Affinage

CACNA1F

Voltage-dependent L-type calcium channel subunit alpha-1F · UniProt O60840

Length
1977 aa
Mass
220.7 kDa
Annotated
2026-04-28
99 papers in source corpus 23 papers cited in narrative 23 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CACNA1F encodes Cav1.4, the pore-forming α1 subunit of a retinal L-type voltage-gated calcium channel that is essential for tonic neurotransmitter release and ribbon synapse formation at photoreceptor terminals. Cav1.4 exhibits unusually slow voltage-dependent inactivation, very low open probability, and small single-channel conductance, generating a sustained window current near photoreceptor resting potentials that supports continuous Ca²⁺ influx (PMID:14973233, PMID:16085774); a C-terminal inhibitory domain (ICDI) suppresses Ca²⁺-dependent inactivation independently of calmodulin, which remains pre-associated with the channel and modulates current density, while PKA phosphorylation of the ICDI promotes calmodulin occupancy and increases open probability (PMID:19717559, PMID:27456671, PMID:27226626). Channel availability is enhanced by CaBP4, which binds the IQ motif in a Ca²⁺-dependent manner to relieve ICDI-mediated inhibition, and by active zone proteins RIM1/2, which potentiate Ca²⁺ entry; synaptic ribbons further stabilize Cav1.4/RIM2 clusters at the active zone (PMID:22936811, PMID:25258313, PMID:26400943, PMID:32249787). Loss-of-function and gain-of-function mutations in CACNA1F cause incomplete X-linked congenital stationary night blindness (CSNB2), with loss of Cav1.4 abolishing photoreceptor ribbon synapses and post-receptoral ERG responses and gain-of-function mutations reducing photoreceptor dynamic range (PMID:16155113, PMID:24051672, PMID:24796500).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2004 High

    Establishing Cav1.4's distinctive biophysical identity resolved why photoreceptors can sustain tonic Ca²⁺ influx: the channel's slow inactivation and large window current near −40 mV are intrinsic properties not dependent on auxiliary β subunits.

    Evidence Heterologous expression with whole-cell patch clamp and CSNB2 mutagenesis in transfected cells

    PMID:14973233

    Open questions at the time
    • Native photoreceptor recordings not performed
    • Temperature dependence not yet assessed
  2. 2004 High

    The discovery that CaBP4 directly binds the Cav1.4 C-terminus and shifts activation voltage identified the first photoreceptor-specific modulator of Cav1.4 gating.

    Evidence Co-immunoprecipitation, electrophysiology in transfected cells, and Cabp4 KO mouse with ERG

    PMID:15452577

    Open questions at the time
    • Structural basis of CaBP4–Cav1.4 interaction not yet resolved
    • Relationship to ICDI not yet defined
  3. 2005 High

    Cacna1f knockout mice demonstrated that Cav1.4 is essential not only for photoreceptor Ca²⁺ signaling but also for the structural assembly and maintenance of ribbon synapses, elevating the channel from a conductance element to a synaptic organizer.

    Evidence Cacna1f KO mouse with ERG, Fluo-4 Ca²⁺ imaging, and immunocytochemistry

    PMID:16155113

    Open questions at the time
    • Molecular mechanism by which Cav1.4 organizes synapse formation unknown
    • Whether cone synapses are equally dependent not fully resolved
  4. 2005 High

    Single-channel recordings revealed Cav1.4's extremely low open probability and small conductance, explaining why large channel numbers are required and why macroscopic inactivation appears slow — the channel simply remains available rather than rapidly inactivating.

    Evidence Cell-attached single-channel recordings in tsA-201 cells with 100 mM Ba²⁺

    PMID:16085774

    Open questions at the time
    • Single-channel behavior in native photoreceptors not recorded
    • Effect of modulators on single-channel properties not tested
  5. 2005 High

    Characterization of the I745T CSNB2 mutation as a gain-of-function (−30 mV activation shift) established that CSNB2 can arise from excessive, not just absent, channel activity — broadening the disease mechanism spectrum.

