ARX

aristaless related homeobox

5 disorders 2 causative 2 untyped 1 no genetic record Xp21.3 gene with protein product

HGNC:18060 Monarch NCBI Gene 170302 ENSG00000004848 UniProt Q96QS3 OMIM 300382

Previous symbols: MRXS1, PRTS, MRX76, MRX54, MRX43, MRX36, MRX29, MRX32, MRX33, MRX38, MRX87. Aliases: ISSX, CT121, EIEE1.

Normal function · from ai-gene-review (Q96QS3, commit 79fe13b38970) · AI-generated, not KB evidence

ARX is a paired homeobox transcription factor that binds cis-regulatory DNA and activates or represses gene expression according to target and cellular context. It acts in the nucleus and participates in neuronal development, pancreatic alpha-cell specification and selected intestinal endocrine lineages. ARX can cooperate with the histone demethylase PHF8 in activating KDM5C. Pathogenic ARX variants cause a spectrum of X-linked neurodevelopmental disorders, including developmental and epileptic encephalopathy, Partington syndrome and lissencephaly with abnormal genitalia.

Recognizes cis-regulatory DNA and regulates RNA polymerase II transcription, repressing targets such as LMO1/SHOX2 and enhancing KDM5C activation together with PHF8. This nuclear activity contributes to neuronal development and selected pancreatic and intestinal endocrine differentiation programs; direct downstream targets for every developmental context remain unresolved.

molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific · directly involved in: neuron development; pancreatic A cell differentiation; intestinal type I enteroendocrine cell differentiation; intestinal type L enteroendocrine cell differentiation · locations: chromatin

In the knowledge base · computed from kb/ at build time

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.

Disorder	Relationship	Where the gene appears
Early-Infantile Developmental and Epileptic Encephalopathy	causative
Non-Syndromic X-Linked Intellectual Disability	causative	mechanism: Convergent Disruption of Neuronal Function subtype: ARX-related scoped to subtype: ARX-related
Lissencephaly Spectrum Disorders	untyped Pathogenic variant	mechanism: ARX-Dependent Interneuron Tangential Migration Failure subtype: ARX-related scoped to subtype: ARX-related
X-Linked Lissencephaly With Abnormal Genitalia (ARX-Related)	untyped Causative	mechanism: ARX Functional Deficiency; ARX-Dependent Transcriptional Program Disruption; Subpallial Interneuron Lineage Program Disruption animal model: Mouse (Mus musculus)
Infantile Spasms	no genetic record	mechanism: Developing brain epileptic network hyperexcitability; Heterogeneous developmental brain etiologies

ClinGen gene–disease validity · snapshot 2026-10-03 · matched to entries by MONDO

An entry matches when ClinGen's MONDO disease is the entry's own disease term, a subtype term, or an exact-match mapping. An amber status marks an entry ClinGen supports the gene for (Definitive, Strong or Moderate) whose own record does not type it. A Limited, Disputed or Refuted tier on such an entry is not a gap.

ClinGen disease	MOI	Classification	dismech entry
genetic developmental and epileptic encephalopathy MONDO:0100062	XL	Definitive 2019-06-04	Genetic Developmental and Epileptic Encephalopathy not named
X-linked complex neurodevelopmental disorder MONDO:0100148	XL	Definitive 2020-12-01	no dismech entry

Mechanism modules · computed from kb/

epilepsy_excitation_inhibition_imbalance via Infantile Spasms
interneuron_specification_tangential_migration_failure via Lissencephaly Spectrum Disorders, X-Linked Lissencephaly With Abnormal Genitalia (ARX-Related) named in the module itself

Identity from HGNC (snapshot 2026-10-01). Page layers are described in the gene pages documentation.