WDR87

WDR87 is a WD40-repeat domain protein that localizes to the manchette and middle piece of the spermatozoa flagellum during spermiogenesis, where it physically interacts with CFAP47 to participate in sperm tail assembly; loss-of-function CFAP47 mutations dramatically reduce WDR87 protein levels, indicating that CFAP47 is required for WDR87 transport during flagella biogenesis (PMID:36571501). Biallelic inactivating mutations in WDR87 have been identified in a family with non-syndromic pediatric cataract, supported by developmental lens expression data (PMID:27878435).

1. 2016 Low

   Whether WDR87 associates with chromatin regulatory complexes was addressed by identifying it as a protein bound to a human Polycomb/Trithorax responsive element (PRE-PIK3C2B), placing it in the context of COMPASS-like complexes.

   Evidence DNA affinity purification followed by mass spectrometry in HEK, U87, and HeLa cell lines

   PMID:27932267

   Open questions at the time

   • Single method (mass spectrometry pulldown) without reciprocal or functional validation of WDR87's specific role at the regulatory element
   • No evidence that WDR87 directly binds DNA versus being an indirect complex component
   • No knockdown or knockout experiment to assess functional contribution
2. 2016 Low

   Whether WDR87 contributes to lens development was addressed by identifying biallelic loss-of-function mutations in a single family with non-syndromic pediatric cataract, establishing a candidate disease gene link.

   Evidence Whole-exome sequencing, positional mapping, and iSyTE developmental lens expression analysis in a single family

   PMID:27878435

   Open questions at the time

   • Single family with no replication cohort or animal model rescue experiment
   • No mechanistic data on how WDR87 loss leads to cataract
   • Expression-based corroboration does not establish causality
3. 2022 Medium

   The subcellular role of WDR87 in spermiogenesis was established by showing it localizes to the manchette and flagellar middle piece, physically interacts with CFAP47, and depends on CFAP47 for its transport and stability during sperm tail assembly.

   Evidence Immunofluorescence, co-immunoprecipitation/pulldown, and immunoblotting in human spermatozoa including CFAP47-mutant samples

   PMID:36571501

   Open questions at the time

   • No WDR87 knockout or knockdown model to assess its independent contribution to flagellar assembly
   • Structural basis of the WDR87–CFAP47 interaction is unknown
   • Whether WDR87 has enzymatic or scaffolding activity in the complex is unresolved

• It remains unknown whether WDR87's roles in flagellar assembly and lens development reflect a shared molecular mechanism or tissue-specific functions, and no direct loss-of-function model for WDR87 has been reported.
• No animal or cellular knockout/knockdown model for WDR87
• No enzymatic activity or structural model determined
• Relationship between chromatin-associated and cytoskeletal functions is unexplored