Where this model is curated
The entry card says what the model is for: which mechanism nodes it links to, how faithfully, and what it found. This page holds the model itself.
- disorder Gout kb/disorders/Gout.yaml
Committed run
From exports/model_runs/urate_homeostasis.json, regenerated by just gen-model-results. Scenario roots link to the mechanism node they drive on the entry page.
Simulation results — 13 scenarios run with dismech-perturb (tellurium / libRoadRunner CVODE) over 500 h; baseline f_exc = 1.0
| Scenario | Serum_Urate (mg/dL) | Activated phenotypes |
|---|---|---|
Healthy baseline
f_exc = 1.0
|
4.995005 | reference |
|
Underexcretion hyperuricemia (f_exc=0.5)
drives
Hyperuricemia
|
9.98004
2.00× baseline
|
Hyperuricemia · moderate |
|
Severe underexcretion (f_exc=0.35)
drives
Hyperuricemia
|
14.245014
2.85× baseline
|
Hyperuricemia · severe |
|
Urate overproduction (purine load)
drives
Hyperuricemia
|
12.487512
2.50× baseline
|
Hyperuricemia · severe |
|
HPRT1 loss-of-function (overproduction; Lesch-Nyhan)
drives
Hyperuricemia
|
12.487512
2.50× baseline
|
Hyperuricemia · severe |
|
PRPS1 superactivity (overproduction)
drives
Hyperuricemia
|
12.487512
2.50× baseline
|
Hyperuricemia · severe |
|
ABCG2 loss-of-function (reduced excretion)
drives
Hyperuricemia
|
9.98004
2.00× baseline
|
Hyperuricemia · moderate |
|
SLC2A9/GLUT9 loss-of-function (renal hypouricemia; protective)
drives
Hyperuricemia
|
1.666111
0.33× baseline
|
Hypouricemia · moderate |
|
SLC22A12/URAT1 loss-of-function (renal hypouricemia; protective)
drives
Hyperuricemia
|
1.9992
0.40× baseline
|
Hypouricemia · mild |
|
Allopurinol (xanthine oxidase inhibitor)
drives
Hyperuricemia
|
3.493014
0.70× baseline
|
none |
|
Febuxostat (potent xanthine oxidase inhibitor)
drives
Hyperuricemia
|
2.49501
0.50× baseline
|
Hypouricemia · mild |
|
Probenecid (uricosuric; increases excretion)
drives
Hyperuricemia
|
5.54939
1.11× baseline
|
none |
|
Pegloticase (recombinant uricase; direct urate degradation)
drives
Hyperuricemia
|
3.846154
0.77× baseline
|
none |
|
Allopurinol + probenecid (dual production + excretion)
drives
Hyperuricemia
|
3.121099
0.62× baseline
|
none |
Derived artifact, regenerated by
just gen-model-results
— not curated evidence. Values rounded to
6 decimals.
Config fc50e6794cdd,
model.xml a3eb6748f4bd.
Phenotypes activate per the curated variable thresholds.
Phenotype thresholds
| Phenotype | Variable | Direction | Threshold | Reading |
|---|---|---|---|---|
| Hyperuricemia | Serum_Urate |
above | 6.8 | absolute |
| Hypouricemia | Serum_Urate |
below | 0.5 | ratio of baseline |
Gene effects
How config.yaml turns a gene perturbation into a model parameter change: the multiplier applied for a loss- or gain-of-function.
| Gene | Parameter | Effect | Rationale |
|---|---|---|---|
HPRT1 |
P |
LoF ×2.5 | HPRT1 (HGPRT) salvages hypoxanthine/guanine; loss-of-function (Lesch-Nyhan / Kelley-Seegmiller) diverts PRPP to de novo purine synthesis, causing urate overproduction. Modeled as increased purine load P. |
PRPS1 |
P |
GoF ×2.5 | PRPS1 superactivity (gain-of-function) increases PRPP availability and drives purine overproduction and hyperuricemia. Modeled as increased P. |
ABCG2 |
f_exc |
LoF ×0.5 | ABCG2 is an apical efflux pump mediating renal and extra-renal urate secretion; the common Q141K loss-of-function variant reduces urate excretion and raises gout risk. Modeled as reduced fractional excretion. |
SLC2A9 |
f_exc |
LoF ×3.0 | SLC2A9 (GLUT9) reabsorbs urate at the basolateral membrane; loss-of- function causes renal hypouricemia by increasing urate excretion (protective). Modeled as increased fractional excretion. |
SLC22A12 |
f_exc |
LoF ×2.5 | SLC22A12 (URAT1) reabsorbs urate at the apical membrane and is the target of uricosurics; loss-of-function causes renal hypouricemia. Modeled as increased fractional excretion. |
Run it locally
uv run python -m dismech.perturb kb/disorders/Gout.yaml --alljust gen-model-results --id urate_homeostasis