Affinage

CHRNA7

Neuronal acetylcholine receptor subunit alpha-7 · UniProt P36544

Length
502 aa
Mass
56.4 kDa
Annotated
2026-06-09
95 papers in source corpus 24 papers cited in narrative 24 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CHRNA7 encodes the α7 subunit of a neuronal nicotinic acetylcholine receptor that functions as a calcium-permeable ligand-gated channel whose activation triggers intracellular signaling cascades across neural, immune, reproductive, and oncogenic contexts (PMID:29129316, PMID:40847805). Functional receptor output is tightly gated by gene dosage: both haploinsufficiency and overexpression reduce α7-associated calcium flux, the latter through ER chaperone induction, ER stress, and failure to incorporate accumulated α7 subunits into surface receptors (PMID:29129316, PMID:34320968). The human-specific partial duplicate CHRFAM7A co-assembles with α7 to form ACh-silent, non-conducting receptors that dominantly suppress channel function while retaining α-bungarotoxin binding (PMID:21718690). CHRNA7 transcription is controlled by AP-2α-mediated repression of the proximal promoter and by inverse-correlated promoter DNA methylation, such that DNMT inhibition, methyl-donor depletion, or HDAC inhibitors de-repress expression (PMID:21979958, PMID:22052086, PMID:30974230); long-range MeCP2-dependent chromatin interactions with the 15q11.2-13.3 PWS imprinting region provide additional transcriptional control lost upon neuronal differentiation (PMID:21840925). Genetic determination of receptor level operates post-transcriptionally, affecting α-bungarotoxin-binding protein without changing RNA (PMID:19368846). Downstream, ligand-activated α7 engages ERK1/2 for neuroprotection against oxidative stress, JAK2/STAT3 in anti-inflammatory signaling and cancer stem-cell maintenance, PI3K/Akt in tumor cell migration and apoptosis resistance, and YAP1 to drive radial glia proliferation at the expense of neuronal differentiation [PMID:28890319, PMID:29274273, PMID:33603170, PMID:26719016, PMID:bio_10.1101_2025.04.10.647795]. The receptor controls hippocampal inhibitory circuit composition (GAD, parvalbumin, GABAA subunits), sensory inhibition responsive to choline, sperm midpiece motility, nicotine reward behavior, and cholinergic anti-inflammatory cytokine suppression, and is acted upon by the endogenous ligand SLURP1 as a functional antagonist of nicotine (PMID:22314319, PMID:24462939, PMID:15944242, PMID:24289814, PMID:40847805, PMID:29545933).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2005 Medium

    Establishing whether α7 nAChR has a peripheral physiological role beyond the brain, the sperm motility phenotype showed the receptor functions as an ionotropic regulator in non-neural cells.

    Evidence Chrna7 null mouse with CASA motility analysis and fluorescent α-bungarotoxin localization to the sperm midpiece

    PMID:15944242

    Open questions at the time
    • Downstream signaling coupling Ca2+ to flagellar motility not defined
    • No human sperm confirmation
    • Whether CHRFAM7A modulates this peripheral function untested
  2. 2005 Medium

    Mapping how CHRNA7 transcription is embedded in the PWS/AS imprinting locus identified an intronic neuronal enhancer, framing the gene's tissue-specific regulation within a complex genomic region.

    Evidence TgPWS/TgAS transgenic mouse with mapped intron 4 breakpoint and quantitative tissue expression

    PMID:16280085

    Open questions at the time
    • Enhancer not validated in isolation
    • Trans-acting factors binding the enhancer unknown
    • Human relevance of the murine breakpoint unclear
  3. 2009 Medium

    Resolving the level at which genetic variation sets receptor abundance, linkage analysis showed Chrna7 genotype controls α-bungarotoxin-binding protein but not RNA, pinpointing post-transcriptional regulation.

    Evidence F2 mouse mapping cross with parallel autoradiographic protein and in situ RNA quantitation

    PMID:19368846

    Open questions at the time
    • Specific post-transcriptional mechanism (translation, assembly, trafficking) not identified
    • Causal variant not cloned
  4. 2011 High

    Defining the function of the human-specific duplicate, co-expression demonstrated CHRFAM7A forms ACh-silent receptors that dominantly suppress α7 channel function, explaining a uniquely human modulator of cholinergic signaling.

    Evidence Electrophysiology in cell lines and Xenopus oocytes, α-bungarotoxin binding, and PNU-120596 allosteric pharmacology

    PMID:21718690

    Open questions at the time
    • Subunit stoichiometry of mixed receptors not resolved
    • In vivo contribution in human tissue not quantified
  5. 2011 High

    Identifying transcriptional and epigenetic control, AP-2α was shown to repress the proximal promoter and promoter DNA methylation was shown to inversely set expression, establishing two layers of CHRNA7 regulation.

    Evidence Promoter mutagenesis, ChIP/EMSA/supershift with AP-2α KD/OE; bisulfite sequencing, DNMT inhibitors, and methyl-donor manipulation

    PMID:21979958 PMID:22052086

    Open questions at the time
    • Signals that recruit AP-2α or set methylation in vivo unknown
    • Interplay between the two mechanisms not dissected
  6. 2011 Medium

    Connecting CHRNA7 to neurodevelopmental disease regulation, MeCP2-dependent long-range chromatin contacts with the PWS imprinting center were shown to modulate transcription and to correlate with reduced expression in Rett and autism brain.

