ProtNLM2 External predictions
View prediction review YAML · CC2D2A-protnlm-predictions-review.yaml · Review status: COMPLETE
The conserved ciliary architecture supports Hedgehog and developmental roles, with kidney-development specificity still uncertain.
Source documents: projects/PROTNLM_EVALUATION/mammal-benchmark/horse40-predictions.csv · projects/PROTNLM_EVALUATION/mammal-benchmark/predictions.jsonl.gz · projects/PROTNLM_EVALUATION/mammal-benchmark/paired-sequences/CC2D2A.json
Review score: 2 = concordant with evidence; 1 = uncertain; 0 = discordant with evidence. This is an assessment score, not a model probability.
COR — Correct novel prediction Review score: 2/2
Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-09-08
Review rationale: Mouse loss of Cc2d2a disrupts embryonic laterality and heart positioning. The conserved horse ciliary scaffold supports this broad developmental role; it is not a cardiac-specific molecular activity. N-terminal differences predominantly involve the human disordered region.
Supporting Evidence:
- PMID:24947469: "Cc2d2a-/- embryos often revealed situs inversus and dextrocardia"
- PMID:24947469: "The mouse Cc2d2a transgene could rescue the axoneme assembly defect in Cc2d2a-/- MEFs"
- file:HORSE/CC2D2A/CC2D2A-bioinformatics/RESULTS.md: "share 90.3% identity among 1478 paired residues."
- file:HORSE/CC2D2A/CC2D2A-bioinformatics/RESULTS.md: "Both intervals fall within the human UniProt record's predicted disordered region 1–241."
COR — Correct novel prediction Review score: 2/2
Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-09-08
Review rationale: Cc2d2a deficiency disrupts Shh-dependent ventral neural patterning through ciliary assembly defects. Conservation of the horse ciliary scaffold supports pathway participation, without implying direct Smoothened binding or receptor activity.
Supporting Evidence:
- PMID:24947469: "the neural tube patterning defect of Cc2d2a-/- embryos mostly affects ventral cell fates, consistent with a perturbation of Shh signaling"
- PMID:24947469: "The mouse Cc2d2a transgene could rescue the axoneme assembly defect in Cc2d2a-/- MEFs"
- file:HORSE/CC2D2A/CC2D2A-bioinformatics/RESULTS.md: "share 90.3% identity among 1478 paired residues."
- file:HORSE/CC2D2A/CC2D2A-bioinformatics/RESULTS.md: "Both intervals fall within the human UniProt record's predicted disordered region 1–241."
UNC — Uncertain Review score: 1/2
Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-09-08
Review rationale: Cc2d2a is required for cilia in developing renal tubules and is associated with renal ciliopathy. The retrieved mouse experiment documents defective renal ciliation, but this alone does not distinguish kidney morphogenesis from ciliary function or later renal homeostasis. A kidney-development-specific phenotype or mechanistic analysis would resolve the broader prediction.
Supporting Evidence:
- PMID:24947469: "Perinatal kidney tubules and tracheal epithelium revealed few cilia in Cc2d2a-/- embryos"
- file:HORSE/CC2D2A/CC2D2A-bioinformatics/RESULTS.md: "share 90.3% identity among 1478 paired residues."
COR — Correct novel prediction Review score: 2/2
Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-09-08
Review rationale: The mouse loss-of-function study links defective cilia-dependent Shh signaling to open neural tube/exencephaly. The conserved horse architecture supports a role in this developmental process, although horse-specific phenotypes have not been measured.
Supporting Evidence:
- PMID:24947469: "disruption of cilia-dependent Shh signalling appears to underlie exencephaly in mutant embryos"
- file:HORSE/CC2D2A/CC2D2A-bioinformatics/RESULTS.md: "share 90.3% identity among 1478 paired residues."
- file:HORSE/CC2D2A/CC2D2A-bioinformatics/RESULTS.md: "Both intervals fall within the human UniProt record's predicted disordered region 1–241."