egl-10
C. elegans
Regulator of G-protein signaling egl-10
What the model saw
Gene: egl-10 Organism: Caenorhabditis elegans Known functions: Regulator of G-protein signaling egl-10. GTPase activator activity.
View unredacted entry
Regulator of G-protein signaling egl-10. GTPase activator activity.
Solver output
EGL-10 is a Regulator of G-protein Signaling (RGS) protein that acts as a GTPase-accelerating protein (GAP) for Gα subunits, specifically Gαo (GOA-1) in C. elegans. By stimulating GTP hydrolysis on Gαo, EGL-10 terminates Gαo signaling, effectively opposing the inhibitory tone that Gαo places on downstream pro-longevity pathways. Gαo signaling in C. elegans suppresses the insulin/IGF-1-like signaling (IIS) pathway indirectly and modulates DAF-16/FOXO nuclear localization; dampening Gαo activity via EGL-10's GAP function can thus relieve inhibition of DAF-16 target genes that promote stress resistance and longevity. Additionally, RGS-mediated attenuation of G-protein signaling is linked to reduced food-sensing and chemosensory inputs that modulate lifespan through neuroendocrine circuits. Loss-of-function in egl-10 leads to hyperactive Gαo signaling, which is associated with reduced lifespan, supporting the view that EGL-10's normal function is pro-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 pro_longevity but the ground truth is anti_longevity. The model's reasoning about EGL-10 as a GAP for Gαo (GOA-1) is mechanistically plausible in isolation, but the model drew the wrong conclusion about the direction of effect. EGL-10 is anti-longevity, meaning its normal function shortens lifespan (or its loss extends lifespan). The model's logic that "loss-of-function in egl-10 leads to hyperactive Gαo signaling, which is associated with reduced lifespan" actually contradicts the ground truth - if egl-10 loss reduces lifespan, then egl-10 would be pro-longevity, but the ground truth says anti-longevity. The model's mechanistic reasoning about the GOA-1/Gαo pathway is partially correct in terms of pathway components, but the directional inference about lifespan effects is wrong. The model showed moderate confidence (0.72) in an incorrect answer, and the mechanistic reasoning, while showing some knowledge of the pathway, ultimately led to the wrong conclusion about the direction of EGL-10's effect on longevity.
Raw API responses
solver
{
"reasoning": "EGL-10 is a Regulator of G-protein Signaling (RGS) protein that acts as a GTPase-accelerating protein (GAP) for Gα subunits, specifically Gαo (GOA-1) in C. elegans. By stimulating GTP hydrolysis on Gαo, EGL-10 terminates Gαo signaling, effectively opposing the inhibitory tone that Gαo places on downstream pro-longevity pathways. Gαo signaling in C. elegans suppresses the insulin/IGF-1-like signaling (IIS) pathway indirectly and modulates DAF-16/FOXO nuclear localization; dampening Gαo activity via EGL-10's GAP function can thus relieve inhibition of DAF-16 target genes that promote stress resistance and longevity. Additionally, RGS-mediated attenuation of G-protein signaling is linked to reduced food-sensing and chemosensory inputs that modulate lifespan through neuroendocrine circuits. Loss-of-function in egl-10 leads to hyperactive Gαo signaling, which is associated with reduced lifespan, supporting the view that EGL-10's normal function is pro-longevity.",
"confidence": 0.72,
"key_pathways": [
"G-protein signaling (Gαo/GOA-1 inactivation)",
"Insulin/IGF-1-like signaling (IIS) / DAF-16 FOXO regulation",
"Neuroendocrine lifespan modulation"
],
"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 EGL-10 as a GAP for Gαo (GOA-1) is mechanistically plausible in isolation, but the model drew the wrong conclusion about the direction of effect. EGL-10 is anti-longevity, meaning its normal function shortens lifespan (or its loss extends lifespan). The model's logic that \"loss-of-function in egl-10 leads to hyperactive Gαo signaling, which is associated with reduced lifespan\" actually contradicts the ground truth - if egl-10 loss reduces lifespan, then egl-10 would be pro-longevity, but the ground truth says anti-longevity. The model's mechanistic reasoning about the GOA-1/Gαo pathway is partially correct in terms of pathway components, but the directional inference about lifespan effects is wrong. The model showed moderate confidence (0.72) in an incorrect answer, and the mechanistic reasoning, while showing some knowledge of the pathway, ultimately led to the wrong conclusion about the direction of EGL-10's effect on longevity.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}