    Evidence 4C chromatin conformation capture confirmed by FISH in neurons plus qRT-PCR in postmortem human cortex

    PMID:21840925

    Open questions at the time
    • Causal direction between chromatin loop loss and expression not proven
    • Mechanism linking the loop to disease phenotype unestablished
  7. 2012 Medium

    Testing what circuit-level role α7 plays, dosage reduction was shown to lower hippocampal inhibitory components, indicating the receptor maintains inhibitory circuit composition.

    Evidence Quantitative immunoblotting of GAD-65 and GABAA receptors in Chrna7 heterozygous hippocampus

    PMID:22314319

    Open questions at the time
    • Functional electrophysiological consequence not measured here
    • Cell-type origin of changes unresolved
  8. 2013 Medium

    Determining α7's role in addiction, bidirectional genetic and pharmacological manipulation showed Chrna7 constrains nicotine reward behavior.

    Evidence Chrna7 KO and gain-of-function mice in nicotine CPP with selective agonist/antagonist and nucleus accumbens expression profiling

    PMID:24289814

    Open questions at the time
    • Circuit through which α7 limits reward not defined
    • Significance of accumbens insulin signaling change unclear
  9. 2014 Medium

    Extending the inhibitory-circuit and behavioral roles, graded genetic models showed dose- and sex-dependent GABAergic remodeling and demonstrated that choline-mediated improvement of sensory inhibition requires functional α7.

    Evidence WT/Het/KO immunoblotting for GABAA subunits, parvalbumin, GAD67; gestational choline supplementation with auditory sensory inhibition and hippocampal α-bungarotoxin binding

    PMID:24462939 PMID:24836856

    Open questions at the time
    • Mechanism linking receptor level to subunit changes unknown
    • Developmental window of choline action not delimited
  10. 2017 Medium

    Mapping downstream effectors, distinct studies established that ligand-activated α7 signals through ERK1/2 for neuroprotection and through JAK2/STAT3 for anti-inflammatory neuroprotection and cancer stem-cell maintenance.

    Evidence siRNA knockdown in SH-SY5Y with ERK1/2 readout; rat PMCAO with VNS and α7 agonist/antagonist measuring p-JAK2/p-STAT3; ESCC cells/xenografts with JAK2/STAT3 and promoter methylation analysis

    PMID:28890319 PMID:29274273 PMID:33603170

    Open questions at the time
    • Direct biochemical link from channel to each kinase cascade not shown
    • Cell-type specificity of pathway selection unresolved
  11. 2017 High

    Clarifying why gene dosage gain is deleterious, iPSC neural progenitors with 15q13.3 duplication revealed that overexpression induces ER chaperones and ER stress, trapping α7 subunits and reducing calcium flux just as haploinsufficiency does.

    Evidence iPSC-derived NPCs from deletion and duplication carriers with calcium flux, chaperone transcriptomics, and ER stress markers

    PMID:29129316

    Open questions at the time
    • Identity of chaperones limiting assembly not pinned down
    • Whether CHRFAM7A contributes to the duplication phenotype not isolated
  12. 2018 Low

    Identifying an endogenous physiological ligand, SLURP1 was shown to act through CHRNA7 as a functional antagonist of nicotine with opposing anti-malignant effects.

    Evidence SLURP1 and nicotine treatment of CHRNA7-high PDAC cells with binding and downstream signaling analysis

    PMID:29545933

    Open questions at the time
    • No defined binding affinity or structural interaction
    • CHRNA7-dependence shown without knockdown rescue across all readouts
  13. 2019 Medium

    Refining epigenetic control, promoter methylation across multiple regions was shown to be pharmacologically reversible by valproate with corresponding expression gains, reinforcing methylation as a tunable regulatory switch.

    Evidence Bisulfite pyrosequencing of human cortex and cell lines with valproate treatment and qRT-PCR

    PMID:30974230

    Open questions at the time
    • Direct versus HDAC-mediated effect of valproate not separated
    • Genotype-methylation causality not established
  14. 2020 Medium

    Demonstrating that expression and trafficking can be simultaneously enhanced therapeutically, lonafarnib was shown to de-repress CHRNA7 via Ras-c-Jun-JNK/DNMT1 and to boost membrane trafficking via CaMKII, increasing ACh-evoked currents and memory.

    Evidence In vivo mouse lonafarnib with CA1 patch-clamp, DNMT1/JNK/c-Jun immunoblotting, membrane fractionation, and pathway pharmacology

    PMID:33447242

    Open questions at the time
    • Whether transcriptional and trafficking effects are mechanistically independent in vivo not fully separated
    • Off-target farnesylation effects not excluded
  15. 2021 High

    Establishing the developmental consequence of duplication in patient cells, iPSC cortical neurons showed CHRNA7 duplication enhances progenitor proliferation while impairing differentiation, maturation, and migration alongside ER stress.

    Evidence iPSC-derived neurons from proband, unaffected mother, and controls with electrophysiology, migration assay, scRNAseq, ER stress markers, and pharmacological rescue

    PMID:34320968

    Open questions at the time
    • Why proband and unaffected mother diverge phenotypically not resolved
    • Effector linking channel activity to migration deficit not identified here
  16. 2025 Medium

    Identifying the proliferation-versus-differentiation effector, nAChR signaling in human radial glia was shown to act through YAP1 to favor proliferation, with CHRNA7 and CHRFAM7A driving distinct transcriptional responses to nicotine.

