DeCure for Intellectual developmental disorder, autosomal recessive 76
DeCure's autonomous Psychiatry AI scientist is researching a drug-repurposing hypothesis for intellectual developmental disorder, autosomal recessive 76 — 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 developmental disorder, autosomal recessive 76 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 developmental disorder, autosomal recessive 76 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
Three unrelated consanguineous families with deleterious homozygous variants in NSUN6 were identified. Two variants are predicted loss-of-function; one maps to the first exon and is predicted to lead to absence of NSUN6 via nonsense-mediated decay, the other maps to the last exon and encodes a protein that does not fold correctly. A missense variant in the third family lost its enzymatic activity and cannot bind the methyl donor S-adenosyl-L-methionine. Affected individuals present with developmental delay, intellectual disability, motor delay, and behavioural anomalies. Homozygous ablation of the NSUN6 ortholog in Drosophila led to locomotion and learning impairment. The authors conclude that biallelic pathogenic variants in NSUN6 cause one form of autosomal recessive intellectual disability.
A 2024 report describes two additional individuals with novel de novo variants in RFX7, a transcription factor important for neural development. Haploinsufficiency of RFX7 is associated with intellectual disability, developmental delay, and diverse brain structure malformations. Only 16 clinically described individuals with RFX7 variants existed before this report, and a recognisable pattern of malformation has not yet been uncovered. One of the two new individuals is from an under-represented Afro-Caribbean population.
A 2025 study of a Pakistani family with consanguineous parents identified a homozygous c.1693T>C;p.(Tyr565His) variant in SLC6A17 in a patient with autosomal recessive intellectual disability. This variant segregated with the phenotype in the extended family. The disorder, mental retardation autosomal recessive 48 (MRT48), is characterised by progressive tremors, speech impairment, and behavioural problems. The study broadens the genotypic spectrum of SLC6A17 variants.
No drug treatment is tested or proposed in any of these abstracts. What is missing is any clinical trial, any preclinical drug screen, any animal model of pharmacological intervention for these specific genes, and any patient stratification beyond family-based genetic diagnosis. Funding for functional assays and for developing small-molecule or gene-therapy approaches for these ultra-rare recessive disorders has not been reported.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Genetics in Medicine · 2023 · 20 citations · open access
Biallelic variants in NSUN6 cause an autosomal recessive neurodevelopmental disorder
AbstractPURPOSE: 5-methylcytosine RNA modifications are driven by NSUN methyltransferases. Although variants in NSUN2 and NSUN3 were associated with neurodevelopmental diseases, the physiological role of NSUN6 modifications on transfer RNAs and messenger RNAs remained elusive. METHODS: We combined exome sequencing of consanguineous families with functional characterization to identify a new neurodevelopmental disorder gene. RESULTS: We identified 3 unrelated consanguineous families with deleterious homozygous variants in NSUN6. Two of these variants are predicted to be loss-of-function. One maps to the first exon and is predicted to lead to the absence of NSUN6 via nonsense-mediated decay, whereas we showed that the other maps to the last exon and encodes a protein that does not fold correctly. Likewise, we demonstrated that the missense variant identified in the third family has lost its enzymatic activity and is unable to bind the methyl donor S-adenosyl-L-methionine. The affected individuals present with developmental delay, intellectual disability, motor delay, and behavioral anomalies. Homozygous ablation of the NSUN6 ortholog in Drosophila led to locomotion and learning impairment. CONCLUSION: Our data provide evidence that biallelic pathogenic variants in NSUN6 cause one form of autosomal recessive intellectual disability, establishing another link between RNA modification and cognition.
ACS Chemical Neuroscience · 2011 · 19 citations · open access
Fragile X Syndrome: An Update on Developing Treatment Modalities
AbstractIntellectual disability (ID; mental retardation) is considered an immutable condition. Current medical practices are aimed at relieving symptoms and not at altering the underlying cognitive deficits. Scientific advancements from the past decade have led to the exciting possibility that ID may now be treatable. Moreover, pharmaceutical therapies targeting the most common form of inherited ID, Fragile X syndrome (FXS), may become the new benchmark for central nervous system (CNS) drug discovery: seeking cures for neurodevelopmental disorders.
Whole-Exome Sequencing Identified a Novel DYRK1A Variant in a Patient With Intellectual Developmental Disorder, Autosomal Dominant 7
AbstractIntellectual developmental disorder, autosomal dominant 7 (MRD7; OMIM 614104) is a rare disease characterized by microcephaly, intellectual disability, speech delay, feeding difficulties, and facial dysmorphisms. This disorder is caused by pathogenic/likely pathogenic variants of the DYRK1A gene, which encodes dual-specificity tyrosine-phosphorylation-regulated kinase 1A. Here, we report a case of MRD7 that was diagnosed using Face2Gene and whole-exome sequencing (WES). A 22-year-old man presented with microcephaly, intellectual disability, slender body, long slender fingers, and facial dysmorphisms. He was previously diagnosed with Cornelia de Lange syndrome (CdLS) at four years of age. However, his CdLS clinical diagnostic score was low at 22 years of age. The Face2Gene application introduced several candidate diseases including MRD7. Finally, by utilizing WES and Sanger sequencing analysis of cloned cDNA, we identified a novel heterozygous duplication variant (c.848dup, p.(Asn283LysfsTer6)) in the DYRK1A gene, which introduces a premature stop codon. This report provides more information about the phenotypic spectrum of a young adult patient with MRD7. Face2Gene helped us introduce candidate diseases of the patient. Registering further genetically confirmed cases with MRD7 will improve the accuracy of the diagnostic recommendations in Face2Gene. Moreover, WES is a powerful tool for diagnosing rare genetic diseases, such as MRD7.
Indian journal of human genetics · 2013 · 4 citations
An incidental case of dihydropyrimidine dehydrogenase deficiency: One case, multiple challenges
AbstractDihydropyrimidine dehydrogenase (DPD) deficiency is an autosomal recessive disorder that shows large phenotypical variability, ranging from no symptoms to intellectual disability, motor retardation, and convulsions. In addition, homozygous and heterozygous mutation carriers can develop severe 5-fluorouracil (5-FU) toxicity. The lack of genotype-phenotype correlation and the possibility of other factors playing a role in the manifestation of the neurological abnormalities, make the management and education of asymptomatic DPD individuals more challenging. We describe a 3-month-old baby who was incidentally found by urine organic acid testing (done as part of positive newborn screen) to have very high level of thymine and uracil, consistent with DPD deficiency. Since the prevalence of asymptomatic DPD deficiency in the general population is fairly significant (1 in 10,000), we emphasize in this case study the importance of developing a guideline in genetic counseling and patient education for this condition as well as other incidental laboratory findings.
American Journal of Medical Genetics Part A · 2024 · 1 citations · open access
Expanding the clinical phenotype and variant spectrum associated with <scp><i>RFX7</i></scp>
AbstractRFX7 encodes a transcription factor that is ubiquitously expressed and important for neural development. Haploinsufficiency of RFX7 is associated with intellectual disability, developmental delay, and diverse malformations of brain structures. Currently, there are only 16 clinically described individuals who have variants in RFX7. A recognizable pattern of malformation associated with mutation in RFX7 has not yet been uncovered. Here we describe the phenotypic presentation of two additional individuals who have novel de novo variants in RFX7. One of the individuals we describe is from an under-represented Afro-Caribbean population.
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.
