OSH6
S. cerevisiae
oxysterol-binding protein OSH6
What the model saw
Gene: OSH6 Organism: Saccharomyces cerevisiae Known functions: oxysterol-binding protein OSH6. lipid binding. phosphatidic acid binding. phosphatidylinositol-3,4-bisphosphate binding. phosphatidylinositol-3,5-bisphosphate binding. phosphatidylinositol-4-phosphate binding. phosphatidylinositol-5-phosphate binding. phosphatidylserine binding. phosphatidylserine-phosphatidylinositol-4-phosphate exchange activity. sterol binding. sterol transfer activity.
View unredacted entry
oxysterol-binding protein OSH6. lipid binding. phosphatidic acid binding. phosphatidylinositol-3,4-bisphosphate binding. phosphatidylinositol-3,5-bisphosphate binding. phosphatidylinositol-4-phosphate binding. phosphatidylinositol-5-phosphate binding. phosphatidylserine binding. phosphatidylserine-phosphatidylinositol-4-phosphate exchange activity. sterol binding. sterol transfer activity.
Solver output
OSH6 is a member of the oxysterol-binding protein (OSBP) family in yeast, functioning as a lipid transfer protein that mediates phosphatidylserine (PS)/phosphatidylinositol-4-phosphate (PI4P) exchange at membrane contact sites, particularly at the ER-plasma membrane interface. This activity regulates the asymmetric distribution of PS in the plasma membrane and contributes to lipid homeostasis. While lipid homeostasis is broadly important for cellular health, OSH6's specific role in PS transport is somewhat redundant with other OSH family members (e.g., OSH7), and its direct connection to established longevity pathways (TOR, sirtuins, autophagy) is not well-defined. The sterol and phosphoinositide binding activities could link it to membrane integrity and nutrient sensing, but the net effect on lifespan is not clearly directional given the redundancy and the complexity of lipid signaling in aging.
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 "unclear" with low confidence (0.38), while the ground truth is "pro_longevity." The model's reasoning about OSH6's function as a PS/PI4P lipid transfer protein is mechanistically accurate, but the model failed to commit to a pro-longevity prediction. The model correctly identified the relevant lipid homeostasis pathways but over-emphasized redundancy with OSH7 and lack of direct connection to canonical longevity pathways as reasons for uncertainty. The model's caution about redundancy is somewhat reasonable given the OSH family, but it missed that OSH6 deletion likely has a measurable lifespan effect. The reasoning quality is low-to-moderate: mechanistic description is accurate but the conclusion is wrong.
Raw API responses
solver
{
"reasoning": "OSH6 is a member of the oxysterol-binding protein (OSBP) family in yeast, functioning as a lipid transfer protein that mediates phosphatidylserine (PS)/phosphatidylinositol-4-phosphate (PI4P) exchange at membrane contact sites, particularly at the ER-plasma membrane interface. This activity regulates the asymmetric distribution of PS in the plasma membrane and contributes to lipid homeostasis. While lipid homeostasis is broadly important for cellular health, OSH6's specific role in PS transport is somewhat redundant with other OSH family members (e.g., OSH7), and its direct connection to established longevity pathways (TOR, sirtuins, autophagy) is not well-defined. The sterol and phosphoinositide binding activities could link it to membrane integrity and nutrient sensing, but the net effect on lifespan is not clearly directional given the redundancy and the complexity of lipid signaling in aging.",
"confidence": 0.38,
"key_pathways": [
"phosphatidylserine-PI4P lipid exchange at ER-PM contact sites",
"sterol/lipid homeostasis",
"phosphoinositide signaling"
],
"mechanism_class": "other",
"longevity_influence": "unclear"
}advisor
{
"notes": "The model predicted \"unclear\" with low confidence (0.38), while the ground truth is \"pro_longevity.\" The model's reasoning about OSH6's function as a PS/PI4P lipid transfer protein is mechanistically accurate, but the model failed to commit to a pro-longevity prediction. The model correctly identified the relevant lipid homeostasis pathways but over-emphasized redundancy with OSH7 and lack of direct connection to canonical longevity pathways as reasons for uncertainty. The model's caution about redundancy is somewhat reasonable given the OSH family, but it missed that OSH6 deletion likely has a measurable lifespan effect. The reasoning quality is low-to-moderate: mechanistic description is accurate but the conclusion is wrong.",
"failure_mode": "appropriately_uncertain",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}