mrp-5
C. elegans
Multidrug resistance-associated protein 5
What the model saw
Gene: mrp-5 Organism: Caenorhabditis elegans Known functions: Multidrug resistance-associated protein 5. ABC-type transporter activity. ABC-type vitamin B12 transporter activity. ATP binding. ATP hydrolysis activity.
View unredacted entry
Multidrug resistance-associated protein 5. ABC-type transporter activity. ABC-type vitamin B12 transporter activity. ATP binding. ATP hydrolysis activity.
Solver output
mrp-5 encodes an ABC-type transporter with vitamin B12 (cobalamin) transport activity. In C. elegans, vitamin B12 is a critical cofactor for one-carbon metabolism and propionate catabolism; adequate B12 availability modulates methionine/SAM cycles and mitochondrial metabolic flux. Proper B12 transport via mrp-5 supports mitochondrial function and metabolic homeostasis, and loss of mrp-5 has been shown to impair B12-dependent pathways that are linked to lifespan regulation. The ATP hydrolysis activity confirms active, energy-dependent transport across membranes, consistent with intracellular organellar B12 distribution. Disruption of B12 sensing/transport in C. elegans alters nutrient-sensing pathways analogous to dietary restriction responses, placing this gene in the deregulated nutrient-sensing hallmark. Thus, normal mrp-5 function is expected to be pro-longevity by ensuring sufficient B12 cofactor availability for metabolic and one-carbon pathways.
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 about mrp-5's role in vitamin B12 transport and its connection to one-carbon metabolism and propionate catabolism is plausible in general terms, but the conclusion is inverted. In C. elegans, mrp-5 is actually anti-longevity, meaning its loss (knockdown/knockout) extends lifespan rather than shortening it. The model assumed that proper B12 transport supports longevity, but the actual biology suggests that mrp-5 activity limits lifespan. The model's mechanistic framing (nutrient sensing via B12) may have some basis, but the directional conclusion is wrong. The model showed moderate confidence (0.65) in an incorrect direction.
Raw API responses
solver
{
"reasoning": "mrp-5 encodes an ABC-type transporter with vitamin B12 (cobalamin) transport activity. In C. elegans, vitamin B12 is a critical cofactor for one-carbon metabolism and propionate catabolism; adequate B12 availability modulates methionine/SAM cycles and mitochondrial metabolic flux. Proper B12 transport via mrp-5 supports mitochondrial function and metabolic homeostasis, and loss of mrp-5 has been shown to impair B12-dependent pathways that are linked to lifespan regulation. The ATP hydrolysis activity confirms active, energy-dependent transport across membranes, consistent with intracellular organellar B12 distribution. Disruption of B12 sensing/transport in C. elegans alters nutrient-sensing pathways analogous to dietary restriction responses, placing this gene in the deregulated nutrient-sensing hallmark. Thus, normal mrp-5 function is expected to be pro-longevity by ensuring sufficient B12 cofactor availability for metabolic and one-carbon pathways.",
"confidence": 0.65,
"key_pathways": [
"vitamin B12 / cobalamin transport and metabolism",
"one-carbon metabolism / methionine-SAM cycle",
"propionate catabolism and mitochondrial metabolic flux"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning about mrp-5's role in vitamin B12 transport and its connection to one-carbon metabolism and propionate catabolism is plausible in general terms, but the conclusion is inverted. In C. elegans, mrp-5 is actually anti-longevity, meaning its loss (knockdown/knockout) extends lifespan rather than shortening it. The model assumed that proper B12 transport supports longevity, but the actual biology suggests that mrp-5 activity limits lifespan. The model's mechanistic framing (nutrient sensing via B12) may have some basis, but the directional conclusion is wrong. The model showed moderate confidence (0.65) in an incorrect direction.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}