PHC1

Chr 12AR

polyhomeotic homolog 1

Also known as: EDR1, HPH1, MCPH11, RAE28

NCBI Gene: 1911 ENSG00000111752 UniProt: P78364 OMIM: 602978

The protein is a component of the Polycomb repressive complex that regulates gene expression through chromatin modification and contains conserved domains that mediate protein-protein interactions with other Polycomb group proteins. Loss-of-function mutations cause primary microcephaly 11, an autosomal recessive disorder characterized by reduced brain size. The high pLI score indicates this gene is highly intolerant to loss-of-function variants, consistent with haploinsufficiency being pathogenic.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene is a homolog of the Drosophila polyhomeotic gene, which is a member of the Polycomb group of genes. The gene product is a component of a multimeric protein complex that contains EDR2 and the vertebrate Polycomb protein BMH1. The gene product, the EDR2 protein, and the Drosophila polyhomeotic protein share 2 highly conserved domains, named homology domains I and II. These domains are involved in protein-protein interactions and may mediate heterodimerization of the protein encoded by this gene and the EDR2 protein. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?Microcephaly 11, primary, autosomal recessiveMIM #615414

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.24

LOEUF· LoF intol.

LOF

Mechanism· predicted