Ask about this productRelated genes to: CHRFAM7A Blocking Peptide
- Gene:
- CHRFAM7A NIH gene
- Name:
- CHRNA7 (exons 5-10) and FAM7A (exons A-E) fusion
- Previous symbol:
- -
- Synonyms:
- D-10, CHRNA7-DR1
- Chromosome:
- 15q13.2
- Locus Type:
- gene with protein product
- Date approved:
- 2001-06-29
- Date modifiied:
- 2016-03-03
Related products to: CHRFAM7A Blocking Peptide
Related articles to: CHRFAM7A Blocking Peptide
- Human-specific segmental duplications (HSDs) contain millions of base pairs of sequence unique to the human genome, including genes that shape neurodevelopment. Despite their young age (<6 million years), HSD genes exhibit widespread regulatory divergence, with paralog-specific expression patterns documented across a variety of tissues and cell types. Using long-read expression and epigenomic data, we show that human-specific paralogs tend to have lower activity than the shared, ancestral ones. To systematically characterize the -regulatory elements (CREs) within HSDs and understand patterns of regulatory change in recently evolved gene families, we conduct a massively parallel reporter assay of 7760 human duplicated and chimpanzee orthologous sequences in lymphoblastoid (GM12878) and neuroblastoma (SH-SY5Y) cell lines. A large proportion (14%-24%) of sequences exhibit differential activity relative to the chimpanzee ortholog (or between human paralogs), mostly with small fold-differences. Combining measured activity levels across all assayed sequences, predicted differences in -regulatory activity correlate with mRNA levels in SH-SY5Y. Differentially active CREs validated for , , and may contribute to paralog-specific expression patterns and thereby to human-specific traits. Although we identify some changes in CRE activity within duplicated regions, consideration of adjacent, unique sequences suggests a larger contribution from genome positional effects. In all, this work shows that functional divergence of duplicated CREs contributes moderately to regulatory divergence of HSD genes and uncovers enhancers that are candidate drivers of human-specific regulatory patterns. - Source: PubMed
Publication date: 2026/06/16
Shew Colin JKaya GulhanMcGinty Sean PDennis Megan Y - The CHRNA7 gene, located on chromosome 15q13.3, encodes the α7 nicotinic acetylcholine receptor (α7 nAChR) subunit and lies within a genomic region characterized by high recombination rates and associations with multiple neuropsychiatric disorders. Within this region, the human specific gene CHRFAM7A arose through partial duplication, rearrangement, and fusion between CHRNA7 and FAM7A. The direct CHRFAM7A allele has been shown to negatively regulate α7 nAChR function. The inverted allele (CHRFAM7AΔ2bp), harboring a two-base pair deletion in exon 6, is linked to schizophrenia, bipolar disorder, and other psychiatric conditions. In this study, we investigated how the presence of the CHRFAM7AΔ2bp allele alters the cellular proteome. Using high-throughput proteomic analysis by liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS), we characterized protein expression in neuronal progenitors differentiated from isogenic human induced pluripotent stem cell (iPSC) lines representing CHRFAM7AΔ2bp and CHRFAM7A-null genotypes. Comparative analysis identified 129 differentially expressed proteins enriched in pathways related to extracellular matrix organization, collagen biosynthesis, and cell adhesion. Functional assays further demonstrated differences in matrix adhesion between CHRFAM7A-null and CHRFAM7AΔ2bp-derived progenitors. These results suggest that the CHRFAM7AΔ2bp variant influences cellular structure through modulation of adhesion matrix-interaction proteins. This work provides insight into molecular mechanisms that may underlie increased neurodisease vulnerability associated with this genotype. - Source: PubMed
Publication date: 2026/06/13
Erickson NatalieIhnatovych IvannaSzabados AndrasSzigeti KingaKabbani Nadine - is a biallelic uniquely human fusion gene present in 99.3% of humans. The direct and inverted alleles likely emerged independently in Africa and East Asia. We uncovered that the inverted allele regulates expression through genetic epistasis. The increase in long to short isoform ratio enhances α-tubulin acetylation leading to microtubule (MT) cytoskeleton phenotypes (cell body: microtubule rich projections; neurite: de-bundling; growth cone: fanning with MT invasion). The MT cytoskeleton gain of function enhances neuronal arborization and functional connectivity in the human brain. Considering that the previously reported direct allele leads to actin cytoskeleton gain of function, we propose that alleles represent binary human genetic background through divergent evolution of the cytoskeleton. In the human brain the two alleles represent distinct brain organization: the direct allele enhances microstructure as measured by diffusion tensor imaging while the inverted allele increases functional connectivity with increased small world propensity. The two types of brain organization likely represent different susceptibility to neuropsychiatric disease and may underlie the allelic disease associations. - Source: PubMed
