DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for erythrocytosis, familial, 3 — screening already-approved drugs against its 3-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleErythrocytosis, familial, 3 maps to a 3-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 erythrocytosis, familial, 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
endothelial PAS domain protein 1 (EPAS1) — EPAS1 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 furan-2-ylmethyldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3H82 · 1.5 Å · ligand N-(furan-2-ylmethyl)-2-nitro-4-(trifluoromethyl)aniline (020). Experimental structure, not a prediction.
What the evidence adds up to
Familial erythrocytosis type 3 is not a term used in these abstracts. The papers describe familial and congenital erythrocytosis with distinct molecular findings. In one English boy and a Finnish family, a de novo G6002A mutation in the erythropoietin receptor gene created a stop codon at amino acid 439, truncating 70 residues from the carboxy terminus. This mutation was associated with high haemoglobin and low serum erythropoietin. The authors recommend that patients with unexplained erythrocytosis and low serum Epo be investigated for EpoR mutations.
Two brothers from a consanguineous marriage had familial erythrocytosis with markedly increased erythropoietin concentration in both plasma and urine, suggesting a congenital defect leading to Epo-dependent polycythaemia. A 10½-year-old girl with polycythaemia had an inappropriately elevated serum erythropoietin that rose further after phlebotomy, consistent with nonautonomous hypersecretion; no specific cause was found, and the authors hypothesised an abnormality in the renal oxygen-sensing mechanism governing Epo synthesis.
A 2024 study using a targeted NGS panel in 118 sporadic patients with idiopathic erythrocytosis found at least one germinal variant in 78 patients (66%). Among those, 55 (70.5%) had one altered gene, 18 (23%) had two, and 5 (6.4%) had three. HFE variants were most common (57.1%), followed by EGLN1 (22.6%), TFR2 (14.1%), JAK2 (11.5%), EPOR (10.3%), and EPAS1 (7.7%). In 23 patients (19.45%), more than one putative variant was found across multiple genes. The authors conclude that erythrocytosis often has a multigenic basis and that a broader NGS panel could reduce the number of cases labelled idiopathic.
What remains missing is a unified classification that distinguishes type 3 from other familial forms, prospective studies linking specific multigenic patterns to clinical outcomes, and trials testing whether genotype-guided management (e.g., phlebotomy targets, iron modulation) improves outcomes. The 2024 study still left 34% of patients without any detected variant, indicating that the genetic architecture is incompletely understood.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
British Journal of Haematology · 1998 · 49 citations · open access
Erythrocytosis due to a mutation in the erythropoietin receptor gene
AbstractFamilial erythrocytosis, associated with high haemoglobin levels and low serum erythropoietin (Epo), has been shown to co-segregate with a sequence repeat polymorphism at the 5' region of the erythropoietin receptor (EpoR) in a large Finnish family. We have investigated the cause of erythrocytosis in an English boy. Sequencing of the cytoplasmic region of the EpoR detected a de novo transition mutation of G to A at nucleotide 6002. This mutation resulted in the formation of a stop codon at amino acid 439 with the loss of 70 amino acids from the carboxy terminus. The mutation (G6002A) has arisen independently in a Finnish family and de novo in this English boy. Patients with unexplained erythrocytosis and low serum Epo levels should be investigated for EpoR mutations.
Two Cases of Familial Erythrocytosis With Increased Erythropoietin Activity in Plasma and Urine
AbstractAbstract Two brothers with familial erythrocytosis born to parents of a consanguinous marriage are described. Two other siblings were unaffected. There was a marked increase in erythropoietin concentration in both the plasma and urine, suggesting that a congenital defect led to erythropoietindependent polycythemia. Other causes of polycythemia were excluded.
Journal of Pediatric Hematology/Oncology · 1998 · 9 citations
Congenital Erythrocytosis With Elevated Erythropoietin Level
AbstractPURPOSE: A child who was extensively evaluated for polycythemia is reported. Polycythemia, or erythrocytosis, is seen rarely in children. The mechanisms for congenital and/or familial erythrocytosis are discussed. PATIENT AND METHODS: A 10 1/2-year-old white girl was referred for evaluation of polycythemia, which was detected incidentally during an emergency room visit for a febrile illness. She underwent extensive evaluation to determine the cause of the polycythemia. The literature was reviewed to determine the occurrence of congenital and/or familial erythrocytosis in children and its various causes. RESULTS: Despite extensive evaluation, no specific cause of the erythrocytosis could be determined in our patient. The erythrocytosis appeared to be secondary to an inappropriately elevated serum erythropoietin concentration. Serum erythropoietin rose further after phlebotomy, suggesting nonautonomous hypersecretion. After a review of the literature, we hypothesize that she had an inappropriate erythropoietin expression related to an abnormality in the renal oxygen-sensing mechanism governing erythropoietin synthesis. DISCUSSION: A discussion of congenital and familial erythrocytosis is presented, and a review of the literature regarding the possible mechanisms causing erythrocytosis is included.
Mediterranean Journal of Hematology and Infectious Diseases · 2024 · 5 citations · open access
Coexistence of multiple gene variants in some patients with erythrocytoses
AbstractBackground: Erythrocytosis is a relatively common condition, however a large proportion of these patients (70%) remain without a clear etiologic explanation. Methods: We set up a targeted NGS panel for patients with erythrocytosis and 118 sporadic patients with idiopathic erythrocytosis were studied. Results: In 40 (34%) patients no variant was found while in 78 (66%) we identified at least one germinal variant; 55 patients (70.5%) had 1 altered gene, 18 (23%) had 2 alterations, and 5 (6.4%) had 3. An altered HFE gene was observed in 51 cases (57.1%), EGLN1 in 18 (22.6%) and EPAS1, EPOR, JAK2, and TFR2 variants in 7.7%, 10.3%, 11.5%, and 14.1% patients, respectively. In 23 patients (19.45%), more than 1 putative variant was found in multiple genes. Conclusions: Genetic variants in patients with erythrocytosis were detected in about 2/3 of our cohort. A NGS panel including more candidate genes should reduce the number of cases diagnosed as “idiopathic” erythrocytosis in whom a cause cannot yet be identified. It is known that HFE variants are common in idiopathic erythrocytosis. TFR2 alterations supports the existence of a relationship between genes involved in iron metabolism and impaired erythropoiesis. Some novel multiple variants were identified. Erythrocytosis appears to be often of multigenic nature.
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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