Cisd2
M. musculus
CDGSH iron sulfur domain 2
What the model saw
Gene: Cisd2 Organism: Mus musculus Known functions: CDGSH iron sulfur domain 2. CDGSH iron-sulfur domain-containing protein 2. 2 iron, 2 sulfur cluster binding. protein homodimerization activity.
View unredacted entry
CDGSH iron sulfur domain 2. CDGSH iron-sulfur domain-containing protein 2. 2 iron, 2 sulfur cluster binding. protein homodimerization activity.
Solver output
CISD2 (also known as NAF-1 or Miner1) is a CDGSH iron-sulfur domain-containing protein that coordinates a [2Fe-2S] cluster and functions at the outer mitochondrial membrane and ER. Its [2Fe-2S] cluster-binding activity is essential for mitochondrial iron homeostasis and electron transport chain integrity. Loss of Cisd2 in mice leads to accelerated aging phenotypes including mitochondrial dysfunction, increased autophagy/mitophagy, and early death, while Cisd2 overexpression extends lifespan in mice. The protein's homodimerization is required for stable [2Fe-2S] cluster coordination, which supports mitochondrial bioenergetics and prevents iron overload-driven oxidative damage. Thus, the normal function of Cisd2 directly opposes mitochondrial deterioration, a core hallmark of 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 correctly predicted pro_longevity for Cisd2 in Mus musculus with high confidence (0.85). The mechanistic reasoning is accurate and detailed: CISD2 (NAF-1/Miner1) is indeed a [2Fe-2S] cluster-containing protein at the outer mitochondrial membrane/ER, and Cisd2 knockout mice show accelerated aging while overexpression extends lifespan. The model correctly identifies mitochondrial iron homeostasis, oxidative stress defense, and mitochondrial bioenergetics as key pathways. The homodimerization point is also accurate. This is a well-reasoned, correct prediction.
Raw API responses
solver
{
"reasoning": "CISD2 (also known as NAF-1 or Miner1) is a CDGSH iron-sulfur domain-containing protein that coordinates a [2Fe-2S] cluster and functions at the outer mitochondrial membrane and ER. Its [2Fe-2S] cluster-binding activity is essential for mitochondrial iron homeostasis and electron transport chain integrity. Loss of Cisd2 in mice leads to accelerated aging phenotypes including mitochondrial dysfunction, increased autophagy/mitophagy, and early death, while Cisd2 overexpression extends lifespan in mice. The protein's homodimerization is required for stable [2Fe-2S] cluster coordination, which supports mitochondrial bioenergetics and prevents iron overload-driven oxidative damage. Thus, the normal function of Cisd2 directly opposes mitochondrial deterioration, a core hallmark of aging.",
"confidence": 0.85,
"key_pathways": [
"mitochondrial iron-sulfur cluster homeostasis",
"mitochondrial membrane integrity and bioenergetics",
"oxidative stress defense"
],
"mechanism_class": "mitochondrial_dysfunction",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for Cisd2 in Mus musculus with high confidence (0.85). The mechanistic reasoning is accurate and detailed: CISD2 (NAF-1/Miner1) is indeed a [2Fe-2S] cluster-containing protein at the outer mitochondrial membrane/ER, and Cisd2 knockout mice show accelerated aging while overexpression extends lifespan. The model correctly identifies mitochondrial iron homeostasis, oxidative stress defense, and mitochondrial bioenergetics as key pathways. The homodimerization point is also accurate. This is a well-reasoned, correct prediction.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}