    Evidence Human cortical organotypic and dissociated cultures with nAChR activation/knockdown, scRNAseq, and YAP1 inhibitor rescue (preprint)

    PMID:bio_10.1101_2025.04.10.647795

    Open questions at the time
    • Preprint, not yet peer-reviewed
    • Biochemical link from channel Ca2+ to YAP1 activation not defined
    • Divergence of CHRNA7 versus CHRFAM7A transcriptional programs not mechanistically explained

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the diverse downstream cascades (ERK1/2, JAK2/STAT3, PI3K/Akt, YAP1) are selected by α7 channel activity in different cell types, and how CHRFAM7A and ER-chaperone trafficking quantitatively tune surface receptor output in human tissue, remains unresolved.
  • No structural model linking channel gating to pathway choice
  • Quantitative contribution of CHRFAM7A to native human receptor pools unmeasured
  • Identity of the ER chaperones limiting assembly not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0098772 molecular function regulator activity 1
Localization
GO:0005886 plasma membrane 3 GO:0005783 endoplasmic reticulum 2
Pathway
R-HSA-112316 Neuronal System 4 R-HSA-162582 Signal Transduction 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-168256 Immune System 3 R-HSA-1266738 Developmental Biology 2
Partners
AP-2ΑCHRFAM7AMECP2SLURP1
Complex memberships
α7 homopentameric nicotinic acetylcholine receptorα7/CHRFAM7A heteromeric (non-conducting) receptor