    Evidence Heterologous expression with whole-cell patch clamp

    PMID:15897456

    Open questions at the time
    • In vivo consequences not yet demonstrated at time of discovery
  6. 2006 Medium

    Systematic analysis of multiple CSNB2 mutations revealed a third pathological mechanism — reduced protein expression/membrane targeting without altered gating — completing a tripartite classification of CSNB2 pathophysiology (loss-of-function, gain-of-function, expression defects).

    Evidence Heterologous expression in oocytes and tsA-201 cells with electrophysiology and Western blot

    PMID:16476079 PMID:17949918

    Open questions at the time
    • Protein trafficking and quality control mechanisms not identified
    • Expression defects not verified in native photoreceptors
  7. 2009 High

    FRET experiments revealed that calmodulin pre-associates with the Cav1.4 C-terminus and that the ICDI domain suppresses Ca²⁺-dependent inactivation without displacing calmodulin, establishing ICDI and calmodulin as mechanistically independent regulators of channel gating.

    Evidence FRET with engineered CFP variants plus whole-cell patch clamp in heterologous cells

    PMID:19717559

    Open questions at the time
    • Structural basis of ICDI–calmodulin coexistence not resolved
    • In vivo significance of calmodulin pre-association not tested
  8. 2012 High

    Defining CaBP4's mechanism as relief of ICDI-mediated inhibition via IQ-motif binding unified two regulatory axes — CaBP4 and ICDI — into a single gating model explaining how photoreceptor-specific modulation increases Cav1.4 availability.

    Evidence FRET and electrophysiology with ICDI-deletion mutants in heterologous expression

    PMID:22936811

    Open questions at the time
    • Stoichiometry of CaBP4 binding in native channels unknown
    • Whether other CaBPs share this mechanism not tested
  9. 2014 High

    NMR structures of CaBP4 in Mg²⁺- and Ca²⁺-bound states provided the first atomic-level model for how Ca²⁺-induced conformational change in CaBP4 exposes residues that contact the Cav1.4 IQ motif, and mutagenesis validated the binding interface.

    Evidence NMR structure determination with mutagenesis of Cav1.4 IQ motif and binding assays

    PMID:25258313

    Open questions at the time
    • No co-crystal or cryo-EM structure of the CaBP4–Cav1.4 complex
    • Whether structural changes propagate to the pore domain not shown
  10. 2014 High

    Identification of retinal auxiliary subunit composition (β2/β2X13 and α2δ4) and their distinct effects on Cav1.4 gating established the native channel complex and explained subunit-specific tuning of activation and inactivation.

    Evidence Co-IP from HEK293 cells and mouse retina, proximity ligation assay, electrophysiology

    PMID:25468907

    Open questions at the time
    • Stoichiometry and subunit arrangement in native photoreceptors not resolved
    • Contribution of other potential auxiliary subunits not excluded
  11. 2015 High

    Conditional RIM1/2 double knockout in rods revealed that active zone RIM proteins potentiate Cav1.4 Ca²⁺ currents and are essential for evoked vesicle release, positioning RIMs as critical upstream facilitators of Cav1.4 function at the synapse.

    Evidence Conditional double KO mouse with rod voltage clamp and vesicle release measurements

    PMID:26400943

    Open questions at the time
    • Direct binding site of RIM on Cav1.4 not mapped
    • Whether RIM modulates Cav1.4 gating or surface expression not distinguished
  12. 2016 High

    PKA phosphorylation within the ICDI motif was shown to promote calmodulin occupancy and increase open probability, revealing a signaling-dependent switch that modulates Cav1.4 activity and could adjust tonic release under varying light conditions.

    Evidence PKA phosphorylation assays with patch clamp and domain-transfer mutagenesis in heterologous cells

    PMID:27456671

    Open questions at the time
    • Physiological PKA activation pathway in photoreceptors not identified
    • In vivo relevance of PKA modulation of Cav1.4 not demonstrated
  13. 2016 High

    Exon 47 splice variant analysis showed that the CTM/ICDI domain encoded by this exon is both necessary for CDI suppression and required for CaBP4-mediated modulation, linking alternative splicing to functional diversity of Cav1.4 in the retina.

