Affinage

PRRT2

Proline-rich transmembrane protein 2 · UniProt Q7Z6L0

Length
340 aa
Mass
34.9 kDa
Annotated
2026-06-10
100 papers in source corpus 23 papers cited in narrative 23 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PRRT2 is a neuron-specific, axonally and presynaptically enriched type II transmembrane protein that acts as a multi-target brake on neuronal excitability and neurotransmitter release (PMID:27052163, PMID:26797119, PMID:32891704). It adopts an N_cyt/C_exo topology in which a second hydrophobic segment spans the membrane while the first forms an intracellular helix-loop-helix and the large proline-rich N-terminus remains cytoplasmic (PMID:26797119). Through this cytoplasmic domain PRRT2 engages the synaptic SNARE machinery (SNAP25, STX1A, STX1B, VAMP2) to selectively block trans-SNARE complex assembly and negatively regulate synaptic vesicle priming, while its interaction with synaptotagmin 1/2 couples release to Ca2+ sensitivity for synchronous transmission (PMID:27052163, PMID:29346777, PMID:30009426, PMID:30347267). PRRT2 additionally restrains intrinsic excitability by directly binding Nav1.2 and Nav1.6 (but not Nav1.1) channels — reducing their surface exposure and Na+ current and shifting inactivation — through a C-terminal intramembrane module that modulates channel gating and an N-terminal proline-rich "antenna" that mediates binding (PMID:29554219, PMID:36958475, PMID:37271286). It also promotes P/Q-type (Cav2.1) Ca2+ channel membrane targeting and active-zone clustering to support presynaptic Ca2+ influx, and interacts with α1/α3 Na+/K+-ATPase pumps to sustain post-firing afterhyperpolarization (PMID:33731672, PMID:34133925). Beyond release, PRRT2 controls synaptic actin dynamics via cofilin to regulate dendritic spine density and supports neuronal migration and synapse formation during development (PMID:33056987, PMID:27172900). Loss of PRRT2 — most commonly through nonsense-mediated decay of truncating-mutation transcripts or mislocalization of missense variants — disrupts these functions, elongates the axon initial segment, and shifts excitatory/inhibitory balance toward network hyperexcitability, producing the spectrum of paroxysmal disorders modeled in KO and knock-in animals (PMID:25457817, PMID:29912316, PMID:31785815, PMID:30980674, PMID:33515674).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 2011 Medium

    Establishing that disease-causing truncating mutations alter PRRT2's subcellular distribution and reduce its abundance gave the first mechanistic link between the gene and a protein with a defined cellular localization, framing the disorders as loss-of-function.

    Evidence Localization assays and Western blotting of mutant vs wild-type PRRT2 in cells and primary neurons, with the first SNAP25 Co-IP

    PMID:22101681 PMID:22832103

    Open questions at the time
    • Did not establish topology or the molecular consequence of SNARE binding
    • Single-lab Co-IP without reciprocal validation at this stage
  2. 2014 Medium

    Identifying nonsense-mediated mRNA decay as the route by which truncating mutations lower PRRT2 levels explained why patients are functionally haploinsufficient and showed that escaped truncated protein mislocalizes.

    Evidence NMD pharmacological and UPF1-siRNA rescue in lymphoblasts plus localization in SH-SY5Y cells

    PMID:25457817

    Open questions at the time
    • Did not quantify dosage threshold for disease
    • Single lab
  3. 2016 High

    Defining PRRT2 as a presynaptically enriched type II transmembrane protein with an intracellular proline-rich domain, and showing its silencing impairs synchronous release and Ca2+ sensitivity, transformed it from a genetic locus into a defined regulator of the release machinery.

    Evidence Topology mapping (immunogold EM, surface biotinylation, live labeling, modeling); shRNA silencing with patch-clamp and EM; reciprocal Co-IP with SNAP-25, Syt1/2, and Intersectin 1

    PMID:26797119 PMID:27052163

    Open questions at the time
    • Did not resolve whether SNARE binding is direct or scaffolded
    • Mechanism of priming suppression not yet reconstituted
  4. 2017 High

    Cerebellar granule-cell-specific conditional knockout recapitulating PKD-like behaviors localized PRRT2's circuit role and tied its SNARE-downregulating activity to a defined behavioral output.

    Evidence Conditional KO mouse, behavioral phenotyping, optogenetic stimulation with cerebellar slice recording, Co-IP with SNARE proteins

    PMID:29056747

    Open questions at the time
    • Did not isolate which downstream effector (SNARE vs channels) drives the cerebellar phenotype
  5. 2018 High

    Reconstitution showing PRRT2's proline-rich domain blocks trans-SNARE assembly, plus discovery of direct Nav1.2/Nav1.6 modulation and STX1B binding, established two parallel mechanisms — release inhibition and Na+ channel suppression — and linked variant severity to molecular efficiency.

