PPP4R1

Chr 18

protein phosphatase 4 regulatory subunit 1

Also known as: MEG1, PP4(Rmeg), PP4R1

NCBI Gene: 9989 ENSG00000154845 UniProt: Q8TF05 OMIM: 604908

This protein serves as a regulatory subunit of serine/threonine-protein phosphatase 4 (PP4) and regulates HDAC3 dephosphorylation and TNF-induced NF-kappa-B signaling pathways. Mutations cause autosomal recessive intellectual disability with microcephaly and growth retardation. The gene is highly constrained against loss-of-function variants (pLI = 1.0, LOEUF = 0.24), indicating intolerance to protein-disrupting mutations.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes one of several alternate regulatory subunits of serine/threonine protein phosphatase 4 (PP4). The protein features multiple HEAT repeats. This protein forms a complex with PP4RC. This complex may have a distinct role from other PP4 complexes, including regulation of HDAC3 (Zhang et al., PMID: 15805470). There is also a transcribed pseudogene on chromosome 20. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2012]

OMIM ResearchGenerating clinical summary…

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.Based on population constraint only.

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