    Evidence Electrophysiology of human retinal splice variants with CaBP4 co-expression in HEK cells

    PMID:27226626

    Open questions at the time
    • Relative abundance of exon 47-containing vs. exon 47-lacking splice variants in human retina not quantified
    • Cell-type-specific splicing patterns not mapped
  14. 2019 Medium

    RIBEYE-KO mice revealed that synaptic ribbons stabilize Cav1.4/RIM2 clusters at rod active zones and are required for darkness-induced enrichment, establishing a structural framework in which ribbons organize the presynaptic Ca²⁺ channel complex.

    Evidence RIBEYE KO mouse with quantitative immunofluorescence of Cav1.4/RIM2 cluster length

    PMID:32249787

    Open questions at the time
    • Direct physical interaction between RIBEYE and Cav1.4 not demonstrated
    • Mechanism of darkness-induced cluster enrichment not elucidated
  15. 2019 Medium

    In vivo rescue of Cav1.4 KO rod terminals by electroporation of α1F cDNA restored ribbon synapse markers and partial vision in adult mice, demonstrating that Cav1.4 is both necessary and sufficient for synapse formation and that adult rod synapses retain plasticity.

    Evidence In vivo electroporation into Cav1.4 KO mouse rods with immunohistochemistry and water maze

    PMID:31335952

    Open questions at the time
    • Electrophysiological function of rescued synapses not assessed
    • Long-term stability of rescued synapses not tested
  16. 2023 Medium

    Gating-charge substitutions R964G and R1288L identified a novel CSNB2 mechanism involving reduced expression and potential omega (gating pore) currents, expanding the pathological spectrum beyond classical pore conductance defects.

    Evidence Whole-cell and gating current recordings with molecular dynamics simulations in heterologous expression

    PMID:36943941

    Open questions at the time
    • Omega currents not directly measured experimentally
    • In vivo consequences of gating-charge mutations not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major open questions include: the cryo-EM structure of native Cav1.4 with its retinal auxiliary subunits and modulators; the molecular mechanism by which Cav1.4 organizes ribbon synapse assembly; whether PKA and other signaling pathways dynamically regulate Cav1.4 in photoreceptors in vivo; and the development of Cav1.4-selective pharmacology for therapeutic intervention in CSNB2.
  • No high-resolution structure of full-length Cav1.4 complex
  • Mechanism linking Ca²⁺ channel to synapse morphogenesis unknown
  • No Cav1.4-selective therapeutic compounds validated in vivo

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005886 plasma membrane 3 GO:0043226 organelle 3
Pathway
R-HSA-112316 Neuronal System 4 R-HSA-1643685 Disease 4 R-HSA-382551 Transport of small molecules 3 GO:0005215 transporter activity 1 R-HSA-162582 Signal Transduction 1
Partners
CABP4CACNA2D4CACNB2CALM1FLNARIMS1RIMS2
Complex memberships
Cav1.4/RIM2/RIBEYE active zone complexCav1.4/β2/α2δ4 L-type calcium channel complex

