k10b4.3
C. elegans
Protein melted homolog
What the model saw
Gene: K10B4.3 Organism: Caenorhabditis elegans Known functions: Protein melted homolog. phosphatidylinositol-5-phosphate binding.
View unredacted entry
Protein melted homolog. phosphatidylinositol-5-phosphate binding.
Solver output
K10B4.3 is the C. elegans homolog of Drosophila Melted, a PH-domain protein that binds phosphatidylinositol-5-phosphate and acts as a positive regulator of the insulin/IGF-1 signaling (IIS) pathway. In Drosophila, Melted promotes TORC1 activity and suppresses FOXO (dFOXO) by stabilizing the interaction between TOR and Myc, thereby enhancing anabolic nutrient sensing. In C. elegans, the IIS pathway converges on the FOXO transcription factor DAF-16; hyperactivation of this pathway shortens lifespan, while its reduction extends it. As a positive effector of PI3K/TOR-dependent nutrient sensing downstream of DAF-2/InsR, the normal function of K10B4.3/melted would be expected to suppress DAF-16 activity and promote growth at the expense of longevity. Phosphatidylinositol-5-phosphate binding further places this protein within the PI3K signaling node that drives pro-growth, anti-longevity outputs.
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 correctly predicted anti_longevity for K10B4.3 (melted homolog). The mechanistic reasoning is well-grounded: it correctly identifies K10B4.3 as the C. elegans homolog of Drosophila Melted, correctly describes Melted's role as a positive regulator of IIS/TOR signaling, and correctly reasons that this would suppress DAF-16/FOXO activity and thus reduce longevity. The reasoning about phosphoinositide signaling is also appropriate given the known PI-5P binding function. The confidence of 0.65 is reasonable given the indirect inference from Drosophila biology. The reasoning is largely sound, though the specific mechanistic details about Melted's role in C. elegans are somewhat inferred from Drosophila data rather than direct C. elegans experimental evidence.
Raw API responses
solver
{
"reasoning": "K10B4.3 is the C. elegans homolog of Drosophila Melted, a PH-domain protein that binds phosphatidylinositol-5-phosphate and acts as a positive regulator of the insulin/IGF-1 signaling (IIS) pathway. In Drosophila, Melted promotes TORC1 activity and suppresses FOXO (dFOXO) by stabilizing the interaction between TOR and Myc, thereby enhancing anabolic nutrient sensing. In C. elegans, the IIS pathway converges on the FOXO transcription factor DAF-16; hyperactivation of this pathway shortens lifespan, while its reduction extends it. As a positive effector of PI3K/TOR-dependent nutrient sensing downstream of DAF-2/InsR, the normal function of K10B4.3/melted would be expected to suppress DAF-16 activity and promote growth at the expense of longevity. Phosphatidylinositol-5-phosphate binding further places this protein within the PI3K signaling node that drives pro-growth, anti-longevity outputs.",
"confidence": 0.65,
"key_pathways": [
"insulin/IGF-1 signaling (IIS) / DAF-2–DAF-16 axis",
"TORC1 nutrient sensing",
"phosphoinositide signaling"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted anti_longevity for K10B4.3 (melted homolog). The mechanistic reasoning is well-grounded: it correctly identifies K10B4.3 as the C. elegans homolog of Drosophila Melted, correctly describes Melted's role as a positive regulator of IIS/TOR signaling, and correctly reasons that this would suppress DAF-16/FOXO activity and thus reduce longevity. The reasoning about phosphoinositide signaling is also appropriate given the known PI-5P binding function. The confidence of 0.65 is reasonable given the indirect inference from Drosophila biology. The reasoning is largely sound, though the specific mechanistic details about Melted's role in C. elegans are somewhat inferred from Drosophila data rather than direct C. elegans experimental evidence.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}