Xpa
M. musculus
xeroderma pigmentosum, complementation group A
What the model saw
Gene: Xpa Organism: Mus musculus Known functions: xeroderma pigmentosum, complementation group A. DNA repair protein complementing XP-A cells homolog. damaged DNA binding. protein domain specific binding. protein homodimerization activity. sequence-specific double-stranded DNA binding.
View unredacted entry
xeroderma pigmentosum, complementation group A. DNA repair protein complementing XP-A cells homolog. damaged DNA binding. protein domain specific binding. protein homodimerization activity. sequence-specific double-stranded DNA binding.
Solver output
XPA (Xeroderma Pigmentosum Complementation Group A) is a central scaffold protein in the nucleotide excision repair (NER) pathway, responsible for recognizing and binding damaged DNA (e.g., UV-induced pyrimidine dimers and bulky adducts) and recruiting downstream repair factors. Its damaged DNA binding and sequence-specific dsDNA binding activities are essential for the damage verification step of NER. Loss of XPA function in mice leads to accelerated accumulation of DNA lesions, increased mutagenesis, and premature aging phenotypes, consistent with the genomic instability hallmark of aging. By maintaining genome integrity through NER, XPA normally suppresses the accumulation of somatic mutations and DNA damage-driven cellular dysfunction that drive aging. Therefore, the normal function of Xpa 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 correctly predicted pro_longevity for Xpa in Mus musculus with high confidence (0.92). The mechanistic reasoning is accurate and detailed: XPA is indeed a central NER scaffold protein involved in damage recognition, and its loss leads to accelerated DNA damage accumulation and premature aging phenotypes. The model correctly identifies the genomic instability mechanism and the key NER pathway. All aspects of the prediction are correct.
Raw API responses
solver
{
"reasoning": "XPA (Xeroderma Pigmentosum Complementation Group A) is a central scaffold protein in the nucleotide excision repair (NER) pathway, responsible for recognizing and binding damaged DNA (e.g., UV-induced pyrimidine dimers and bulky adducts) and recruiting downstream repair factors. Its damaged DNA binding and sequence-specific dsDNA binding activities are essential for the damage verification step of NER. Loss of XPA function in mice leads to accelerated accumulation of DNA lesions, increased mutagenesis, and premature aging phenotypes, consistent with the genomic instability hallmark of aging. By maintaining genome integrity through NER, XPA normally suppresses the accumulation of somatic mutations and DNA damage-driven cellular dysfunction that drive aging. Therefore, the normal function of Xpa is pro-longevity.",
"confidence": 0.92,
"key_pathways": [
"nucleotide excision repair (NER)",
"DNA damage recognition and verification",
"genome integrity maintenance"
],
"mechanism_class": "genomic_instability",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for Xpa in Mus musculus with high confidence (0.92). The mechanistic reasoning is accurate and detailed: XPA is indeed a central NER scaffold protein involved in damage recognition, and its loss leads to accelerated DNA damage accumulation and premature aging phenotypes. The model correctly identifies the genomic instability mechanism and the key NER pathway. All aspects of the prediction are correct.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}