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 CACNA1F encodes the pore-forming α1 subunit of Cav1.4, an L-type calcium channel with unusually slow voltage-dependent inactivation kinetics not affected by Ca2+ ions or auxiliary β subunits, supporting a large window current activating near -40 mV, making it suited for tonic Ca2+ influx at photoreceptor resting potentials. Four CSNB2 missense mutations were introduced; only G369D affected channel activation properties. Heterologous expression in transfected cells + whole-cell patch clamp + immunohistochemistry + site-directed mutagenesis The Journal of neuroscience High 14973233
2004 CaBP4 directly associates with the C-terminal domain of the Cav1.4 α1-subunit and shifts Cav1.4 activation to hyperpolarized voltages in transfected cells, indicating CaBP4 regulates Ca2+ influx at photoreceptor synaptic terminals. Co-immunoprecipitation/direct binding assay + electrophysiology in transfected cells + Cabp4 knockout mouse with ERG and immunocytochemistry Nature neuroscience High 15452577
2005 Loss-of-function mutation in Cacna1f (exon 7 insertion) abolishes Ca2+ channel function in photoreceptors, causing 90% reduction in Ca2+ signals at photoreceptor synapses, absence of post-receptoral ERG responses, loss of Ca v1.4 protein in the outer plexiform layer, profound loss of photoreceptor ribbon synapses, and abnormal dendritic sprouting of second-order neurons—establishing Cav1.4 as essential for functional assembly and maintenance of photoreceptor ribbon synapses. Cacna1f knockout mouse (Cre-lox) + ERG + calcium imaging (Fluo-4) + immunocytochemistry Human molecular genetics High 16155113
2005 The CSNB2 missense mutation I745T in transmembrane segment IIS6 of CACNA1F causes an approximately -30 mV shift in voltage dependence of Cav1.4 channel activation and significantly slower inactivation kinetics, constituting a gain-of-function mechanism with increased channel activity. Heterologous expression system + whole-cell patch clamp electrophysiology Proceedings of the National Academy of Sciences of the United States of America High 15897456
2005 Single Cav1.4 channels have a very low open probability (<0.015), brief open durations, and a small single-channel conductance (~4 pS in Ba2+, ~21 pS in monovalent ions), in contrast to Cav1.2 (~20 pS); sustained activity throughout depolarization explains the slow macroscopic inactivation kinetics, indicating that large numbers of channels are needed for significant whole-cell current. Cell-attached patch single-channel recordings in tsA-201 cells with 100 mM Ba2+ as charge carrier Biophysical journal High 16085774
2006 CSNB2 missense mutations G1007R and R1049W produce full-length Cav1.4 protein that targets to the membrane but does not support ionic currents (loss-of-function), while F742C (S6 domain II) causes a ~21 mV hyperpolarizing shift in activation and inactivation with slower inactivation kinetics (gain-of-function), demonstrating that CSNB2 pathology can result from either gain- or loss-of-function mechanisms. Heterologous expression in HEK tsA-201 cells + whole-cell patch clamp Neuroscience Medium 17949918
2006 CSNB2 missense mutations R508Q and L1364H alter Cav1.4 channel expression density rather than gating properties; both reduce total α1 protein expression in a temperature-dependent manner, indicating a pathological mechanism distinct from gating changes. Heterologous expression in Xenopus oocytes and tsA-201 cells + electrophysiology + Western blot Journal of neurochemistry Medium 16476079
2007 Increasing temperature from 23°C to 37°C accelerates Cav1.4 inactivation kinetics ~50-fold (Q10 = 18.8, Ea = 221 kJ/mol) compared to ~10-fold for Cav1.2, yet the Cav1.4 window current is preserved at near-physiological temperatures, supporting continued tonic glutamate release from photoreceptors. Whole-cell patch clamp of transiently expressed human Cav1.4 cDNA at multiple temperatures Neuroscience Medium 18206315
