The reviewed human protein is CaV3.1, UniProt O43497, HGNC:1394, NCBI Gene 8913. The authenticated primary record contains a 2,377-residue displayed sequence (sequence version 3; CRC64 1C9F7C557D9D32DF) and 35 named alternative products. Their source names, accession suffixes and VSP sequence notes are preserved exactly. Product name 5 is the displayed O43497-1 sequence; product names must not be inferred from accession suffixes. No O43497-14 product is invented. The review retains all 41 source assertions, including their evidence, references, qualifiers and supporting entities. None is a NOT or isoform-specific GOA assertion.
The core activity is low-voltage-activated, T-type calcium conductance across the plasma membrane. Calcium entry contributes to depolarization and firing behavior. Cardiac nodal functions are specialized physiological contexts of this conductance, rather than additional molecular mechanisms. The description distinguishes adult inherited SCA42 gating changes from particular severe childhood de novo gain-of-function variants. Disease associations are not interpreted as clinical recommendations.
The unchanged normal research wrapper was attempted in isolated storage on 2026-10-04, using Falcon with perplexity-lite fallback and installed deep-research-client 0.2.7rc1. Both providers failed; wrapper exit status was 1, elapsed time 4.56 seconds, and no provider report was produced. The full trace digest is a2c6c25757a0aa37de6cbfa3b0f1b83ec2fa4a95172d84fa5018db295afe78fa. No manual text is presented as a provider-generated report. This file records the manual research.
Seven GOA-linked PMID caches and one Reactome narrative were reviewed. Six publication caches are abstract-only; PMID:26715324 includes full text. Read scope for that paper included expression constructs, immunolocalization, electrophysiology, differentiation results and discussion; supplementary images were not independently inspected. The PubMed search representation for PMID:21084288 exposed its Figure 1 caption, which corroborates CaV3.1 co-immunoprecipitation. Direct full-text access attempts were unsuccessful. Thus the visible evidence, rather than a presumed complete article, bounds the judgments below.
Two additional primary mouse papers, PMID:16690884 and PMID:21406960, were read through official PubMed search results. Their successful normal publication caches were subsequently recovered, verified and imported without modification. The 2006 paper remains abstract-only; the 2011 paper supplies full text, whose CaV3.1-specific Results, Discussion and Methods were read. Direct PubMed opening subsequently returned a browser challenge/limited page; the earlier available abstracts and Figure 1 caption are preserved in the TMP research record. A primary UniProt donor entry could not be fully loaded; GOA records the ISS source as Q5SUG4, and UniProt's mouse caveolin-3 interaction table independently names Q5SUG4 as Cacna1g. No full donor GOA inventory or sequence comparison is claimed.
PMID:10648811(https://pubmed.ncbi.nlm.nih.gov/10648811/) characterizes a human brain T-type channel in an expression system. Its historical title names CaV3.1c. The publisher's corrigendum explicitly corrects the expressed cDNA to human CaV3.1a: an 18-residue exon in the original sequence figure was erroneous and absent from the expressed clone; the corrected accession is AF190860. The source PMID and fetched title remain unchanged. This correction prevents a false isoform inference without invalidating the calcium-channel electrophysiology. Historical clone nomenclature is not used to relabel the current 35-product UniProt inventory.
PMID:9495342(https://pubmed.ncbi.nlm.nih.gov/9495342/) describes a rat brain clone expressed in Xenopus oocytes and identifies/maps the human gene. The available abstract supports the T-type channel discovery but does not show a native human multiprotein preparation. The source TAS channel-complex assertion remains recorded, with UNDECIDED review because its complete native-complex evidence was not recovered. A rat-focused abstract is not evidence that a human annotation was misattributed.
PMID:26715324(https://pubmed.ncbi.nlm.nih.gov/26715324/) tests a short human transcript, NM_198382.2/BC110995.1. Its c.5075G>A substitution corresponds to c.5144G>A in the longer NM_018896.4 transcript. The construct contains an IRES-EGFP reporter; it is not described here as a direct CaV3.1-GFP fusion. The whole-cell recordings use extracellular calcium and potassium-channel blockers. Wild-type channel activation occurs at negative potentials; the recurrent ataxia substitution shifts activation and steady-state inactivation positively. Current amplitude is reduced at the smaller depolarizations but not at the higher tested potentials. These results do not justify calling the mutant a null channel or the wild-type channel high-voltage activated.
