ArticleAmerican journal of human genetics2019
HNRNPR Variants that Impair Homeobox Gene Expression Drive Developmental Disorders in Humans.
Article in American journal of human genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- HNRNPC haploinsufficiency affects alternative splicing of intellectual disability-associated genes and causes a neurodevelopmental disorder.American journal of human genetics · 2023Pooled it
- LC-MS profiling ofbioRxiv : the preprint server for biology · 2026Article
- De novo variants in the splicing factor gene SF3B1 are associated with neurodevelopmental disorders.Nature communications · 2026Article
- Neurod2 knockdown inmicroPublication biology · 2026Article
- Identification of metabolic reprogramming-associated biomarkers in endometriosis through integrated bioinformatics analysis.Hereditas · 2025Article
- Analysis of immune cell infiltration landscape and identification of diagnostic biomarkers in ankylosing spondylitis.APL bioengineering · 2025Article
- Contributions of Folded and Disordered Domains to RNA Binding by HNRNPR.bioRxiv : the preprint server for biology · 2025Article
- An evolutionarily conserved tryptophan cage promotes folding of the extended RNA recognition motif in the hnRNPR-like protein family.Protein science : a publication of the Protein Society · 2025Article
- Article
- Modeling craniofacial spliceosomopathies: a pathway toward deciphering disease mechanisms.Frontiers in cell and developmental biology · 2025Review
- Diagnostic Utility of Whole Genome Sequencing After Negative Karyotyping/Chromosomal Microarray in Infants Born With Multiple Congenital Anomalies.Journal of Korean medical science · 2024Article
- Comment on Gustavson syndrome is caused by an in-frame deletion in RBMX associated with potentially disturbed SH3 domain interactions.European journal of human genetics : EJHG · 2024Article
- hnRNPs: roles in neurodevelopment and implication for brain disorders.Frontiers in molecular neuroscience · 2024Review
- A Palindrome-Like Structure on 16p13.3 Is Associated with the Formation of Complex Structural Variations andHuman mutation · 2023Article
- High expression of HNRNPR in ESCA combined withJournal of translational medicine · 2022Article
- Decreased spliceosome fidelity and egl-8 intron retention inhibit mTORC1 signaling to promote longevity.Nature aging · 2022Article
- Variant-specific effects define the phenotypic spectrum of HNRNPH2-associated neurodevelopmental disorders in males.Human genetics · 2022Article
- Loss of full-length hnRNP R isoform impairs DNA damage response in motoneurons by inhibiting Yb1 recruitment to chromatin.Nucleic acids research · 2021Article
- Phenotypes and genotypes in non-consanguineous and consanguineous primary microcephaly: High incidence of epilepsy.Molecular genetics & genomic medicine · 2021Article
- Rare deleterious mutations of HNRNP genes result in shared neurodevelopmental disorders.Genome medicine · 2021Article
Corrections and comments
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Authors and funding
20 authors at 9 institutions in 4 countries.
Funding
Abstract
The heterogeneous nuclear ribonucleoprotein (HNRNP) genes code for a set of RNA-binding proteins that function primarily in the spliceosome C complex. Pathogenic variants in these genes can drive neurodegeneration, through a mechanism involving excessive stress-granule formation, or developmental defects, through mechanisms that are not known. Here, we report four unrelated individuals who have truncating or missense variants in the same C-terminal region of hnRNPR and who have multisystem developmental defects including abnormalities of the brain and skeleton, dysmorphic facies, brachydactyly, seizures, and hypoplastic external genitalia. We further identified in the literature a fifth individual with a truncating variant. RNA sequencing of primary fibroblasts reveals that these HNRNPR variants drive significant changes in the expression of several homeobox genes, as well as other transcription factors, such as LHX9, TBX1, and multiple HOX genes, that are considered fundamental regulators of embryonic and gonad development. Higher levels of retained intronic HOX sequences and lost splicing events in the HOX cluster are observed in cells carrying HNRNPR variants, suggesting that impaired splicing is at least partially driving HOX deregulation. At basal levels, stress-granule formation appears normal in primary and transfected cells expressing HNRNPR variants. However, these cells reveal profound recovery defects, where stress granules fail to disassemble properly, after exposure to oxidative stress. This study establishes an essential role for HNRNPR in human development and points to a mechanism that may unify other "spliceosomopathies" linked to variants that drive multi-system congenital defects and are found in hnRNPs.
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