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2011 CHRFAM7A (the partial duplication of CHRNA7) acts as a dominant negative regulator of α7*nAChR function. Co-expression of α7 and CHRFAM7A in cell lines and Xenopus oocytes caused significant reduction of ACh-evoked current amplitude without reducing α-bungarotoxin binding, indicating formation of non-functional (ACh-silent) receptors. The allosteric modulator PNU-120596 produced a larger increase in ACh-evoked current in cells co-expressing the duplicate, consistent with a population of closed, non-conducting α7 receptors. Functional electrophysiology (ACh-evoked currents) in cell lines and Xenopus oocytes; radioligand binding with [125I]-α-bungarotoxin; allosteric modulator pharmacology Biochemical pharmacology High 21718690
2017 In iPSC-derived neural progenitor cells from individuals with 15q13.3 duplications, increased CHRNA7 mRNA expression is associated with higher expression of nAChR-specific and resident ER chaperones, indicating increased ER stress and inefficient receptor assembly, resulting in accumulation of α7 subunits in the ER rather than incorporation into functional cell-surface receptors. Both deletions (haploinsufficiency) and duplications (ER stress/trafficking failure) lead to decreased α7 nAChR-associated calcium flux. iPSC-derived neural progenitor cells from human subjects with deletions and duplications; calcium flux assay; mRNA expression analysis of chaperones; ER stress markers American journal of human genetics High 29129316
2011 CHRNA7 transcription is repressed by the transcription factor AP-2α. A 230-bp proximal promoter fragment necessary for transcription in neuroblastoma cells contains a functional AP-2α binding site; mutation of this site, AP-2α knockdown, and AP-2α overexpression all modulate CHRNA7 transcription. AP-2α binding was confirmed by EMSA, supershift assay, and chromatin immunoprecipitation. Promoter mutagenesis; AP-2α knockdown and overexpression; EMSA; supershift assay; chromatin immunoprecipitation (ChIP); reporter assay in neuroblastoma cells The Journal of biological chemistry High 21979958
2011 DNA methylation of the CHRNA7 proximal promoter inversely correlates with CHRNA7 mRNA expression across human tissue types and cell lines. Treatment with DNA methyltransferase inhibitors (5-aza-2-deoxycytidine, zebularine) restored or increased CHRNA7 expression in cells with hypermethylated promoters, while removal of the methyl donor methionine increased transcription. Bisulfite sequencing confirmed hypermethylation of the proximal promoter in silenced cells. Bisulfite sequencing PCR; methylation-sensitive restriction enzyme analysis (MSRE); DNMT inhibitor treatment; methyl donor manipulation; qRT-PCR across multiple human tissue types Journal of molecular neuroscience : MN High 22052086
2005 Chrna7 knock-out mice display significantly impaired sperm motility characterized by reduced swimming velocities, failure to maintain vigorous swimming, and lower levels of hyperactivated swimming, with no differences in sperm number, morphology, viability, or spontaneous acrosome reaction rate. Fluorescent α-bungarotoxin localized nAChR binding sites (primarily CHRNA7) to the midpiece of sperm, suggesting an ionotropic role in motility. Chrna7 null mouse genetic model; computer-assisted sperm analysis (CASA); fluorescent α-bungarotoxin-TRITC binding localization; immunoblot; RT-PCR Biology of reproduction Medium 15944242
2012 Reduced Chrna7 expression in heterozygous C3H mice leads to significant decreases in hippocampal GAD-65 and GABAA receptor levels, indicating that α7*nAChR expression level controls inhibitory circuit components in the hippocampus. Chrna7 heterozygous null mice; quantitative Western immunoblotting for GAD-65, GABAA receptors, GABA, GAT-1 in hippocampus Neuroscience Medium 22314319
2014 Reduced Chrna7 expression in C3H mice is associated with increases in hippocampal parvalbumin and GAD67, and complex alterations in GABAA receptor subunits (decreased α3, α4, and δ subunits in KO; increased δ in Het; increased γ2 in KO). These changes are sex- and gene-dose-dependent. Chrna7 wild-type, heterozygous, and knockout C3H mice; quantitative Western immunoblotting for parvalbumin, GAD67, and GABAA receptor subunits Neuroscience Medium 24836856
2014 Gestational choline supplementation improves sensory inhibition via α7 nAChRs; DBA/2 mice heterozygous or null-mutant for Chrna7 fail to show improvement in sensory inhibition with choline supplementation, whereas wild-type mice do. This demonstrates that choline's effect on sensory inhibition requires functional CHRNA7. Chrna7 null mutation DBA/2 mice; gestational choline supplementation; auditory sensory inhibition testing; [125I]-α-bungarotoxin binding in hippocampus Brain research Medium 24462939
2017 CHRNA7 mediates nicotine-induced signaling in ESCC cancer cells by activating the JAK2/STAT3 signaling pathway to enhance cancer stem cell properties. Dextromethorphan non-competitively inhibited nicotine binding to CHRNA7, while metformin downregulated CHRNA7 expression by antagonizing nicotine-induced promoter DNA hypomethylation. ESCC cell lines and mouse xenograft models; pharmacological inhibition with dextromethorphan and metformin; Western blot for JAK2/STAT3 pathway; promoter methylation analysis; cancer stem cell assays Oncogene Medium 33603170
2017 Arctic Aβ40 blocks the neuroprotective effect of nicotine mediated through CHRNA7 by inhibiting the ERK1/2 pathway downstream of CHRNA7. CHRNA7 knockdown by siRNA in SH-SY5Y cells abolished nicotine's neuroprotective effect, and ERK1/2 activation was shown to mediate neuroprotection against oxidative stress via CHRNA7. Human neuroblastoma SH-SY5Y cells; siRNA knockdown of CHRNA7; pharmacological nicotine stimulation; Western blot for ERK1/2 phosphorylation; cell viability/survival assays; oxidative stress challenge Neurochemistry international Medium 28890319
2017 VNS-induced neuroprotection in permanent cerebral ischemia requires α7nAChR, which activates the JAK2/STAT3 anti-inflammatory pathway. Pharmacological antagonism of α7nAChR attenuated VNS neuroprotection and decreased p-JAK2 and p-STAT3 levels in ischemic penumbra; α7nAChR agonism partially substituted for VNS. Rat PMCAO model; α7nAChR antagonist and agonist pharmacology; Western blot for α7nAChR, p-JAK2, p-STAT3; neurological function scoring; cerebral infarct volume measurement Medical science monitor Medium 29274273
2013 Chrna7 regulates nicotine conditioned place preference in mice. α7 knockout mice show nicotine CPP at sub-threshold doses, while gain-of-function α7 mice do not display nicotine preference. An α7-selective agonist (PHA-543613) dose-dependently blocked nicotine CPP, reversed by the selective antagonist MLA. Chrna7 KO in nucleus accumbens is associated with increased insulin signaling. Chrna7 KO and gain-of-function mouse models; nicotine conditioned place preference (CPP) behavioral assay; selective α7 agonist/antagonist pharmacology; microarray and qPCR of nucleus accumbens; Western blotting for insulin signaling Genes, brain, and behavior Medium 24289814
