mvk-1
C. elegans
GHMP kinase C-terminal domain-containing protein
What the model saw
Gene: mvk-1 Organism: Caenorhabditis elegans Known functions: GHMP kinase C-terminal domain-containing protein. ATP binding. mevalonate kinase activity.
View unredacted entry
GHMP kinase C-terminal domain-containing protein. ATP binding. mevalonate kinase activity.
Solver output
mvk-1 encodes mevalonate kinase, which catalyzes the ATP-dependent phosphorylation of mevalonate to mevalonate-5-phosphate, a committed and rate-limiting step in the mevalonate/isoprenoid biosynthesis pathway. This pathway produces cholesterol, isoprenoids, and other sterol-derived metabolites that feed into downstream signaling networks including sterol-dependent regulation of growth and nutrient sensing. In C. elegans, the mevalonate pathway supports production of isoprenoids required for protein prenylation (e.g., farnesylation and geranylgeranylation of Ras/Rho GTPases), which promotes pro-growth, pro-aging signaling analogous to TOR and insulin/IGF-1 pathway activity. Elevated flux through the mevalonate pathway thus supports anabolic, growth-promoting states that are generally associated with shortened lifespan, while inhibition of this pathway (e.g., by statins) is linked to longevity benefits in multiple organisms. Therefore, the normal function of mvk-1 in sustaining mevalonate pathway flux is predicted to be anti-longevity.
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 anti_longevity but the ground truth is pro_longevity. The model's reasoning follows a plausible but ultimately incorrect logic: it assumes that mevalonate pathway activity promotes aging (analogous to TOR/IIS signaling), and therefore mvk-1 should be anti-longevity. However, in C. elegans, mvk-1 appears to be pro-longevity, suggesting that mevalonate kinase activity (or the downstream products it generates) actually supports longevity rather than shortening it. The model's mechanistic reasoning about the mevalonate pathway promoting pro-growth/pro-aging signaling is a reasonable hypothesis but is contradicted by the actual experimental data. The model was fairly confident (0.72) in its wrong prediction. The reasoning quality is low because it relied on an oversimplified analogy to TOR/IIS signaling without considering that mevalonate pathway products (like ubiquinone/CoQ) are essential for mitochondrial function and could be pro-longevity in C. elegans.
Raw API responses
solver
{
"reasoning": "mvk-1 encodes mevalonate kinase, which catalyzes the ATP-dependent phosphorylation of mevalonate to mevalonate-5-phosphate, a committed and rate-limiting step in the mevalonate/isoprenoid biosynthesis pathway. This pathway produces cholesterol, isoprenoids, and other sterol-derived metabolites that feed into downstream signaling networks including sterol-dependent regulation of growth and nutrient sensing. In C. elegans, the mevalonate pathway supports production of isoprenoids required for protein prenylation (e.g., farnesylation and geranylgeranylation of Ras/Rho GTPases), which promotes pro-growth, pro-aging signaling analogous to TOR and insulin/IGF-1 pathway activity. Elevated flux through the mevalonate pathway thus supports anabolic, growth-promoting states that are generally associated with shortened lifespan, while inhibition of this pathway (e.g., by statins) is linked to longevity benefits in multiple organisms. Therefore, the normal function of mvk-1 in sustaining mevalonate pathway flux is predicted to be anti-longevity.",
"confidence": 0.72,
"key_pathways": [
"mevalonate/isoprenoid biosynthesis pathway",
"protein prenylation (Ras/Rho GTPase farnesylation/geranylgeranylation)",
"sterol and cholesterol biosynthesis"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model predicted anti_longevity but the ground truth is pro_longevity. The model's reasoning follows a plausible but ultimately incorrect logic: it assumes that mevalonate pathway activity promotes aging (analogous to TOR/IIS signaling), and therefore mvk-1 should be anti-longevity. However, in C. elegans, mvk-1 appears to be pro-longevity, suggesting that mevalonate kinase activity (or the downstream products it generates) actually supports longevity rather than shortening it. The model's mechanistic reasoning about the mevalonate pathway promoting pro-growth/pro-aging signaling is a reasonable hypothesis but is contradicted by the actual experimental data. The model was fairly confident (0.72) in its wrong prediction. The reasoning quality is low because it relied on an oversimplified analogy to TOR/IIS signaling without considering that mevalonate pathway products (like ubiquinone/CoQ) are essential for mitochondrial function and could be pro-longevity in C. elegans.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}