DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Carpenter syndrome — 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 moduleCarpenter syndrome 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 carpenter syndrome 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
RAB23, member RAS oncogene family (RAB23) — RAB23 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 gdpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8YL3 · 1.2 Å · ligand GUANOSINE-5'-DIPHOSPHATE (GDP). Experimental structure, not a prediction.
What the evidence adds up to
Carpenter syndrome is an autosomal recessive disorder with an estimated prevalence of one per million births. It is caused by mutations in the RAB23 gene, which encodes a small GTPase involved in cellular trafficking and signal transduction. As of 2022, 100 patients had been reported and 14 mutations in RAB23 had been identified. A 2012 study of a consanguineous Emirati family found a homozygous splice-site mutation (c.482-1G>A) that produced an eight-nucleotide deletion, a frameshift, and a premature stop codon at position 161; the resulting truncated protein lacks the C-terminal cysteine needed for membrane association.
The core features are craniosynostosis (premature fusion of coronal and sagittal sutures), soft-tissue syndactyly (most often between the third and fourth fingers), brachydactyly, and preaxial polydactyly of the toes. Craniosynostosis can produce a pointed head (acrocephaly) or, in severe cases, a cloverleaf skull, and may cause raised intracranial pressure and craniofacial asymmetry. Facial characteristics include a flat nasal bridge, down-slanting palpebral fissures, low-set and abnormally shaped ears, underdeveloped jaws, and abnormal eye shape. Vision problems and small primary teeth are also reported. Congenital heart disease, obesity, hypogenitalism, umbilical hernia, and mental retardation are described in the syndrome. A 2014 case added previously unreported prenatal findings of a large ovarian cyst and heterotaxy with malrotation of stomach, intestine, and liver. A 2024 case report noted an unusual association with chronic kidney disease, but this is a single observation and no shared genetic pathway has been established.
No drug treatment for the syndrome itself is described in any of these abstracts. Management is symptomatic: surgery may be needed for life-threatening heart defects and to separate fused skull bones to allow head growth. The 1987 review argued that Goodman and Summit syndromes fall within the clinical spectrum of Carpenter syndrome, but this was based on literature review and personal communication, not on molecular data. What remains missing are prospective natural-history studies, any clinical trial of a pharmacological intervention, and a clear understanding of whether the RAB23 pathway can be modulated. Patient stratification by specific mutation type has not been attempted in a treatment context, and funding for such work has not been reported.
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 · 1987 · 73 citations
Acrocephalopolysyndactyly type II—Carpenter syndrome: Clinical spectrum and an attempt at unification with Goodman and Summit syndromes
AbstractCarpenter syndrome (ACPS type II) was first described by Carpenter in 1901. The syndrome consists of acrocephaly, soft tissue syndactyly, brachy- or agenesis mesophalangy of the hands and feet, preaxial polydactyly, congenital heart disease, mental retardation, hypogenitalism, obesity, and umbilical hernia. Here we review the literature on Carpenter syndrome and add 2 affected sibs with marked intrafamilial variability. This review showed that 2 reported variations of Carpenter syndrome, Goodman and Summitt syndromes, actually fall within the clinical spectrum of this disorder. This confirms earlier suggestions of Gorlin (personal communication 1982) and Hall et al [Am J Med Genet 5:423-434, 1980].
American Journal of Medical Genetics Part A · 2014 · 9 citations
Prenatal diagnosis of Carpenter syndrome: Looking beyond craniosynostosis and polysyndactyly
AbstractCarpenter syndrome is an autosomal recessive disorder comprising craniosynostosis, polysyndactyly, and brachydactyly. It occurs in approximately 1 birth per million. We present a patient with Carpenter syndrome (confirmed by molecular diagnosis) who has several unique and previously unreported manifestations including a large ovarian cyst and heterotaxy with malrotation of stomach, intestine, and liver. These findings were first noted by prenatal ultrasound and may assist in prenatally diagnosing additional cases of Carpenter syndrome.
Scholars Journal of Medical Case Reports · 2022 · 1 citations · open access
Carpenter Syndrome: Report of Two Cases
AbstractCarpenter syndrome (MIM 201000) is a rare autosomal recessive disorder characterized by combination of acrocephaly, syndactyly and brachydactyly in the hands as well as syndactyly and preaxial polydactyly of the toes. Other variable features can be present. 100 patients have been reported until now, with 14 mutations in the conserved sequence encoding the ras-like in rat brain 23 (RAB23) gen identified. We report here two Moroccan cases with a typical clinical picture of carpenter syndrome.
