DeCure for Syndromic X-linked intellectual disability 94
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for syndromic X-linked intellectual disability 94 — screening already-approved drugs against its 1-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 94 maps to a 1-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 94 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.
What the evidence adds up to
The 2002 study identified a novel 2 bp deletion (564delGT) in the TM4SF2 gene that segregates with mental retardation in the MRX58 family. The deletion causes a frameshift and a stop codon six amino acids downstream. This finding came from screening probands from 14 XLMR families (10 linked to Xp11 and four small families with no linkage data). At that time, only nine non-syndromic XLMR genes had been cloned, including TM4SF2, FMR2, OPHN1, GDI1, PAK3, RSK2, IL1RAPL, ARHGEF6, and MECP2. The study supported the hypothesis that different XLMR conditions, especially non-syndromic forms, result from mutations in the same gene.
A 2019 review of the ARX gene states that mutations in ARX are responsible for about 9.5% of XLID cases. The ARX gene is located on Xp22.13 and encodes a highly conserved protein involved in the Wnt/β-catenin signalling pathway. The review notes that ARX deficiency can cause irreversible defects, mainly in brain, leading to XLID. The authors performed bioinformatics analysis of molecular features, second and quaternary structures, and a phylogeny tree of ARX protein, concluding that the functional domains are highly conserved and that mutations are predicted to be highly pathogenic.
A 2017 review of X-linked intellectual disability states that deleterious mutations in about 10% of X-chromosome genes are implicated in causing XLID disorders in about 50% of families. The remaining XLID genes are expected to be rare and even private to individual families. At least 209 different XLID disorders have been described, including 143 forms of syndromic mental retardation. Fragile X syndrome is the most frequent and most studied XLID syndrome. It is now possible to identify 64% of the genetic defects in XLID families with obligate female carriers. Most mutated genes are thought to influence development, cell migration, formation and maintenance of neural networks, and cell-to-cell communication in the brain.
What is still missing for syndromic X-linked intellectual disability 94 specifically is any clinical trial testing a drug or intervention. No treatment data exist in these abstracts. The genetic basis is heterogeneous, with many genes rare or private to single families, making patient stratification difficult. Funding for functional studies and for developing animal models of specific mutations, such as the TM4SF2 deletion, is lacking. No clinical trial design has been proposed.
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 Medical Genetics · 2002 · 43 citations · open access
A novel 2 bp deletion in the <i>TM4SF2</i> gene is associated with MRX58
AbstractX linked mental retardation (XLMR) represents around 5% of all MR, with a prevalence of 1 in 600 males.1,2 Fifteen to twenty percent of the total XLMR is the result of the fragile X syndrome.3 Non-fragile X mental retardation was subdivided into syndromal and non-syndromal conditions by Neri et al 4 in 1991. The syndromal XLMR entities (MRXS) are those in which there is a specific pattern of physical, neurological, or metabolic abnormalities associated with the presence of mental retardation.5 Non-syndromic XLMR (MRX) are conditions in which a gene mutation causes mental retardation in the absence of other distinctive dysmorphic, metabolic, or neurological features.6 At present, XLMR conditions consist of 136 MRXS7 and 75 MRX8 entities. To date, 35 genes have been cloned. However, so far only nine non-syndromic XLMR genes have been identified: TM4SF2 , FMR2 , OPHN1 (MRX60), GDI1 (MRX41, MRX48), PAK3 (MRX30, MRX47), RSK2 (MRX19), IL1RAPL (MRX34), ARHGEF6 (MRX46), and MECP2 (MRX16).9–18
TM4SF2 , a member of the transmembrane 4 superfamily, maps to Xp11.4 and is one of the genes associated with non-syndromic XLMR.9 Mutations in TM4SF2 have been previously described in two families (L28 and T15) with non-syndromic XLMR. As a part of our XLMR candidate gene testing, we have screened probands from 14 XLMR families (10 linked to Xp11 and four small families with no linkage data) for mutations in the TM4SF2 gene. Here we report a novel 2 bp deletion (564delGT), which segregates with mental retardation in the MRX58 family. The deletion causes a frameshift and a subsequent stop codon six amino acids downstream (stop codon 192). This finding supports the hypothesis that different XLMR conditions, especially non-syndromic XLMR, result from mutations in the same gene.
### Patients
Probands from 14 XLMR families (three MRXS and …
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.
Encyclopedia of Life Sciences · 2017 · 0 citations
Genetics of <scp>X</scp> ‐Linked Intellectual Disability
AbstractAbstract X‐linked intellectual disability (XLID), formerly called mental retardation , refers to a group of inherited disorders characterised by varying degrees of intellectual disability caused by mutations in various genes present on the X‐chromosome. Deleterious mutations in ∼ 10% of X‐chromosome X genes are implicated in causing XLID disorders in ∼ 50% of families. The remaining XLID genes are expected to be rare and even private to individual families. Historically, XLID is divided into syndromic (IDXS) and nonsyndromic (IDX). At least 209 different XLID disorders have been described including 143 forms of syndromic mental retardation. Fragile X syndrome is the most frequent syndrome and most studied XLID syndrome. It is now possible to identify 64% of the genetic defects in XLID families with obligate female carriers. Most of the mutated genes in XLID are thought to influence development, cell migration, formation and maintenance of neural networks and cell‐to‐cell communication in the brain. Thus, the diagnosis of intellectual disability in a child has an enormous impact in most affected families. Genetic counselling is strongly recommended to family members. Key Concepts X‐linked intellectual disability (XLID) is a very heterogeneous set of conditions responsible for a large proportion of inherited mental retardation. XLID can be divided into syndromic (MRID) and nonsyndromic (IDX). Genes involved in XLID influence development, cell migration, formation and maintenance of neural networks and cell‐to‐cell communication in the brain. Intellectual disability phenotype can emerge as the final common pathway for many different types of abnormal cellular processing. Genetic counselling is an important part in general management in the case of intellectual disability.
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.