2015 CHRNA7 overexpression in LoVo colorectal cancer cells reduces cell migration and invasion via activation of the PI3K/Akt signaling pathway, accompanied by reduced MMP-1 and MMP-9 expression. Blocking PI3K/Akt with LY294002 restored migration/invasion in CHRNA7-overexpressing cells. CHRNA7 overexpression plasmid in LoVo cells; Transwell migration/invasion assays; Western blot and gelatin zymography for MMP-1, MMP-9; PI3K/Akt pathway pharmacological inhibition (LY294002) Oncology reports Medium 26719016
2016 Silencing of α7-nAChR (CHRNA7) in AGS gastric cancer cells by siRNA enhances ixabepilone-induced apoptosis, associated with failure to upregulate Bcl-2 and anti-apoptotic Mcl-1 isoform (which are upregulated in scrambled control cells after ixabepilone), and increased cleaved PARP. pAKT and AKT levels were similarly reduced in both groups by ixabepilone. siRNA knockdown of CHRNA7 in AGS cells; ixabepilone cytotoxicity (MTT assay); flow cytometry/annexin V apoptosis assay; Western blot for AKT, pAKT, Mcl-1, Bcl-2, Bad, Bax, cleaved PARP Tumour biology Low 26790437
2009 Chrna7 genotype is linked to α7 nicotinic receptor protein levels (measured by α-bungarotoxin binding) in hippocampus and striatum of F2 mice, but not to α7 RNA levels, suggesting the genetic influence on receptor expression operates at the post-transcriptional level. F2 mice from C3H/Ibg × DBA/2 cross; quantitative autoradiography of [125I]-α-bungarotoxin binding; quantitative in situ hybridization for α7 RNA; linkage analysis Brain research Medium 19368846
2011 MeCP2-bound chromatin in the 15q11.2-13.3 region physically interacts (via 4C chromatin conformation capture) with two sites flanking CHRNA7 in neurons, and this interaction is lost upon neuronal differentiation. Reduced CHRNA7 expression was found in postmortem frontal cortex from Rett syndrome and autism patients, suggesting that long-range chromatin interactions with the PWS-IC modulate CHRNA7 transcription. Chromosome conformation capture on chip (4C) in human SH-SY5Y neuroblastoma cells; FISH to confirm PWS-IC/CHRNA7 interaction in neurons; qRT-PCR of CHRNA7 in postmortem human brain (Rett, autism, controls) Human molecular genetics Medium 21840925
2019 DNA methylation at multiple regions of the CHRNA7 promoter regulates its transcription. Valproate (a mood stabilizer/HDAC inhibitor) causes demethylation of the CHRNA7 promoter and increases CHRNA7 expression in HeLa cells; combined valproate and nicotine treatment also increases expression in SH-SY5Y cells. Genotypic variants influence methylation levels at the CHRNA7 promoter. Bisulfite pyrosequencing of CHRNA7 promoter regions in human temporal cortex and cell lines; valproate treatment; qRT-PCR of CHRNA7 expression; correlation of methylation and expression Neuroscience letters Medium 30974230
2020 Farnesyl transferase inhibitor lonafarnib increases α7nAChR expression through inhibiting DNA methylation of CHRNA7 via the Ras-c-Jun-JNK pathway (reduced DNMT1), and independently increases α7nAChR membrane trafficking via CaMKII pathway, leading to enhanced ACh-evoked currents and spatial memory in mice. In vivo mouse lonafarnib administration; patch-clamp electrophysiology (ACh-evoked I_ACh) in hippocampal CA1; Western blot for DNMT1, p-JNK, p-c-Jun, α7nAChR expression and membrane fractionation; JNK activator and CaMKII inhibitor pharmacology; spatial memory testing Frontiers in pharmacology Medium 33447242
2005 Chrna7 contains a putative neuronal transcriptional enhancer within the PWS/AS deletion region (intron 4 region). In a transgenic mouse model (TgPWS/TgAS) with deletion of this region, Chrna7 expression in brain is reduced ~1.7-fold, while expression in neonatal liver and spleen is paradoxically increased >15-fold due to transgene immunoglobulin enhancer effects. A Chrna7-Tg fusion transcript mapped the telomeric deletion breakpoint to Chrna7 intron 4. TgPWS/TgAS transgenic mouse model with large chromosomal deletion; RT-PCR and fusion transcript cloning; quantitative gene expression analysis across brain and peripheral tissues BMC genomics Medium 16280085
2021 In iPSC-derived cortical neurons from an autistic proband (but not his unaffected mother) carrying a 15q13.3 CHRNA7 duplication, CHRNA7 duplication causes enhanced neural progenitor proliferation, impaired neuronal differentiation/maturation/migration, and increased ER stress. Neuronal migration deficit could be pharmacologically rescued. Both affected and unaffected carriers showed increased action potential firing and elevated cholinergic activity consistent with increased homomeric CHRNA7 channel activity. iPSC-derived cortical excitatory and inhibitory neurons from proband, unaffected mother, and unrelated controls; electrophysiology; neuronal migration assay; ER stress markers; pharmacological rescue; single-cell RNA sequencing; gene expression analysis BMC biology High 34320968
2025 CHRNA7 and CHRFAM7A are expressed in SOX2+ radial glia progenitors in developing human cortex. nAChR activation increases radial glia (RG) proliferation while decreasing neuronal differentiation; nAChR knockdown has the opposite effect. YAP1 is identified as a downstream effector of nAChR signaling, and YAP1 inhibition reverses nicotine-induced phenotypic alterations in outer radial glia (oRG) cells. CHRNA7 and CHRFAM7A selectively modulate different transcriptional changes in excitatory neurons following nicotine exposure. Human cortical organotypic slice cultures and dissociated cultures; nAChR pharmacological activation and knockdown; single-cell RNA sequencing; YAP1 inhibitor pharmacological rescue; RG proliferation and differentiation assays bioRxivpreprint Medium bio_10.1101_2025.04.10.647795
2018 SLURP1 (Secreted Ly-6/uPAR-Related Protein 1) is an endogenous ligand that acts on CHRNA7 in PDAC cells in a CHRNA7-dependent manner with anti-malignant effects, opposing the pro-malignant effects of nicotine. In CHRNA7-high cells, SLURP1 and nicotine abolish each other's effects through functional antagonism without reciprocally interfering with receptor binding or downstream signaling. CHRNA7-high COLO357 and PANC-1 cancer cell cultures; SLURP1 and nicotine treatment; receptor binding analysis; downstream signaling; cell viability/malignancy assays Oncotarget Low 29545933
2023 GTS-21 (a selective α7 nAChR agonist) promotes regulatory T cell (Treg) development from TCR-activated human CD4+ T cells. CHRNA7 mRNA was profoundly suppressed upon TCR activation (days 4-7 vs day 1), while CHRFAM7A (dominant-negative regulator) remained constant. GTS-21 did not alter CD4+ T cell proliferation but significantly promoted Treg development even with high dupα7 expression. Human CD4+ T cell culture; TCR activation; GTS-21 pharmacological treatment; flow cytometry for Treg markers; RT-PCR for CHRNA7 and CHRFAM7A mRNA International journal of molecular sciences Low 37569633
2024 α7nAChR activation in human granulosa cells (GCs) reduces hypoxia-induced elevations of IL-6, CXCL8, and IL-1B. CHRNA7 activation with selective agonist PNU 282987 acutely elevated intracellular Ca2+ in GCs, confirming functional receptor expression. Proteomic analysis revealed that CHRNA7 activation decreased several collagen protein levels in hypoxic GCs. Human granulosa cells from IVF patients; PNU 282987 pharmacological activation; Ca2+ imaging; cytokine mRNA measurement; proteomics; immunohistochemistry in human and primate ovaries Biology of reproduction Medium 40847805