    Evidence In vitro single-vesicle/bulk fusion assays with disease-variant mutagenesis; HEK-cell Nav reconstitution with patch-clamp and biotinylation validated in iPSC and KO neurons; STX1B Co-IP with family segregation

    PMID:29346777 PMID:29554219 PMID:30009426 PMID:30347267

    Open questions at the time
    • Did not define how a single protein coordinates SNARE and channel targets in vivo
    • AIS elongation mechanism downstream of Na+ channel changes unresolved
  6. 2019 High

    Knock-in of a frameshift mutation phenocopying KO, plus KO synapse-type-specific electrophysiology and missense membrane-targeting screens, confirmed haploinsufficiency as the disease mechanism and showed PRRT2 differentially shapes excitatory versus inhibitory transmission and E/I balance.

    Evidence Knock-in vs KO mouse comparison with mRNA half-life assays; KO hippocampal neuron patch-clamp and MEA; surface biotinylation of 13 missense variants

    PMID:29912316 PMID:30980674 PMID:31785815

    Open questions at the time
    • Did not map how opposing excitatory/inhibitory effects integrate at network scale
    • Structural basis of C-terminal missense mistargeting not defined
  7. 2020 Medium

    Identifying cofilin as the effector for PRRT2's control of synaptic actin, and detailing cerebellar parallel-fiber/Purkinje-cell dysfunction, separated PRRT2's structural (spine/actin) role from its release role and connected cortical cerebellar deficits to motor abnormalities.

    Evidence shRNA silencing with live actin imaging and cofilin phospho-mimetic rescue; KO cerebellar EM, slice electrophysiology, and behavior

    PMID:32891704 PMID:33056987

    Open questions at the time
    • Cofilin rescue did not restore release defects, leaving the link between actin and release unexplained
    • Mechanism connecting PRRT2 to cofilin activity not resolved
  8. 2021 High

    Discovery of direct PRRT2 interactions with Na+/K+-ATPase pumps and P/Q-type Ca2+ channels, alongside KO granule-cell Na+ channel and AIS phenotypes, expanded PRRT2 into a hub coordinating Ca2+ influx, ion homeostasis, and intrinsic excitability at the active zone.

    Evidence Pulldown proteomics, Co-IP, colocalization and afterhyperpolarization recordings (NKA); Co-IP/pull-down/proteomics with Ca2+ imaging and EPSCs (Cav2.1); KO granule-cell patch-clamp and slice recordings

    PMID:33515674 PMID:33731672 PMID:34133925

    Open questions at the time
    • Did not establish stoichiometry or whether these interactions occur simultaneously in one complex
    • Structural interface with channels/pumps not resolved
  9. 2023 Medium

    Domain dissection assigning gating modulation to the C-terminal intramembrane helix-loop-helix and target binding to the N-terminal proline-rich antenna, with disease residues A320/V286 mapped to the Nav1.2 interface, provided a structure-function model distinguishing loss- from gain-of-function variants.

    Evidence Molecular dynamics simulations, isolated-domain and full-length binding assays, surface biotinylation, and patch-clamp in HEK cells

    PMID:36958475 PMID:37271286

    Open questions at the time
    • Predictions rely on simulation and single-lab biochemistry without an experimental structure
    • Did not test whether the same domains govern SNARE and channel binding identically

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PRRT2 physically and temporally coordinates its many partners — SNAREs, synaptotagmin, Nav and Cav channels, Na+/K+-ATPase, and the cofilin/actin system — into a unified presynaptic regulatory program remains unresolved.
  • No experimental structure of PRRT2 or its complexes
  • Stoichiometry and competition among partners undefined
  • How haploinsufficiency selectively produces paroxysmal rather than constant dysfunction is unexplained

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 5 GO:0140313 molecular sequestering activity 2 GO:0008092 cytoskeletal protein binding 1
Localization
GO:0005886 plasma membrane 3 GO:0005829 cytosol 2
Pathway
R-HSA-112316 Neuronal System 3 R-HSA-1266738 Developmental Biology 2 R-HSA-5653656 Vesicle-mediated transport 2
Partners
CACNA1AITSN1SCN2ASNAP25STX1ASTX1BSYT1VAMP2
Complex memberships
SNARE complex

