DeCure for Intellectual disability, autosomal dominant 9
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for intellectual disability, autosomal dominant 9 — 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 moduleIntellectual disability, autosomal dominant 9 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 intellectual disability, autosomal dominant 9 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
kinesin family member 1A (KIF1A) — KIF1A 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 gtpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8UTS · 2.7 Å · ligand GUANOSINE-5'-TRIPHOSPHATE (GTP). Experimental structure, not a prediction.
What the evidence adds up to
Pathogenic variants in the X-linked gene USP9X cause syndromic intellectual disability in both sexes, with a reported penetrance of 95% in females and frequent de novo occurrence. A 2022 study identified a truncating variant, c.885_889delAAAAG, p.(Lys296Serfs*4), in two non-twin female siblings with phenotypic features of female-specific syndromic intellectual disability (MIM 300969, also known as MRX99F). X-inactivation analysis, RNA-Seq, and full quad exome sequencing failed to identify a modifier explaining the reduced penetrance in this family. The authors concluded that incomplete penetrance should be considered when evaluating USP9X variants in females.
A 2019 case report described a pregnant woman with intellectual disability who carried a chromosomal microdeletion 46,XX,del(11)(q24). Her fetus inherited the same deletion, 46,XN,del(11)(q24)mat, mapped by SNP-array and FISH to 11q24.1-q25. Both mother and fetus were diagnosed with Jacobsen syndrome. The authors recommended combined cytogenetic and molecular techniques for diagnosing intellectual disability in such families.
A 2020 report described two siblings with an unbalanced translocation, 46,XX,der(15)t(10;15)(q24.3;26.1)mat, resulting in distal trisomy 10q and monosomy 15q. Both conditions are rare and have distinctive clinical profiles. The origin of intellectual disability remains unknown in up to 60% of cases, and de novo mutations are a common cause in sporadic cases.
A 2025 study identified a homozygous missense variant, c.1693T>C;p.(Tyr565His), in SLC6A17 in a Pakistani family with autosomal recessive intellectual disability (MRT 48, OMIM 616269). The index patient was born to consanguineous parents and presented with progressive tremors, speech impairment, and behavioural problems. The variant segregated with the phenotype in the extended family. The study broadened the genotypic spectrum of SLC6A17 variants but did not test any intervention. No pharmacological treatments for intellectual disability were evaluated in any of these reports. What remains missing are large-scale functional studies to clarify penetrance modifiers, systematic screening of copy-number variants in undiagnosed cases, and any clinical trial designed to test a drug in patients with these specific genetic diagnoses.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
American Journal of Medical Genetics Part A · 2022 · 4 citations
Exome and <scp>RNA‐Seq</scp> analyses of an incomplete penetrance variant in <scp><i>USP9X</i></scp> in female‐specific syndromic intellectual disability
AbstractPathogenic variants in USP9X, on X chromosome, have been implicated in syndromic intellectual disability (ID) in both males and females with distinct craniofacial features. We report a truncating variant, c.885_889delAAAAG, p.(Lys296Serfs*4), in the USP9X gene with incomplete penetrance in two nontwin female siblings with phenotypic resemblance to female-specific syndromic ID (MIM 300969, also known as MRX99F). To investigate the possible genetic etiology of the reduced penetrance, X-inactivation, RNA-Seq, and full quad exome analyses were attempted, but failed to identify a promising candidate modifier. While the penetrance of pathogenic variants in USP9X in female appears to be high (95%) and the variants frequently occur de novo, incomplete penetrance should be considered.
[Prenatal diagnosis of Jacobsen syndrome in a fetus carried by a pregnant woman with intellectual disability].
AbstractOBJECTIVE: To assess the value of combined cytogenetic and molecular techniques for the prenatal diagnosis of a pregnant woman with intellectual disability (ID). METHODS: The fetus and its parents were subjected to G-banding karyotyping analysis, single nucleotide polymorphism array (SNP-array) and fluorescence in situ hybridization (FISH) analysis. RESULTS: G-banding karyotype analysis revealed that the woman has carried a chromosomal microdeletion 46,XX,del(11)(q24), and the fetus was a carrier of 46,XN,del(11)(q24)mat. Subsequent SNP-array and FISH analysis of the pregnant woman indicated that the microdeletion has mapped to 11q24.1-q25. Both the pregnant woman and her fetus were diagnosed with Jacobsen syndrome. CONCLUSION: Combined use of cytogenetic and molecular genetic techniques can facilitate diagnosis of patients with intellectual disability.
Iowa Research Online (The University of Iowa) · 2022 · 0 citations · open access
Behavioral and brain phenotypes of mouse models of Bardet-Biedl Syndrome
AbstractIntellectual disability (ID) is one of the most common neurodevelopmental disorders, affecting 1% of the population globally. Clinically, ID is characterized by a deficit in intellectual functioning and adaptive functioning. There are limited pharmacological interventions for ID, partially due to a poor understanding of ID and the heterogeneous nature of ID In addition, there are limited mouse models of ID.
Dusunen Adam The Journal of Psychiatry and Neurological Sciences · 2020 · 0 citations · open access
10q distal trisomy and 15q monosomy as a rare genetic cause for intellectual disability
AbstractIntellectual disability (ID) is defined as a neurodevelopmental disorder. The prevalence is 1% to 3%. Genetic factors strongly contribute to the etiology of ID; however, the origin remains unknown in up to 60% of the cases. De novo mutations are a common genetic cause in sporadic cases of ID. This report describes the cases of 2 siblings with distinctive phenotypical features and neurodevelopmental disorders with an unbalanced translocation, (46,XX,der[15]t[10;15][q24.3;26.1]mat), resulting in trisomy of the long arm of chromosome 10 and monosomy of the long arm of chromosome 15. The cases are thought to be associated with distal trisomy 10q syndrome and monosomy 15q syndrome. Both trisomy 10q and monosomy 15q syndromes are rare diseases with distinctive clinical profiles.
Biallelic Variant in <scp> <i>SLC6A17</i> </scp> in a Pakistani Family With Autosomal Recessive Intellectual Disability
AbstractAutosomal recessive intellectual disability affects 1%-3% of the general population and is a major concern in countries where consanguineous marriages are common. Mental retardation autosomal recessive 48 (MRT 48) (OMIM 616269) is a recessive syndromic disorder characterized by progressive tremors, speech impairment, and behavioral problems. In the present study, we highlight a family with a case of MRT 48. The index patient was second born to healthy consanguineous parents with a history of intellectual disability. Whole exome sequencing of the patient was performed, which revealed a homozygous c.1693T>C;p.(Tyr565His) variant in the SLC6A17 gene. The variant segregated in the extended family with the phenotype. This study broadens the genotypic spectrum of SLC6A17 variants.
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.
