DeCure for Neutropenia, severe congenital, 2, autosomal dominant
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for neutropenia, severe congenital, 2, autosomal dominant — 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 moduleNeutropenia, severe congenital, 2, autosomal dominant 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 neutropenia, severe congenital, 2, autosomal dominant 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
TEK receptor tyrosine kinase (TEK) — TEK 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 ndgdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2GY5 · 2.9 Å · ligand 2-acetamido-2-deoxy-alpha-D-glucopyranose (NDG). Experimental structure, not a prediction.
What the evidence adds up to
Severe congenital neutropenia has an estimated incidence of 1 in 200,000 individuals of European descent, with many cases inherited in an autosomal dominant pattern. A 2009 perspective article notes that the molecular basis of the autosomal recessive form was discovered by Rolf Kostmann in 1950, but for more than 50 years its molecular aetiology remained enigmatic, with advances only occurring in the years before that article. A separate 2009 report describes a five-generation family segregating a novel single nucleotide variant in TCIRG1, with perfect cosegregation: all 11 affected individuals carried the variant, none of the unaffected did. Western blot showed reduced TCIRG1 protein levels in affected individuals compared to healthy controls. Two unrelated patients with severe congenital neutropenia, identified by independent investigators, were heterozygous for different, rare, highly conserved coding variants in TCIRG1. The genetic basis for more than 30% of cases remains unknown.
A 2018 case report describes a 5-year-old girl with severe congenital neutropenia presenting with recurrent skin and respiratory infections. Sequence analysis of ELANE and HAX1 genes identified a heterozygous mutation in exon 2 of ELANE: c.157C > G (p.His53Asp), not previously described at the exon coding level. Given the autosomal dominant inheritance and the mutation’s location within a hotspot, it was considered clinically relevant. The authors recommend screening ELANE in patients with congenital neutropenia of no obvious aetiology, and note that detailed medical history and clinical evaluation can prevent unnecessary investigations.
No treatment, response rates, survival data, or sample sizes beyond the single case and the 11-member family are reported in these abstracts. No drug is mentioned. What is still missing is a complete genetic explanation for the more than 30% of cases with unknown cause, and any prospective trial design or patient stratification that could test whether identifying these rare variants leads to different clinical management or outcomes. Funding for systematic sequencing of unexplained cases and for functional validation of novel variants is lacking.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Haematologica · 2009 · 15 citations · open access
Molecular basis of congenital neutropenia
AbstractIn 1950 Rolf Kostmann discovered autosomal recessive severe congenital neutropenia and for more than 50 years its molecular etiology has remained enigmatic. In the last years, however, there have been impressive advances in this field. In this perspective article, Dr. Klein summarizes our current knowledge of the molecular basis of congenital neutropenia. See related paper on page 1449.
Dialnet (Universidad de la Rioja) · 2009 · 3 citations
PRODUCTIONS OF GREEK AND ROMAN DRAMA ON THE CZECH STAGE 2001-2009
AbstractSevere congenital neutropenia (SCN) is a rare hematopoietic disorder, with estimated incidence of 1 in 200,000 individuals of European descent, many cases of which are inherited in an autosomal dominant pattern. Despite the fact that several causal genes have been identified, the genetic basis for >30% of cases remains unknown. We report a five-generation family segregating a novel single nucleotide variant (SNV) in TCIRG1. There is perfect cosegregation of the SNV with congenital neutropenia in this family; all 11 affected, but none of the unaffected, individuals carry this novel SNV. Western blot analysis show reduced levels of TCIRG1 protein in affected individuals, compared to healthy controls. Two unrelated patients with SCN, identified by independent investigators, are heterozygous for different, rare, highly conserved, coding variants in TCIRG1.
Journal of Pediatric Genetics · 2018 · 2 citations · open access
Description of an ELANE Mutation in a Girl with Severe Congenital Neutropenia: A Paradigm of Targeted Genetic Screening Based on Clinical Findings
AbstractAbstract We describe the case of a 5-year-old girl with severe congenital neutropenia presenting with recurrent skin and respiratory infections. Sequence analysis of ELANE and HAX1 genes identified a mutation in heterozygous state in exon 2 of the ELANE gene: c.157C > G (p.His53Asp), not previously described in the literature at the exon coding level. Given the autosomal dominant inheritance and the location of the mutation within a “hotspot,” this mutation was considered as clinically relevant. ELANE should be screened in patients with congenital neutropenia of no obvious etiology. A detailed medical history and clinical evaluation can prevent unnecessary investigations allowing for a targeted diagnostic strategy.
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.