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2011 Truncating mutations in PRRT2 alter the subcellular localization of the PRRT2 protein, as demonstrated by direct experiment in cells expressing mutant versus wild-type PRRT2. Subcellular localization assay in cells expressing truncating mutants vs wild-type PRRT2 Nature genetics Medium 22101681
2011 PRRT2 localizes to axons but not to dendritic processes in primary neuronal culture; truncating mutations associated with PKD/IC lead to dramatically reduced PRRT2 protein levels in neurons. PRRT2 was reported to interact with the t-SNARE SNAP25. Primary neuronal culture immunostaining; Western blotting of mutant vs wild-type expressing neurons; co-immunoprecipitation with SNAP25 Cell reports Medium 22832103
2016 PRRT2 is enriched in presynaptic terminals; its silencing decreases synapse number and increases docked synaptic vesicles at rest. PRRT2-silenced neurons show severe impairment of synchronous neurotransmitter release, decreased release probability and Ca2+ sensitivity, and increased asynchronous/synchronous release ratio. PRRT2 directly interacts with SNAP-25 and synaptotagmin 1/2. shRNA silencing in primary neurons; electrophysiology (patch-clamp); electron microscopy; co-immunoprecipitation of PRRT2 with SNAP-25 and Syt1/2 Cell reports High 27052163
2016 PRRT2 adopts a type II transmembrane topology in which only the second hydrophobic segment spans the plasma membrane, the first hydrophobic segment forms an intracellular helix-loop-helix without crossing the membrane, and the large proline-rich N-terminal domain is intracellular (N_cyt/C_exo). PRRT2 interacts with Intersectin 1, an intracellular protein involved in synaptic vesicle cycling. Live immunolabeling, immunogold electron microscopy, surface biotinylation, computational modeling, co-immunoprecipitation with Intersectin 1 The Journal of biological chemistry High 26797119
2017 PRRT2 is a presynaptic protein that interacts with components of the SNARE complex and downregulates its formation. Loss-of-function in cerebellar granule cells causes PKD-like phenotypes; PRRT2 KO mice with granule cell-specific deletion recapitulate behavioral phenotypes, and cerebellar slice recordings show optogenetic stimulation of granule cells causes transient elevation followed by suppression of Purkinje cell firing. Co-immunoprecipitation with SNARE complex proteins; conditional KO mouse (cerebellar granule cell-specific); behavioral phenotyping; optogenetic stimulation with extracellular recording in cerebellar slices Cell research High 29056747
2018 PRRT2 directly interacts with Nav1.2 and Nav1.6 (but not Nav1.1) channels, decreases their membrane surface exposure and Na+ current amplitude, induces a negative shift in voltage-dependence of inactivation, and slows recovery from inactivation. Loss of PRRT2 leads to increased Na+ currents and axon initial segment elongation in iPSC-derived neurons from homozygous patients and PRRT2 KO mice. HEK-293 cells stably expressing Nav subtypes; patch-clamp electrophysiology; surface biotinylation; co-immunoprecipitation in brain tissue; iPSC-derived neurons; multi-electrode array; PRRT2 KO mouse primary neurons Brain : a journal of neurology High 29554219
2018 PRRT2 selectively blocks trans-SNARE complex assembly and negatively regulates synaptic vesicle priming, mediated by weak interactions of the N-terminal proline-rich domain with synaptic SNARE proteins. Disease-associated PRRT2 mutations disrupt this SNARE-modulatory function with efficiencies corresponding to phenotypic severity. Reconstituted single-vesicle and bulk fusion assays; live cell imaging of single exocytotic events in PC12 cells; biophysical analysis; mutagenesis of PRRT2 disease variants Cell reports High 29346777
2015 Mutant PRRT2 (PKC-associated mutations) interferes with SNAP25 and GRIA1 (GluA1, AMPA receptor subunit) interactions; co-transfection with mutant PRRT2 increases GRIA1 surface distribution. Higher glutamate levels were observed in plasma of PKC patients and culture medium of Prrt2-knockdown neurons. Co-immunoprecipitation (PRRT2 with SNAP25 and GRIA1); live-labeling of surface GRIA1; double immunostaining; PRRT2 knockdown in neurons International journal of molecular sciences Medium 25915028
