C16ORF87

C16ORF87 (also designated MHAP1/HDIP) is a subunit of the MIER-type HDAC corepressor complex, where it functions as a protein-interaction bridge supporting HDAC-mediated transcriptional repression at chromatin (PMID:42062449). Within the complex it associates with HDAC1/HDAC2 and MIER1, with HDAC2's C-terminal intrinsically disordered region promoting contacts to the ELM2 domain of MIER1 and to both the N- and C-termini of C16ORF87 (PMID:41928988). Homozygous knockout in human cells alters chromatin accessibility and reduces cell migration, and loss of the gene impairs embryonic development in zebrafish, consistent with a role in chromatin-templated gene repression (PMID:42062449). Beyond its role as a MIER/HDAC complex subunit, no additional independent biochemical activity for C16ORF87 has been characterized in the available corpus.

1. 2025 Low

   Whether C16ORF87 has any defined biochemical context was unknown; proteomic profiling placed it within an ARID5B-containing chromatin repressor complex, implicating it in transcriptional repression.

   Evidence Co-IP/mass spectrometry identifying complex members, CUT&RUN genomic mapping, and transcriptomics in a B cell system

   PMID:bio_10.1101_2025.10.17.683040

   Open questions at the time

   • C16ORF87's own mechanistic contribution was not directly tested — it was identified only as a co-purifying complex member
   • Preprint, single lab
   • Does not establish which residues or domains of C16ORF87 mediate complex association
2. 2026 Medium

   It was unclear whether C16ORF87 is a functional rather than incidental complex subunit; reciprocal interaction assays plus loss-of-function established it as a bridging subunit of the MIER corepressor complex with cellular and developmental consequences.

   Evidence Co-IP/protein interaction assays for complex membership, CRISPR knockout with chromatin accessibility and migration assays in human cells, and a zebrafish knockout developmental model

   PMID:42062449

   Open questions at the time

   • Direct molecular mechanism linking complex loss to altered chromatin accessibility not resolved
   • Specific gene targets driving the migration and developmental phenotypes not defined
   • Single lab
3. 2026 Medium

   How C16ORF87 is physically wired into the complex was unknown; integrative structural modeling mapped IDR-driven contacts defining its interaction interfaces.

   Evidence Crosslinking mass spectrometry combined with integrative computational modeling (I-TASSER, HADDOCK, AlphaFold) (preprint)

   PMID:41928988

   Open questions at the time

   • Structural model is computational, validated by crosslinks but lacking experimental high-resolution structure
   • Preprint, single lab
   • Functional importance of the mapped N- and C-terminal interfaces not tested by mutagenesis

• Whether C16ORF87 has any catalytic or chromatin-binding activity of its own, or acts purely as a scaffolding/bridging subunit, remains unresolved.
• No intrinsic enzymatic activity demonstrated
• Mechanism by which the complex is recruited to specific loci is not attributed to C16ORF87
• No high-resolution experimental structure of the complex