DeCure for Arthrogryposis, renal dysfunction, and cholestasis 1
DeCure's autonomous Nephrology AI scientist is researching a drug-repurposing hypothesis for arthrogryposis, renal dysfunction, and cholestasis 1 — screening already-approved drugs against its 4-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleArthrogryposis, renal dysfunction, and cholestasis 1 maps to a 4-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 arthrogryposis, renal dysfunction, and cholestasis 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
fibrillin 1 (FBN1) — FBN1 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 1UZK · 1.35 Å · ligand none (apo structure). Experimental structure, not a prediction.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Case Reports in Genetics · 2020 · 10 citations · open access
A Novel Mutation of <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mi>V</mml:mi><mml:mi>P</mml:mi><mml:mi>S</mml:mi><mml:mn>33</mml:mn><mml:mi>B</mml:mi></mml:math> Gene Associated with Incomplete Arthrogryposis-Renal Dysfunction-Cholestasis Phenotype
AbstractArthrogryposis-renal dysfunction-cholestasis (ARC) syndrome is an autosomal recessive disorder caused by mutations of the <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M2"><mml:mi>V</mml:mi><mml:mi>P</mml:mi><mml:mi>S</mml:mi><mml:mn>33</mml:mn><mml:mi>B</mml:mi></mml:math> encoding the vacuolar protein sorting 33B (VPS33B), which is involved in the intracellular protein sorting and vesicular trafficking. We report a rare case of ARC syndrome without arthrogryposis caused by a novel mutation of <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M3"><mml:mi>V</mml:mi><mml:mi>P</mml:mi><mml:mi>S</mml:mi><mml:mn>33</mml:mn><mml:mi>B</mml:mi></mml:math>. A female patient of Greek origin presented on the 14 th day of life with renal tubular acidosis, Fanconi syndrome, nephrogenic diabetes insipidus, and cholestasis with normal gamma-glutamyl transpeptidase, without arthrogryposis and dysmorphic features. She was born to apparently healthy, nonconsanguineous parents. Additional features included dry and scaling skin, generalized hypotonia, hypoplastic corpus callosum, neurodevelopmental delay, failure to thrive, short stature, recurrent febrile episodes with and without infections, and gastrointestinal bleeding. DNA testing revealed that the patient was homozygous for the novel c.1098_1099delTG (p.Glu367Alafs<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M4"><mml:mi>∗</mml:mi></mml:math>17) mutation of exon 14 of <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M5"><mml:mi>V</mml:mi><mml:mi>P</mml:mi><mml:mi>S</mml:mi><mml:mn>33</mml:mn><mml:mi>B</mml:mi></mml:math> gene (NM_018668) on chromosome 15q26.1, leading to a nonsense frameshift variant of VPS33B with premature termination of translation. Her parents were heterozygous for the same <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M6"><mml:mi>V</mml:mi><mml:mi>P</mml:mi><mml:mi>S</mml:mi><mml:mn>33</mml:mn><mml:mi>B</mml:mi></mml:math> mutation. The prognosis was predictably poor in the context of the intractable polyuria necessitating long-term parenteral fluid administration via indwelling central catheter leading to catheter-related sepsis, to which she eventually succumbed at the age of 7 months. This is the first published <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M7"><mml:mi>V</mml:mi><mml:mi>P</mml:mi><mml:mi>S</mml:mi><mml:mn>33</mml:mn><mml:mi>B</mml:mi></mml:math> mutation in an ARC patient of Greek origin. The current case adds to the spectrum of ARC-associated <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M8"><mml:mi>V</mml:mi><mml:mi>P</mml:mi><mml:mi>S</mml:mi><mml:mn>33</mml:mn><mml:mi>B</mml:mi></mml:math> mutations and provides evidence supporting the existence of incomplete ARC phenotype. Increased awareness and early genetic testing for ARC are suggested in cases with isolated cholestasis and/or renal tubular dysfunction, even in the absence of arthrogryposis.
Arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome: a rare cause of cholestasis
AbstractArthrogryposis-renal dysfunction-cholestasis (ARC) syndrome is a rare autosomal recessive disorder with classical features of congenital joint contractures, renal tubular dysfunction and cholestatic jaundice. Some patients have additional features including ichthyosis, platelet anomalies, agenesis of the corpus callosum, congenital cardiovascular anomalies, deafness, recurrent infection, and internal bleeding. Here we report two Egyptian patients from two different families with this rare disorder.
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.
