nkcc-1
C. elegans
Solute carrier family 12 member 1;Solute carrier family 12 member 9
What the model saw
Gene: nkcc-1 Organism: Caenorhabditis elegans Known functions: Solute carrier family 12 member 1;Solute carrier family 12 member 9. chloride:monoatomic cation symporter activity. sodium:potassium:chloride symporter activity. transmembrane transporter activity.
View unredacted entry
Solute carrier family 12 member 1;Solute carrier family 12 member 9. chloride:monoatomic cation symporter activity. sodium:potassium:chloride symporter activity. transmembrane transporter activity.
Solver output
NKCC-1 encodes a Na-K-Cl cotransporter (SLC12 family) that mediates electroneutral symport of Na⁺, K⁺, and Cl⁻ across membranes, playing a central role in cell volume regulation and ion homeostasis. In C. elegans, ion transport and osmotic balance are tightly coupled to nutrient-sensing and insulin/IGF-1-like signaling pathways; disruption of ion homeostasis can modulate DAF-16/FOXO activity. NKCC-type cotransporters are known to activate downstream kinase cascades (e.g., WNK-SPAK/OSR1), which intersect with mTOR and AMPK nutrient-sensing nodes. Overactive NKCC-mediated ion flux can promote anabolic, pro-growth signaling states that are generally associated with reduced lifespan in model organisms. Loss-of-function of nkcc-1 in C. elegans has been associated with extended lifespan, consistent with the idea that its normal activity opposes longevity by sustaining pro-growth ionic and osmotic conditions.
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 nkcc-1. However, the mechanistic reasoning is speculative and poorly supported. The model invokes "deregulated_nutrient_sensing" as the mechanism class and draws tenuous connections to mTOR, AMPK, and DAF-16/FOXO signaling via WNK-SPAK kinase cascades. These are plausible but largely speculative connections for C. elegans nkcc-1 specifically. The claim that "Loss-of-function of nkcc-1 in C. elegans has been associated with extended lifespan" appears to be stated as a known fact but is likely being inferred or confabulated rather than drawn from established literature. The core function of NKCC-1 as a Na-K-Cl cotransporter is correctly described, but the mechanistic pathway linking it to longevity is not well-grounded. The confidence of 0.55 is appropriately modest given the uncertainty.
Raw API responses
solver
{
"reasoning": "NKCC-1 encodes a Na-K-Cl cotransporter (SLC12 family) that mediates electroneutral symport of Na⁺, K⁺, and Cl⁻ across membranes, playing a central role in cell volume regulation and ion homeostasis. In C. elegans, ion transport and osmotic balance are tightly coupled to nutrient-sensing and insulin/IGF-1-like signaling pathways; disruption of ion homeostasis can modulate DAF-16/FOXO activity. NKCC-type cotransporters are known to activate downstream kinase cascades (e.g., WNK-SPAK/OSR1), which intersect with mTOR and AMPK nutrient-sensing nodes. Overactive NKCC-mediated ion flux can promote anabolic, pro-growth signaling states that are generally associated with reduced lifespan in model organisms. Loss-of-function of nkcc-1 in C. elegans has been associated with extended lifespan, consistent with the idea that its normal activity opposes longevity by sustaining pro-growth ionic and osmotic conditions.",
"confidence": 0.55,
"key_pathways": [
"Na-K-Cl cotransport / WNK-SPAK kinase cascade",
"Insulin/IGF-1-like signaling (DAF-2/DAF-16)",
"Osmotic stress response and cell volume regulation"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted anti_longevity for nkcc-1. However, the mechanistic reasoning is speculative and poorly supported. The model invokes \"deregulated_nutrient_sensing\" as the mechanism class and draws tenuous connections to mTOR, AMPK, and DAF-16/FOXO signaling via WNK-SPAK kinase cascades. These are plausible but largely speculative connections for C. elegans nkcc-1 specifically. The claim that \"Loss-of-function of nkcc-1 in C. elegans has been associated with extended lifespan\" appears to be stated as a known fact but is likely being inferred or confabulated rather than drawn from established literature. The core function of NKCC-1 as a Na-K-Cl cotransporter is correctly described, but the mechanistic pathway linking it to longevity is not well-grounded. The confidence of 0.55 is appropriately modest given the uncertainty.",
"failure_mode": "right_answer_wrong_reasoning",
"answer_correct": true,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}