| Characteristic | TTC39C (target: UniProt A0A2K5UJ34, *Macaca fascicularis*) | Evidence from related TTC39 family members / broader inference | Evidence strength / notes | Key citations |
|---|---|---|---|---|
| Protein identity and family membership | A0A2K5UJ34 is annotated as tetratricopeptide repeat domain-containing protein 39C (TTC39C) from *Macaca fascicularis*; UniProt states it belongs to the TTC39 family and contains IML2/TPR_39 and TPR-like helical domains. | TTC39B is a functionally characterized paralog in the same family; reviews of HDL genetics and LXR biology treat TTC39B as the causal gene at its GWAS locus and as a scaffold/adaptor-like regulator of lipid metabolism. | Direct family assignment is strong from UniProt/domain annotation; functional interpretation relies partly on paralogy to TTC39B because TTC39C-specific mechanistic literature is sparse. | (pqac-00000002, pqac-00000007, pqac-00000008) |
| Domain structure | TTC39C is predicted to contain tetratricopeptide repeat (TPR)-like helical domains. | TPR motifs are 34-aa helix-turn-helix repeats that stack into superhelical scaffolds and commonly mediate protein-protein interactions; TPR proteins often function as adaptors/scaffolds and can include intrinsically disordered regions that expand interaction flexibility. | Strong structural inference: TPR architecture strongly supports a non-enzymatic interaction/scaffold role rather than catalytic activity. | (pqac-00000007, pqac-00000008, pqac-00000009) |
| Subcellular localization | TTC39C has limited direct mammalian localization data in the available sources. | A 2024 ciliary gene discovery study reported that TTC39A/C emerged as strong candidate ciliary genes and experimentally confirmed TTC39A/C localization to sensory-neuron cilia in *C. elegans* (head amphid and tail phasmid cilia). | Best direct localization evidence available for TTC39C-related sequence is ciliary, but from *C. elegans* rather than macaque; conservation makes this useful but still inferential for *M. fascicularis*. | (pqac-00000000) |
| Primary molecular function | No direct biochemical activity has been demonstrated for macaque TTC39C in the available sources; no evidence supports enzyme or transporter activity. | TTC39B is described as a scaffolding protein that promotes ubiquitination and proteasomal degradation of liver X receptor alpha (LXRα), thereby regulating lipid metabolism. Given shared TTC39 family membership and TPR scaffold architecture, TTC39C is most plausibly an interaction scaffold/adaptor rather than an enzyme. | Functional inference is moderate: strong for “scaffold/adaptor-like” class, weak for exact TTC39C client proteins. | (pqac-00000002, pqac-00000004, pqac-00000006, pqac-00000007) |
| Biochemical/signaling pathways | No TTC39C-specific pathway has been directly established in the available literature. | TTC39B acts in the LXR-cholesterol homeostasis axis: increased HDL-C-associated alleles reduce hepatic TTC39B expression; TTC39B promotes LXR ubiquitination/degradation; LXR controls cholesterol efflux and reverse cholesterol transport genes such as **ABCA1** and **ABCG1**. | Strong for TTC39B pathway biology, indirect for TTC39C. TTC39C may participate in related protein-interaction networks or in ciliary signaling, but direct evidence is lacking. | (pqac-00000002, pqac-00000001, pqac-00000004, pqac-00000005) |
| Disease/genetic association relevance | No TTC39C-specific disease association was established in the available sources. | TTC39B variants are associated with HDL cholesterol levels in human genetics studies; a TTC39B variant was also associated with gallbladder disease risk in women, supporting physiologic relevance in hepatobiliary lipid handling. | Useful family-level context, but should not be over-assigned to TTC39C. | (pqac-00000002, pqac-00000003) |
| Current overall interpretation for functional annotation | TTC39C is best annotated as a likely intracellular, non-catalytic TPR-domain protein with probable scaffold/adaptor function. Available direct localization evidence points to cilia, while family-level mechanistic evidence suggests TTC39 proteins can organize regulatory protein complexes. | Related-family evidence most strongly supports a role in protein-protein interaction networks; TTC39B specifically links the family to ubiquitin-dependent control of LXR and cholesterol metabolism. | Recommended annotation wording: “putative TPR-repeat scaffold/adaptor protein; ciliary localization supported by orthologous evidence; precise macaque biochemical function remains unresolved.” | (pqac-00000000, pqac-00000002, pqac-00000007, pqac-00000008, pqac-00000009) |


*Table: This table summarizes what can be stated directly about TTC39C and what must be inferred from TTC39 family biology, especially TTC39B. It is useful for distinguishing high-confidence observations from family-based functional inference during annotation.*