Publication date: 2026/05/18
Rosas NicolásIhnatovych IvannaReeves Jack ACortes Gomez EduardoDorn Ryu PSandhu HarneetSzombathy AnnaBergsland NielsSule NorbertMuldoon SarahZivadinov RobertBenedict Ralph H BBennett David AWang JianminSzigeti Kinga - Nicotinic acetylcholine receptor of α7 type (α7-nAChR) is a ligand-gated ion channel composed of five identical α7 subunits. Secreted lymphocyte antigen-6 urokinase-type plasminogen activator receptor (Ly6/uPAR)-related protein-1 (SLURP-1) controls carcinoma progression by negative modulation of oncogenic α7-nAChR. In this study, we observed dramatic decrease of SLURP-1 plasma level in patients with metastatic melanoma. We suggested usage of recombinant analog of human SLURP-1 (rSLURP-1) to compensate this deficiency for metastatic melanoma treatment. rSLURP-1 did not affect viability of different patient-derived metastatic melanoma cells, but reduced migration of some of them. Metastatic melanoma cells of other lines were resistant to rSLURP-1. Antimigratory rSLURP-1 effect was mediated by α7-nAChR, whereas resistance to rSLURP-1 correlated with overexpression of human-specific gene, which encodes the α7 subunit with truncated N-terminal region (dupα7) able to form hybrid α7/dupα7-nAChR channels. Electrophysiological study in oocytes showed that rSLURP-1 inhibits α7/dupα7-nAChR weaker than α7-nAChR. In contrast, "Oncotag" peptide, which mimics the loop I of SLURP-1, inhibited α7/dupα7- and α7-nAChRs with similar efficiency. Oncotag suppressed metastatic melanoma cell migration independently on dupα7 expression. Computer modeling provided rationale for altered activities of rSLURP-1 and Oncotag on α7/dupα7-nAChR. The Cancer Genome Atlas Program (TCGA) database analysis revealed correlation between and gene expression and worse survival prognosis for patients with metastatic melanoma. Thus, ) low plasma SLURP-1 level may be a specific marker of metastatic melanoma development, ) metastatic melanoma progression can be controlled by α7-nAChR inhibition, and ) dupα7 overexpression is a new molecular mechanism of melanoma resistance to internal cholinergic control and new target for melanoma treatment. Metastatic melanoma is aggressive skin tumor often resistant to standard therapies. High α7-nAChR expression negatively correlates with survival of patients with metastatic melanoma, who are characterized by SLURP-1 drop in the plasma. Targeting α7-nAChR with recombinant SLURP-1 could significantly suppress metastatic melanoma cell migration; however, overexpression of human-specific dupα7 subunit forming hybrid α7/dupα7-nAChRs causes melanoma resistance to SLURP-1. This resistance can be overcome by the SLURP-1 mimicking peptide Oncotag, which exhibits activity against hybrid α7/dupα7-nAChRs. - Source: PubMed
Publication date: 2026/04/16
Kirichenko Artem VBychkov Maxim LKulbatskii Dmitry SShlepova Olga VShulepko Mikhail AGornostaeva Tamara YaOrekhov Philipp SParamonov Alexander SMikhaylova Irina NBurova Olga SMedyanik Igor AYashin Konstantin SWang HongshuangWang XiaohuiKirpichnikov Mikhail PShenkarev Zakhar OLyukmanova Ekaterina N - Cryptococcus neoformans meningitis (CM), a severe AIDS-defining illness with high mortality, remains refractory to effective therapies. This study investigated the mechanisms underlying Cryptococcus neoformans (Cn)-induced disruption of the blood-brain barrier (BBB). Using in vitro models of cerebral microvascular endothelial cells, we demonstrated that Cn disrupted the BBB via adhesion and invasion, leading to pyroptosis in these cells. Furthermore, our findings revealed that Cn induced upregulation of the α7 nicotinic acetylcholine receptor (α7nAChR). Importantly, inhibition of α7nAChR alleviated pyroptosis caused by Cn. Interestingly, the CHRFAM7A gene product, a duplicated α7nAChR subunit, negatively regulated its activity, thereby mitigating Cn-induced pyroptosis in cerebral microvascular endothelial cells. Fungal ergosterol, a key virulence factor, plays a critical role in this process. It slowed the wound healing in cell scratch assays and induced pyroptosis in cerebral microvascular endothelial cells. Consistent with in vitro findings, in vivo experiments using immunosuppressed mouse models demonstrated that Cn increased BBB permeability, as evidenced by enhanced Evans blue leakage and reduced ZO-1 expression in the cerebral cortex. Additionally, Cn reduced vascular activity and regulated pyroptosis-related proteins in the mouse cerebral cortex. Notably, both pharmacological inhibition of α7nAChR with MLA and its genetic modulation via CHRFAM7A overexpression conferred significant survival benefits and alleviated Cn-induced pathological damage in mice. These findings provide novel insights and potential therapeutic targets for the prevention and treatment of CM. - Source: PubMed
Publication date: 2026/02/12
Chen JingyuZhou BingliangZou JinhuWang PenghuiMeng XiangshunHuang PengweiChen JieCao Hong