2008 The nob2 Cacna1f mouse N-terminus (altered by ETn alternative splicing) fails to interact with filamin cytoskeletal proteins in biochemical pull-down assays, while wild-type Cav1.4 N-terminus does bind filamin, revealing a cytoskeletal interaction domain in the channel N-terminus. Biochemical pull-down assay + mRNA cloning/sequencing + Western blot + electrophysiology PloS one Medium 18596967
2009 Calmodulin is pre-associated with the C-terminus of Cav1.4 (demonstrated by FRET), increases Cav1.4 current density, and slows voltage-dependent inactivation; the C-terminal ICDI domain selectively abolishes Ca2+-dependent inactivation without displacing calmodulin, indicating that ICDI and calmodulin act independently on different aspects of Cav1.4 gating. FRET with genetically engineered CFP variants + whole-cell patch clamp electrophysiology The Journal of biological chemistry High 19717559
2012 CaBP4 dramatically increases Cav1.4 channel availability by binding to the IQ motif (demonstrated by FRET) and relieving inhibitory effects of the C-terminal ICDI domain; this effect is absent in a Cav1.4 ICDI-deletion mutant. Disease-causing CaBP4 mutants interact with Cav1.4 but only partially preserve the channel-activating effect, reducing channel availability. FRET experiments + whole-cell patch clamp electrophysiology in heterologous expression system with domain deletion mutants The Journal of biological chemistry High 22936811
2013 The gain-of-function I745T Cav1.4 mutation in IT mice reduces the dynamic range of photoreceptor activity, disrupts outer plexiform layer organization, produces variably immature photoreceptor synaptic structures, reduces outer nuclear layer size, and shortens cone outer segments, confirming that hyperpolarizing shift in channel activation impairs retinal function. Knock-in mouse model (IT mouse) + ERG + retinal morphology + behavioral paradigms Channels (Austin, Tex.) High 24051672
2014 Cav1.4 channels in photoreceptors form a complex with auxiliary subunits β2 (including a variant β2X13) and α2δ4; these subunits were co-immunoprecipitated from transfected HEK293 cells and mouse retina, and confirmed in outer plexiform layer by proximity ligation assay. α2δ4 confers weaker voltage-dependent activation than α2δ1, and β2X13 (vs β2a) increases voltage-dependent inactivation specifically for Cav1.4. Co-immunoprecipitation from HEK293 cells and mouse retina + proximity ligation assay + whole-cell patch clamp in HEK293T cells The Journal of biological chemistry High 25468907
2014 NMR structures of CaBP4 in Mg2+- and Ca2+-bound states show that Ca2+ binding induces a closed-to-open transition in the C-lobe; exposed residues (Phe137, Glu168, Leu207, Phe214, Met251, Phe264, Leu268) in Ca2+-bound CaBP4 contact the IQ motif in Cav1.4, and the Cav1.4 mutant Y1595E strongly impairs CaBP4 binding, establishing a structural model for CaBP4-mediated channel activation. NMR structure determination + mutagenesis of Cav1.4 IQ motif + binding assay The Journal of biological chemistry High 25258313
2014 The CSNB2 loss-of-function mutation L860P reduces the number of functional channels at the plasma membrane (shown by gating current and noise analyses) due to a proline predicted to break an amphipathic helix near IIIS1, causing increased channel turnover. The C-terminal truncation R1827X causes gain-of-function via hyperpolarizing shift and increased single-channel activity, but unmasks Ca2+-dependent inactivation by removing the CTM, preventing continuous Ca2+ influx—demonstrating two mechanistically distinct ends of the CSNB2 functional spectrum. Whole-cell and single-channel patch clamp + gating current analysis + non-stationary noise analysis in heterologous expression Biochimica et biophysica acta High 24796500
