DeCure for Syndromic X-linked intellectual disability Najm type
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for syndromic X-linked intellectual disability Najm type — screening already-approved drugs against its 2-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleSyndromic X-linked intellectual disability Najm type maps to a 2-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for syndromic x-linked intellectual disability najm type is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
calcium/calmodulin dependent serine protein kinase (CASK) — CASK is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet 2r,3s,4r,5rdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3C0I · 1.85 Å · ligand [(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] dihydrogen phosphate (3AM). Experimental structure, not a prediction.
What the evidence adds up to
The 2019 review states that ARX gene mutations are responsible for about 9.5% of X-linked intellectual disability (XLID) cases, and that XLID has a prevalence of 2.6 per 1,000 in the general population, accounting for over 10% of all intellectual disability. Two thirds of XLID cases are thought to be non-syndromic. The ARX gene is located on Xp22.13 and encodes a highly conserved protein involved in the Wnt/β-catenin signalling pathway. The review predicts that mutations in this gene are highly pathogenic because the functional domains of the ARX protein are highly conserved across species, and that its deficiency causes irreversible defects mainly in brain development.
The 2016 chapter reports that more than 110 mutations have been described in ARX. The phenotype always includes intellectual disability and often includes epilepsy, infantile spasms, hand dystonia, lissencephaly, autism, or dysarthria. The chapter notes that ARX is one of the most frequently mutated XLID genes, after FMR1 and MECP2. No quantitative survival or response data are given in either of these two reviews.
The 2015 paper describes two brothers with non-syndromic X-linked intellectual disability carrying a novel NLGN4X splicing mutation (g.1202C>A). The mutation was identified by X exome sequencing and confirmed by Sanger sequencing. The mother was heterozygous with a skewed X inactivation pattern (100%) and was not affected. The mutation was absent in a non-affected daughter. The paper does not report any treatment or intervention; it only confirms the efficiency of X exome sequencing for identifying specific genetic conditions not clinically suspected. No drug is mentioned in any of the three abstracts.
What is still missing for syndromic X-linked intellectual disability Najm type specifically is any clinical trial, any drug tested, any quantitative outcome data such as survival or response rates, and any patient stratification. The abstracts provide no evidence for any treatment. The Najm type is not named in these abstracts, so its molecular distinction from other ARX-related syndromes remains unaddressed. Funding for natural history studies and for development of animal models would be needed before any drug could be considered.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Journal of genetics and molecular biology · 2019 · 4 citations
ARX gene with an impressive role in X-linked intellectual disability
AbstractIntellectual disability is the most common neurodevelopmental defect in the worldwide. X-linked intellectual disability (XLID) is the frequent form of intellectual disability which includes a heterogeneous group of inherited disorders emerging as various degrees of intellectual disabilities. XLID has a prevalence of 2.6 cases per 1,000 in the general population and accounts for over 10% of all cases of intellectual disability. Based on associated phenotypes, XLID is subdivided into syndromic (S-XLID) and non-syndromic (NS-XLID) forms; where two third of XLID cases are thought to be non-syndromic. Among the non-syndromic form, the aristalessrelated homeobox gene (ARX) gene is one of the ideal candidates to be evaluated in NS-XLID, since its mutations are responsible for about 9.5% of XLID cases. The ARX is located on the Xp22.13 genomic region and encodes a highly conserved protein with a considerable role in Wnt/β-catenin signaling pathway. Base on review literature, mutations in ARX gene has a particular influence on the critical processes associated with the brain development. Our results in bioinformatics study of molecular features, second and quaternary structures of ARX gene and also the phylogeny tree of ARX protein is showed that the ARX is a highly conserved protein with a substantial role in an important developmental pathway and its deficiency can cause irreversible defects, mainly in brain, that leads to the development of XLID as a common form of intellectual disability and also, the sequence alignment of this protein with other spices confirms that the functional domains of ARX protein are highly conserved, thus it has been predicted that the mutations of this gene is highly pathogenic. Alongside, we mainly focused to gather the data addressing the structural properties of ARX protein and bioinformatics assay of this protein to find the important role of ARX gene in the integrity of normal brain development.
Oxford University Press eBooks · 2016 · 3 citations
Developmental Abnormalities Due to Mutations in the Aristaless-Related Homeobox Gene
AbstractAbstract Intellectual disability is a broad spectrum of neurodevelopmental disorders of the brain that combined affect approximately one in 50 individuals worldwide. X-linked intellectual disabilities represent a group of disorders where mutations arise on the X-chromosome. XLID is clinically complex and genetically heterogeneous. In excess of 100 genes are currently known. One of the most frequently mutated XLID genes (after e.g. FMR1 or MECP2) is the Aristaless related homeobox (ARX) gene. More than 110 mutations have been reported in ARX. The phenotype always involves intellectual disability and often also epilepsy, infantile spasms, hand dystonia, lissencephaly, autism or dysarthria. This chapter summarizes currently known mutations in ARX and their clinical manifestations and explores what is known about the underlying molecular and cellular mechanisms.
Greater South Information System · 2015 · 0 citations · open access
Non-Syndromic X Linked Intellectual Disability in Two Brothers with A Novel NLGN4X Gene Splicing Mutation (NC_018934.2: g. 1202C>A)
AbstractX-linked Intellectual Disability (XLID) is an extremely heterogeneous disorder for which many of the causative genes are still unknown.So far, more than one hundred genes of the X chromosome have been found to be altered in males manifesting intellectual disability (ID).NLGN4X is an XLID gene, which has been found, involved in autism and Asperger syndrome involving causative coding mutations.Up to now a few pathological mutations in the promoter and the 5' UTR have been identified.Here we report a non-syndromic X linked Intellectual disability in two brothers with a novel NLGN4X splicing mutation predicted to have a pathogenic effect by the activation of an exonic cryptic acceptor site, with presence of one or more cryptic branch point(s).This mutation g.1202C>A (Genbank accession number NC_018934.2) was identified through X exome sequencing.It was confirmed by Sanger sequencing.The mother was heterozygous with a skewed X inactivation pattern (100%).She is not affected.This variant was predicted to change the splicing process leading to potential alteration of the mRNA.This mutation segregates with the pathological phenotype in all the affected males.However, it was absent in the non-affected daughter, we suggest that it could be in favor of genotype-phenotype correlation.This study also confirms the efficiency of X exome sequencing for identifying specific genetic conditions not clinically suspected.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
