DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Harel-Yoon syndrome — 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 moduleHarel-Yoon syndrome 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 harel-yoon syndrome 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
chromodomain helicase DNA binding protein 5 (CHD5) — CHD5 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 apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6GUU · 2.95 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Harel-Yoon syndrome is caused by mutations in the ATAD3A gene on chromosome 1p36.33, a gene involved in mitochondrial DNA stabilisation, mitochondrial fission/fusion regulation, and cholesterol homeostasis. Two case reports describe novel mutations. In a 2023 report, an 11-year-old boy of consanguineous Egyptian parents with neuroregression, ptosis, and progressive impaired vision was found to carry a novel ATAD3A deletion (c.624_644del). In a 2025 report, a 34-day-old female infant presenting with intermittent irritability, poor feeding, hyperammonaemia, lactic acidosis, and cardiomyopathy was found to have a de novo heterozygous missense variant (c.1582C>T, p.Arg528Trp), classified as pathogenic by ACMG guidelines. Both parents in the second case were phenotypically normal and non-consanguineous.
The 2023 case documented characteristic features of neurodevelopmental delay, hypotonia, and peripheral neuropathy, but also added novel features: fatiguable ptosis, facial weakness, progressive bulbar palsy, obsessive-compulsive disorder, and cone system dysfunction documented by electroretinogram and optical coherence tomography. The 2025 case added cardiac insufficiency and cardiomyopathy to the recognised phenotype. Neither report provides survival data, response rates, or sample sizes beyond single patients. No treatment was tested or recommended in either study.
The two reports expand the known genotype-phenotype spectrum of Harel-Yoon syndrome but remain single-case descriptions. What is still missing is any systematic trial design, any patient stratification by mutation type or age, and any funding for natural history studies or preclinical work that could identify druggable pathways. Without these, the clinical utility of the genetic findings remains limited to diagnosis.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Ophthalmic Genetics · 2023 · 9 citations
Harel Yoon syndrome: a novel mutation in ATAD3A gene and expansion of the clinical spectrum
AbstractBACKGROUND: Harel-Yoon syndrome (HAYOS) is a recently described neurodevelopmental disorder characterized by psychomotor delay, truncal hypotonia, appendicular spasticity, and peripheral neuropathy. It is caused by mutations in ATAD3A gene located on chromosome 1p.36.33 whose functions include mitochondrial DNA stabilization, the regulation of mitochondrial fission/fusion, and cholesterol homeostasis. MATERIALS AND METHODS: An 11-year-old male patient of consanguineous Egyptian parents, who present with neuroregression and ptosis along with progressive impaired vision, undergoes complete ophthalmological and neurological examination. Additionally, color fundus photography, fundus autofluorescence (FAF), spectral domain optical coherence tomography (SD-OCT) of both the macula and optic nerve head, full field electroretinogram (ERG), and visual field perimetry were obtained. Whole-exome sequencing and mitochondrial genome sequencing were done in a commercial laboratory from a peripheral blood sample. RESULTS: A novel mutation in ATAD3A gene c.624_644del was identified by whole-exome sequencing consistent with a diagnosis of Harel-Yoon Syndrome (HAYOS). The 11-year-old boy had characteristic features of neurodevelopmental delay, hypotonia, and peripheral neuropathy. However, we documented some novel features as fatiguable ptosis, facial weakness, progressive bulbar palsy, obsessive-compulsive disorder (OCD) in addition to cone system dysfunction. CONCLUSION: Our study reports a novel mutation in ATAD3A gene and expands the clinical spectrum of Harel-Yoon Syndrome. Future research aiming at better understanding of gene function will lead to better genotype-phenotype correlation and could pave the way to more treatment options.
AIMS Allergy and Immunology · 2025 · 0 citations · open access
A case report of Harel-Yoon syndrome associated with ATAD3A gene variants
AbstractIn this study, we reported a rare case of Harel-Yoon syndrome (HAYOS) caused by a mutation in the ATAD3A gene on chromosome 1p36.33. A 34-day-old female infant presented with the chief complaints of “intermittent irritability and poor feeding for 8 days, worsening over the past hour.” Laboratory investigations revealed hyperammonemia and lactic acidosis. Cardiac injury biomarkers and inflammatory markers were elevated. Echocardiography indicated cardiac insufficiency and cardiomyopathy. Both parents were phenotypically normal, non-consanguineous, and had no family history of inherited disorders. Further whole-exome sequencing (including mitochondrial DNA) identified a heterozygous missense variant, c.1582C>T (p.Arg528Trp), in the ATAD3A gene in the proband. This was confirmed to be a de novo variant, leading to a diagnosis of HAYOS. This variant was classified as pathogenic according to the American College of Medical Genetics and Genomics (ACMG) guidelines and constitutes the genetic etiology of HAYOS in this patient. We summarized the clinical characteristics of this case and reviewed the relevant literature. This report expands the known genotype-phenotype spectrum associated with ATAD3A gene variants and enhances clinical recognition and diagnostic capabilities for this rare disorder.
Harel Yoon syndrome: a novel mutation in ATAD3A gene and expansion of the clinical spectrum
AbstractHarel-Yoon syndrome (HAYOS) is a recently described neurodevelopmental disorder characterized by psychomotor delay, truncal hypotonia, appendicular spasticity, and peripheral neuropathy. It is caused by mutations in ATAD3A gene located on chromosome 1p.36.33 whose functions include mitochondrial DNA stabilization, the regulation of mitochondrial fission/fusion, and cholesterol homeostasis. An 11-year-old male patient of consanguineous Egyptian parents, who present with neuroregression and ptosis along with progressive impaired vision, undergoes complete ophthalmological and neurological examination. Additionally, color fundus photography, fundus autofluorescence (FAF), spectral domain optical coherence tomography (SD-OCT) of both the macula and optic nerve head, full field electroretinogram (ERG), and visual field perimetry were obtained. Whole-exome sequencing and mitochondrial genome sequencing were done in a commercial laboratory from a peripheral blood sample. A novel mutation in ATAD3A gene c.624_644del was identified by whole-exome sequencing consistent with a diagnosis of Harel-Yoon Syndrome (HAYOS). The 11-year-old boy had characteristic features of neurodevelopmental delay, hypotonia, and peripheral neuropathy. However, we documented some novel features as fatiguable ptosis, facial weakness, progressive bulbar palsy, obsessive-compulsive disorder (OCD) in addition to cone system dysfunction. Our study reports a novel mutation in ATAD3A gene and expands the clinical spectrum of Harel-Yoon Syndrome. Future research aiming at better understanding of gene function will lead to better genotype-phenotype correlation and could pave the way to more treatment options.
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.
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