CACNA1F

Summary: The rat-derived outer-segment location is not independently resolved.

Reason: The preserved Ensembl source identifies rat Cacna1f G3V9W8 and ENSRNOP00000061835. Official rat gene curation lists an outer-segment pool, but its underlying localization assay was not recovered. The available human channel recordings and retinal transcript studies do not distinguish outer segments from other retinal compartments. Neither synaptic function nor RNA in retinal layers disproves this additional location; the precise transfer remains unresolved.

Summary: Refine the generic ion-channel mapping to high voltage-gated calcium channel activity.

Reason: The broad InterPro channel mapping is consistent with a membrane pore but does not convey calcium selectivity and voltage gating. Wild-type and variant CaV1.4 current recordings directly establish this L-type channel function; high-voltage-gated calcium channel activity is already independently annotated to CACNA1F.

Proposed replacements: high voltage-gated calcium channel activity

Summary: CACNA1F directly forms a voltage-gated calcium-conducting pore.

Reason: The primary study records wild-type and I745T CaV1.4 currents and altered voltage dependence. Indexed primary Methods identify tsA-201 cells coexpressing alpha1F with alpha2delta1 and beta2a or beta3. This supports the alpha1F channel activity and distinguishes auxiliary-subunit modulation from the pore itself. The paper uses I745T numbering; the reviewed record uses I756T, and no unverified coordinate remapping is performed.

Summary: Human CaV1.4 splice variants retain voltage-gated calcium channel activity.

Reason: The complete abstract reports channel gating differences among C-terminal splice variants. Indexed primary Methods identify human CaV1.4 constructs with beta2x13 and alpha2delta4 in HEK-293T whole-cell recordings. Exon 47 deletion permits strong calcium-dependent inactivation and shifts activation; it is not valid to describe every CACNA1F product as lacking calcium-dependent inactivation.

Summary: The domain mapping correctly identifies a voltage-gated calcium channel.

Reason: Independent recordings of human CaV1.4 corroborate the InterPro inference. This assertion concerns the channel activity shared by the tested wild-type/splice constructs, without assuming identical kinetics for all six reviewed products.

Summary: The genetically supported channel-activity assertion is independently established by electrophysiology.

Reason: PMID:12111638 reports human CACNA1F mutation families and mouse retinal expression, rather than a channel-current assay visible in its abstract. The preserved experimental annotation is retained with curator deference because independent primary wild-type and mutant recordings establish the same activity. Retinal-layer RNA expression is not substituted for subcellular protein localization.

Summary: CaV1.4 alpha1F is the pore-bearing component of a voltage-gated calcium channel complex.

Reason: The conserved complex annotation is consistent with functional coexpression of CACNA1F with beta and alpha2delta subunits. The PAINT node is retained as phylogenetic provenance; human CACNA1F among descendant evidence is legitimate target grounding, not circularity. The complete ancestral tree and node placement were not independently reconstructed.

Summary: The experimental CaV1.4 channel complex contains CACNA1F and auxiliary subunits.

Reason: Indexed primary Methods describe tsA-201 expression of wild-type or I745T alpha1F with alpha2delta1 and beta2a or beta3 and recording of calcium/barium currents. This substantiates complex participation; auxiliary proteins do not supply the alpha1F pore activity.

Summary: The automated complex mapping is corroborated by defined functional channel assemblies.

Reason: Human alpha1F was functionally coexpressed with beta and alpha2delta subunits in the inspected primary work. The combined mapping is retained at the complex level without inferring an exclusive endogenous auxiliary-subunit composition in every retinal cell.

Summary: Refine generic ion transport to calcium import across the plasma membrane.

Reason: The alpha1F pore carries inward calcium current during voltage-clamp activation. This directly supplies the transport step, rather than merely being required for a downstream retinal phenotype. The existing calcium-import annotation is a more informative description of the same work than generic monoatomic-ion transport.

Proposed replacements: calcium ion import across plasma membrane

Summary: CaV1.4-dependent calcium entry supports visual signal transmission.

Reason: The retinal pore couples membrane voltage to transmitter-release signaling. Human mutation and splice studies establish CACNA1F-associated visual dysfunction and independent electrophysiology explains the channel step; the protein therefore performs work in visual perception rather than being only a disease marker.

Summary: CACNA1F splice disruption establishes a cone-rod visual phenotype.

Reason: The complete structured abstract reports sequencing and RNA analysis of human CACNA1F, identifying altered splicing associated with CORDX3. Although the fetched publication category is COMMENT_EDITORIAL/Letter, the paper contains primary family and transcript data. Predicted truncation/deletion is distinguished from a directly measured channel defect.

Summary: Human CACNA1F mutation families support its role in visual perception.