2014 Truncating PRRT2 mutations lead to nonsense-mediated mRNA decay (NMD), reducing PRRT2 mRNA and protein levels; inhibition of NMD rescues truncated PRRT2 mRNA. The small fraction of undegraded truncated protein mislocalizes from membrane to cytoplasm and nucleus. NMD inhibitors (emetine, cycloheximide) in lymphoblasts; UPF1 siRNA silencing; Western blot; subcellular localization of mutant PRRT2 in SH-SY5Y cells Parkinsonism & related disorders Medium 25457817
2016 PRRT2 is expressed both pre- and post-synaptically; knockdown of Prrt2 in vivo (by in utero electroporation of shRNA) delays neuronal migration during embryonic development and markedly decreases synaptic density after birth. Truncating mutants accumulate in the cytoplasm and fail to reach the cell membrane. Synaptic membrane fractionation; immunostaining; in utero electroporation of shRNA in cortical neurons; confocal microscopy of subcellular localization Oncotarget Medium 27172900
2016 PRRT2 KO mice display paroxysmal movements at locomotion onset, abnormal motor behaviors, increased sensitivity to convulsants. Cerebellar patch-clamp shows higher excitatory strength at parallel fiber-Purkinje cell synapses during high-frequency stimulation. β-galactosidase reporter mapping reveals highest PRRT2 expression in cerebellum, hindbrain and spinal cord. Constitutive PRRT2 KO mouse; β-galactosidase reporter staining; patch-clamp electrophysiology in hippocampal and cerebellar slices; behavioral testing; pentylenetetrazol sensitivity Neurobiology of disease High 28007585
2019 Constitutive PRRT2 KO in hippocampal neurons decreases excitatory synapse number without affecting inhibitory synapses. Excitatory KO neurons show slowed exocytosis kinetics, weakened spontaneous and evoked synaptic transmission, and markedly increased facilitation. Inhibitory neurons show strengthened basal transmission and faster depression. At the network level, these effects result in heightened spontaneous and evoked activity and increased excitability of excitatory neurons. PRRT2 KO primary hippocampal neurons; live imaging (vesicle fusion); patch-clamp electrophysiology; multi-electrode array; acute hippocampal slices Cerebral cortex High 29912316
2019 PRRT2 frameshift mutation (c.649_650InsC) reduces PRRT2 mRNA stability (shortened half-life), leading to loss of function. Knock-in mice expressing this mutation phenocopy KO mice (same rotarod/balance beam impairment, seizure sensitivity, altered SNARE complex, synaptic vesicle number changes). Truncated PRRT2 protein was undetectable in KI brain tissue. Prrt2 knock-in (KI) and KO mouse comparison; mRNA half-life measurement; behavioral testing; Western blot; SNARE complex assay; electron microscopy of synaptic vesicles Biochemical and biophysical research communications High 31785815
2019 PRRT2 missense variants clustering near the C-terminus frequently impair protein targeting to the plasma membrane; 8 of 13 missense variants tested showed decreased membrane localization, while benign variants showed normal membrane localization similar to wild-type. Confocal microscopy of mutant PRRT2 subcellular localization; cell surface biotinylation assay in transfected cells Epilepsia Medium 30980674
2018 PRRT2 directly interacts with STX1B (syntaxin 1B), a SNARE protein critical for neurotransmitter release; a truncating variant (p.Ser208Ilefs*17) lacking the helix-loop-helix domain fails to bind STX1B. The variant also abolishes normal membrane localization of PRRT2. Co-immunoprecipitation of PRRT2 with STX1B; Western blot; immunofluorescence subcellular localization in HeLa and N2A cells; whole exome sequencing with family segregation Epilepsia Medium 30009426
2018 PRRT2 negatively regulates SNARE complex assembly through interaction with SNAP25, STX1A, and VAMP2 in the M1 motor cortex. In PRRT2 truncated mutant rats, release of amino acid neurotransmitters is increased, GRIA1 protein levels are significantly increased, GABRA1 levels are reduced, mEPSC frequency and amplitude are increased, mIPSC amplitude is decreased, and the E/I balance is disrupted. PRRT2 truncated mutant rat model; Co-immunoprecipitation of SNARE proteins; neurotransmitter HPLC measurement; Western blot; patch-clamp (mEPSC/mIPSC) Neurobiology of disease Medium 30347267
