PCGF2

Chr 17

polycomb group ring finger 2

Also known as: MEL-18, RNF110, TPFS, ZNF144

NCBI Gene: 7703 ENSG00000277258 UniProt: P35227

The protein is a transcriptional repressor that functions as a component of Polycomb repressive complex 1 (PRC1), maintaining transcriptional silencing of developmental genes including Hox genes through chromatin modification. Mutations cause Turnpenny-Fry syndrome with autosomal dominant inheritance. The gene is highly constrained against loss-of-function variants (pLI 0.86, LOEUF 0.41), indicating intolerance to gene disruption.

ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene contains a RING finger motif and is similar to the polycomb group (PcG) gene products. PcG gene products form complexes via protein-protein interaction and maintain the transcription repression of genes involved in embryogenesis, cell cycles, and tumorigenesis. This protein was shown to act as a negative regulator of transcription and has tumor suppressor activity. The expression of this gene was detected in various tumor cells, but is limited in neural organs in normal tissues. Knockout studies in mice suggested that this protein may negatively regulate the expression of different cytokines, chemokines, and chemokine receptors, and thus plays an important role in lymphocyte differentiation and migration, as well as in immune responses. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtTurnpenny-Fry syndrome

Clinical highlights

Gene-disease validity (ClinGen)

turnpenny-fry syndrome · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Gain of function is the curated mechanism (Gene2Phenotype), so a variant that simply removes the protein may not be the pathogenic class here — missense variants in functional domains often carry more weight.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.41

LOEUF

GOF*

Mechanism· G2P

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