DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for transcobalamin II deficiency — 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 moduleTranscobalamin II deficiency 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
approvedHydroxocobalaminApproved drugapprovedCyanocobalaminApproved drug
Structures already discussed alongside transcobalamin ii deficiency in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
The surface-exposed lipo-protein of BtuG2 — Hydroxocobalamin has a real, experimentally solved structure in complex with this target (PDB 8BB0, 1.5 Å). This is the drug's own deposited structure, not a prediction, and confirms it is a structurally characterised molecule rather than an untested guess.
Loading structure…
helix sheet i2adrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8BB0 · 1.5 Å · ligand Hydroxocobalamin (I2A). Experimental structure, not a prediction.
What the evidence adds up to
Transcobalamin II deficiency is an autosomal recessive disorder in which a defective plasma protein cannot transport vitamin B12 into cells. Fewer than 50 cases have been reported globally, giving a prevalence below 1 in 1,000,000. The presenting features in early infancy include failure to thrive, diarrhoea, megaloblastic anaemia, pancytopenia, neurological abnormalities, and recurrent infections linked to immune abnormalities. Serum cobalamin levels are often normal because most endogenous cobalamin is carried on R proteins, not on transcobalamin II. Diagnosis is confirmed by genetic analysis of the TCN2 gene. In a 2022 case, a 2.2-month-old Chinese girl with diarrhoea, fever and poor feeding had two novel compound-heterozygous mutations (c.754-12C>G and c.1031_1032delGA). In a 2025 report, a child first admitted at age five with haemoglobin 49 g/L required erythrocyte transfusion; bone marrow analyses ruled out myelodysplastic syndrome and haematologic malignancies, and iron and folate therapies were ineffective.
Cyanocobalamin (vitamin B12) can normalise haemoglobin and reduce splenomegaly. In the 2025 case, cyanocobalamin raised haemoglobin to 130 g/L. However, long-term follow-up of five patients from one institution found that minimal treatment may be dangerous: haematological normality can be maintained while neurological development still suffers, and damage sustained early in life may be irreversible. Two of those five patients had long-term neurological sequelae. The adequate therapeutic dose of vitamin B12 to allow normal neurological function is not easily determined. In a 2018 diagnostic study of B12 deficiency in 136 patients (70 with deficiency), the oral “beefy red” patch had the highest diagnostic validity (Youden index 0.84) and reliability (91.9%), and combining it with serum cobalamin below 350 pg/mL gave accuracy of 0.81 and reliability of 90.4%. That study was not specific to transcobalamin II deficiency.
What is still missing: prospective data on optimal B12 dosing schedules that prevent neurological damage, systematic long-term follow-up in more than a handful of patients, and any controlled trial of treatment regimens. The condition is so rare that no trial has been possible, and patient stratification by genotype or age at diagnosis has not been attempted.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Journal of Inherited Metabolic Disease · 2013 · 81 citations
Update on transcobalamin deficiency: clinical presentation, treatment and outcome
AbstractTranscobalamin (TC) transports cobalamin from blood into cells. TC deficiency is a rare autosomal recessive disorder usually presenting in early infancy with failure to thrive, weakness, diarrhoea, pallor, anemia, and pancytopenia or agammaglobulinemia. It can sometimes resemble neonatal leukemia or severe combined immunodeficiency disease. Diagnosis of TC deficiency is suspected based on megaloblastic anemia, elevation of total plasma homocysteine, and blood or urine methylmalonic acid. It is confirmed by studying the synthesis of TC in cultured fibroblasts, or by molecular analysis of the TCN2 gene. TC deficiency is treatable with supplemental cobalamin, but the optimal type, route and frequency of cobalamin administration and long term patient outcomes are unknown. Here we present a series of 30 patients with TC deficiency, including an update on multiple previously published patients, in order to evaluate the different treatment strategies and provide information about long term outcome. Based on the data presented, current practice appears to favour treatment of individuals with TC deficiency by intramuscular injections of hydroxy- or cyanocobalamin. In most cases presented, at least weekly injections (1 mg IM) were necessary to ensure optimal treatment. Most centres adjusted the treatment regimen based on monitoring CBC, total plasma homocysteine, plasma and urine methylmalonic acid, as well as, clinical status. Finally, continuing IM treatment into adulthood appears to be beneficial.