2020 PRRT2 silencing in non-neuronal cell lines inhibits cell motility, increases cell aggregation, promotes filopodia protrusion, and alters focal adhesion turnover — all processes involving actin cytoskeleton. In hippocampal neurons, PRRT2 silencing reduces synaptic filamentous actin, perturbs actin dynamics, and decreases dendritic spine density and maturation. Cofilin is identified as the effector: PRRT2 silencing unbalances cofilin activity, causing cofilin-actin rod formation; expression of phospho-mimetic cofilin (S3E) rescues spine defects but not neurotransmitter release alterations. shRNA silencing in non-neuronal cells and hippocampal neurons; live imaging of actin dynamics; phalloidin staining; dendritic spine morphometry; cofilin phospho-mimetic rescue experiment Cell death & disease Medium 33056987
2021 PRRT2 directly interacts with α1 and α3 Na+/K+ ATPase (NKA) pumps in mouse brain. PRRT2 deficiency impairs NKA function during neuronal stimulation (without affecting expression or surface exposure), increases clustering of α3-NKA on plasma membrane, and reduces the NKA-dependent afterhyperpolarization following high-frequency firing. Re-expression of PRRT2 rescues all these phenotypes. Pulldown-based proteomics of mouse brain; co-immunoprecipitation; immunofluorescence colocalization; electrophysiology (afterhyperpolarization recording); PRRT2 re-expression rescue Cell death & disease High 33731672
2021 PRRT2 directly interacts with P/Q-type (Cav2.1) Ca2+ channels via Co-IP, pull-down, and proteomics. PRRT2 deletion reduces P/Q-type channel membrane targeting (without changing total expression), decreases P/Q-type Ca2+ channel clustering at the presynaptic active zone, and reduces P/Q-dependent presynaptic Ca2+ signal and EPSC amplitude. Co-immunoprecipitation; pull-down assays; proteomics; surface biotinylation; electrophysiology (evoked EPSCs, somatic Ca2+ currents); two-photon imaging of presynaptic Ca2+ signals; PRRT2 acute and constitutive deletion Cell reports High 34133925
2021 PRRT2 KO cerebellar granule cells display increased Na+ channel expression, increased Na+ current amplitude, and increased axon initial segment length, leading to enhanced intrinsic excitability and greater action potential discharge in response to mossy fiber activation, without changes at mossy fiber-GC synapses. PRRT2 KO primary cerebellar granule cells; patch-clamp electrophysiology (transient and persistent Na+ currents, AIS measurement); acute cerebellar slice recordings with mossy fiber stimulation Neurobiology of disease High 33515674
2020 PRRT2 is presynaptically localized in the cerebellar molecular layer (in granule cell axons/parallel fibers); PRRT2 KO mice have increased numbers of docked vesicles but decreased total vesicle numbers in cerebellar molecular layer synapses. KO mice show reduced parallel fiber facilitation and reduced Purkinje cell excitability, establishing cerebellar cortical dysfunction as a mechanism promoting disinhibition of cerebellar nuclei and motor abnormalities. lacZ reporter and RT-PCR for expression mapping; electron microscopy of cerebellar synapses; patch-clamp electrophysiology in cerebellar slices (parallel fiber-PC synapses, PC intrinsic excitability); behavioral motor tests; PRRT2 KO mouse Neuroscience High 32891704
2023 The intramembrane COOH-terminal domain of PRRT2 is sufficient to modulate Nav1.2 Na+ current and channel biophysical properties, while the NH2-terminal cytoplasmic proline-rich region acts as a binding antenna for Nav1.2 channels. Both domains together (full-length PRRT2) show stronger Nav1.2 binding than either domain alone. The COOH-terminal domain maintains stable helix-loop-helix conformation in the membrane bilayer. Molecular dynamics simulations; biochemical binding/affinity assays (isolated domains vs full-length); patch-clamp electrophysiology in HEK cells expressing domain constructs; surface biotinylation The Journal of biological chemistry Medium 36958475
2023 PRRT2 missense mutations in the transmembrane domain (A320V and V286M) differentially affect Nav1.2 binding and function: A320V shows decreased Nav1.2 binding and loss-of-function (no Nav1.2 modulation), while V286M shows increased binding and gain-of-function (more pronounced inactivation shift and slower recovery). Both mutations implicate residues A320 and V286 as part of the PRRT2-Nav1.2 interaction site. Molecular dynamics simulations; affinity/binding assays; surface biotinylation; patch-clamp electrophysiology in HEK cells expressing Nav1.2 Neurobiology of disease Medium 37271286