Source papers

Stage 0 corpus · 95 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 Genomic organization and partial duplication of the human alpha7 neuronal nicotinic acetylcholine receptor gene (CHRNA7). Genomics 218 9782083
2001 Linkage disequilibrium for schizophrenia at the chromosome 15q13-14 locus of the alpha7-nicotinic acetylcholine receptor subunit gene (CHRNA7). American journal of medical genetics 161 11424985
2021 A role of the subdiaphragmatic vagus nerve in depression-like phenotypes in mice after fecal microbiota transplantation from Chrna7 knock-out mice with depression-like phenotypes. Brain, behavior, and immunity 147 33422641
2015 The human CHRNA7 and CHRFAM7A genes: A review of the genetics, regulation, and function. Neuropharmacology 147 25701707
2007 Genotype effects of CHRNA7, CNR1 and COMT in schizophrenia: interactions with tobacco and cannabis use. The British journal of psychiatry : the journal of mental science 124 17978319
2010 Structures and molecular mechanisms for common 15q13.3 microduplications involving CHRNA7: benign or pathological? Human mutation 112 20506139
2011 The chimeric gene CHRFAM7A, a partial duplication of the CHRNA7 gene, is a dominant negative regulator of α7*nAChR function. Biochemical pharmacology 111 21718690
2002 A 3-Mb map of a large Segmental duplication overlapping the alpha7-nicotinic acetylcholine receptor gene (CHRNA7) at human 15q13-q14. Genomics 99 11829490
2015 The human clinical phenotypes of altered CHRNA7 copy number. Biochemical pharmacology 96 26095975
2000 Haplotype transmission disequilibrium and evidence for linkage of the CHRNA7 gene region to schizophrenia in Southern African Bantu families. American journal of medical genetics 95 10893497
2012 Identification of single gene deletions at 15q13.3: further evidence that CHRNA7 causes the 15q13.3 microdeletion syndrome phenotype. Clinical genetics 88 22775350
2009 Association of the 5'-upstream regulatory region of the alpha7 nicotinic acetylcholine receptor subunit gene (CHRNA7) with schizophrenia. Schizophrenia research 86 19181484
1994 Molecular cloning and chromosomal localization of the human alpha 7-nicotinic receptor subunit gene (CHRNA7). Genomics 82 8188270
2011 15q11.2-13.3 chromatin analysis reveals epigenetic regulation of CHRNA7 with deficiencies in Rett and autism brain. Human molecular genetics 80 21840925
2009 Differential regulation of alpha7 nicotinic receptor gene (CHRNA7) expression in schizophrenic smokers. Journal of molecular neuroscience : MN 79 19680823
2015 Perinatal Phosphatidylcholine Supplementation and Early Childhood Behavior Problems: Evidence for CHRNA7 Moderation. The American journal of psychiatry 74 26651393
2001 Evidence for linkage disequilibrium between the alpha 7-nicotinic receptor gene (CHRNA7) locus and schizophrenia in Azorean families. American journal of medical genetics 65 11803513
2005 Mice deficient in CHRNA7, a subunit of the nicotinic acetylcholine receptor, produce sperm with impaired motility. Biology of reproduction 62 15944242
2017 The Cognitive and Behavioral Phenotypes of Individuals with CHRNA7 Duplications. Journal of autism and developmental disorders 57 27853923
2013 Dysfunction of SHANK2 and CHRNA7 in a patient with intellectual disability and language impairment supports genetic epistasis of the two loci. Clinical genetics 57 23350639
2017 Nicotinic Acetylcholine Receptor Alpha7 Subunit Mediates Vagus Nerve Stimulation-Induced Neuroprotection in Acute Permanent Cerebral Ischemia by a7nAchR/JAK2 Pathway. Medical science monitor : international medical journal of experimental and clinical research 53 29274273
2007 APOE, ACT and CHRNA7 genes in the conversion from amnestic mild cognitive impairment to Alzheimer's disease. Neurobiology of aging 53 18078695
1998 No evidence for linkage of the CHRNA7 gene region in Canadian schizophrenia families. American journal of medical genetics 51 9754620
2010 A 15q13.3 homozygous microdeletion associated with a severe neurodevelopmental disorder suggests putative functions of the TRPM1, CHRNA7, and other homozygously deleted genes. American journal of medical genetics. Part A 47 20425840
2022 A role of gut-microbiota-brain axis via subdiaphragmatic vagus nerve in depression-like phenotypes in Chrna7 knock-out mice. Progress in neuro-psychopharmacology & biological psychiatry 46 36191806
2017 Functional Consequences of CHRNA7 Copy-Number Alterations in Induced Pluripotent Stem Cells and Neural Progenitor Cells. American journal of human genetics 44 29129316
2015 Analysis of CHRNA7 rare variants in autism spectrum disorder susceptibility. American journal of medical genetics. Part A 43 25655306
2011 Homozygous deletion of chromosome 15q13.3 including CHRNA7 causes severe mental retardation, seizures, muscular hypotonia, and the loss of KLF13 and TRPM1 potentially cause macrocytosis and congenital retinal dysfunction in siblings. European journal of medical genetics 43 21596161
2002 Evaluation of the positional candidate gene CHRNA7 at the juvenile myoclonic epilepsy locus (EJM2) on chromosome 15q13-14. Epilepsy research 42 12049804
2012 Reduced Chrna7 expression in mice is associated with decreases in hippocampal markers of inhibitory function: implications for neuropsychiatric diseases. Neuroscience 37 22314319
2011 A small homozygous microdeletion of 15q13.3 including the CHRNA7 gene in a girl with a spectrum of severe neurodevelopmental features. American journal of medical genetics. Part A 37 21990074