That study observed both cytoplasmic and plasma-membrane immunoreactivity for wild-type and mutant channels, using NaK-ATPase as a membrane marker. Cytoplasmic localization is retained as an observed non-core pool; it is not converted to soluble cytosolic calcium-channel activity. The tested iPSC-derived Purkinje-cell differentiation and morphology showed no obvious difference. This result does not establish normal neuronal firing, which was not the endpoint of that differentiation analysis.
PMID:26456284(https://pubmed.ncbi.nlm.nih.gov/26456284/) independently identifies R1715H in inherited adult ataxia families and reports a positive activation shift in recombinant channels with modeling of altered neuronal excitability. Its available abstract and PMID:26715324 support altered gating in SCA42. In contrast, PMID:29878067(https://pubmed.ncbi.nlm.nih.gov/29878067/) studies A961T/M1531V in four children with severe cerebellar disease and finds slower inactivation and greater window current. Those findings support variant-specific gain of function in the childhood phenotype; they must not be generalized to all CACNA1G disease alleles.
PMID:21084288(https://pubmed.ncbi.nlm.nih.gov/21084288/) foregrounds CaV3.2 but explicitly includes CaV3.1 co-immunoprecipitation with caveolin-3 and CaV3.1 current measurements. Its Figure 1 caption describes neonatal mouse ventricular-cell and transfected HEK293-cell assays, including negative controls. The scaffold-protein-binding IPI assertion is therefore retained as non-core association evidence. Direct GST-pulldown binding to caveolin's N terminus and the strong caveolin-dependent current/PKA modulation concern CaV3.2 in the visible evidence. Caveolin-3 coexpression did not alter peak CaV3.1 current density. Neither the paralog-specific regulatory effect nor a claim of absent CaV3.1 assays is transferred from the title.
GO:0008332 specifies low-voltage calcium-channel activity; GO:0008331 specifies high-voltage activity. Both are children of voltage-gated calcium-channel activity. Human target electrophysiology therefore supports MODIFY of the high-voltage IBA to GO:0008332. GOA records ancestral node PANTHER:PTN001295293. This judgment concerns the incompatibility between the inherited high-voltage state and a directly characterized T-type target, not the number of donors or the target's presence among them. The complete PAINT family tree and positive IBD placement were not reconstructed. Local IRD rows referring to this ancestor in a different family context are not substituted for that missing evidence; no specific ancestral gain/loss scenario is invented.
GO:0005891 denotes a channel-forming protein complex. Its ancestor GO:0032991 requires multiple macromolecules acting as a stable functional assembly. A functional pore polypeptide alone does not establish that assertion. The four complex rows are now UNDECIDED: native assembly evidence, the precise ISS donor evidence and the positive PAINT evidence remain unresolved. Caveolin association is not used as channel-complex proof. Low-voltage electrophysiology directly contradicts the high-voltage activity IBA, whereas autonomous T-type function does not disprove optional complex membership; the two PAINT judgments therefore have different evidential strength. No fixed high-voltage auxiliary composition or loss of ancestral complex membership is inferred. The core remains plasma-membrane calcium conductance without an in_complex assertion.
The source's broad channel, ion-transport and membrane annotations are refined where a clearly supported more informative term exists. The core summary uses one molecular activity (GO:0008332), direct calcium import across plasma membrane (GO:0098703), and plasma membrane (GO:0005886). No new process annotation is proposed, and no disease or downstream phenotype is promoted to a core molecular function.
PMID:16690884(https://pubmed.ncbi.nlm.nih.gov/16690884/) reports that mouse Cacna1g disruption removes T-type current from isolated SAN and AV-node cells and slows pacemaking and AV conduction. The channel contributes the inward current, so this is direct electrical participation rather than necessity alone. The study also reports no altered right-atrial excitability or detectable T-type current in the sampled atrial myocytes. It supports nodal physiology while limiting an unqualified claim about working-myocyte contraction.
PMID:21406960(https://pubmed.ncbi.nlm.nih.gov/21406960/) further separates the contributions of CaV3.1 and CaV1.3 in mouse AV-node cells. Loss of CaV3.1 destabilizes pacing and limits high stimulated rates; loss of CaV1.3 abolishes spontaneous automaticity under the tested conditions. CaV3.1 is therefore not described as the sole generator of every AV-node action potential. The corresponding human rows retain their ISS provenance.
