Evidence map›Paper›PMID 21718690›Full record

ArticleBiochemical pharmacology2011

The chimeric gene CHRFAM7A, a partial duplication of the CHRNA7 gene, is a dominant negative regulator of α7*nAChR function.

Tanguy Araud, Sharon Graw, Ralph Berger, Michael Lee, Estele Neveu, Daniel Bertrand, Sherry Leonard

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In one paragraph

Article in Biochemical pharmacology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
82citing papers in PubMed, 1 pooled it
2.9field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

82 citing papers in PubMed, 1 synthesis or guideline pooled it, 118 citations in OpenAlex.

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  6. A complete diploid human genome benchmark for personalized genomics.bioRxiv : the preprint server for biology · 2025
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22 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 4 institutions in 2 countries.

Tanguy AraudDepartment of Neurosciences Medical Faculty, University of Geneva, Geneva, Switzerland. Sherry.Leonard@ucdenver.edu
Sharon Graw
Ralph Berger
Michael Lee
Estele Neveu
Daniel Bertrand
Sherry Leonard
University of Colorado Denver · USHiQScreen (Switzerland) · CHUniversity of Geneva · CHVeterans Health Administration · US

Funding

Regulation of Alpha 7 Nicotinic Receptor Assembly in Human SmokersR01DA009457 · NIDA · UNIVERSITY OF COLORADO DENVER · PI LEONARD, SHERRY · 1995 to 2011
$2.8M
Regulation of the Human a7 Nicotinic Receptor Gene in SchizophreniaR01MH081177 · NIMH · UNIVERSITY OF COLORADO DENVER · PI LEONARD, SHERRY · 2007 to 2011
$1.7M
NIDA NIH HHS MH81174, DA09457NIDA NIH HHS R01 DA009457NIMH NIH HHS R01 MH081177
6 · The paper itself

Abstract

The human α7 neuronal nicotinic acetylcholine receptor gene (CHRNA7) is a candidate gene for schizophrenia and an important drug target for cognitive deficits in the disorder. Activation of the α7*nAChR, results in opening of the channel and entry of mono- and divalent cations, including Ca(2+), that presynaptically participates to neurotransmitter release and postsynaptically to down-stream changes in gene expression. Schizophrenic patients have low levels of α7*nAChR, as measured by binding of the ligand [(125)I]-α-bungarotoxin (I-BTX). The structure of the gene, CHRNA7, is complex. During evolution, CHRNA7 was partially duplicated as a chimeric gene (CHRFAM7A), which is expressed in the human brain and elsewhere in the body. The association between a 2bp deletion in CHRFAM7A and schizophrenia suggested that this duplicate gene might contribute to cognitive impairment. To examine the putative contribution of CHRFAM7A on receptor function, co-expression of α7 and the duplicate genes was carried out in cell lines and Xenopus oocytes. Expression of the duplicate alone yielded protein expression but no functional receptor and co-expression with α7 caused a significant reduction of the amplitude of the ACh-evoked currents. Reduced current amplitude was not correlated with a reduction of I-BTX binding, suggesting the presence of non-functional (ACh-silent) receptors. This hypothesis is supported by a larger increase of the ACh-evoked current by the allosteric modulator 1-(5-chloro-2,4-dimethoxy-phenyl)-3-(5-methyl-isoxazol-3-yl)-urea (PNU-120596) in cells expressing the duplicate than in the control. These results suggest that CHRFAM7A acts as a dominant negative modulator of CHRNA7 function and is critical for receptor regulation in humans.

Indexed as

Genes, DuplicateAllosteric Regulationalpha7 Nicotinic Acetylcholine ReceptorAnimalsBungarotoxinsCell Line, TumorCloning, MolecularElectrophysiological PhenomenaFemaleGenetic LinkageHumansIsoxazolesLigandsMultigene FamilyOocytesPatch-Clamp Techniques1-(5-chloro-2,4-dimethoxyphenyl)-3-(5-methylisoxazol-3-yl)ureaalpha7 Nicotinic Acetylcholine ReceptorBungarotoxinsChrna7 protein, humanIsoxazolesLigandsPhenylurea CompoundsReceptors, NicotinicRNA

Identifiers

PMID21718690
PMCPMC3162115
OpenAlexW2072807117

What OpenQuestion holds

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Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.