Affinage

CACNG5

Voltage-dependent calcium channel gamma-5 subunit · UniProt Q9UF02

Length
275 aa
Mass
30.9 kDa
Annotated
2026-04-28
9 papers in source corpus 2 papers cited in narrative 2 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CACNG5 is a member of the voltage-dependent calcium channel gamma subunit family, identified through genomic sequence analysis as arising from tandem and chromosomal duplication of ancestral CACNG1/CACNG2 loci on chromosomes 16 and 17 (PMID:10613843). Overexpression of CACNG5 suppresses p38 MAPK pathway activation and reduces dopaminergic neuron apoptosis in an MPTP mouse model, and CACNG5 expression is negatively regulated by miR-96 (PMID:30486773). Detailed mechanistic characterization of its calcium channel-regulatory function remains lacking.

Mechanistic history

Synthesis pass · year-by-year structured walk · 2 steps
  1. 1999 Medium

    Establishing CACNG5 as a bona fide gamma subunit family member resolved the question of how many gamma subunit genes exist and how they arose, showing tandem and chromosomal duplication from CACNG1/CACNG2 ancestors.

    Evidence Low-stringency genomic sequence analysis and syntenic mapping across human chromosomes 16/17

    PMID:10613843

    Open questions at the time
    • No electrophysiological reconstitution to demonstrate channel-modulatory activity
    • Expression pattern across tissues not characterized in this study
    • No protein-level validation of CACNG5 product
  2. 2018 Low

    Linking CACNG5 to the p38 MAPK/apoptosis axis provided the first functional readout for this gene, showing that its upregulation (via miR-96 inhibition) suppresses dopaminergic neuron death in a Parkinson's disease model.

    Evidence miR-96 mimic/inhibitor and CACNG5 overexpression in MPTP mouse model and SH-SY5Y cells; Western blot for p-p38MAPK, c-Fos, iNOS, Bax; TUNEL staining

    PMID:30486773

    Open questions at the time
    • No direct luciferase reporter assay described to confirm miR-96 binding to CACNG5 3′UTR
    • Single-lab finding with no independent replication
    • Mechanism linking a calcium channel subunit to p38 MAPK suppression is unexplained

Open questions

Synthesis pass · forward-looking unresolved questions
  • Whether CACNG5 modulates voltage-dependent calcium channel gating, trafficking, or surface expression — the canonical function expected of gamma subunits — has never been directly tested.
  • No electrophysiological characterization of CACNG5 effects on calcium currents
  • No structural or biochemical data on CACNG5 integration into channel complexes
  • Relationship between channel-modulatory role and MAPK-pathway effects is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Pathway
R-HSA-162582 Signal Transduction 1

Evidence

Reading pass · 2 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 CACNG5 was identified as a novel voltage-dependent Ca2+ channel gamma subunit gene, located on chromosomes 16/17, arising through tandem and chromosome duplication events from CACNG1/CACNG2 ancestors, consistent with membership in the gamma subunit gene family. Low-stringency genomic sequence analysis of targeted chromosomal regions based on syntenic prediction from known CACNG1 and CACNG2 loci Genome research Medium 10613843
2018 CACNG5 was identified as a direct target gene of miR-96; inhibition of miR-96 increased CACNG5 expression, which in turn suppressed p38MAPK pathway activation (reduced p-p38MAPK, c-Fos, iNOS, Bax) and decreased dopaminergic neuron apoptosis in an MPTP mouse model of Parkinson's disease. miR-96 mimic/inhibitor treatment and CACNG5 overexpression plasmid in MPTP mouse model and SH-SY5Y cells; TUNEL staining, Western blot for MAPK pathway components; target validation implied by luciferase or expression rescue Molecular medicine (Cambridge, Mass.) Low 30486773

Source papers

Stage 0 corpus · 9 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Identification of three novel Ca(2+) channel gamma subunit genes reveals molecular diversification by tandem and chromosome duplication. Genome research 55 10613843
2016 Evaluation of voltage-dependent calcium channel γ gene families identified several novel potential susceptible genes to schizophrenia. Scientific reports 54 27102562
2018 Suppressed microRNA-96 inhibits iNOS expression and dopaminergic neuron apoptosis through inactivating the MAPK signaling pathway by targeting CACNG5 in mice with Parkinson's disease. Molecular medicine (Cambridge, Mass.) 32 30486773
2019 Proestrus Differentially Regulates Expression of Ion Channel and Calcium Homeostasis Genes in GnRH Neurons of Mice. Frontiers in molecular neuroscience 20 31213979
2019 Exploring the molecular basis of neuronal excitability in a vocal learner. BMC genomics 8 31375088
2018 LncRNA LINC00880 promotes cell proliferation, migration, and invasion while inhibiting apoptosis by targeting CACNG5 through the MAPK signaling pathway in spinal cord ependymoma. Journal of cellular physiology 8 29215699
2024 Study on analgesic effect of Shentong Zhuyu Decoction in neuropathic pain rats by network pharmacology and RNA-Seq. Journal of ethnopharmacology 6 38615700
2023 [Changes in Expression of Genes Associated with Calcium Processes in the Hippocampus in Mice Exposed to Chronic Social Stress]. Molekuliarnaia biologiia 0 37000665
2021 Retraction. Journal of cellular physiology 0 34287864