A Rare Case of Carpenter Syndrome and Its Unique Association With Chronic Kidney Disease
AbstractCarpenter syndrome, characterized by RAB23 mutations, is a rare autosomal recessive disorder distinguished by unique features such as craniofacial anomalies, congenital heart disease, brachydactyly, and obesity. This syndrome's rarity, with an estimated prevalence of one in a million births, poses diagnostic challenges due to its diverse clinical spectrum. Notably, this case report highlights an unusual association of Carpenter syndrome with chronic kidney disease (CKD), underscoring the need for further exploration into the syndromic interplay and shared genetic pathways. The distinctive manifestation of CKD in the context of Carpenter syndrome adds a novel dimension, emphasizing the importance of timely diagnosis and comprehensive care. Further research is warranted to unravel the intricate genetic and molecular pathways underlying the syndrome's diverse manifestations, shedding light on potential shared mechanisms and paving the way for targeted interventions and enhanced patient care.
Scholars International Journal of Biochemistry · 2019 · 0 citations · open access
Carpenter Syndrome—A Genetic Disease
AbstractCarpenter syndrome is a condition characterized by the premature fusion of certain skull bones (craniosynostosis), abnormalities of the fingers and toes, and other developmental problems. Craniosynostosis prevents the skull from growing normally, frequently giving the head a pointed appearance (acrocephaly). Mutated genes cause Carpenter syndrome, and they are passed from parent to child during fetal development. These genes cause the coronal (from ear to ear) and sagittal (top of head, front to back) sutures to fuse together prematurely (craniosynostosis). Treatment of Carpenter syndrome depends on the symptoms the individual has and the severity of the condition. Surgery may be needed if a life-threatening heart defect is present. Surgery may also be used to correct craniosynostosis by separating the abnormally fused skull bones to allow for growth of the head. Craniosynostosis prevents the skull from growing normally, frequently giving the head a pointed appearance (acrocephaly). In severely affected individuals, the abnormal fusion of the skull bones results in a deformity called a cloverleaf skull. Craniosynostosis can cause differences between the two sides of the head and face (craniofacial asymmetry). Early fusion of the skull bones can affect the development of the brain and lead to increased pressure within the skull (intracranial pressure). Premature fusion of the skull bones can cause several characteristic facial features in people with Carpenter syndrome. Distinctive facial features may include a flat nasal bridge, outside corners of the eyes that point downward (down-slanting palpebral fissures), lowset and abnormally shaped ears, underdeveloped upper and lower jaws, and abnormal eye shape. Some affected individuals also have dental abnormalities including small primary (baby) teeth. Vision problems also frequently occur.Abnormalities of the fingers and toes include fusion of the skin between two or more fingers or toes (cutaneous syndactyly), unusually short fingers or toes (brachydactyly), or extra fingers or toes (polydactyly). In Carpenter syndrome, cutaneous syndactyly is most common between the third (middle) and fourth (ring) fingers, and polydactyly frequently occurs next to the big or second toe or the fifth (pinky) finger.
INDIGO (University of Illinois at Chicago) · 2012 · 0 citations · open access
Supplementary Material for: A Novel Aberrant Splice Site Mutation in <b><i>RAB23</i></b> Leads to an Eight Nucleotide Deletion in the mRNA and Is Responsible for Carpenter Syndrome in a Consanguineous Emirati Family
AbstractCarpenter syndrome is caused by mutations in the <i>RAB23</i> gene that encodes a small GTPase of the Rab subfamily of proteins. Rab proteins are known to be involved in the regulation of cellular trafficking and signal transduction. Currently, only few mutations in <i>RAB23 </i>have been reported in patients with Carpenter syndrome. In this paper, we report the clinical features, molecular and functional analysis of 2 children from an Emirati consanguineous family with this syndrome. The affected children exhibit the typical features including craniosynostosis, typical facial appearance, polysyndactyly, and obesity. Molecular analysis of the <i>RAB23</i> gene revealed a homozygous mutation affecting the first nucleotide of the acceptor splice site of exon 5 (c.482-1G>A). This mutation affects the authentic mRNA splicing and activates a cryptic acceptor site within exon 5. Thus, the erroneous splicing results in an eight nucleotide deletion, followed by a frameshift and premature termination codon at position 161 (p.V161fsX3). Due to the loss of the C-terminally prenylatable cysteine residue, the truncated protein will probably fail to associate with the target cellular membranes due to the absence of the necessary lipid modification. The p.V161fsX3 extends the spectrum of <i>RAB23</i> mutations and points to the crucial role of prenylation in the pathogenesis of Carpenter syndrome within this family.
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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