2015 Active zone proteins RIM1 and RIM2 potently facilitate Ca2+ entry through Cav1.4 channels in mouse rod photoreceptors; conditional double knockout of RIM1/2 from rods causes profound reduction in Ca2+ currents and a 4-fold reduction in spontaneous miniature release with near-complete absence of evoked release, without changing Cav1.4 protein expression or ribbon morphology at synapses. Conditional double knockout mouse + whole-cell voltage clamp of rods + measurement of spontaneous and evoked vesicle release + immunostaining The Journal of neuroscience High 26400943
2016 PKA phosphorylates Cav1.4 within the C-terminal ICDI motif, promoting calmodulin occupancy on the channel, increasing channel open probability (PO) and Ca2+-dependent inactivation. Introduction of ICDI1.4 into Cav1.3 or Cav1.2 channels confers this novel form of PKA modulation. Whole-cell patch clamp + PKA phosphorylation assays + domain transfer mutagenesis in heterologous expression Nature communications High 27456671
2016 Exon 47 of Cav1.4 encodes structural determinants within the C-terminal automodulatory domain (CTM) that suppress Ca2+-dependent inactivation (CDI) and cause a positive shift in voltage-dependent activation; splice variants lacking exon 47 show intense CDI and activate at more hyperpolarized voltages. Exon 47 is also necessary for CaBP4-mediated modulation of channel activation. Characterization of human retinal splice variants + electrophysiology in HEK cells + CaBP4 co-expression assays The Journal of biological chemistry High 27226626
2019 Synaptic ribbons stabilize Cav1.4/RIM2 protein clusters at rod photoreceptor active zones and are required for darkness-induced enrichment of Cav1.4/RIM2 at the active zone; in RIBEYE knockout mice lacking ribbons, Cav1.4/RIM2 clusters are destabilized and dark-adaptation-induced increases in cluster length are absent. RIBEYE knockout mouse analysis + quantitative immunofluorescence of Cav1.4/RIM2 cluster length + correlation analysis with ribbon length Scientific reports Medium 32249787
2019 Introduction of Cav α1F into Cav1.4 knockout rod terminals by in vivo electroporation rescues synaptic development markers (PSD-95 expression, elongated ribbons) and partial visual function even in mature animals, establishing Cav1.4 as both necessary and sufficient for rod ribbon synapse formation and demonstrating synaptic plasticity in adult rods. In vivo electroporation into Cav1.4 KO mouse rods + immunohistochemistry (PSD-95, ribbons) + vision-guided water maze Investigative ophthalmology & visual science Medium 31335952
2016 Genetic deletion of Cav1.4 (Cacna1f) in rd1 mice impairs calpain activation during photoreceptor degeneration and provides a short-term delay in rod degeneration, establishing Cav1.4-mediated Ca2+ influx as a contributor to calpain-dependent photoreceptor cell death. Cacna1f x rd1 double mutant mouse + OCT longitudinal imaging + TUNEL assay + calpain activation assay PloS one Medium 27270916
2023 Two gating-charge substitutions in Cav1.4 S4 voltage sensors (R964G and R1288L) reduce channel expression, decrease ON gating currents, shift activation threshold to more hyperpolarized voltages, and the R1288L mutation is predicted by molecular dynamics simulation to form water wires (omega currents) in both resting and active channel states—identifying a novel pathological mechanism in CSNB2. Whole-cell patch clamp + gating current recordings + single-channel recordings + molecular dynamics simulations in heterologous expression Channels (Austin, Tex.) Medium 36943941
2026 CaV3 channel antagonists ML218 and Z944 inhibit CaV1.4 channels (IC50 ~2 µM and ~30 µM, respectively); structure-based modeling and mutagenesis identified methionine M1004 within the dihydropyridine (DHP)-binding site as critical for ML218 potency—M1004 mutation had 10-fold greater impact than the conserved T1007 DHP-sensitivity residue, establishing the ML218 binding mechanism on CaV1.4. Electrophysiology in HEK293T cells + structure-based homology modeling + site-directed mutagenesis at DHP-binding site The Journal of general physiology Medium 41489546