2019 Effect of donepezil on the expression and responsiveness to LPS of CHRNA7 and CHRFAM7A in macrophages: A possible link to the cholinergic anti-inflammatory pathway. Journal of neuroimmunology 35 31048268
2017 Chrna7 deficient mice manifest no consistent neuropsychiatric and behavioral phenotypes. Scientific reports 35 28045139
2014 CHRNA7 triplication associated with cognitive impairment and neuropsychiatric phenotypes in a three-generation pedigree. European journal of human genetics : EJHG 35 24424125
2021 Repurposing dextromethorphan and metformin for treating nicotine-induced cancer by directly targeting CHRNA7 to inhibit JAK2/STAT3/SOX2 signaling. Oncogene 33 33603170
2013 Association of the Nicotinic Receptor α7 Subunit Gene (CHRNA7) with Schizophrenia and Visual Backward Masking. Frontiers in psychiatry 33 24155726
2013 CHRNA7 polymorphisms and response to cholinesterase inhibitors in Alzheimer's disease. PloS one 29 24391883
2014 Effect of APOE and CHRNA7 genotypes on the cognitive response to cholinesterase inhibitor treatment at different stages of Alzheimer's disease. American journal of Alzheimer's disease and other dementias 28 24951635
1999 Localization of mRNA for CHRNA7 in human fetal brain. Neuroreport 28 10439438
2016 An acetylcholine alpha7 positive allosteric modulator rescues a schizophrenia-associated brain endophenotype in the 15q13.3 microdeletion, encompassing CHRNA7. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology 27 27061851
2013 Genetic variation within the Chrna7 gene modulates nicotine reward-like phenotypes in mice. Genes, brain, and behavior 26 24289814
2018 Endogenous CHRNA7-ligand SLURP1 as a potential tumor suppressor and anti-nicotinic factor in pancreatic cancer. Oncotarget 25 29545933
2017 Effect of Genetic Polymorphisms (SNPs) in CHRNA7 Gene on Response to Acetylcholinesterase Inhibitors (AChEI) in Patients with Alzheimer's Disease. Current drug targets 24 26424395
2014 Long-term improvements in sensory inhibition with gestational choline supplementation linked to α7 nicotinic receptors through studies in Chrna7 null mutation mice. Brain research 23 24462939
2001 No association between CHRNA7 microsatellite markers and attention-deficit hyperactivity disorder. American journal of medical genetics 22 11803515
2011 In search of allosteric modulators of a7-nAChR by solvent density guided virtual screening. Journal of biomolecular structure & dynamics 21 21294583
2015 Expression of CHRFAM7A and CHRNA7 in neuronal cells and postmortem brain of HIV-infected patients: considerations for HIV-associated neurocognitive disorder. Journal of neurovirology 19 26567012
2010 Evidence for association of the non-duplicated region of CHRNA7 gene with bipolar disorder but not with Schizophrenia. Psychiatric genetics 19 20463630
2018 Association and cis-mQTL analysis of variants in CHRNA3-A5, CHRNA7, CHRNB2, and CHRNB4 in relation to nicotine dependence in a Chinese Han population. Translational psychiatry 18 29666375
2016 CHRNA7 Gene and Response to Cholinesterase Inhibitors in an Italian Cohort of Alzheimer's Disease Patients. Journal of Alzheimer's disease : JAD 18 27104904
2015 Association Study of CHRNA7 Promoter Variants with Sensory and Sensorimotor Gating in Schizophrenia Patients and Healthy Controls: A Danish Case-Control Study. Neuromolecular medicine 18 26376812
2006 Linkage disequilibrium analysis of the CHRNA7 gene and its partially duplicated region in schizophrenia. Neuroscience research 18 17113175
2016 CHRNA7 Polymorphisms and Dementia Risk: Interactions with Apolipoprotein ε4 and Cigarette Smoking. Scientific reports 17 27249957
2011 CHRNA7 haplotypes are associated with impaired attention in euthymic bipolar disorder. Journal of affective disorders 17 21550667
2021 Altered neuronal physiology, development, and function associated with a common chromosome 15 duplication involving CHRNA7. BMC biology 15 34320968
2016 Silencing A7-nAChR levels increases the sensitivity of gastric cancer cells to ixabepilone treatment. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 15 26790437
2019 Genes Involved in Neurodevelopment, Neuroplasticity and Major Depression: No Association for CACNA1C, CHRNA7 and MAPK1. Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology 14 31352702
2015 CHRNA7 inhibits cell invasion and metastasis of LoVo human colorectal cancer cells through PI3K/Akt signaling. Oncology reports 14 26719016
2012 Genetic variations in CHRNA7 or CHRFAM7 and susceptibility to dementia. Current drug targets 14 22300029
2011 Promoter methylation and tissue-specific transcription of the α7 nicotinic receptor gene, CHRNA7. Journal of molecular neuroscience : MN 14 22052086
2010 Genetic Association Study of the Alpha 7 Nicotinic Receptor (CHRNA7) with the Development of Schizophrenia and Bipolar Disorder in Korean Population. Psychiatry investigation 14 20927308
2018 CHRNA7 copy number gains are enriched in adolescents with major depressive and anxiety disorders. Journal of affective disorders 13 30029151
2012 No effect of polymorphisms in the non-duplicated region of the CHRNA7 gene on sensory gating P50 ratios in patients with schizophrenia and bipolar disorder. Psychiatry research 13 22981153
2011 Transcriptional repression of the α7 nicotinic acetylcholine receptor subunit gene (CHRNA7) by activating protein-2α (AP-2α). The Journal of biological chemistry 13 21979958
