These computational predictions are reviewed separately from the GOA annotation set used for this review. The assessments below are from this project and do not constitute official GO annotations or endorsement by GO/UniProt. They are not included in the existing annotation review above.
ProtNLM2 External predictions
View prediction review YAML · CC2D2A-protnlm-predictions-review.yaml · Review status: COMPLETE
ProtNLM2 (UniProt API snapshot 2026-09-08) emitted four GO biological-process terms for A0A5F5PJ44, a horse CC2D2A splice model that retains the coiled coils and C2 domain of this MKS-module ciliary transition-zone scaffold. Smoothened signaling pathway is biologically supported by mouse Cc2d2a loss-of-function data transferred within the CC2D2A orthogroup, but the horse gene already carries it in GOA on its canonical product A0A5F5PUW7, so it is CNN. Neural tube closure is supported by the mouse null, whose open neural tube the authors trace to defective cilia-based Shh signalling, and is absent from horse GOA, so it is COR. Heart development and kidney development record organ-level phenotypes of ciliary loss (laterality-driven and cushion-cilia heart defects, prenatal renal cysts); CC2D2A performs no step of either process, the mouse review marks both source annotations as over-annotations not suitable for ortholog transfer, and both are NPI.
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.
Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-09-08
Review rationale: The prediction is not in horse GOA for either CC2D2A product. Mouse Cc2d2a mutants show dextrocardia with situs inversus and atrioventricular septal defects in which atrioventricular-cushion cilia are absent, so the heart phenotype is real. It is, however, a downstream consequence of loss of cilia at the node and in the cushions: CC2D2A is a transition-zone and subdistal-appendage scaffold that performs no step of heart development. The mouse gene review marks the mouse heart development IMP as an over-annotation for this reason and states that it should not be transferred to orthologs, and no horse or PAINT evidence supports an organ-development role. The prediction is therefore refuted as a functional claim for the horse protein.
Supporting Evidence: - PMID:24947469: "Cc2d2a-/- embryos often revealed situs inversus and dextrocardia"
- PMID:25807483: "In Cc2d2a mutant embryo, while cilia were abundant in outflow cushions, they were absent in AV cushions"
- PMID:25807483: "Cc2d2a mutant embryos die prenatally with AVSD"
Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-09-08
Review rationale: The horse CC2D2A gene already carries smoothened signaling pathway in GOA (Ensembl Compara IEA from mouse on the canonical product A0A5F5PUW7), and the horse canonical-product review keeps it as a true but non-core process. In mouse, Cc2d2a-null fibroblasts show strongly reduced ciliary Smoothened after SAG stimulation and null embryos lose Shh-dependent ventral neural-tube fates. A0A5F5PJ44 is a splice model of the same gene that retains the coiled coils and C2 domain at high identity to human CC2D2A, so the orthologous transfer is justified. CC2D2A contributes by gating ciliary membrane composition, not by any receptor or transducer activity.
Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-09-08
Review rationale: The prediction is not in horse GOA. Cc2d2a loss in mouse leaves perinatal kidney tubules with few cilia, and a forward-genetic Cc2d2a line develops prenatal cystic kidney disease, but these are ciliopathy phenotypes of a protein that acts at the transition zone and mother centriole of essentially all ciliated cells; CC2D2A performs no step of kidney development. The mouse gene review marks the mouse kidney development IMP as an over-annotation on these grounds and advises against transfer to orthologs, and PAINT propagates no organ-development term in this family. The prediction is therefore refuted as a functional claim for the horse protein.
Supporting Evidence: - PMID:24947469: "Perinatal kidney tubules and tracheal epithelium revealed few cilia in Cc2d2a-/- embryos"
- PMID:27002738: "Severe cystic disease was identified only in lines with cilia-related mutations including Bicc1, Cc2d2a, Tmem67, Cep290 and Pkd1"
Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-09-08
Review rationale: Neural tube closure is not in horse GOA for either CC2D2A product. The targeted mouse Cc2d2a null has an open neural tube, and the authors trace it to loss of neural-tube cilia and cilia-based Shh signalling; the mouse gene review keeps this IMP as a valid non-core process. The horse protein is an ortholog in the same CC2D2A subfamily with high identity across its coiled-coil and C2-domain scaffold, so the transfer is an orthology inference rather than a horse observation. The term describes a developmental consequence of the core ciliogenesis role, not a CC2D2A activity.