PDR18
S. cerevisiae
ATP-binding cassette multidrug transporter PDR18
What the model saw
Gene: PDR18 Organism: Saccharomyces cerevisiae Known functions: ATP-binding cassette multidrug transporter PDR18. ABC-type transporter activity. ABC-type xenobiotic transporter activity. ATP binding. ATP hydrolysis activity. ATPase-coupled transmembrane transporter activity. protein binding.
View unredacted entry
ATP-binding cassette multidrug transporter PDR18. ABC-type transporter activity. ABC-type xenobiotic transporter activity. ATP binding. ATP hydrolysis activity. ATPase-coupled transmembrane transporter activity. protein binding.
Solver output
PDR18 encodes an ABC-type multidrug/xenobiotic transporter that uses ATP hydrolysis to actively efflux toxic compounds and xenobiotics across the plasma membrane. By expelling harmful exogenous and endogenous toxic molecules, PDR18 reduces intracellular accumulation of damaging substances that would otherwise cause proteotoxic stress, lipid peroxidation, and genomic damage. In yeast, the PDR (Pleiotropic Drug Resistance) network is closely linked to stress resistance and chronological/replicative lifespan; enhanced efflux capacity reduces cellular damage load. PDR18 has also been specifically implicated in ergosterol homeostasis and membrane lipid composition, which affects membrane integrity and stress resilience — a key determinant of yeast longevity. Thus, its normal function in detoxification and membrane protection is expected to promote longevity rather than oppose it.
GenAge curators classify each gene's normal function as promoting (Pro-Longevity) or opposing (Anti-Longevity) longevity, based on synthesis across studies. Loss-of-function effects can vary from this depending on the manipulation.
Advisor judgment
The model predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning is plausible on the surface — PDR18 is indeed an ABC transporter involved in drug resistance and ergosterol homeostasis — but it reached the wrong conclusion. In yeast longevity studies, deletion of PDR18 has been shown to extend lifespan, meaning the gene's normal activity is anti-longevity. The model's logic that detoxification and membrane protection would promote longevity is intuitive but incorrect for this specific gene. The model had moderate confidence (0.65) but was still wrong. The mechanistic reasoning about ergosterol and membrane integrity is partially relevant but misapplied in terms of the direction of effect on longevity.
Raw API responses
solver
{
"reasoning": "PDR18 encodes an ABC-type multidrug/xenobiotic transporter that uses ATP hydrolysis to actively efflux toxic compounds and xenobiotics across the plasma membrane. By expelling harmful exogenous and endogenous toxic molecules, PDR18 reduces intracellular accumulation of damaging substances that would otherwise cause proteotoxic stress, lipid peroxidation, and genomic damage. In yeast, the PDR (Pleiotropic Drug Resistance) network is closely linked to stress resistance and chronological/replicative lifespan; enhanced efflux capacity reduces cellular damage load. PDR18 has also been specifically implicated in ergosterol homeostasis and membrane lipid composition, which affects membrane integrity and stress resilience — a key determinant of yeast longevity. Thus, its normal function in detoxification and membrane protection is expected to promote longevity rather than oppose it.",
"confidence": 0.65,
"key_pathways": [
"ABC transporter / pleiotropic drug resistance (PDR) network",
"xenobiotic/toxin efflux and detoxification",
"ergosterol homeostasis and membrane integrity"
],
"mechanism_class": "other",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning is plausible on the surface — PDR18 is indeed an ABC transporter involved in drug resistance and ergosterol homeostasis — but it reached the wrong conclusion. In yeast longevity studies, deletion of PDR18 has been shown to extend lifespan, meaning the gene's normal activity is anti-longevity. The model's logic that detoxification and membrane protection would promote longevity is intuitive but incorrect for this specific gene. The model had moderate confidence (0.65) but was still wrong. The mechanistic reasoning about ergosterol and membrane integrity is partially relevant but misapplied in terms of the direction of effect on longevity.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 3,
"ground_truth_questionable": false
}