature2014PMID 25363760
Function
Transcription factor (PubMed:22194193, PubMed:31691806). Binds to specific sequence motif 5'-TAATTA-3' in regulatory elements of target genes, such as histone demethylase KDM5C (PubMed:22194193, PubMed:31691806). Positively modulates transcription of KDM5C (PubMed:31691806). Activates expression of KDM5C synergistically with histone lysine demethylase PHF8 and perhaps in competition with transcription regulator ZNF711; synergy may be related to enrichment of histone H3K4me3 in regulatory elements (PubMed:31691806). Required for normal brain development (PubMed:11889467, PubMed:12379852, PubMed:14722918). Plays a role in neuronal proliferation, interneuronal migration and differentiation in the embryonic forebrain (By similarity). May also be involved in axonal guidance in the floor plate (By similarity)
Disease associations
Lissencephaly, X-linked 2LISX2
A classic type lissencephaly associated with abnormal genitalia. Patients have severe congenital or postnatal microcephaly, lissencephaly, agenesis of the corpus callosum, neonatal-onset intractable epilepsy, poor temperature regulation, chronic diarrhea, and ambiguous or underdeveloped genitalia.
Developmental and epileptic encephalopathy 1DEE1
A severe form of epilepsy characterized by frequent tonic seizures or spasms beginning in infancy with a specific EEG finding of suppression-burst patterns, characterized by high-voltage bursts alternating with almost flat suppression phases. Patients may progress to West syndrome, which is characterized by tonic spasms with clustering, arrest of psychomotor development, and hypsarrhythmia on EEG.
Partington syndromePRTS
An X-linked developmental disorder characterized by intellectual disability, episodic dystonic hand movements, lower limb spasticity, and dysarthria.
Intellectual developmental disorder, X-linked 29XLID29
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Intellectual deficiency is the only primary symptom of non-syndromic X-linked forms, while syndromic intellectual disability presents with associated physical, neurological and/or psychiatric manifestations.
Agenesis of the corpus callosum, with abnormal genitaliaACCAG
An X-linked syndrome with variable expression in females. It is characterized by agenesis of corpus callosum, intellectual disability and seizures. Manifestations in surviving males include severe acquired micrencephaly, intellectual disability, limb contractures, scoliosis, tapered fingers with hyperconvex nails, a characteristic face with large eyes, prominent supraorbital ridges, synophrys, optic atrophy, broad alveolar ridges, and seizures. Urologic anomalies include renal dysplasia, cryptorchidism, and hypospadias.
Sources
Last updated 5/6/2026, 5:24:53 AM