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 Exome sequencing identifies truncating mutations in PRRT2 that cause paroxysmal kinesigenic dyskinesia. Nature genetics 377 22101681
2011 Identification of PRRT2 as the causative gene of paroxysmal kinesigenic dyskinesias. Brain : a journal of neurology 230 22120146
2015 The evolving spectrum of PRRT2-associated paroxysmal diseases. Brain : a journal of neurology 214 26598493
2012 PRRT2 mutations cause benign familial infantile epilepsy and infantile convulsions with choreoathetosis syndrome. American journal of human genetics 212 22243967
2011 Mutations in the gene PRRT2 cause paroxysmal kinesigenic dyskinesia with infantile convulsions. Cell reports 210 22832103
2012 PRRT2 gene mutations: from paroxysmal dyskinesia to episodic ataxia and hemiplegic migraine. Neurology 132 23077024
2016 PRRT2 Is a Key Component of the Ca(2+)-Dependent Neurotransmitter Release Machinery. Cell reports 127 27052163
2018 PRRT2 controls neuronal excitability by negatively modulating Na+ channel 1.2/1.6 activity. Brain : a journal of neurology 106 29554219
2012 PRRT2 mutations in familial infantile seizures, paroxysmal dyskinesia, and hemiplegic migraine. Neurology 95 23077026
2012 PRRT2 mutations cause hemiplegic migraine. Neurology 91 23077016
2012 PRRT2 mutations: a major cause of paroxysmal kinesigenic dyskinesia in the European population. Neurology 87 22744660
2017 PRRT2 deficiency induces paroxysmal kinesigenic dyskinesia by regulating synaptic transmission in cerebellum. Cell research 86 29056747
2013 PRRT2 mutations and paroxysmal disorders. European journal of neurology 85 23398397
2012 Familial PRRT2 mutation with heterogeneous paroxysmal disorders including paroxysmal torticollis and hemiplegic migraine. Developmental medicine and child neurology 83 22845787
2012 PRRT2 mutations are the major cause of benign familial infantile seizures. Human mutation 80 22623405
2011 Targeted genomic sequencing identifies PRRT2 mutations as a cause of paroxysmal kinesigenic choreoathetosis. Journal of medical genetics 80 22131361
2013 Role of PRRT2 in common paroxysmal neurological disorders: a gene with remarkable pleiotropy. Journal of medical genetics 79 23343561
2011 Mutations in PRRT2 result in paroxysmal dyskinesias with marked variability in clinical expression. Journal of medical genetics 79 22209761
2012 Mutations in PRRT2 responsible for paroxysmal kinesigenic dyskinesias also cause benign familial infantile convulsions. Journal of human genetics 74 22399141
2012 Homozygous c.649dupC mutation in PRRT2 worsens the BFIS/PKD phenotype with mental retardation, episodic ataxia, and absences. Epilepsia 74 23126439
2012 PRRT2 links infantile convulsions and paroxysmal dyskinesia with migraine. Neurology 73 23077017
2012 PRRT2 phenotypes and penetrance of paroxysmal kinesigenic dyskinesia and infantile convulsions. Neurology 71 22875091
2012 PRRT2 phenotypic spectrum includes sporadic and fever-related infantile seizures. Neurology 70 23077018
2015 Severe phenotypic spectrum of biallelic mutations in PRRT2 gene. Journal of neurology, neurosurgery, and psychiatry 68 25595153
2018 PRRT2 Regulates Synaptic Fusion by Directly Modulating SNARE Complex Assembly. Cell reports 65 29346777
2016 PRRT2: from Paroxysmal Disorders to Regulation of Synaptic Function. Trends in neurosciences 65 27624551
2016 The PRRT2 knockout mouse recapitulates the neurological diseases associated with PRRT2 mutations. Neurobiology of disease 64 28007585
2015 PRRT2 Mutant Leads to Dysfunction of Glutamate Signaling. International journal of molecular sciences 58 25915028
2016 A Novel Topology of Proline-rich Transmembrane Protein 2 (PRRT2): HINTS FOR AN INTRACELLULAR FUNCTION AT THE SYNAPSE. The Journal of biological chemistry 56 26797119
2013 PRRT2-related disorders: further PKD and ICCA cases and review of the literature. Journal of neurology 55 23299620
2016 PRRT2 mutations lead to neuronal dysfunction and neurodevelopmental defects. Oncotarget 50 27172900
2012 PRRT2 mutations in paroxysmal kinesigenic dyskinesia with infantile convulsions in a Taiwanese cohort. PloS one 46 22870186
2013 Clinical features of childhood-onset paroxysmal kinesigenic dyskinesia with PRRT2 gene mutations. Developmental medicine and child neurology 41 23363396
2012 Novel PRRT2 mutations in paroxysmal dyskinesia patients with variant inheritance and phenotypes. Genes, brain, and behavior 39 23190448
2021 The Spectrum of PRRT2-Associated Disorders: Update on Clinical Features and Pathophysiology. Frontiers in neurology 37 33746883
2021 Hemiplegic Migraine Associated With PRRT2 Variations: A Clinical and Genetic Study. Neurology 37 34649875
2013 Clinico-genetic comparisons of paroxysmal kinesigenic dyskinesia patients with and without PRRT2 mutations. European journal of neurology 34 23551744
