DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for GAPO syndrome — 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 moduleGAPO syndrome 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 gapo 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
ANTXR cell adhesion molecule 1 (ANTXR1) — ANTXR1 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 3N2N · 1.8 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
GAPO syndrome is an autosomal recessive disorder caused by biallelic loss-of-function mutations in the ANTXR1 gene. The acronym stands for growth retardation, alopecia, pseudoanodontia (failure of tooth eruption), and optic atrophy. A 2025 review of 105 clinical cases confirmed the multisystemic nature of the condition, with skeletal, dermatological, and ophthalmological manifestations being primary. Histological findings across reported cases point to excessive extracellular matrix deposition as central to the pathogenesis, and the evidence suggests ANTXR1 is an important regulator of extracellular matrix homeostasis.
The earliest known affected individuals died at 39 and 37 years, according to a 1984 report that described three affected brothers and noted only nine known cases at that time. By 2014, about 35 cases had been reported. A 1993 study of three relatives in a Turkish kindred noted slight clinical variations including some body hair, white eyelashes, deep furrows on the sternum and back, disproportional body build, and minor skeletal abnormalities, and suggested the athletic appearance of affected individuals is likely due to excessive connective tissue. A 1995 report described a 9-year-old girl as the fifteenth known case.
Whole exome sequencing in 2014 identified three novel homozygous mutations in ANTXR1 in five affected individuals from three Turkish kindreds: a frame-shift (c.1220_1221insT; p.Ala408Cysfs*2), a splice site (c.411A>G; p.Gln137Gln), and a non-synonymous (c.1150G>A; p.Gly384Ser) mutation. A 2025 case report confirmed the diagnosis in a female child through genetic testing after clinical and radiographic features suggested the syndrome. No drug treatment or targeted therapy for GAPO syndrome has been tested in any clinical trial reported in these abstracts. What is still missing is any funded effort to develop a therapy, a trial design that could target extracellular matrix dysregulation, and a sufficiently large and well-characterised patient cohort to enable stratification by specific ANTXR1 mutation type.
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 · 1984 · 28 citations
GAPO syndrome: Report of three affected brothers
AbstractWe present a sibship of three brothers affected with the GAPO syndrome. This is a rare and very characteristic autosomal-recessive trait whose main manifestations are growth retardation, alopecia, pseudo anodontia, and optic atrophy. So far nine affected individuals are known (4 males and 5 females). Two of them, the patient of Andersen and Pindborg cited in Tipton and Gorlin [1983] and one of the cases of Wajntal et al [1982], died at 39 and 37 years respectively.
American Journal of Medical Genetics Part A · 2014 · 27 citations · open access
Whole exome sequencing identifies three novel mutations in <i>ANTXR1</i> in families with GAPO syndrome
AbstractGAPO syndrome (OMIM#230740) is the acronym for growth retardation, alopecia, pseudoanodontia, and optic atrophy. About 35 cases have been reported, making it among one of the rarest recessive conditions. Distinctive craniofacial features including alopecia, rarefaction of eyebrows and eyelashes, frontal bossing, high forehead, mid-facial hypoplasia, hypertelorism, and thickened eyelids and lips make GAPO syndrome a clinically recognizable phenotype. While this genomic study was in progress mutations in ANTXR1 were reported to cause GAPO syndrome. In our study we performed whole exome sequencing (WES) for five affected individuals from three Turkish kindreds segregating the GAPO trait. Exome sequencing analysis identified three novel homozygous mutations including; one frame-shift (c.1220_1221insT; p.Ala408Cysfs*2), one splice site (c.411A>G; p.Gln137Gln), and one non-synonymous (c.1150G>A; p.Gly384Ser) mutation in the ANTXR1 gene. Our studies expand the allelic spectrum in this rare condition and potentially provide insight into the role of ANTXR1 in the regulation of the extracellular matrix.
American Journal of Medical Genetics · 1993 · 25 citations
GAPO syndrome in three relatives in a Turkish kindred
AbstractGAPO syndrome in 2 sibs (brother and sister) and in a first cousin presented slight variations in the clinical picture. These include presence of some body hair, white eyelashes, deep furrows on sternum and back, disproportional body build, and minor skeletal abnormalities. It has been suggested that the athletic appearance of affected individuals is most likely due to the excessive amount of connective tissue.
American Journal of Medical Genetics · 1995 · 18 citations
GAPO syndrome: A new case
AbstractThe fifteenth known case of GAPO syndrome is presented: a probable autosomal-recessive condition of growth retardation, alopecia, pseudoanodontia (failure of tooth eruption), and optic atrophy. This article contains the clinical report of a 9-year-old girl and a short review of the hitherto-known cases. The syndrome could be attributed to either ectodermal dysplasia or perhaps an accumulation of extracellular connective tissue matrix.
Journal of Indian Academy of Oral Medicine and Radiology · 2025 · 0 citations · open access
GAPO Syndrome – Diagnosis of a Rare Case Report and Review
AbstractAbstract GAPO syndrome is an unusual genetic disorder with an autosomal recessive trait inheritance. The syndrome is caused due a genetic defect or alterations in the ANTXR1/TEM8 gene. GAPO has major features such as growth retardation, sparse hair, pseudo anodontia, and optic atrophy. In this article, we are reporting a female child patient with syndromic features. Based on the patient’s history, clinical presentation, and radiographic features, we arrived at a provisional diagnosis of GAPO syndrome and advised genetic testing, which confirmed our diagnosis.
GAPO syndrome: a comprehensive examination and review of 105 clinical cases
AbstractGrowth retardation, alopecia, pseudoanodontia and optic atrophy (GAPO) syndrome is a rare autosomal recessive disorder caused by biallelic pathogenic variants in the ANTXR1 gene. While significant progress has been made in understanding its molecular basis, no systematic description of the clinical phenotype is available. We conducted a comprehensive review of 105 cases reported in the available literature since the first description of GAPO syndrome in 1947. We summarise here the current understanding of the clinical phenotype and the genetic basis of the condition. Our findings point out the multisystemic nature of GAPO syndrome, primarily featuring skeletal, dermatological and ophthalmological manifestations. The condition is caused by the biallelic loss-of-function of ANTXR1 . Histological findings throughout the reported cases underscore the critical role of excessive extracellular matrix deposition in the pathogenesis of GAPO syndrome. The evidence gathered suggests ANTXR1 as an important regulator of extracellular matrix homeostasis. This study highlights the clinical and molecular spectrum of GAPO syndrome. Early recognition, multidisciplinary care and genetic counselling are essential for improving patient outcomes. Future studies should focus on targeted therapies addressing extracellular matrix dysregulation.
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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