The checked ontology places SA-node action potential within SA-node-to-atrial-cell signaling, GO:0086018, and AV-node action potential within AV-node-to-His-cell signaling, GO:0086027. A nodal calcium current can therefore contribute to these electrical-signaling processes without acting as a gap-junction pore or being expressed in the receiving cell. These tissue-specific assertions are retained as non-core. Local ontology definitions/OWL restrictions came from the 2026-03-25 OAK snapshot, cross-checked where accessible against official current term pages; the local snapshot is not claimed current.
The PMID:26786210 publisher full text was accessed externally, but the canonical cache remains abstract-only and its YAML access flag is true. The developmental section places Cacna1g among functional channels downregulated after Isl1 deficiency. GO:0003163 concerns node formation and maturation; regulated expression does not demonstrate the channel executing that process. Its NAS row is MARK_AS_OVER_ANNOTATED. The contraction-linked action-potential ISS row remains UNDECIDED specifically because the precise donor and ventricular/developmental contractile-cell context has not been verified. The right-atrial negative result is explicit contrary evidence for that tested setting, not a claim of uncertainty about the atrium or absence of every cardiac CaV3.1 function.
The complete R-HSA-9700701 narrative includes CACNA1G among T-type calcium channels and discusses their blocker interactions. It supports channel context; this cache does not contain the full structured entity/compartment record. Plasma-membrane localization is independently corroborated by PMID:26715324. No treatment claim is inferred from the narrative's drug-use examples. No CACNA1G/O43497 row was found in the local GO-CAM index in this review pass.
Follow-up decisions: 12 ACCEPT, 13 KEEP_AS_NON_CORE, 10 MODIFY, one MARK_AS_OVER_ANNOTATED and five UNDECIDED; zero PENDING, REMOVE or NEW. The original 41 annotation source records and 35 alternative products are unchanged. Normal donor caches have been reconciled. Final validation/render and independent ROOT review are recorded with the final TMP handoff; canonical publication remains ROOT-owned. No canonical source or review was edited by this draft.
This pass applies the annotation-reviewer and core-function-synthesizer instructions to all 41 rows, but is not an independent peer review: the same agent authored the draft. A separate ROOT peer remains required.
The cited primary expression study reports lower Cacna1g transcript levels in mouse SAN after conditional Isl1 deletion. Its authors restrict their study to expression analysis and call for further functional/developmental work. This supports Cacna1g regulation in the developmental program without proving that the channel directs morphogenesis. The other cited ISL1 study was accessible, but the find operation did not expose Cacna1g in its main text; that absence is not used as evidence against a supplemental result. No canonical publication cache was modified.
The recovered PMID:16690884 abstract matches the earlier official PubMed reading. The recovered PMID:21406960 full text confirms the CaV3.1-specific pacing interpretation and identifies recordings from adult female mice aged 2–4 months at 36 degrees C. Neither donor paper is a direct human experiment or a developmental morphogenesis assay. Exact fetched titles and access flags were added to the final reference list, with the references attached to the corresponding existing ISS rows. The annotation and product inventories, decisions and core function are unchanged.
The channel-complex question was checked against actual ontology definitions and a primary structural purification study by Walsh and colleagues, DOI:10.1074/jbc.M109.017152. Its introduction, methods and relevant results describe tagged rat CaV3.1 expressed in Sf9 cells and purified as a single polypeptide; the authors distinguish this from the auxiliary-subunit-containing cardiac L-type preparation. They state that no mandatory T-type auxiliary subunits had been identified, while discussing current enhancement by optional alpha2delta coexpression. These findings establish autonomous channel architecture, not absence of every native regulatory assembly. The study was consulted externally; no new canonical publication cache or provider report was created. Original cloning full text and the exact native ISS/PAINT complex evidence remain unverified. Consequently, UNDECIDED replaces the four unsupported complex ACCEPTs rather than making an unsupported universal no-complex claim.
The remaining contraction-related uncertainty concerns untested ventricular or developmental settings; the reviewed atrial experiment is a negative result. The NAS node-development decision now follows the distinction between regulated channel expression and demonstrated formation/maturation activity. All 41 source records, 35 products, the core function and the existing reference identities/titles remain unchanged. The external full-text reading and the abstract-only canonical cache are recorded separately for the developmental review.