Source papers

Stage 0 corpus · 99 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 Essential role of Ca2+-binding protein 4, a Cav1.4 channel regulator, in photoreceptor synaptic function. Nature neuroscience 245 15452577
2005 Mutation of the calcium channel gene Cacna1f disrupts calcium signaling, synaptic transmission and cellular organization in mouse retina. Human molecular genetics 214 16155113
2006 The nob2 mouse, a null mutation in Cacna1f: anatomical and functional abnormalities in the outer retina and their consequences on ganglion cell visual responses. Visual neuroscience 174 16597347
2004 The CACNA1F gene encodes an L-type calcium channel with unique biophysical properties and tissue distribution. The Journal of neuroscience : the official journal of the Society for Neuroscience 159 14973233
1985 Advanced seminoma: treatment with cis-platinum-based combination chemotherapy or carboplatin (JM8). British journal of cancer 123 3893507
2005 A CACNA1F mutation identified in an X-linked retinal disorder shifts the voltage dependence of Cav1.4 channel activation. Proceedings of the National Academy of Sciences of the United States of America 109 15897456
1987 Carboplatin (CBDCA, JM-8) and VP-16-213 in previously untreated patients with small-cell lung cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 99 2821197
1987 Carboplatin (Paraplatin; JM8) and etoposide (VP-16) as first-line combination therapy for small-cell lung cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 97 3027268
2006 X linked cone-rod dystrophy, CORDX3, is caused by a mutation in the CACNA1F gene. Journal of medical genetics 75 16505158
2001 A summary of 20 CACNA1F mutations identified in 36 families with incomplete X-linked congenital stationary night blindness, and characterization of splice variants. Human genetics 74 11281458
2000 Clinical variability among patients with incomplete X-linked congenital stationary night blindness and a founder mutation in CACNA1F. Canadian journal of ophthalmology. Journal canadien d'ophtalmologie 72 10900517
2002 Thirty distinct CACNA1F mutations in 33 families with incomplete type of XLCSNB and Cacna1f expression profiling in mouse retina. European journal of human genetics : EJHG 68 12111638
2005 Clinical manifestations of a unique X-linked retinal disorder in a large New Zealand family with a novel mutation in CACNA1F, the gene responsible for CSNB2. Clinical & experimental ophthalmology 66 15807819
2013 Cav1.4 IT mouse as model for vision impairment in human congenital stationary night blindness type 2. Channels (Austin, Tex.) 53 24051672
2014 Characterization of Cav1.4 complexes (α11.4, β2, and α2δ4) in HEK293T cells and in the retina. The Journal of biological chemistry 52 25468907
2007 A novel CACNA1F gene mutation causes Aland Island eye disease. Investigative ophthalmology & visual science 50 17525176
1986 Ototoxicity of cisplatin vs. platinum analogs CBDCA (JM-8) and CHIP (JM-9). Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery 48 3086808
2015 RIM1/2-Mediated Facilitation of Cav1.4 Channel Opening Is Required for Ca2+-Stimulated Release in Mouse Rod Photoreceptors. The Journal of neuroscience : the official journal of the Society for Neuroscience 46 26400943
2012 Complex regulation of voltage-dependent activation and inactivation properties of retinal voltage-gated Cav1.4 L-type Ca2+ channels by Ca2+-binding protein 4 (CaBP4). The Journal of biological chemistry 44 22936811
1995 Overproduction, purification, and biochemical characterization of a xylanase (Xys1) from Streptomyces halstedii JM8. Applied and environmental microbiology 43 7793962
2001 Novel CACNA1F mutations in Japanese patients with incomplete congenital stationary night blindness. Investigative ophthalmology & visual science 40 11381068
2013 Mosaic synaptopathy and functional defects in Cav1.4 heterozygous mice and human carriers of CSNB2. Human molecular genetics 38 24163243
1985 Carboplatin (JM8) as a single agent and in combination in the treatment of small cell lung cancer. Cancer treatment reviews 37 3002624
2003 Retinal and optic disc atrophy associated with a CACNA1F mutation in a Japanese family. Archives of ophthalmology (Chicago, Ill. : 1960) 36 12860808
2005 Novel mutations in CACNA1F and NYX in Dutch families with X-linked congenital stationary night blindness. Molecular vision 34 15761389
2005 Cav1.4 encodes a calcium channel with low open probability and unitary conductance. Biophysical journal 34 16085774
2001 Expression of the genes coding for the xylanase Xys1 and the cellulase Cel1 from the straw-decomposing Streptomyces halstedii JM8 cloned into the amino-acid producer Brevibacterium lactofermentum ATCC13869. Archives of microbiology 34 11797049
2020 Synaptic ribbons foster active zone stability and illumination-dependent active zone enrichment of RIM2 and Cav1.4 in photoreceptor synapses. Scientific reports 32 32249787
2003 Mutations in the CACNA1F and NYX genes in British CSNBX families. Human mutation 32 12552565
1992 Cloning and nucleotide sequence of celA1, and endo-beta-1,4-glucanase-encoding gene from Streptomyces halstedii JM8. Journal of bacteriology 32 1400190
