CACNA1C encodes the alpha1C pore of the L-type calcium channel CaV1.2. Human channel expression, pore mutagenesis and electrophysiology establish voltage-dependent calcium conductance. Cardiac calcium entry contributes to electrical excitation and triggers RyR2-mediated release from the sarcoplasmic reticulum. The same channel unit is modulated by auxiliary subunits, calmodulin, phosphorylation and alternative splicing. This synthesis separates the calcium-conducting pore from its regulators and from the downstream release pore. PMID:8392192(https://pubmed.ncbi.nlm.nih.gov/8392192/), PMID:8099908(https://pubmed.ncbi.nlm.nih.gov/8099908/), PMID:27481713(https://pubmed.ncbi.nlm.nih.gov/27481713/), PMID:34072954(https://pubmed.ncbi.nlm.nih.gov/34072954/).
All 136 source assertions were assessed, preserving the 137 raw GOA records represented by them, every original reference, qualifier and partner, and all 37 named products. The one collapsed source duplicate differs by assigner/date. Decisions are 91 ACCEPT, 31 KEEP_AS_NON_CORE, 6 MODIFY and 8 UNDECIDED. No NEW annotation is proposed. Five broad channel, transport or membrane assertions are refined to existing high-voltage channel, calcium-import or plasma-membrane terms; the sixth refinement specifies alpha-actinin binding for the curated ACTN1 association. There is one integrated pore-function core, rather than separate calcium-binding, calmodulin-binding and auxiliary-regulation cores.
The 37 product names and IDs are retained literally. The source record itself cautions that experimental confirmation may be lacking for some isoforms. Particular human splice constructs, engineered variants and rodent orthologs are identified where they bear on a decision; the experiments do not validate every current named product individually. Mutants with reduced current density and increased window or persistent current are not reduced to a universal gain- or loss-of-function label. E1115K mutant monovalent permeability is likewise not assigned to the normal calcium-selective channel. PMID:25260352(https://pubmed.ncbi.nlm.nih.gov/25260352/), PMID:30023270(https://pubmed.ncbi.nlm.nih.gov/30023270/), PMID:30172029(https://pubmed.ncbi.nlm.nih.gov/30172029/).
The supported generic associations are retained as non-core under the standing project instruction. Their retention does not transfer a partner's activity to CACNA1C. Human induced-neuron IP-MS establishes a coassociation framework for the 16 PMID:37207277 edges; each exact partner is also recorded in UniProt. Individual supplementary target statistics and pair-specific reverse-IP validation were not inspected, so purified binary affinity and physiological mechanism are not claimed. The earlier ACTN1/PICK1 screen includes retesting, but its individual target table entries were not inspected either. The ACTN1 identity supports the narrow GO:0051393 refinement without transferring the separately reported ACTN2 mechanism. PMID:37207277(https://pubmed.ncbi.nlm.nih.gov/37207277/), PMID:21653829(https://pubmed.ncbi.nlm.nih.gov/21653829/), official alpha-actinin-binding definition.
The beta-subunit assertions retain their exact accessions and isoform suffixes. The available PMID:18535142 experiments use human vascular alpha1C, beta2d and calmodulin, including beta-free conditions; they do not independently resolve every original beta1/beta3 interaction assay. Retention combines explicit curated edges with established channel-complex evidence. Calmodulin binding is mechanistic channel feedback, but the purified reagent does not establish three separate CALM-gene experiments. Native rat postsynaptic preparations, human short CaBP1 and recombinant channel-fragment assays are kept distinct. PMID:18535142(https://pubmed.ncbi.nlm.nih.gov/18535142/), PMID:15140941(https://pubmed.ncbi.nlm.nih.gov/15140941/).
Eight assertions remain UNDECIDED: immune-system development, eye development, Z-disc location, positive adenylate-cyclase regulation, two AV-node-specific assertions, intercellular electrical coupling, and the specifically atrial action-potential process. These are not declarations that the curated functions are false. Clinical abnormalities or expression patterns do not independently resolve every developmental step, and the relevant complete target or donor experiments were not inspected. The broad cardiac, developmental and intracellular-trafficking assertions with sufficient independent support remain retained.
PMID:26253506 explicitly reports first-degree AV block; that observation is preserved. Its inspected functional work uses human R518C/H channels in HEK293 cells, with mixed gating/current-density effects and surface fluorescence. The source-specific AV-node cellular mechanism remains unresolved. PMID:11576544 instead concerns alpha1C-region binding to ryanodine receptors. This supports intracellular excitation-contraction coupling, while GO:0086064 explicitly concerns current passing between adjacent cardiac cells. The complete paper is unavailable in the normal cache, so the latter TAS assignment remains uncertain. PMID:26253506(https://pubmed.ncbi.nlm.nih.gov/26253506/), PMID:11576544(https://pubmed.ncbi.nlm.nih.gov/11576544/), GO:0086064.
The normal record for PMID:14140941 is genuinely a 1964 Dutch digitalis-associated tachycardia paper, with no abstract. Its postsynaptic-density evidence was not verified. The original machine reference is preserved and marked UNVERIFIED. PMID:15140941 independently supports postsynaptic CaV1.2, allowing retention of the broad location without using the older citation as positive support. It is a plausible intended citation, but no official identifier replacement is asserted. PMID:14140941(https://pubmed.ncbi.nlm.nih.gov/14140941/), PMID:15140941(https://pubmed.ncbi.nlm.nih.gov/15140941/).
Complete available canonical abstracts were read. Selected actual Methods, Results and Discussion sections were inspected where they resolved construct identity, channel measurements or fine annotation scope; individual images and supplementary tables were not examined. The source-specific reference assessments state those boundaries. A full-text flag does not establish complete access: the canonical PMID:15140941 HTML omits Results, which were read separately through primary PMC in the bounded consultation. The canonical PMID:34072954 cache is abstract-only and remains unchanged despite a fuller fetched variant. Conversely, PMID:30023270 has no abstract but does provide an actual full XML body from which selected experiments were read.
The normal PMID:15454078 cache is abstract-only. Selected author-uploaded primary text additionally informed clinical/developmental context and the expression systems. This does not establish a full-paper or supplementary-data reading. Human and rodent preparations remain separate throughout: for example, PMID:34163037 tests human L614R with human auxiliaries and other variants in a mouse backbone with rat auxiliaries. PMID:15454078(https://pubmed.ncbi.nlm.nih.gov/15454078/), author-uploaded primary text, PMID:34163037(https://pubmed.ncbi.nlm.nih.gov/34163037/).
Three correction notices were checked through indexed official primary text. The PMID:20953164 correction changes an affiliation. The PMID:29742403 correction replaces duplicated exemplary Figure 7 traces; corrected images were not inspected, and this is not described as replacing all surface-expression data. The PMID:34163037 correction adds an omitted author middle initial. These notices provide supplementary access context and are not fabricated normal caches. 2010 correction, 2018 correction, 2021 correction.
One normal deep-research invocation attempted Falcon followed by perplexity-lite. Both failed with DNS errors and produced no provider output. The review therefore uses the primary-source and curated-record reading documented above; no provider-named research file was authored.
Normal candidate validation passed with references, GOA, schema, best-practice and term checks enabled. The 22 warnings are the expected generic-binding advisories under the standing task-specific retention policy. Status is DRAFT because those warnings remain, although all 136 decisions have been assessed and the eight uncertainties are explicit. All 49 original reference ID/title pairs and all source/product fields are unchanged; the immutable UniProt source is added as the fiftieth reference. Thirteen short quotation entries are exact substrings of normal canonical caches, with at most 20 total quoted words per source including repeated core anchors.
The independently approved review passed full normal canonical validation and status reporting, retaining DRAFT with 22 standing-policy binding advisories. All 136 source assertions, all 37 named products and source-cache bytes are preserved. The standard CREATE history record passed history validation.