PPP1R21
Chr 2ARprotein phosphatase 1 regulatory subunit 21
Also known as: CCDC128, FERRY2, Fy-2, KLRAQ1, NEDHFBA
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.
Primary Disease Associations & Inheritance
Strong evidence — appropriate for clinical testing
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Tolerant to missense variation
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
261 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 6 | 2 | 17 | 0 | 25 |
Likely Pathogenic | 3 | 0 | 6 | 0 | 9 |
VUS | 0 | 149 | 10 | 0 | 159 |
Likely Benign | 0 | 8 | 4 | 20 | 32 |
Benign | 0 | 0 | 2 | 3 | 5 |
Conflicting | — | 2 | |||
| Total | 9 | 159 | 39 | 23 | 232 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
PPP1R21 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools