DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for proximal symphalangism 1A — 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 moduleProximal symphalangism 1A 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 proximal symphalangism 1a 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
growth differentiation factor 5 (GDF5) — GDF5 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 ipadrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2BHK · 2.4 Å · ligand ISOPROPYL ALCOHOL (IPA). Experimental structure, not a prediction.
What the evidence adds up to
Proximal symphalangism 1A is an autosomal dominant disorder characterised by multiple joint fusions. Two genes are implicated in the condition. A 2016 report on a British family identified a recurrent missense mutation in GDF5 (p.R438L) as the cause of proximal symphalangism in that pedigree. The same report stresses the value of taking a three-generation family history and conducting detailed clinical examinations of children with fixed planovalgus feet to detect rare skeletal dysplasias causing pain and deformity.
The NOG gene on chromosome 17q22 is the other known cause. A 2002 study of an Italian family with father and son affected by bilateral symphalangism found a novel NOG mutation, P35S, arising from a c.914C>T transition. A different mutation at the same codon (P35R) had been described previously, and the authors note that codon 35 is conserved across noggin gene orthologs, suggesting it plays an important role in NOG function. That paper was the first description of a NOG mutation after the initial report linking NOG to symphalangism.
A 2017 study of a five-generation Chinese family with autosomal dominant proximal symphalangism screened NOG and GDF5 by PCR and direct sequencing. It identified a novel heterozygous missense mutation in NOG, c.502 T>C, which substitutes phenylalanine with leucine at residue 168 (p.F168L). This mutation co-segregated with the limb phenotype in all family members and was absent from public databases (dbSNP and ExAC) and 200 control individuals. The authors conclude that c.502 T>C is a novel pathogenic mutation for proximal symphalangism in that family.
No drug, treatment, or intervention is mentioned in any of these abstracts. The evidence consists entirely of genetic linkage and mutation identification in small families. What is missing for any therapeutic development is a molecular understanding of how these mutations disrupt joint formation, an animal model that recapitulates the phenotype, and any preclinical or clinical testing of a compound. No trial design, patient stratification strategy, or funding for such work is 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.
World Journal of Orthopedics · 2016 · 8 citations · open access
Recurrent missense mutation of <i>GDF5</i> (<i>p.R438L</i>) causes proximal symphalangism in a British family
Abstractgene. This report highlights the importance of thorough history taking, including a three generation family history, and detailed clinical examination of children with fixed planovalgus feet and other family members to detect rare skeletal dysplasia conditions causing pain and deformity, and provides details of the spectrum of problems associated with SYM1B.
Identification of a novel NOG mutation in a Chinese family with proximal symphalangism
AbstractObjective
To identify the pathogenic mutation underlying proximal symphalangism in a Chinese family.
Methods
A five-generation family showing an autosomal dominant transmission of proximal symphalangism was examined. To screen the pathogenic mutation in NOG and GDF5, we PCR-amplified the exons and exon-intron boundaries of the two genes and sequenced them directly after purification.
Results
We found a novel heterozygous missense mutation, c. 502 T>C, in NOG. This mutation led to a substitution of phenylalanine by leucine at amino acid residue 168 of Noggin (p.F168L). The mutation co-segregated with the limb phenotype of all the family members but was not present in public databases (dbSNP and ExAC) or 200 control individuals.
Conclusion
The c. 502 T>C mutation in NOG is a novel pathogenic mutation for the proximal symphalangism phenotype in this family.
Key words:
Proximal symphalangism; the NOG gene; Pathogenic mutation
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.
