DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Noonan syndrome 3 — screening already-approved drugs against its 7-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleNoonan syndrome 3 maps to a 7-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 noonan syndrome 3 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
clathrin heavy chain (CLTC) — CLTC 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 4-nitrophenyldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6E4L · 1.6 Å · ligand 5-bromo-N-(4-nitrophenyl)thiophene-2-sulfonamide (HRS). Experimental structure, not a prediction.
What the evidence adds up to
Noonan syndrome is an autosomal dominant multisystem disorder caused by dysregulation of the RAS/MAPK pathway. In a 2015 cohort of 50 Brazilian probands who had tested negative for variants in the 11 known Noonan syndrome genes, whole-exome sequencing identified rare missense variants in SOS2 in 4% and in LZTR1 in 8%. SOS2 variants were seen in patients with marked ectodermal involvement, similar to patients with SOS1 mutations. The authors estimated that mutations in these two genes account for approximately 3% of all Noonan syndrome cases. The functional role of LZTR1 in the RAS/MAPK pathway was not known at the time.
A 2009 report described two siblings with Noonan syndrome who carried an apparently balanced insertion of chromosome 12, inherited from a phenotypically normal mother who had mosaicism for the derivative chromosome. No mutations were found in PTPN11, KRAS, SOS1, or RAF1. Microarray analysis showed no gains or losses near the three breakpoints, and neither the PTPN11 nor KRAS region on chromosome 12 was involved. The authors hypothesised that other Noonan syndrome candidate genes might lie in the breakpoint regions.
The estimated incidence of Noonan syndrome ranges from 1 per 1,000–2,500 live births to 1–2 per 20,000 newborns, depending on the source. A 2018 case report of a 5-year-old boy with Noonan syndrome who could produce only a few meaningful words found bilateral mild conductive hearing loss at low frequencies on audiological tests. Auditory brainstem response recordings showed normal absolute latency of wave V but prolonged interpeak latencies for waves I-V, I-II, and II-III, while the interpeak latency for waves III-V was abnormally shorter. The authors noted that no publication on auditory electrophysiological tests in Noonan syndrome patients had appeared in the 55 years since the syndrome was described.
What remains missing are functional studies to clarify LZTR1’s role in RAS/MAPK signalling, molecular characterisation of the chromosome 12 breakpoint regions in the 2009 family, and systematic auditory electrophysiological evaluation protocols for Noonan syndrome patients. No drug treatment is discussed in any of these abstracts.
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 · 2015 · 245 citations · open access
Rare variants in <i>SOS2</i> and <i>LZTR1</i> are associated with Noonan syndrome
AbstractBACKGROUND: Noonan syndrome is an autosomal dominant, multisystemic disorder caused by dysregulation of the RAS/mitogen activated protein kinase (MAPK) pathway. Heterozygous, pathogenic variants in 11 known genes account for approximately 80% of cases. The identification of novel genes associated with Noonan syndrome has become increasingly challenging, since they might be responsible for very small fractions of the cases. METHODS: A cohort of 50 Brazilian probands negative for pathogenic variants in the known genes associated with Noonan syndrome was tested through whole-exome sequencing along with the relatives in the familial cases. Families from the USA and Poland with mutations in the newly identified genes were included subsequently. RESULTS: We identified rare, segregating or de novo missense variants in SOS2 and LZTR1 in 4% and 8%, respectively, of the 50 Brazilian probands. SOS2 and LZTR1 variants were also found to segregate in one American and one Polish family. Notably, SOS2 variants were identified in patients with marked ectodermal involvement, similar to patients with SOS1 mutations. CONCLUSIONS: We identified two novel genes, SOS2 and LZTR1, associated with Noonan syndrome, thereby expanding the molecular spectrum of RASopathies. Mutations in these genes are responsible for approximately 3% of all patients with Noonan syndrome. While SOS2 is a natural candidate, because of its homology with SOS1, the functional role of LZTR1 in the RAS/MAPK pathway is not known, and it could not have been identified without the large pedigrees. Additional functional studies are needed to elucidate the role of LZTR1 in RAS/MAPK signalling and in the pathogenesis of Noonan syndrome.
