DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for frontometaphyseal dysplasia 1 — 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 moduleFrontometaphyseal dysplasia 1 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 frontometaphyseal dysplasia 1 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
mitogen-activated protein kinase kinase kinase 7 (MAP3K7) — MAP3K7 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 adndrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2EVA · 2.0 Å · ligand ADENOSINE (ADN). Experimental structure, not a prediction.
What the evidence adds up to
Frontometaphyseal dysplasia is an uncommon genetic syndrome affecting bone and connective tissue, characterised by hyperostosis of the skull, prominence of the supraorbital ridges, and long bones with flared metaphyses. Diagnosis in the neonatal period is difficult; two newborn boys with radiographic findings were reported in 1995. Fewer than two dozen cases had been reported by 1980, and a survey of published examples at that time provided evidence for X-linked inheritance, with severe manifestations in males and extremely variable manifestations in females.
Approximately 50% of patients have gain-of-function mutations in the X-linked gene FLNA. More recently, an autosomal dominant form caused by mutations in MAP3K7 was characterised, accounting for the condition in most patients who lack a FLNA mutation. A cohort of 20 individuals with autosomal dominant frontometaphyseal dysplasia was clinically evaluated in 2017. This cohort included 15 individuals with a recurrent mutation (c.1454C>T) in MAP3K7, three individuals with missense mutations in the N-terminal kinase domain of TAK1 (encoded by MAP3K7), and two individuals with missense variants in TAB2, which encodes TAK1-associated binding protein 2.
Individuals with the autosomal dominant form are more likely to be deaf, have scoliosis, cervical fusions, and a cleft palate compared to those with the X-linked form. Features found only in the autosomal dominant form in that review included valgus deformity of the feet and predisposition to keloid scarring. Intellectual disability was present in a small number of subjects with autosomal dominant frontometaphyseal dysplasia but has not been described in the X-linked form. No drug treatment or intervention was studied in any of these reports. What is still missing is any clinical trial, any tested therapy, any patient stratification by specific mutation, and any funding directed toward treatment development for this rare disorder.
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 · 1995 · 193 citations
AbstractFrontometaphyseal dysplasia (FMD) is an uncommon genetic syndrome affecting bone and connective tissue. This condition is characterized by hyperostosis of the skull and prominence of the supraorbital ridges; long bones have flared metaphyses. Frontometaphyseal dysplasia is an X-linked dominant trait with more severe manifestations in males and with extreme variability in females. Diagnosis in the neonatal period is difficult. We present 2 newborn boys with the radiographic findings of FMD.
American Journal of Medical Genetics · 1980 · 41 citations
Frontometaphyseal dysplasia—evidence for X‐linked inheritance
AbstractFewer than two dozen cases of frontometaphyseal dysplasia have been reported, some doubly or erroneously. In most reports, no information is available on possible variable manifestations in female relatives. Statements that the disorder is inherited as a dominant trait, and as an X-linked recessive have caused us to consider genetic heterogeneity. A recent large kindred prompted us to survey all published examples. We asked authors to reexamine the families they studied for any expression in relatives. In some cases, no further information could be elicited, but some additional information was gathered and pedigrees modified. This evidence was sufficient to indicate X-linked inheritance, with severe manifestations in males and extremely variable manifestations in females.
American Journal of Medical Genetics Part A · 2017 · 32 citations · open access
Autosomal dominant frontometaphyseal dysplasia: Delineation of the clinical phenotype
AbstractFrontometaphyseal dysplasia (FMD) is caused by gain-of-function mutations in the X-linked gene FLNA in approximately 50% of patients. Recently we characterized an autosomal dominant form of FMD (AD-FMD) caused by mutations in MAP3K7, which accounts for the condition in the majority of patients who lack a FLNA mutation. We previously also described a patient with a de novo variant in TAB2, which we hypothesized was causative of another form of AD-FMD. In this study, a cohort of 20 individuals with AD-FMD is clinically evaluated. This cohort consists of 15 individuals with the recently described, recurrent mutation (c.1454C>T) in MAP3K7, as well as three individuals with missense mutations that result in substitutions in the N-terminal kinase domain of TGFβ-activated kinase 1 (TAK1), encoded by MAP3K7. Additionally, two individuals have missense variants in the gene TAB2, which encodes a protein with a close functional relationship to TAK1, TAK1-associated binding protein 2 (TAB2). Although the X-linked and autosomal dominant forms of FMD are very similar, there are distinctions to be made between the two conditions. Individuals with AD-FMD have characteristic facial features, and are more likely to be deaf, have scoliosis and cervical fusions, and have a cleft palate. Furthermore, there are features only found in AD-FMD in our review of the literature including valgus deformity of the feet and predisposition to keloid scarring. Finally, intellectual disability is present in a small number of subjects with AD-FMD but has not been described in association with X-linked FMD.
Human Genome Variation · 2021 · 5 citations · open access
A novel TAB2 mutation detected in a putative case of frontometaphyseal dysplasia
AbstractFrontometaphyseal dysplasia (FMD) type 2 is an autosomal dominant disorder characterized by skeletal abnormalities and caused by MAP3K7 mutation. We identified a novel missense mutation in TAB2 associated with FMD in a child with multiple congenital malformations. This case was diagnosed as FMD due to joint contractures and bone deformities. This is the third report of FMD caused by a TAB2 mutation located in the TAK1-binding region.
American Journal of Medical Genetics Part A · 2021 · 0 citations
X‐linked frontometaphyseal dysplasia with severe scoliosis and spinal cord compromise in an Indian boy
AbstractFrontometaphyseal dysplasia (FMD) is a rare genetic disorder with morphological abnormalities of the skeletal and extra skeletal tissues. It belongs to the group of otopalatodigital spectrum disorders. Here we report a 12-year-old boy from India with features of frontometaphyseal dysplasia who had severe scoliosis with neurological complications due to spinal cord compromise. Clinical examination of his mother also revealed mild features of FMD. The manuscript highlights the clinical presentation of the disorder and discusses the clinical heterogeneity of the otopalatodigital spectrum disorders.
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.
