t28a8.6

C. elegans

SPK domain-containing protein

What the model saw

Gene: T28A8.6
Organism: Caenorhabditis elegans
Known functions: SPK domain-containing protein. cysteine-type endopeptidase activity.

View unredacted entry

SPK domain-containing protein. cysteine-type endopeptidase activity.

Solver output

Predicted influence

Unclear

Confidence

35%

Mechanism

Loss of proteostasis

Reasoning

T28A8.6 encodes an SPK domain-containing protein with cysteine-type endopeptidase (cysteine protease) activity. Cysteine proteases in C. elegans can participate in diverse proteolytic pathways including lysosomal/autophagic protein degradation, apoptosis, and innate immunity. The SPK domain is associated with a subset of cysteine proteases, but its specific substrate targets and pathway context in C. elegans are not well characterized. Without knowing whether this protease promotes beneficial protein quality control (pro-longevity) or drives damaging proteolysis or apoptosis (anti-longevity), the directionality of its effect on lifespan cannot be confidently assigned from these annotations alone.

Key pathways

cysteine protease activityproteostasis/protein degradationSPK domain protease function

Longevity influence

Anti-longevity

Lifespan effect

Increase

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

Answer

✗Incorrect

Mechanism

✗Incorrect

Reasoning quality

2/5

Failure mode

Appropriately uncertain

Notes

The model predicted "unclear" with low confidence (0.35), while the ground truth is "anti_longevity." The model's reasoning about cysteine proteases and SPK domain proteins is plausible but generic, and it ultimately declined to make a directional prediction. The model correctly identified relevant biological pathways (cysteine protease activity, proteostasis) but failed to commit to the correct answer. This is a case of appropriate uncertainty given limited information, but the prediction is still wrong relative to the ground truth.

Raw API responses

solver

{
  "reasoning": "T28A8.6 encodes an SPK domain-containing protein with cysteine-type endopeptidase (cysteine protease) activity. Cysteine proteases in C. elegans can participate in diverse proteolytic pathways including lysosomal/autophagic protein degradation, apoptosis, and innate immunity. The SPK domain is associated with a subset of cysteine proteases, but its specific substrate targets and pathway context in C. elegans are not well characterized. Without knowing whether this protease promotes beneficial protein quality control (pro-longevity) or drives damaging proteolysis or apoptosis (anti-longevity), the directionality of its effect on lifespan cannot be confidently assigned from these annotations alone.",
  "confidence": 0.35,
  "key_pathways": [
    "cysteine protease activity",
    "proteostasis/protein degradation",
    "SPK domain protease function"
  ],
  "mechanism_class": "loss_of_proteostasis",
  "longevity_influence": "unclear"
}

advisor

{
  "notes": "The model predicted \"unclear\" with low confidence (0.35), while the ground truth is \"anti_longevity.\" The model's reasoning about cysteine proteases and SPK domain proteins is plausible but generic, and it ultimately declined to make a directional prediction. The model correctly identified relevant biological pathways (cysteine protease activity, proteostasis) but failed to commit to the correct answer. This is a case of appropriate uncertainty given limited information, but the prediction is still wrong relative to the ground truth.",
  "failure_mode": "appropriately_uncertain",
  "answer_correct": false,
  "mechanism_correct": false,
  "reasoning_quality": 2,
  "ground_truth_questionable": false
}