Postgraduate Medical Journal · 1987 · 13 citations · open access
Colobomata associated with Noonan’s syndrome
AbstractA patient with Noonan's syndrome and fundal colobomata in both eyes is described. To our knowledge, this is the first report of the association of colobomata with Noonan's syndrome. Although the patient had poor sight since early childhood and dyspnea on exertion as a teenager, the diagnosis of Noonan's syndrome was not made until early adulthood. We hope this report will encourage recognition of this syndrome and its implications at an earlier stage.
American Journal of Medical Genetics Part A · 2009 · 8 citations · open access
Molecular characterization of a balanced rearrangement of chromosome 12 in two siblings with Noonan syndrome
AbstractThe etiology of Noonan syndrome (NS) has been greatly elucidated with the discovery of the disease causative genes PTPN11, KRAS, SOS1, and RAF1, all involved in the RAS/MAPK-signaling cascade. Given that overall mutations are identified in about 70% of patients, identification of other NS associated genes remains a high priority to fully understand the etiopathogenesis of the condition. We report two affected siblings with an apparently balanced rearrangement of chromosome 12 ins(12)(q12p11.2p12.3) which segregates with the Noonan phenotype. The rearrangement was inherited from the phenotypically normal mother who had mosaicism for the derivative chromosome 12. There were no mutations of PTPN11, KRAS, SOS1, or RAF1 genes detected in the probands. Using fluorescence in situ hybridization analysis we identified the three breakpoints involved at 12p12.3, 12p11.2, and 12q12. By microarray analysis, there were no gains or losses near the breakpoints. Neither, the PTPN11 or KRAS region on chromosome 12 was involved in the rearrangement. We hypothesize that other NS candidate gene(s) may be located in the breakpoint regions of chromosome 12 causing the Noonan phenotype in both of these children.
AbstractNoonan syndrome is a relatively common dysmorphic syndrome. The typical features include short stature, cardiovascular abnormalities and a characteristic facies. Children with Noonan syndrome have a considerable number of potential health problems, which are highlighted in this article. However, most individuals with this condition live a normal life.
Clinical and Genetic Characteristics of Noonan Syndrome and Noonan-like Diseases
AbstractNoonan syndrome (NS) is a group of inherited autosomal dominant diseases characterized by a disturbance of the RAS-MAPK signaling pathway and leading to various clinical manifestations. The prevalence in the world is estimated at 1–2 per 20 000 newborns. The review discusses the molecular genetic causes of the disease, the characteristics of the clinical manifestations of the disease, and the methods of molecular genetic diagnosis.
Noonan syndrome with somnambulism: A rare case report
AbstractNoonan syndrome is an autosomal dominant, genetic, multisystem disorder with a prevalence of 1 in 1000-2500 live births. Characteristic features of the condition include distinctive myopathic facial features, hypertelorism, short and broad nose, webbed neck, and low set ears. About 10% of the subjects have auditory defects due to sensorineural hearing loss. The patient also has short stature, chest deformity (superior pectus carinatum and inferior pectus excavatum), widely spaced nipples, and delayed puberty. A rare psychiatric manifestation of somnambulism and somniloquy in a case of Noonan syndrome is reported.
Journal of Medical Science And clinical Research · 2019 · 1 citations · open access
Noonan Syndrome – A Case Report
AbstractNoonan syndrome is an autosomal dominant multisystem disorder, associated with cardiac anomalies and a distinctive facial appearance, characterized by genetic heterogeneity. Noonan syndrome affects both females and males, and has an estimated incidence of 1 per 1,000-2,500 live births. The present report aims at presenting the oro-facial findings in a case of Noonan syndrome in a 16 year-old male.
Function and Disability Journal · 2018 · 0 citations · open access
The Results of ABR in a Child with Noonan Syndrome: Necessity of Renewing the Evaluation Protocols of Syndromes
Abstract55 years after discovering NS, there was not even one publication regarding the use of auditory electrophysiological tests for analyzing the central auditory nervous system in NS patients. This is an attempt to attract attention of scientists and clinicians in using AEPs for evaluating the function of CANS in NS. Readers can find a report about the results of audiological tests and auditory brainstem response (ABR) findings in a 5-year old Malay boy with NS. It should be noted that he could only produce a few meaningful words. The results of audiological tests showed bilateral mild conductive hearing loss at low frequencies. ABR recordings showed good waveform morphology but the results were atypical. That is, absolute latency of wave V was normal but interpeak latencies of waves I-V, I-II, II-III were prolonged. Conversely, interpeak latency of waves III-V was abnormally shorter.
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.
