DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for properdin deficiency, X-linked — 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 moduleProperdin deficiency, X-linked 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 properdin deficiency, x-linked 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
complement factor properdin (CFP) — CFP 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 bgcdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6RUS · 2.8 Å · ligand beta-D-glucopyranose (BGC). Experimental structure, not a prediction.
What the evidence adds up to
Properdin deficiency is an X-linked condition. Two variants have been described based on properdin concentrations in serum. Type 1 is characterised by extremely low properdin concentrations, less than 0.1 mg/l. Type 2 shows detectable properdin at about 2 mg/l. In one report, a 58-year-old male and his 29-year-old nephew, both clinically healthy, had type 2 deficiency. Three female relatives had moderately low properdin concentrations, consistent with X-linked inheritance. In another family, three males also had detectable properdin, while eight males from three other families had no detectable properdin. The properdin detected in type 2 had subunits of normal molecular weight (52 kilodaltons) but eluted at a lower molecular weight than normal properdin on gel filtration, suggesting impaired oligomer formation.
Functional studies show that type 2 properdin-deficient serum does not support fluid-phase C3 cleavage in the presence of alternative pathway activators such as inulin and zymosan, and does not support efficient lysis of guinea pig erythrocytes in agarose gel. Rabbit erythrocytes are lysed, but at a slow rate. Type 1 serum does not support lysis of rabbit erythrocytes in the same assay. Partially purified properdin from a type 2 male was hemolytically active, and function was also demonstrated in a serum bactericidal assay using IgG-presensitised serogroup W-135 meningococci. These results indicate that the low concentration of properdin in type 2 retains some functional activity, but the serum is still impaired in alternative pathway activation.
Recombinant studies have identified functional roles for individual thrombospondin type 1 repeats (TSRs) in the properdin monomer. Removal of TSR5 prevents binding to both C3b and sulfatide. Properdin nicked in TSR5 by tryptic digestion cannot bind C3b but retains sulfatide binding. Removal of TSR4 prevents stabilisation of the C3b-Bb complex but allows C3b and sulfatide binding. Removal of TSR3 does not affect these functions or oligomer formation. Removal of TSR6 prevents oligomerisation. The N-linked carbohydrate is not required for oligomerisation or C3b-Bb stabilisation. These data map C3b binding and sulfatide binding to TSR5, and C3b-Bb stabilisation to TSR4.
What is still missing is a systematic understanding of the clinical spectrum of properdin deficiency, particularly the infection risk and meningococcal susceptibility in type 2 compared to type 1. No large cohort studies or controlled treatment trials exist. The rarity of the condition limits patient stratification and funding for natural history studies. No gene therapy or targeted replacement strategy has been tested in humans.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
The Journal of Immunology · 1995 · 68 citations
Characterization of mutant forms of recombinant human properdin lacking single thrombospondin type I repeats. Identification of modules important for function
AbstractProperdin is a serum glycoprotein that up-regulates the alternative pathway of complement by stabilizing the C3b-Bb complex. It also binds sulfated glycoconjugates, such as sulfatide, in vitro. Properdin is composed of cyclic dimers, trimers, and tetramers of a 53-kDa monomeric subunit. The monomer contains an N-terminal region of no known homology and six thrombospondin type 1 repeats (TSRs) of approximately 60 amino acids. To identify the regions of properdin important for function, we have expressed human properdin, and mutant forms each lacking a single TSR, in Chinese hamster ovary cells. In addition, limited tryptic digestion yielded "nicked" properdin by the cleavage of one peptide bond in TSR5. The structural and functional properties of these altered forms of properdin were investigated. Properdin "nicked" in TSR5 is unable to bind C3b but retains its overall structure and its ability to bind sulfatide. The removal of TSR5 prevents C3b and sulfatide binding. Properdin lacking TSR4 is unable to stabilize the C3b-Bb complex but is able to bind C3b and sulfatide, and shows the presence of monomers and dimers in an electron microscope. Properdin without TSR3 is able to stabilize the C3b-Bb complex, to bind C3b and sulfatide, and forms dimers, trimers, and tetramers. Properdin lacking TSR6 is unable to form oligomers. The N-linked carbohydrate of properdin is not required for oligomerization or stabilization of the C3b-Bb complex. The results implicate TSR5 in both C3b and sulfatide binding, and suggest that TSR4 may also be involved in stabilization of the C3b-Bb complex.
A Second Variant of Properdin Deficiency: The Detection of Properdin at Low Concentrations in Affected Males
AbstractA selective deficiency of properdin (P) was identified in a 58-year-old male and in his 29-year-old nephew, both of whom were clinically healthy. As determined by different immunochemical methods P at low concentrations (about 2 mg/l) was detectable in serum and plasma. Three female relatives, including the mother and daughter of one of the P-deficient males showed moderately low P concentrations. The findings clearly suggested that the deficiency was inherited as an X-linked trait. Three males belonging to another family with P deficiency also showed detectable P concentrations. By contrast, no P (less than 0.1 mg/l) was found in 8 males belonging to three other families. We suggest that there are two variants of X-linked P deficiency: P deficiency type 1, characterized by extremely low P concentrations (less than 0.1 mg/l); and P deficiency type 2 recognizable by P concentrations of about 2 mg/l. The P detected in P deficiency type 2 had subunits of normal molecular weight (52 kilodaltons), but eluted in a lower molecular weight range than did the P of normal serum, either on gel filtration (Ultrogel AcA 22) or on size exclusion chromatography (TSK-4000). The evidence suggested that the P concentration may be one determinant of P oligomer formation. P-deficient serum type 2 did not support fluid phase C3 cleavage in the presence of such alternative pathway activators as inulin and zymosan, nor did it support efficient lysis of guinea pig erythrocytes in agarose gel. By contrast, rabbit erythrocytes were efficiently lyzed, but at a slow rate. P-deficient serum type 1 did not support lysis of rabbit erythrocytes in the assay system used. The reaction was clearly promoted by very low concentrations of purified P. Partially purified P from a male with P deficiency type 2 was shown to be hemolytically active. Further evidence of P function in P deficiency type 2 was obtained by using IgG-presensitized serogroup W-135 meningococci in an alternative pathway-mediated serum bactericidal assay.
Steroid Sulfatase Activity in Nails: Screening for X‐Linked Ichthyosis
AbstractX-linked ichthyosis is generally diagnosed by a deficiency of steroid sulfatase activity in fibroblasts or leukocytes. We established a method of assaying nail steroid sulfatase activity for diagnostic use. Nail samples were easy to collect and handle, and satisfied the screening criteria of accuracy, sensitivity, and stability. The detergents Tween 20 and Triton-X 100, which enhance nail STS activity, enabled us to assay the activity with small amounts of nails. The detergent-facilitated assay was also suitable for use with pediatric patients, from whom small amounts of nails were collected.
Journal of Inherited Metabolic Disease · 1992 · 12 citations
The molecular basis of X‐linked immunodeficiency disease
AbstractThe molecular bases of the X-linked immunodeficiency diseases remain largely undetermined. Two of the genes involved in these diseases have been isolated, namely the genes for X-linked chronic granulomatous disease and properdin deficiency, and substantial progress has now been made in identifying the genes which are defective in the other five diseases, Wiskott-Aldrich syndrome, X-linked severe combined immunodeficiency, X-linked agammaglobulinaemia, X-linked hyper-IgM and X-linked lymphoproliferative syndrome. We review here the nature of the diseases, progress made in identifying and isolating the genes involved and the prospects for improved prenatal detection, carrier status determination and treatment of these life-threatening conditions.
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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