ArticleGenetics in medicine : official journal of the American College of Medical Genetics2021
Variants in PRKAR1B cause a neurodevelopmental disorder with autism spectrum disorder, apraxia, and insensitivity to pain.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02450851 (Clinical and Genetic Evaluation of Patients With Undiagnosed Disorders Through the Undiagnosed Diseases Network), which is not on this map. Cited by 24 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.
Clinical and Genetic Evaluation of Patients With Undiagnosed Disorders Through the Undiagnosed Diseases Network
Who cites it
24 citing papers in PubMed, 27 citations in OpenAlex.
- Selective knockout of PKA regulatory subunits reveal opposite catalytic and metabolic consequences with implications for Alzheimer's disease.bioRxiv : the preprint server for biology · 2026Article
- The tyrosine phosphatase STEP is a developmental suppressor of synaptogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Functional divergence of protein kinase A regulatory subunit Iβ variants: the importance of N3A motifs in PKA regulation.The FEBS journal · 2026Article
- Expansion of the Phenotypic and Genotypic Spectrum for PRKAR1B -Related Marbach-Schaaf Neurodevelopmental Syndrome: A Case Series.Clinical genetics · 2026Article
- PRKAR1B as an oncogenic biomarker for diagnostic and prognostic stratification of tumor immunity, proliferation, and migration in head and neck squamous cell carcinoma.Frontiers in immunology · 2026Article
- Investigation of psychosocial stress and DNA methylation in genes related to immune response, metabolism, and calcium signaling among African American and White middle-aged adults.Environmental epigenetics · 2026Article
- Conformational Dynamics and Allostery in the cAMP-Protein Kinase A Signalosome.Advances in experimental medicine and biology · 2026Review
- Review
- N3A motifs in RIβ mediate allosteric crosstalk between cAMP and ATP in PKA activation.Protein science : a publication of the Protein Society · 2025Article
- Allosteric modulation of protein kinase A in individuals affected by NLPD-PKA, a neurodegenerative disease in which the PRKAR1B L50R variant is expressed.The FEBS journal · 2025Article
- Protein kinase A: a quirky prototype.The FEBS journal · 2025Article
- Aberrant phase separation of two PKA RIβ neurological disorder mutants leads to mechanistically distinct signaling deficits.Cell reports · 2025Article
- Transcriptomic Dysregulation in Animal Models of Attention-Deficit Hyperactivity Disorder and Nicotine Dependence Suggests Shared Neural Mechanisms.Brain and behavior · 2025Article
- Case Report: A rare chromosomal imbalance with dup 7q36.3-qter and del 7pter-p22.3 arising from parental pericentric inversion.Frontiers in genetics · 2025Article
- Early disruption of the CREB pathway drives dendritic morphological alterations in FTD/ALS cortical neurons.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- A mutation in the PRKAR1B gene drives pathological mechanisms of neurodegeneration across species.Brain : a journal of neurology · 2024Article
- 7p22.3 microdeletion: a case study of a patient with congenital heart defect, neurodevelopmental delay and epilepsy.Orphanet journal of rare diseases · 2024Article
- Protein Kinase A in neurological disorders.Journal of neurodevelopmental disorders · 2024Review
- High-dimensional phenotyping to define the genetic basis of cellular morphology.Nature communications · 2024Article
- KnockoffTrio: A knockoff framework for the identification of putative causal variants in genome-wide association studies with trio design.American journal of human genetics · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
30 authors at 20 institutions in 2 countries.
Funding
Abstract
purposeWe characterize the clinical and molecular phenotypes of six unrelated individuals with intellectual disability and autism spectrum disorder who carry heterozygous missense variants of the PRKAR1B gene, which encodes the R1β subunit of the cyclic AMP-dependent protein kinase A (PKA).
methodsVariants of PRKAR1B were identified by single- or trio-exome analysis. We contacted the families and physicians of the six individuals to collect phenotypic information, performed in vitro analyses of the identified PRKAR1B-variants, and investigated PRKAR1B expression during embryonic development.
resultsRecent studies of large patient cohorts with neurodevelopmental disorders found significant enrichment of de novo missense variants in PRKAR1B. In our cohort, de novo origin of the PRKAR1B variants could be confirmed in five of six individuals, and four carried the same heterozygous de novo variant c.1003C>T (p.Arg335Trp; NM_001164760). Global developmental delay, autism spectrum disorder, and apraxia/dyspraxia have been reported in all six, and reduced pain sensitivity was found in three individuals carrying the c.1003C>T variant. PRKAR1B expression in the brain was demonstrated during human embryonal development. Additionally, in vitro analyses revealed altered basal PKA activity in cells transfected with variant-harboring PRKAR1B expression constructs.
conclusionOur study provides strong evidence for a PRKAR1B-related neurodevelopmental disorder.
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.