tom-1
C. elegans
Lethal giant larvae homologue 2 domain-containing protein;V-SNARE coiled-coil homology domain-containing protein
What the model saw
Gene: tom-1 Organism: Caenorhabditis elegans Known functions: Lethal giant larvae homologue 2 domain-containing protein;V-SNARE coiled-coil homology domain-containing protein. GTPase activator activity. myosin II binding.
View unredacted entry
Lethal giant larvae homologue 2 domain-containing protein;V-SNARE coiled-coil homology domain-containing protein. GTPase activator activity. myosin II binding.
Solver output
tom-1 encodes a tomosyn homolog in C. elegans, containing a V-SNARE coiled-coil homology domain and a Lethal giant larvae (Lgl) homology domain. Tomosyn acts as a negative regulator of SNARE-mediated vesicle fusion by competing with synaptobrevin/VAMP for SNARE complex assembly, thereby inhibiting neurotransmitter and neuropeptide secretion. Its GTPase activator activity and myosin II binding further position it as a brake on vesicle exocytosis and cytoskeletal dynamics. In C. elegans, reduced synaptic inhibition (e.g., via loss of negative regulators of secretion) has been linked to enhanced neuropeptide signaling that can promote longevity, suggesting that tom-1's normal function—suppressing vesicle fusion—opposes pro-longevity secretory signaling. Additionally, Lgl-domain proteins participate in cell polarity and tissue organization; loss of Lgl function in other contexts promotes growth/proliferation, consistent with tom-1 normally restraining pathways that, when active, extend lifespan.
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 about tom-1 as a negative regulator of SNARE-mediated vesicle fusion is mechanistically plausible in general terms, but the model then incorrectly inferred that this function would make tom-1 anti-longevity. The model reasoned that tom-1 suppresses pro-longevity secretory signaling, but the actual finding is that tom-1 is pro-longevity. The model's logic was inverted - it correctly identified tom-1 as a brake on vesicle exocytosis but drew the wrong conclusion about the longevity consequence. The confidence of 0.62 is moderate but the prediction is still clearly wrong. The mechanistic reasoning about SNARE inhibition is partially correct in terms of molecular function, but the downstream longevity inference is incorrect.
Raw API responses
solver
{
"reasoning": "tom-1 encodes a tomosyn homolog in C. elegans, containing a V-SNARE coiled-coil homology domain and a Lethal giant larvae (Lgl) homology domain. Tomosyn acts as a negative regulator of SNARE-mediated vesicle fusion by competing with synaptobrevin/VAMP for SNARE complex assembly, thereby inhibiting neurotransmitter and neuropeptide secretion. Its GTPase activator activity and myosin II binding further position it as a brake on vesicle exocytosis and cytoskeletal dynamics. In C. elegans, reduced synaptic inhibition (e.g., via loss of negative regulators of secretion) has been linked to enhanced neuropeptide signaling that can promote longevity, suggesting that tom-1's normal function—suppressing vesicle fusion—opposes pro-longevity secretory signaling. Additionally, Lgl-domain proteins participate in cell polarity and tissue organization; loss of Lgl function in other contexts promotes growth/proliferation, consistent with tom-1 normally restraining pathways that, when active, extend lifespan.",
"confidence": 0.62,
"key_pathways": [
"SNARE-mediated vesicle fusion / neurotransmitter secretion",
"neuropeptide intercellular signaling",
"myosin II cytoskeletal regulation"
],
"mechanism_class": "altered_intercellular_communication",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model predicted anti_longevity but the ground truth is pro_longevity. The model's reasoning about tom-1 as a negative regulator of SNARE-mediated vesicle fusion is mechanistically plausible in general terms, but the model then incorrectly inferred that this function would make tom-1 anti-longevity. The model reasoned that tom-1 suppresses pro-longevity secretory signaling, but the actual finding is that tom-1 is pro-longevity. The model's logic was inverted - it correctly identified tom-1 as a brake on vesicle exocytosis but drew the wrong conclusion about the longevity consequence. The confidence of 0.62 is moderate but the prediction is still clearly wrong. The mechanistic reasoning about SNARE inhibition is partially correct in terms of molecular function, but the downstream longevity inference is incorrect.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}