New England Journal of Medicine · 1980 · 62 citations
Studies of a Patient with Megaloblastic Anemia and an Abnormal Transcobalamin II
AbstractTRANSCOBALAMIN II, a 38,000-dalton plasma protein, has a single binding site for cobalamin (vitamin B12) and functions as the major protein for transporting cobalamin to various tissues.1 2 3 4 Table 1 lists the characteristics of four cases of hereditary absence of transcobalamin II as previously described.5 6 7 These characteristics suggested simple cobalamin deficiency, but since about 70 to 90 per cent of the endogenous cobalamin in serum is found on cobalamin-binding proteins known as R proteins, 1 and only 10 to 30 per cent of serum cobalamin is bound to transcobalamin II, the serum cobalamin levels were all considered normal. All the patients had . . .
Journal of Neurology Neurosurgery & Psychiatry · 1982 · 38 citations · open access
Neurological involvement in hereditary transcobalamin II deficiency.
AbstractA case of hereditary transcobalamin II deficiency with neurological involvement is described. The patient presented in early infancy with megaloblastic anaemia and was treated with folinic acid from 6 weeks of age. The diagnosis of transcobalamin II deficiency was not made until he was 2 years old when he showed severely retarded intellectual development, ataxia and pyramidal deficit in the limbs. Following treatment with hydroxocobalamin, his condition has slowly improved but he has remained with a severe neurological deficit. The consequences of vitamin B12 deficiency on neurological development in infancy are discussed.
Turkish Journal of Hematology · 2019 · 32 citations · open access
Different Presentations of Patients with Transcobalamin II Deficiency: A Single-Center Experience from Turkey
AbstractObjective: Transcobalamin II deficiency is a rare autosomal recessive disease characterized by decreased cobalamin availability, which in turn causes accumulation of homocysteine and methylmalonic acid. The presenting clinical features are failure to thrive, diarrhea, megaloblastic anemia, pancytopenia, neurologic abnormalities, and also recurrent infections due to immune abnormalities in early infancy. Materials and Methods: Here, we report the clinical and laboratory features of six children with transcobalamin II deficiency who were all molecularly confirmed. Results: gene mutation was detected in one of the remaining patients. Conclusion: Transcobalamin II deficiency should be considered in the differential diagnosis of infants with immunological abnormalities as well as cytopenia and neurological dysfunction. Early recognition of this rare condition and initiation of adequate treatment is critical for control of the disease and better prognosis.
Archives of Disease in Childhood · 1995 · 21 citations · open access
Long-term follow up of patients with transcobalamin II deficiency.
AbstractFive cases of transcobalamin II deficiency presenting to our institution were reviewed. A delay in diagnosis often led to acute deterioration. Two patients have long term neurological sequelae. Minimal treatment in these patients may be dangerous. While haematological normality may be maintained, the adequate therapeutic dose of vitamin B-12 to allow normal neurological development and function is not easily determined and damage sustained early in life may be irreversible.
Therapeutics and Clinical Risk Management · 2018 · 9 citations · open access
Diagnostic value of oral “beefy red” patch in vitamin B12 deficiency
AbstractBACKGROUND: Vitamin B12 deficiency, which may cause serious neuropsychiatric damage, is common in the elderly. The non-specific clinical features of B12 deficiency and unreliable serum parameters make diagnosis difficult. We aimed to evaluate the value of oral "beefy red" patches as a clinical marker of B12 deficiency. METHODS: A diagnostic study was conducted in patients complaining of oral soreness, burning sensation, or severe recurrent oral ulcers. Patients underwent clinical examination and laboratory investigations, including complete blood count and estimation of serum B12, folate, iron, and ferritin levels. Resolution of clinical signs and symptoms after 1 month of B12 supplement was regarded as the diagnostic gold standard. RESULTS: Of 136 patients, 70 had B12 deficiency. Among these patients, the oral "beefy red" patch was observed in 61, abnormal mean corpuscular volume (MCV) was noted in 30, and serum cobalamin levels <200 and <350 pg/mL were seen in 59 and 67 cases, respectively. The "beefy red" patch demonstrated the highest diagnostic validity (Youden index 0.84) and reliability (consistency 91.9% [95% CI: 87.3%-96.5%]), followed by the serum cobalamin levels and MCV. The combination of "beefy red" patch with cobalamin <350 pg/mL exhibited better diagnostic value than the combination of "beefy red" patch with cobalamin <200 pg/mL, with accuracy of 0.81 vs 0.74 and reliability of 90.4% (95% CI: 85.5%-95.4%) vs 86.8% (95% CI: 81.1%-92.5%). CONCLUSION: The combination of oral "beefy red" patch and serum cobalamin level <350 pg/mL appears to be useful for diagnosis of B12 deficiency.
