DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for KBG syndrome — screening already-approved drugs against its 7-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleKBG syndrome maps to a 7-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 kbg 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
collagen type II alpha 1 chain (COL2A1) — COL2A1 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 p33drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5NIR · 1.74 Å · ligand 3,6,9,12,15,18-HEXAOXAICOSANE-1,20-DIOL (P33). Experimental structure, not a prediction.
What the evidence adds up to
Growth hormone therapy was given to a girl with KBG syndrome and short stature. Over one year her height standard deviation score rose from –3.3 to –1.9, and her height velocity increased from 4.2 cm/year to 9.8 cm/year. No adverse reactions were reported. The authors state that growth hormone was effective in this girl and in most children with KBG syndrome and short stature during the first year of therapy, but the evidence is limited to a single case report and a literature review that is not described in detail.
A Chinese study of three unreported patients and 186 previously reported cases found that patients with ANKRD11 gene mutations had a significantly higher frequency of macrodontia, long philtrum, abnormal eyebrows, widely spaced eyes, anteverted nares, eyelid ptosis, brachydactyly, and brachycephaly, and a significantly lower risk of congenital heart disease and frontal bossing. Intellectual disability was significantly milder in patients carrying truncating variants located between repression domain 1 and the activation domain than in those with mutations disrupting repression domain 2 alone or disrupting all functional domains. This suggests that the location of the mutation within the gene may predict the severity of intellectual disability.
A separate family study identified a heterozygous c.4398_4401del frameshift variant in ANKRD11 in a proband, his mother, and his sister, all of whom had KBG syndrome. This variant was absent in the unaffected father. The authors concluded that this variant probably underlies the syndrome in that pedigree. A 2023 study on missense variants in ANKRD11 confirmed that these variants cause KBG syndrome by impairing the stability or transcriptional activity of the encoded protein, but the abstract provides no patient-level outcome data.
What is still missing: prospective controlled trials of growth hormone in KBG syndrome, any data on long-term safety or adult height outcomes, and any treatment studies that address the intellectual disability or other neurodevelopmental features. No drug other than growth hormone has been tested in this population. Patient stratification by genotype is suggested by the Chinese study but has not been used to guide treatment in a trial.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
World Journal of Clinical Cases · 2020 · 15 citations · open access
Growth hormone therapy for children with KBG syndrome: A case report and review of literature
AbstractBACKGROUND: The incidence of short stature in KBG syndrome is relatively high. Data on the therapeutic effects of growth hormone (GH) on children with KBG syndrome accompanied by short stature in the previous literature has not been summarized. CASE SUMMARY: = 0.001). There were no adverse reactions reported after GH treatment. CONCLUSION: GH treatment is effective in our girl and most children with KBG syndrome accompanied by short stature during the first year of therapy.
Translational Pediatrics · 2021 · 14 citations · open access
Comprehensive analysis of clinical spectrum and genotype associations in Chinese and literature reported KBG syndrome
AbstractBACKGROUND: gene variant types, the 16q24.3 microdeletion, and the clinical spectrum of KBG syndrome. METHODS: The genetic etiology of three unreported KBG patients was identified by whole exome sequencing and confirmed via Sanger sequencing. Literature review was conducted to summarize the phenotype-genotype relationship based on three unreported Chinese cases and 186 reported cases. RESULTS: gene mutations showed significantly higher frequency of malformations including macrodontia, long philtrum, abnormal eyebrows, widely spaced eyes, anteverted nares, eyelid ptosis, brachydactyly, brachycephaly (P<0.05), and significantly lower risk of congenital heart diseases and frontal bossing (P<0.05). The intellectual disability (ID) was significantly milder among patients carrying truncating variants located between repression domain 1 (RD1) and activation domain (AD) than those carrying mutations disrupting repression domain 2 (RD2) alone and disrupting all functional domain (RD1, AD or RD2) (P<0.05). CONCLUSIONS: gene variants disrupting RD1 and RD2 or RD2 alone are more likely to have more severe ID, which warrants different intervention strategies for KBG syndrome.
[Analysis of ANKRD11 gene variant in a family affected with KBG syndrome].
AbstractOBJECTIVE: To explore the genetic basis for a pedigree affected with KBG syndrome. METHODS: Clinical data of three patients from the pedigree (the proband, his mother and sister) was collected. Genomic DNA was extracted from peripheral blood samples and subjected to whole exome sequencing (WES). Suspected variant was verified by Sanger sequencing. RESULTS: The proband was found to harbor a heterozygous c.4398_4401del (p.Glu1467AsnfsTer63) frameshift variant of the ANKRD11 gene by WES. Sanger sequencing confirmed that the same variant was also present in his mother and sister, but not in his father. CONCLUSION: The c.4398_4401de (p.Glu1467AsnfsTer63) variation of the ANKRD11 gene probably underlies the KBG syndrome in this pedigree.
International Journal of Paediatric Dentistry · 2009 · 5 citations · open access
Poster Session P18/Syndromes and Genetics/Oral Medicine and Pathology
AbstractPURPOSE: This investigation sought to identify the common manifestations of KBG syndrome in the literature and to determine the major oral abnormalities in a 12-year-old Chinese boy. METHODS: PUBMED search, using the keyword phrase "KBG syndrome," produced 20 articles. Due to the disparities in the quality of evaluations in the reports, any physical feature that was not discussed was assumed to be absent. RESULTS: Of the 54 cases, including the present case, 36 (67%) were males. Mental retardation or global developmental delay was reported in 42 (78%) cases, while 46 (85%) exhibited shortness of stature. Oral features occurred in 53 (98%) cases; macrodontia was present in 49 (96%) cases; the present case was the only one with hyperdontia and a talon cusp. Other features were craniofacial anomalies, followed by abnormalities of the nose, hand, mouth, eyes, eyebrows, philtrum, costovertebrae, ears, and, less frequently, low hairline and lower extremity abnormalities. CONCLUSIONS: Cardinal features of KBG syndrome include facial dysmorphism, short stature, skeletal anomalies, and mild developmental delay; intraorally, macrodontia of the maxillary central incisors occurs in most cases. This is the first known report of KBG syndrome in a Chinese subject and the only case with hyperdontia and a talon cusp.
Genetics in Medicine · 2023 · 4 citations · open access
Missense variants in ANKRD11 cause KBG syndrome by impairment of stability or transcriptional activity of the encoded protein
AbstractCorrection to: Genetics in Medicine 2022; https://doi.org/10.1016/j.gim.2022.06.007, published online 14 July 2022. In the article “Missense variants in ANKRD11 cause KBG syndrome by impairment of stability or transcriptional activity of the encoded protein” (Genet Med 2022;24:2051–2064), the following update was made. On page 2060, Figure 3 had an error in the artwork (the EGFP and Merged fluorescence imaging of ANKRD11 p.Leu509Pro and p.Arg2512Gln are identical). The revised Figure 3 is shown below. The authors would like to apologize for any inconvenience this may have caused. The article has been corrected online and can be accessed at https://doi.org/10.1016/j.gim.2022.06.007. Missense variants in ANKRD11 cause KBG syndrome by impairment of stability or transcriptional activity of the encoded proteinGenetics in MedicineVol. 24Issue 10PreviewAlthough haploinsufficiency of ANKRD11 is among the most common genetic causes of neurodevelopmental disorders, the role of rare ANKRD11 missense variation remains unclear. We characterized clinical, molecular, and functional spectra of ANKRD11 missense variants. Full-Text PDF Open Access
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.