Reason: The primary study identifies a retinal calcium-channel gene and multiple pathogenic variants in CSNB2 families. Its historical 1966-residue sequence corresponds to the source record of isoform 2 and does not replace the current 1977-residue reference. The channel-mediated retinal signaling mechanism has independent experimental support.

Summary: Human truncating variants link the retinal channel to visual perception.

Reason: The complete abstract reports six predicted protein-truncating variants in the CACNA1F study of incomplete-CSNB families. These human genetics data support the existing visual-process annotation together with independent pore recordings. The abstract predicts loss of function; it is not described as measuring every variant current.

Summary: CaV1.4 is an L-type high voltage-gated calcium channel.

Reason: The PAINT-inferred molecular function matches independent CACNA1F current recordings and the reviewed L-type channel identity. Relatively negative activation and splice-dependent shifts within the L-type family do not convert CaV1.4 into a T-type low-voltage channel. Node placement and all descendant experiments were not independently reconstructed.

Summary: The ARBA high-voltage-gated calcium channel assignment is supported by direct target evidence.

Reason: The channel is an L-type alpha1F calcium pore; wild-type and C-terminal splice-variant electrophysiology corroborate its classification. Variant-specific activation shifts and calcium-dependent inactivation are retained as kinetic differences within that activity.

Summary: Refine membrane localization to the plasma membrane where CaV1.4 currents are measured.

Reason: Whole-cell recordings of human CaV1.4 constructs in tsA-201 cells establish an active plasma-membrane pool: calcium or barium crosses the cell surface through the expressed voltage-gated channels. This directly supports the plasma-membrane refinement. The generic UniProt membrane annotation supplies no independent compartment specificity, and these heterologous recordings do not resolve a fine native retinal compartment.

Proposed replacements: plasma membrane

Summary: Refine the broad membrane mapping to plasma membrane.

Reason: The InterPro and UniProt subcellular mapping supports membrane association. Independent whole-cell current measurements of human CaV1.4 constructs in tsA-201 and HEK293T cells establish a functional plasma-membrane pool and justify the more specific term. UniProt itself records only generic membrane localization; the refinement rests on the electrophysiology, consistent with the independently retained calcium-import function.

Proposed replacements: plasma membrane

Summary: The rat-derived neuronal-cell-body location remains source-limited.

Reason: The exact rat Cacna1f donor and Ensembl product are retained. Official donor identity is established, but the original target-protein localization experiment was not recovered. Mouse retinal-layer transcript expression in PMID:12111638 is not subcellular protein localization, and channel recordings do not resolve this neuronal pool. The annotation is not rejected on tissue or species grounds.

Summary: The specific perikaryon transfer is not independently resolved.

Reason: The rat donor curation lists perikaryon, but the underlying protein-localization assay and transfer to the human product remain unavailable. The shared channel mechanism and retinal RNA expression do not independently identify this compartment. This uncertainty preserves the donor assertion without declaring it false.

Summary: The exact light-detection scope remains unresolved despite an established role in retinal signal transmission.

Reason: CaV1.4 provides voltage-gated calcium entry coupled to photoreceptor transmitter release. GO:0050908 describes a series of events receiving light and converting it to a molecular signal, so its scope cannot be reduced to photon binding alone. PMID:7571473 reports abnormal postsynaptic ERG components, but also a subnormal photopic a-wave; it does not establish that every upstream detection component is intact. These observations question the precision of the detection term without independently resolving whether the curated process includes this channel-dependent step. Retain UNDECIDED for that process boundary and the unverified original target association. The full clinical study remains unavailable; neither its date nor an abstract omission proves a defective IMP annotation. The separately supported visual-perception and calcium-import assertions remain accepted.

Summary: Refine generic transmembrane transport to calcium import across the plasma membrane.

Reason: Voltage-gated inward calcium currents establish the ion and direction of transport performed by the alpha1F pore. The existing calcium-import term describes this same mechanism more precisely than the generic transport mapping.

Proposed replacements: calcium ion import across plasma membrane

Summary: CACNA1F directly mediates calcium movement across a membrane.

Reason: The calcium-conducting pore activity is demonstrated by heterologous recordings and modulated by voltage, splice form and auxiliary proteins. The InterPro inference is corroborated by target experiments and consistent with the more specific existing plasma-membrane import assertion.

Summary: CaV1.4 pore opening permits calcium import across the plasma membrane.

Reason: The conserved import assertion is independently supported by inward calcium currents through expressed CACNA1F. CACNA1F itself supplies the pore for this step; calcium sensing by CaBP4 and downstream transmitter secretion are separate molecular operations. The PAINT provenance is retained without a claim of independent reconstruction of its ancestral node.