Frontiers in Genetics · 2022 · 4 citations · open access
Case report: Novel compound-heterozygous mutations in the TCN2 gene identified in a chinese girl with transcobalamin deficiency
AbstractTranscobalamin (TC) deficiency is a rare autosomal recessive disease characterized by megaloblastic anemia. It is caused by cellular vitamin B12 depletion, which subsequently results in elevated levels of homocysteine and methylmalonic acid. This disease is usually diagnosed by genetic analysis of the TCN2 gene. Here, we described a 2.2-month-old Chinese girl with TC deficiency presenting with diarrhea, fever and poor feeding. Whole-exome sequencing detected a pair of compound-heterozygous mutations in TCN2 gene, c.754-12C&gt;G and c.1031_1032delGA (p.R344Tfs*20). To our knowledge, it is the first time that they were identified and reported in TC deficiency. This study contributes to a better understanding of the TC deficiency, expanding the spectrum of TCN2 mutations in this disorder and also supporting the early diagnosis and proper treatment of similar cases in the future.
Journal of Human Immunity · 2025 · 1 citations · open access
Expanding the Allelic Spectrum of TCN2: A Case Report on Transcobalamin II Deficiency
AbstractIntroduction Transcobalamin II deficiency is a rare autosomal recessive disorder classified as an inborn error of immunity. Transcobalamin II is a plasma protein essential for the absorption, transport, and cellular utilization of vitamin B12. Its deficiency leads to diverse clinical manifestations, including gastrointestinal disturbances, failure to thrive, megaloblastic anemia, pancytopenia, agammaglobulinemia, neurological impairments, metabolic abnormalities, and recurrent infections. According to Orphanet and PubMed, fewer than 50 cases have been reported globally, suggesting a prevalence of less than 1 in 1,000,000. Materials and Methods Genomic DNA was extracted from peripheral blood leukocytes using phenol-chloroform extraction. Whole-exome sequencing was performed on a DNBSEQ-G50 (MGI, China) using the Exome Capture V5 Probe Set (MGI, China). Secondary data processing of FASTQ files was performed using ZLIMS (MGI, China), and tertiary analysis involved the Annovar software, followed by variant filtering. Detected variants were evaluated using the Varsome software. Clinically significant variants were confirmed by Sanger sequencing on a 3500 Genetic Analyzer (Thermo Scientific, USA). Results Two novel heterozygous variants in the TCN2 gene (NM_000355.3) were identified, neither reported in the gnomAD Exomes database. These included a splice-site variant c.1223-2 A&gt;G (VarSome classification: likely pathogenic) and a coding region variant c.154C&gt;T, p.Pro52Ser (VarSome classification: uncertain significance). The compound heterozygous genotype was consistent with the patient’s clinical presentation. The patient was first admitted at age five with an acute anemic crisis (hemoglobin 49 g/L), required erythrocyte transfusion. Subsequent evaluations revealed persistent megaloblastic anemia, hyperbilirubinemia, and mild splenomegaly. Bone marrow analyses excluded myelodysplastic syndrome and hematologic malignancies. Iron and folate therapies were ineffective; however, cyanocobalamin normalized hemoglobin levels (130 g/L) and reduced splenomegaly. Mild intellectual impairment was noted during follow-up. Conclusion Transcobalamin II deficiency typically manifests in early childhood with symptoms such as developmental delays, hypotonia, diarrhea, pallor, anemia, pancytopenia, and agammaglobulinemia. This case contributes to the understanding of the condition, expands the allelic spectrum of TCN2, and supports the optimization of treatment strategies for this rare condition.
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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