2013 A novel large in-frame deletion within the CACNA1F gene associates with a cone-rod dystrophy 3-like phenotype. PloS one 31 24124559
2016 Characterization of C-terminal Splice Variants of Cav1.4 Ca2+ Channels in Human Retina. The Journal of biological chemistry 30 27226626
2008 Modified Ca(v)1.4 expression in the Cacna1f(nob2) mouse due to alternative splicing of an ETn inserted in exon 2. PloS one 30 18596967
2007 Temperature dependence of Cav1.4 calcium channel gating. Neuroscience 30 18206315
2006 Effects of congenital stationary night blindness type 2 mutations R508Q and L1364H on Cav1.4 L-type Ca2+ channel function and expression. Journal of neurochemistry 30 16476079
1997 Analysis of xysA, a gene from Streptomyces halstedii JM8 that encodes a 45-kilodalton modular xylanase, Xys1. Applied and environmental microbiology 29 9251186
2011 A novel p.Gly603Arg mutation in CACNA1F causes Åland island eye disease and incomplete congenital stationary night blindness phenotypes in a family. Molecular vision 28 22194652
2007 Functional analysis of congenital stationary night blindness type-2 CACNA1F mutations F742C, G1007R, and R1049W. Neuroscience 28 17949918
2019 Where are the missing gene defects in inherited retinal disorders? Intronic and synonymous variants contribute at least to 4% of CACNA1F-mediated inherited retinal disorders. Human mutation 27 30825406
2010 Congenital stationary night blindness in mice - a tale of two Cacna1f mutants. Advances in experimental medicine and biology 27 20238058
2017 The importance of genetic testing as demonstrated by two cases of CACNA1F-associated retinal generation misdiagnosed as LCA. Molecular vision 26 29062221
2009 Calmodulin is a functional regulator of Cav1.4 L-type Ca2+ channels. The Journal of biological chemistry 26 19717559
2014 Spectrum of Cav1.4 dysfunction in congenital stationary night blindness type 2. Biochimica et biophysica acta 25 24796500
2016 Protein kinase A modulation of CaV1.4 calcium channels. Nature communications 23 27456671
2003 Posttranslational processing of the xylanase Xys1L from Streptomyces halstedii JM8 is carried out by secreted serine proteases. Microbiology (Reading, England) 23 12855715
2000 Isolation and characterization of a calcium channel gene, Cacna1f, the murine orthologue of the gene for incomplete X-linked congenital stationary night blindness. Genomics 23 10873387
2003 A novel CACNA1F mutation in a french family with the incomplete type of X-linked congenital stationary night blindness. American journal of ophthalmology 21 12719097
1997 Two genes encoding an endoglucanase and a cellulose-binding protein are clustered and co-regulated by a TTA codon in Streptomyces halstedii JM8. The Biochemical journal 21 9182697
2021 Cav1.4 dysfunction and congenital stationary night blindness type 2. Pflugers Archiv : European journal of physiology 20 34212239
2020 Using an integrative machine learning approach utilising homology modelling to clinically interpret genetic variants: CACNA1F as an exemplar. European journal of human genetics : EJHG 19 32313206
2015 Gain-of-function nature of Cav1.4 L-type calcium channels alters firing properties of mouse retinal ganglion cells. Channels (Austin, Tex.) 19 26274509
2018 Cone dystrophy and ectopic synaptogenesis in a Cacna1f loss of function model of congenital stationary night blindness (CSNB2A). Channels (Austin, Tex.) 16 29179637
2005 Identification of the sequences involved in the glucose-repressed transcription of the Streptomyces halstedii JM8 xysA promoter. Gene 16 15850758
2014 Structural insights into activation of the retinal L-type Ca²⁺ channel (Cav1.4) by Ca²⁺-binding protein 4 (CaBP4). The Journal of biological chemistry 15 25258313
1994 Differential scanning calorimetric study of the thermal stability of xylanase from Streptomyces halstedii JM8. Biochemistry 15 7947789
2021 Optic Atrophy and Inner Retinal Thinning in CACNA1F-related Congenital Stationary Night Blindness. Genes 14 33668843
2016 Cav1.4 L-Type Calcium Channels Contribute to Calpain Activation in Degenerating Photoreceptors of rd1 Mice. PloS one 14 27270916
2013 Visual signal pathway reorganization in the Cacna1f mutant rat model. Investigative ophthalmology & visual science 14 23425697
2008 A naturally-occurring mutation in Cacna1f in a rat model of congenital stationary night blindness. Molecular vision 14 18246026
2001 Construction of a xylanase-producing strain of Brevibacterium lactofermentum by stable integration of an engineered xysA gene from Streptomyces halstedii JM8. Applied and environmental microbiology 13 11722888
2021 A Novel Splice-Site Variant in CACNA1F Causes a Phenotype Synonymous with Åland Island Eye Disease and Incomplete Congenital Stationary Night Blindness. Genes 12 33513752
2018 Photoreceptor degeneration in a new Cacna1f mutant mouse model. Experimental eye research 11 30445045
2019 Rescue of Rod Synapses by Induction of Cav Alpha 1F in the Mature Cav1.4 Knock-Out Mouse Retina. Investigative ophthalmology & visual science 10 31335952
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