ARX

Protein identityUniProt · HPA

UniProt accession

Q96QS3

Gene

ARX

Ensembl

ENSG00000004848

Chromosome

X

Canonical length

562 aa

Protein class

Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins, Transcription factors

OverviewNCBI Gene

This gene is a homeobox-containing gene expressed during development. The expressed protein contains two conserved domains, a C-peptide (or aristaless domain) and the prd-like class homeobox domain. It is a member of the group-II aristaless-related protein family whose members are expressed primarily in the central and/or peripheral nervous system. This gene is thought to be involved in CNS development. Expansion of a polyalanine tract and other mutations in this gene cause X-linked cognitive disability and epilepsy. [provided by RefSeq, Jul 2016]

Canonical amino-acid sequenceUniProt

562 residues, UniProt reviewed canonical sequence.

>Q96QS3|ARX
     1  MSNQYQEEGC SERPECKSKS PTLLSSYCID SILGRRSPCK MRLLGAAQSL PAPLTSRADP
    61  EKAVQGSPKS SSAPFEAELH LPPKLRRLYG PGGGRLLQGA AAAAAAAAAA AAAAATATAG
   121  PRGEAPPPPP PTARPGERPD GAGAAAAAAA AAAAAWDTLK ISQAPQVSIS RSKSYRENGA
   181  PFVPPPPALD ELGGPGGVTH PEERLGVAGG PGSAPAAGGG TGTEDDEEEL LEDEEDEDEE
   241  EELLEDDEEE LLEDDARALL KEPRRCPVAA TGAVAAAAAA AVATEGGELS PKEELLLHPE
   301  DAEGKDGEDS VCLSAGSDSE EGLLKRKQRR YRTTFTSYQL EELERAFQKT HYPDVFTREE
   361  LAMRLDLTEA RVQVWFQNRR AKWRKREKAG AQTHPPGLPF PGPLSATHPL SPYLDASPFP
   421  PHHPALDSAW TAAAAAAAAA FPSLPPPPGS ASLPPSGAPL GLSTFLGAAV FRHPAFISPA
   481  FGRLFSTMAP LTSASTAAAL LRQPTPAVEG AVASGALADP ATAAADRRAS SIAALRLKAK
   541  EHAAQLTQLN ILPGTSTGKE VC

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ARX can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.66

Highest tissue expression

78 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ARX.

Disease | AllUniProt

Conditions ARX is implicated in, by any mechanism.

• Lissencephaly, X-linked 2 (LISX2) MIM:300215
• Developmental and epileptic encephalopathy 1 (DEE1) MIM:308350
• Partington syndrome (PRTS) MIM:309510
• Intellectual developmental disorder, X-linked 29 (XLID29) MIM:300419
• Agenesis of the corpus callosum, with abnormal genitalia (ACCAG) MIM:300004

Disease | GeneticClinVar

142 pathogenic / likely-pathogenic of 973 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Developmental and epileptic encephalopathy, 1
• Intellectual disability, X-linked, with or without seizures, ARX-related
• X-linked lissencephaly with abnormal genitalia
• Corpus callosum agenesis-abnormal genitalia syndrome
• Partington syndrome

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.39

gnomAD pLI

0.91

gnomAD missense Z

2.05

DepMap mean gene effect

0.02

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 0% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• axon guidance
• cell proliferation in forebrain
• cerebral cortex GABAergic interneuron migration
• cerebral cortex tangential migration
• embryonic olfactory bulb interneuron precursor migration
• epithelial cell fate commitment
• globus pallidus development
• lipid digestion
• negative regulation of transcription by RNA polymerase II
• neuron development
• neuron fate commitment
• organ growth
• positive regulation of gene expression
• positive regulation of organ growth
• positive regulation of transcription by RNA polymerase II
• regulation of epithelial cell proliferation
• regulation of transcription by RNA polymerase II

Molecular functions

• chromatin binding
• DNA-binding transcription activator activity, RNA polymerase II-specific
• DNA-binding transcription factor activity, RNA polymerase II-specific
• DNA-binding transcription repressor activity, RNA polymerase II-specific
• RNA polymerase II cis-regulatory region sequence-specific DNA binding
• RNA polymerase II transcription regulatory region sequence-specific DNA binding
• sequence-specific double-stranded DNA binding

Cellular components

• chromatin
• nucleus

Protein domainsUniProt · Pfam · InterPro

• Homeodomain
• OAR domain
• Homedomain-like superfamily
• Homeobox, conserved site
• Paired Homeobox Transcription Factors
• Homeodomain
• OAR motif

KeywordsUniProt

• Developmental protein
• Differentiation
• DNA-binding
• Epilepsy
• Homeobox
• Intellectual disability
• Lissencephaly
• Neurogenesis
• Nucleus
• Transcription
• Transcription regulation
• Triplet repeat expansion

InteractionsUniProt · HPA

Protein binding partners of ARX in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• ACTN1
• PICK1