ArticleHuman mutation2019
Biallelic loss of function variants in PPP1R21 cause a neurodevelopmental syndrome with impaired endocytic function.
Article in Human mutation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 19 citations in OpenAlex.
- PPP1R21-Related neurodevelopmental disorder: Phenotypic delineation, variant spectrum, and pathophysiological mechanisms.Neurogenetics · 2026Review
- Base editing-derived models of human WDR34 and WDR60 disease alleles replicate retrograde intraflagellar transport (IFT) and hedgehog signaling defects.Communications biology · 2026Article
- Genetic Investigation of Corrected QT Interval Sensitivity to Oral Bepridil Hydrochloride Hydrate in Patients With Atrial Fibrillation.Journal of the American Heart Association · 2026Article
- A novel mouse model of rare neurodevelopmental disorder, TBCK Syndrome.bioRxiv : the preprint server for biology · 2026Article
- Review: Utility of mass spectrometry in rare disease research and diagnosis.NPJ genomic medicine · 2025Review
- Neurogenetic disorders associated with mutations in the FERRY complex: a novel disease class?Biology open · 2025Review
- Expanding the phenotype of PPP1R21-related neurodevelopmental disorder.Clinical genetics · 2024Article
- Implication of transcription factor FOXD2 dysfunction in syndromic congenital anomalies of the kidney and urinary tract (CAKUT).Kidney international · 2024Article
- Sex-Hormone-Binding Globulin Gene Polymorphisms and Breast Cancer Risk in Caucasian Women of Russia.International journal of molecular sciences · 2024Article
- Integrated multi-omics for rapid rare disease diagnosis on a national scale.Nature medicine · 2023Article
- A Homozygous PPP1R21 Splice Variant Associated with Severe Developmental Delay, Absence of Speech, and Muscle Weakness Leads to Activated Proteasome Function.Molecular neurobiology · 2023Article
- The role of serine/threonine phosphatases in human development: Evidence from congenital disorders.Frontiers in cell and developmental biology · 2022Review
- Combining exome/genome sequencing with data repository analysis reveals novel gene-disease associations for a wide range of genetic disorders.Genetics in medicine : official journal of the American College of Medical Genetics · 2021Article
- Isolated Hypomethylation ofDiagnostics (Basel, Switzerland) · 2021Article
- The Results of Whole Exome Sequencing Performed On Previously Undiagnosed Pediatric Neurology Patients.Iranian journal of child neurology · 2021Article
- Article
- Comparative exome sequencing reveals novel candidate genes for retinitis pigmentosa.EBioMedicine · 2020Article
- Characterization of thyroid cancer driven by known and novel ALK fusions.Endocrine-related cancer · 2019Article
- Biallelic loss of function variants in PPP1R21 cause a neurodevelopmental syndrome with impaired endocytic function.Human mutation · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
34 authors at 16 institutions in 12 countries.
Funding
Abstract
Next-generation sequencing (NGS) has been instrumental in solving the genetic basis of rare inherited diseases, especially neurodevelopmental syndromes. However, functional workup is essential for precise phenotype definition and to understand the underlying disease mechanisms. Using whole exome (WES) and whole genome sequencing (WGS) in four independent families with hypotonia, neurodevelopmental delay, facial dysmorphism, loss of white matter, and thinning of the corpus callosum, we identified four previously unreported homozygous truncating PPP1R21 alleles: c.347delT p.(Ile116Lysfs*25), c.2170_2171insGGTA p.(Ile724Argfs*8), c.1607dupT p.(Leu536Phefs*7), c.2063delA p.(Lys688Serfs*26) and found that PPP1R21 was absent in fibroblasts of an affected individual, supporting the allele's loss of function effect. PPP1R21 function had not been studied except that a large scale affinity proteomics approach suggested an interaction with PIBF1 defective in Joubert syndrome. Our co-immunoprecipitation studies did not confirm this but in contrast defined the localization of PPP1R21 to the early endosome. Consistent with the subcellular expression pattern and the clinical phenotype exhibiting features of storage diseases, we found patient fibroblasts exhibited a delay in clearance of transferrin-488 while uptake was normal. In summary, we delineate a novel neurodevelopmental syndrome caused by biallelic PPP1R21 loss of function variants, and suggest a role of PPP1R21 within the endosomal sorting process or endosome maturation pathway.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.