PPP1R21

Chr 2

protein phosphatase 1 regulatory subunit 21

Also known as: CCDC128, FERRY2, Fy-2, KLRAQ1, NEDHFBA

NCBI Gene: 129285 ENSG00000162869 UniProt: Q6ZMI0

PPP1R21 encodes a component of the FERRY complex that binds mRNA and mediates endosomal transport of specific mRNAs and ribosomes to early endosomes. Mutations cause autosomal recessive neurodevelopmental disorder with hypotonia, facial dysmorphism, and brain abnormalities. The gene shows low constraint to loss-of-function variants (pLI nearly zero), consistent with its recessive inheritance pattern.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

Enables RNA binding activity. Located in early endosome. [provided by Alliance of Genome Resources, Jul 2025]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtNeurodevelopmental disorder with hypotonia, facial dysmorphism, and brain abnormalities

Clinical highlights

Gene-disease validity (ClinGen)

neurodevelopmental disorder with hypotonia, facial dysmorphism, and brain abnormalities · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.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

0.69

LOEUF

LOF

Mechanism· G2P

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GeneReview available — PPP1R21