2020 Exosomal release of microRNA-454 by breast cancer cells sustains biological properties of cancer stem cells via the PRRT2/Wnt axis in ovarian cancer. Life sciences 31 32598931
2019 Constitutive Inactivation of the PRRT2 Gene Alters Short-Term Synaptic Plasticity and Promotes Network Hyperexcitability in Hippocampal Neurons. Cerebral cortex (New York, N.Y. : 1991) 30 29912316
2012 PRRT2 mutation in Japanese children with benign infantile epilepsy. Brain & development 30 23131349
2016 Paroxysmal hypnogenic dyskinesia is associated with mutations in the PRRT2 gene. Neurology. Genetics 28 27123484
2020 The Phenotypic Spectrum of PRRT2-Associated Paroxysmal Neurologic Disorders in Childhood. Biomedicines 27 33126500
2014 PRRT2: a major cause of infantile epilepsy and other paroxysmal disorders of childhood. Progress in brain research 27 25194488
2013 PRRT2 mutations: exploring the phenotypical boundaries. Journal of neurology, neurosurgery, and psychiatry 27 24101679
2012 Genetic analysis of PRRT2 for benign infantile epilepsy, infantile convulsions with choreoathetosis syndrome, and benign convulsions with mild gastroenteritis. Brain & development 27 23073245
2018 PRRT2 deficiency induces paroxysmal kinesigenic dyskinesia by influencing synaptic function in the primary motor cortex of rats. Neurobiology of disease 26 30347267
2013 Mutations in PRRT2 result in familial infantile seizures with heterogeneous phenotypes including febrile convulsions and probable SUDEP. Epilepsy research 26 23352743
2022 Features Differ Between Paroxysmal Kinesigenic Dyskinesia Patients with PRRT2 and TMEM151A Variants. Movement disorders : official journal of the Movement Disorder Society 24 35083789
2012 PRRT2 c.649dupC mutation derived from de novo in paroxysmal kinesigenic dyskinesia. CNS neuroscience & therapeutics 24 23176561
2014 PRRT2 truncated mutations lead to nonsense-mediated mRNA decay in Paroxysmal Kinesigenic Dyskinesia. Parkinsonism & related disorders 23 25457817
2013 Altered intrinsic brain activity in patients with paroxysmal kinesigenic dyskinesia by PRRT2 mutation: altered brain activity by PRRT2 mutation. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 23 23532549
2012 Phenotypic overlap among paroxysmal dyskinesia subtypes: Lesson from a family with PRRT2 gene mutation. Brain & development 23 22902309
2020 Novel and de novo point and large microdeletion mutation in PRRT2-related epilepsy. Brain and behavior 22 32237035
2019 PRRT2 missense mutations cluster near C-terminus and frequently lead to protein mislocalization. Epilepsia 22 30980674
2012 Novel PRRT2 mutation in an African-American family with paroxysmal kinesigenic dyskinesia. BMC neurology 22 22985072
2012 PRRT2 mutation causes benign familial infantile convulsions. Neurology 22 23077019
2016 Expanding phenotype of PRRT2 gene mutations: A new case with epilepsy and benign myoclonus of early infancy. European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society 21 26876767
2020 Clinical spectrum and genotype-phenotype correlations in PRRT2 Italian patients. European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society 20 32651081
2020 Presynaptic PRRT2 Deficiency Causes Cerebellar Dysfunction and Paroxysmal Kinesigenic Dyskinesia. Neuroscience 20 32891704
2012 PRRT2 mutation causes paroxysmal kinesigenic dyskinesia and hemiplegic migraine in monozygotic twins. European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society 20 23182655
2021 PRRT2 modulates presynaptic Ca2+ influx by interacting with P/Q-type channels. Cell reports 19 34133925
2019 Functional study and pathogenicity classification of PRRT2 missense variants in PRRT2-related disorders. CNS neuroscience & therapeutics 19 31124310
2016 Mutation Analysis of MR-1, SLC2A1, and CLCN1 in 28 PRRT2-negative Paroxysmal Kinesigenic Dyskinesia Patients. Chinese medical journal 19 27098784
2013 PRRT2 mutation screening in patients with paroxysmal kinesigenic dyskinesia from Southwest China. European journal of neurology 19 23496026
2021 An interaction between PRRT2 and Na+/K+ ATPase contributes to the control of neuronal excitability. Cell death & disease 17 33731672
2014 PRRT2 mutations are related to febrile seizures in epileptic patients. International journal of molecular sciences 17 25522171
2022 Cerebellum Dysfunction in Patients With PRRT2-Related Paroxysmal Dyskinesia. Neurology 16 35058336
2021 Increased responsiveness at the cerebellar input stage in the PRRT2 knockout model of paroxysmal kinesigenic dyskinesia. Neurobiology of disease 16 33515674
2019 PRRT2 mutations in Japanese patients with benign infantile epilepsy and paroxysmal kinesigenic dyskinesia. Seizure 16 31154286
