Chronic Benign TubularProteinuria from Compound Heterozygous Mutations in CUBN: A Case Report
Bibliographic record
Abstract
Introduction: Proteinuria is a commonly used parameter for predicting decline in renal filtration function. Cubilin, encoded by CUBN, is a critical protein involved in low molecular weight protein reabsorption in the proximal tubule. Mutations in CUBN lead to Imerslund-Gräsbeck syndrome (IGS), a disorder characterized by vitamin B12 deficiency (and consequences related to that) with or without proteinuria. Recent evidence suggests that C-terminal mutations in CUBN may lead to proteinuria without other features of IGS. Case Description: We report a case of a 47 year-old male with chronic, albumin-predominant, subnephrotic range proteinuria since his teenage years, but preserved eGFR. Neither ACE inhibition nor AT-II receptor blockade reduced his degree of proteinuria. Genetic testing identified three distinct pathogenic mutations in CUBN that were confirmed by parental cascade testing to be compound heterozygosity. All mutations were downstream of the vitamin B12-intrinsic factor binding domain of cubilin, two of which conferred stop-gain sequences. The patient had normal vitamin B12 levels and did not exhibit megaloblastic anemia, growth retardation, or any other features of IGS. Renal biopsy was not pursued for this patient as diagnostic clarification was achieved by non-invasive genetic testing alone. Discussion: This case report presents the first long-term follow-up of a patient with CUBN mutations, demonstrating eGFR stability despite chronic proteinuria. We highlight several important lessons. First, not all proteinuria is made equal, and forms of tubular proteinuria can exist without compromising renal filtration function. Second, identifying genetic forms of tubular proteinuria is key to avoiding ineffective interventions (e.g. ACE inhibition, AT-II receptor blockade) and unnecessary invasive procedures (e.g. renal biopsy). Third, the location of CUBN mutations dictate phenotypic consequences, with C-terminal mutations leading to proteinuria without vitamin B12 deficiency.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.002 | 0.002 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.004 | 0.002 |
| Science and technology studies | 0.003 | 0.002 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.002 | 0.003 |
| Research integrity | 0.006 | 0.003 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".