2005 Genetic mapping of putative Chrna7 and Luzp2 neuronal transcriptional enhancers due to impact of a transgene-insertion and 6.8 Mb deletion in a mouse model of Prader-Willi and Angelman syndromes. BMC genomics 13 16280085
2014 Reduced CHRNA7 expression in C3H mice is associated with increases in hippocampal parvalbumin and glutamate decarboxylase-67 (GAD67) as well as altered levels of GABA(A) receptor subunits. Neuroscience 12 24836856
2018 Genetic variation in CHRNA7 and CHRFAM7A is associated with nicotine dependence and response to varenicline treatment. European journal of human genetics : EJHG 11 30089821
2024 Splenic nerve denervation attenuates depression-like behaviors in Chrna7 knock-out mice via the spleen-gut-brain axis. Journal of affective disorders 10 38944290
2017 CHRNA7 Deletions are Enriched in Risperidone-Treated Children and Adolescents. Journal of child and adolescent psychopharmacology 10 28817303
2022 Polymorphisms in alpha 7 nicotinic acetylcholine receptor gene, CHRNA7, and its partially duplicated gene, CHRFAM7A, associate with increased inflammatory response in human peripheral mononuclear cells. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 9 35344211
2013 Mosaic 15q13.3 deletion including CHRNA7 gene in monozygotic twins. European journal of medical genetics 9 23454271
2019 DNA methylation regulates CHRNA7 transcription and can be modulated by valproate. Neuroscience letters 8 30974230
2017 Homology Modeling and Protein Interaction Map of CHRNA7 Neurogenesis Protein. Annals of neurosciences 8 28867899
2022 The Natural Compound Dehydrocrenatidine Attenuates Nicotine-Induced Stemness and Epithelial-Mesenchymal Transition in Hepatocellular Carcinoma by Regulating a7nAChR-Jak2 Signaling Pathways. Disease markers 7 35111269
2016 Cholinergic modulation of auditory P3 event-related potentials as indexed by CHRNA4 and CHRNA7 genotype variation in healthy volunteers. Neuroscience letters 7 27109789
2009 Chrna7 genotype is linked with alpha7 nicotinic receptor expression but not alpha7 RNA levels. Brain research 7 19368846
2024 The Prenatal Hypoxic Pathology Associated with Maternal Stress Predisposes to Dysregulated Expression of the chrna7 Gene and the Subsequent Development of Nicotine Addiction in Adult Offspring. Neuroendocrinology 6 38198758
2023 The holistic approach to the CHRNA7 gene, hsa-miR-3158-5p, and 15q13.3 hotspot CNVs in migraineurs. Molecular pain 6 36604774
2020 Farnesyl Transferase Inhibitor Lonafarnib Enhances α7nAChR Expression Through Inhibiting DNA Methylation of CHRNA7 and Increases α7nAChR Membrane Trafficking. Frontiers in pharmacology 6 33447242
2017 Arctic Aβ40 blocks the nicotine-induced neuroprotective effect of CHRNA7 by inhibiting the ERK1/2 pathway in human neuroblastoma cells. Neurochemistry international 6 28890319
2023 GTS-21 Enhances Regulatory T Cell Development from T Cell Receptor-Activated Human CD4+ T Cells Exhibiting Varied Levels of CHRNA7 and CHRFAM7A Expression. International journal of molecular sciences 5 37569633
2021 Screening for Copy Number Variations of the 15q13.3 Hotspot in CHRNA7 Gene and Expression in Patients with Migraines. Current issues in molecular biology 5 34563047
2015 Is Chromosome 15q13.3 Duplication Involving CHRNA7 Associated With Oral Clefts? Child neurology open 5 28503599
2015 Effects of a7nAChR agonist on the tissue estrogen receptor expression of castrated rats. International journal of clinical and experimental pathology 4 26722551
2024 Sinomenine modulates the metabolic reprogramming induced by sepsis via CHRNA7. Life sciences 2 39722318
2023 Effects of Different Exercise Types on Chrna7 and Chrfam7a Expression in Healthy Normal Weight and Overweight Type 2 Diabetic Adults. Biomedicines 2 36831101
2018 Copy number variations in healthy subjects. Case study: iPSC line CSSi005-A (3544) production from an individual with variation in 15q13.3 chromosome duplicating gene CHRNA7. Stem cell research 2 30218896
2025 Genetic counseling of prenatally detected familial 15q13.2q13.3 microdeletion encompassing CHRNA7 and OTUD7A with asymptomatic carriers in the family. Taiwanese journal of obstetrics & gynecology 1 40049827
2024 Electroacupuncture alleviates paradoxical sleep deprivation-induced postoperative hyperalgesia via a7nAChR mediated BDNF/TrkB-KCC2 signaling pathway in the spinal cord. IBRO neuroscience reports 1 39559484
2024 Prenatal Hypoxia Predisposes to Impaired Expression of the chrna4 and chrna7 Genes in Adult Rats without Affecting Acetylcholine Metabolism during Embryonic Development. Biochemistry. Biokhimiia 1 39647824
2021 Rapid-Onset Obesity Due to Impulsive Food-Seeking Behavior in a Puerto Rican Child With CHRNA7 15q13.3 Microdeletion. Cureus 1 33884253
2015 Analysis of the CHRNA7 gene mutation and polymorphism in Southern Han Chinese patients with nocturnal frontal epilepsy. Asian Pacific journal of tropical medicine 1 25975508
2026 Activation of the alpha 7 nicotinic acetylcholine receptor (CHRNA7) limits hypoxia-induced inflammatory responses and regulates collagens in cultured human granulosa cells†. Biology of reproduction 0 40847805
2026 Signal-Level Determinants of Cognitive Decline With PPIs versus H2RAs: Transportome (CBLIF/TCN2) and CHRNA7 Nodes. Molecular nutrition & food research 0 41663888
2025 Intestinal microbiota improves inflammation and cognitive function in the brain of a7nAChR deficient rat through the gut brain axis. Scientific reports 0 40419554

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