2012 The PRRT2 mutation c.649dupC is the so far most frequent cause of benign familial infantile convulsions. Seizure 16 22877996
2012 PRRT2 is mutated in familial and non-familial benign infantile seizures. European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society 16 22902423
2021 Penetrance estimation of PRRT2 variants in paroxysmal kinesigenic dyskinesia and infantile convulsions. Frontiers of medicine 15 34825340
2014 Atypical course in individuals from Spanish families with benign familial infantile seizures and mutations in the PRRT2 gene. Epilepsy research 15 25060993
2023 PRRT2-positive self-limited infantile epilepsy: Initial seizure characteristics and response to sodium channel blockers. Epilepsia open 14 36775847
2020 Brain structural connectome in relation to PRRT2 mutations in paroxysmal kinesigenic dyskinesia. Human brain mapping 14 32592228
2019 Clinical features of patients with paroxysmal kinesigenic dyskinesia, mutation screening of PRRT2 and the effects of morning draughts of oxcarbazepine. BMC pediatrics 14 31722684
2019 PRRT2 gene variant in a child with dysmorphic features, congenital microcephaly, and severe epileptic seizures: genotype-phenotype correlation? Italian journal of pediatrics 14 31801583
2013 Mutation analysis of PRRT2 in two Chinese BFIS families and nomenclature of PRRT2 related paroxysmal diseases. Neuroscience letters 14 23896529
2021 PRRT2 variants and effectiveness of various antiepileptic drugs in self-limited familial infantile epilepsy. Seizure 13 34298454
2013 Girl with a PRRT2 mutation and infantile focal epilepsy with bilateral spikes. Brain & development 13 23768507
2020 Different experiences of two PRRT2-associated self-limited familial infantile epilepsy. Acta neurologica Belgica 12 32246320
2018 A PRRT2 variant in a Chinese family with paroxysmal kinesigenic dyskinesia and benign familial infantile seizures results in loss of interaction with STX1B. Epilepsia 12 30009426
2014 Heterogeneous pattern of selective pressure for PRRT2 in human populations, but no association with autism spectrum disorders. PloS one 12 24594579
2013 Clinical and polygraphic study of familial paroxysmal kinesigenic dyskinesia with PRRT2 mutation. Epileptic disorders : international epilepsy journal with videotape 12 23771590
2013 Phenotypes and PRRT2 mutations in Chinese families with benign familial infantile epilepsy and infantile convulsions with paroxysmal choreoathetosis. BMC neurology 12 24370076
2020 Familial hemiplegic migraine with a PRRT2 mutation: Phenotypic variations and carbamazepine efficacy. Brain & development 11 31902651
2019 PRRT2 frameshift mutation reduces its mRNA stability resulting loss of function in paroxysmal kinesigenic dyskinesia. Biochemical and biophysical research communications 11 31785815
2018 PRRT2 mutations in a cohort of Chinese families with paroxysmal kinesigenic dyskinesia and genotype-phenotype correlation reanalysis in literatures. The International journal of neuroscience 11 29285950
2014 Reduced Penetrance of PRRT2 Mutation in a Chinese Family With Infantile Convulsion and Choreoathetosis Syndrome. Journal of child neurology 11 25403460
2023 Missense mutations in the membrane domain of PRRT2 affect its interaction with Nav1.2 voltage-gated sodium channels. Neurobiology of disease 10 37271286
2020 Proline-rich transmembrane protein 2 (PRRT2) regulates the actin cytoskeleton during synaptogenesis. Cell death & disease 10 33056987
2014 Successful control with carbamazepine of family with paroxysmal kinesigenic dyskinesia of PRRT2 mutation. BioMedicine 10 25520928
2013 Mutations in PRRT2 are not a common cause of infantile epileptic encephalopathies. Epilepsia 10 23566103
2023 The intramembrane COOH-terminal domain of PRRT2 regulates voltage-dependent Na+ channels. The Journal of biological chemistry 9 36958475
2022 Efficacy, Tolerability, and Retention of Antiseizure Medications in PRRT2-Associated Infantile Epilepsy. Neurology. Genetics 9 36187725
2021 Age-dependent neurological phenotypes in a mouse model of PRRT2-related diseases. Neurogenetics 9 34101060
2014 Unusual variability of PRRT2 linked phenotypes within a family. European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society 9 24755245
2016 Focal seizures and epileptic spasms in a child with Down syndrome from a family with a PRRT2 mutation. Brain & development 8 26867511
2016 Paroxysmal kinesigenic dyskinesia in a patient with a PRRT2 mutation and centrotemporal spike discharges on electroencephalogram: case report of a 10-year-old girl. Korean journal of pediatrics 8 28018471
2022 Characteristics of infantile convulsions and choreoathetosis syndrome caused by PRRT2 mutation. Pediatric investigation 7 35382417

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