| Category | Finding for human CWC27 | Evidence / details | Citation |
|---|---|---|---|
| Gene identity | **CWC27** is the approved human gene; major aliases include **SDCCAG10**, **NY-CO-10**, **serologically defined colon cancer antigen 10**, and **Cyp54** | Matches the requested UniProt-centered identity and the spliceosome-associated cyclophilin literature | (pqac-00000000, pqac-00000004) |
| Protein family | Nuclear **cyclophilin-type** spliceosome-associated protein | Classified among the human nuclear cyclophilins / “spliceophilins” | (pqac-00000000, pqac-00000004) |
| Protein architecture | N-terminal **cyclophilin/PPIase-like domain** plus a **large C-terminal low-complexity, repetitive, largely unstructured region** | Review and disease papers describe a structured N-terminus and elongated solvent-exposed C-terminus of unknown/interaction-focused function | (pqac-00000005, pqac-00000017) |
| Structural size/features | Only the **isomerase-like N-terminal domain** has been structurally resolved in detail in spliceosome studies; roughly **~200 C-terminal residues** remain structurally uncharacterized in cryo-EM models | Cryo-EM models place the PPIase-like domain in Bact complexes, while the distal C-terminus is not resolved | (pqac-00000005) |
| Enzymatic status | **Catalytically inactive** as a peptidyl-prolyl cis-trans isomerase | Despite cyclophilin fold membership, CWC27 lacks measurable PPIase activity | (pqac-00000008, pqac-00000017) |
| Active-site alteration | In the S1/proline-binding pocket, canonical catalytic **Trp** is replaced by **Glu122** | This **Glu122 substitution** is the key structural explanation for loss of isomerase activity | (pqac-00000005) |
| Cyclosporin binding | **Does not bind cyclosporin A** under tested conditions | Family-wide biochemical analysis found no evidence of CsA binding for SDCCAG10/CWC27 | (pqac-00000015) |
| Substrate specificity / ligand preference | Retains the ability to **bind proline-containing peptides/proline**, but does **not catalyze cis-trans isomerization** | Literature describes preserved proline recognition despite loss of catalytic turnover; likely supports interaction-based rather than enzymatic function | (pqac-00000005, pqac-00000008, pqac-00000017) |
| Primary molecular role | **Splicing factor / spliceosome-associated scaffold** rather than enzyme | Current understanding is that CWC27 contributes through protein-protein interactions during spliceosome activation and EJC recruitment | (pqac-00000001, pqac-00000017, pqac-00000018) |
| Subcellular localization | Primarily **nuclear**; broader cyclophilin tables also list **nucleus and cytosol** | Functional role is nuclear because it acts on the spliceosome during pre-mRNA splicing | (pqac-00000004, pqac-00000018) |
| Spliceosome stage | Enriched in the **activated Bact spliceosome** and present with moderate abundance in **C complex**; released before stable B* progression / complete EJC assembly | Structural and functional studies place CWC27 in late assembly/activation stages of the major spliceosome | (pqac-00000005, pqac-00000017, pqac-00000019) |
| Spliceosome neighborhood | In Bact, the PPIase-like domain contacts **PRPF8**, **BUD31**, **RNF113**, and **U5 snRNP 200K** in different structural states | These contacts position CWC27 at the spliceosome surface where it can coordinate factor recruitment/remodeling | (pqac-00000005) |
| Key protein-protein interaction | Forms a **heterodimer with CWC22** | The CWC27–CWC22 complex is proposed to create a landing platform for EJC factor recruitment | (pqac-00000001, pqac-00000017, pqac-00000018) |
| Link to EJC assembly | Helps recruit **EIF4A3** (core EJC helicase) via the **CWC27/CWC22 platform** | CWC27 leaves before full EJC assembly, consistent with a transient assembly-factor role | (pqac-00000001, pqac-00000017, pqac-00000018) |
| Functional pathway | Participates in **pre-mRNA splicing** and mechanistically links spliceosome activation to **exon junction complex deposition** | Places CWC27 in the broader RNA-processing pathway rather than a standalone catalytic pathway | (pqac-00000011, pqac-00000018, pqac-00000019) |
| In vivo functional evidence | Mouse **Cwc27** mutant retina shows **257 differential splicing events** versus wild type | Most abundant defects were **intron retention** followed by **exon skipping**; supports bona fide in vivo splicing-factor function | (pqac-00000010) |
| Splicing-sensitive genes/examples | Differentially spliced retinal genes include **Cnga1, Prpf6, and Rpgrip1** | These changes help connect CWC27 dysfunction to retinal physiology and disease | (pqac-00000010) |
| Disease association | Biallelic deleterious variants cause a **CWC27-related spliceosomopathy** with **retinal degeneration/retinitis pigmentosa**, short stature, skeletal anomalies, and neurological features | Human genetics and review literature consistently place retinal degeneration at the core of the phenotype spectrum | (pqac-00000003, pqac-00000008, pqac-00000017) |
| Retinal degeneration evidence | In the **Cwc27K338fs/K338fs** mouse, retinal dysfunction appears by **3 months** and photoreceptor loss by **4 months** | Provides direct in vivo support for a causal role in retinal degeneration pathogenesis | (pqac-00000017) |
| Mechanistic disease interpretation | Aberrant splicing in mutant retina is associated with **ER-stress/CHOP positivity** and cell-type-specific transcriptomic disruption, especially in rod photoreceptors and Müller glia | Supports the view that disease arises from splicing defects rather than loss of cyclophilin enzymatic catalysis | (pqac-00000001, pqac-00000010) |


*Table: This table summarizes the key molecular, biochemical, cellular, and disease-related properties of human CWC27 from the cited literature. It highlights why CWC27 is best understood as a catalytically inactive spliceosomal cyclophilin that helps organize splicing and EJC recruitment, with strong links to retinal degeneration.*