ArticlePLoS genetics2018
Mutations in Diphosphoinositol-Pentakisphosphate Kinase PPIP5K2 are associated with hearing loss in human and mouse.
Article in PLoS genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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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.
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Who cites it
29 citing papers in PubMed, 49 citations in OpenAlex.
- Three phosphatase families form a community: The phosphohydrolases that act upon inositol pyrophosphates.FEBS letters · 2026Review
- Inositol pyrophosphate kinases in health and disease.FEBS letters · 2026Review
- Proteomic Analysis Provides Insights Into PPIP5K2 Function and Its Impact on Corneal Energy Metabolism.Investigative ophthalmology & visual science · 2025Article
- A small signaling domain controls PPIP5K phosphatase activity in phosphate homeostasis.Nature communications · 2025Article
- Identification of Keratoconus-Related Phenotypes in Three Ppip5k2 Mouse Models.Investigative ophthalmology & visual science · 2024Article
- Autosomal recessive non-syndromic hearing loss genes in Pakistan during the previous three decades.Journal of cellular and molecular medicine · 2024Review
- Machine learning nominates the inositol pathway and novel genes in Parkinson's disease.Brain : a journal of neurology · 2024Article
- PPIP5K2 Facilitates Proliferation and Metastasis of Non-Small Lung Cancer (NSCLC) through AKT Signaling Pathway.Cancers · 2024Article
- Kcs1 and Vip1: The Key Enzymes behind Inositol Pyrophosphate Signaling inBiomolecules · 2024Review
- Protein pyrophosphorylation by inositol phosphates: a novel post-translational modification in plants?Frontiers in plant science · 2024Review
- One Scaffold, Two Conformations: The Ring-Flip of the Messenger InsPBiomolecules · 2023Article
- Capillary electrophoresis mass spectrometry identifies new isomers of inositol pyrophosphates in mammalian tissues.Chemical science · 2023Article
- ARNSHL gene identification: past, present and future.Molecular genetics and genomics : MGG · 2022Review
- PPIP5K2 promotes colorectal carcinoma pathogenesis through facilitating DNA homologous recombination repair.Oncogene · 2021Article
- Progress in protecting vestibular hair cells.Archives of toxicology · 2021Review
- The Asp1 pyrophosphatase from S. pombe hosts a [2Fe-2S]Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2021Article
- MINPP1 prevents intracellular accumulation of the chelator inositol hexakisphosphate and is mutated in Pontocerebellar Hypoplasia.Nature communications · 2020Article
- Small fish, big prospects: using zebrafish to unravel the mechanisms of hereditary hearing loss.Hearing research · 2020Article
- Rapid stimulation of cellular Pi uptake by the inositol pyrophosphate InsPChemical science · 2020Article
- Inositol Pyrophosphates: Signaling Molecules with Pleiotropic Actions in Mammals.Molecules (Basel, Switzerland) · 2020Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Autosomal recessive nonsyndromic hearing loss is a genetically heterogeneous disorder. Here, we report a severe-to-profound sensorineural hearing loss locus, DFNB100 on chromosome 5q13.2-q23.2. Exome enrichment followed by massive parallel sequencing revealed a c.2510G>A transition variant in PPIP5K2 that segregated with DFNB100-associated hearing loss in two large apparently unrelated Pakistani families. PPIP5Ks enzymes interconvert 5-IP7 and IP8, two key members of the inositol pyrophosphate (PP-IP) cell-signaling family. Their actions at the interface of cell signaling and bioenergetic homeostasis can impact many biological processes. The c.2510G>A transition variant is predicted to substitute a highly invariant arginine residue with histidine (p.Arg837His) in the phosphatase domain of PPIP5K2. Biochemical studies revealed that the p.Arg837His variant reduces the phosphatase activity of PPIP5K2 and elevates its kinase activity. We found that in mouse inner ear, PPIP5K2 is expressed in the cochlear and vestibular sensory hair cells, supporting cells and spiral ganglion neurons. Mice homozygous for a targeted deletion of the Ppip5k2 phosphatase domain exhibit degeneration of cochlear outer hair cells and elevated hearing thresholds. Our demonstration that PPIP5K2 has a role in hearing in humans indicates that PP-IP signaling is important to hair cell maintenance and function within inner ear.
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Registered trials
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