Ask about this productRelated genes to: GRM6 Blocking Peptide
- Gene:
- GRM6 NIH gene
- Name:
- glutamate metabotropic receptor 6
- Previous symbol:
- -
- Synonyms:
- GPRC1F, mGlu6, MGLUR6, CSNB1B
- Chromosome:
- 5q35.3
- Locus Type:
- gene with protein product
- Date approved:
- 1993-10-22
- Date modifiied:
- 2019-04-23
Related products to: GRM6 Blocking Peptide
Related articles to: GRM6 Blocking Peptide
- The metabotropic glutamate receptor 6 (mGluR6), encoded by , is a core component of the ON-bipolar signaling cascade in the retina, but its role in human retinal development remains unclear. Here, we used temporally controlled CRISPR-based genetic ablation in human induced pluripotent stem cell-derived retinal organoids to define the developmental functions of mGluR6. Unexpectedly, we found that mGluR6 is expressed not only in depolarizing ON-bipolar cells but also transiently in cone photoreceptors during human retinal development, a pattern not observed in the mouse retina. Early loss of prior to synaptogenesis disrupted cone pedicle architecture, leading to mislocalization of synaptic proteins including Bassoon, ELFN2, and TRPM1, and ultimately resulting in widening or duplication of the outer plexiform layer (OPL). In contrast, deletion after synapse formation did not alter OPL synapses or morphology, revealing a temporally restricted requirement for mGluR6 during circuit assembly. These findings uncover a previously unrecognized role for mGluR6 in coordinating cone terminal targeting and synaptic layer assembly during human retinal development and highlight the power of temporally controlled genetic manipulation in organoid systems to reveal species-specific mechanisms of neural circuit formation. - Source: PubMed
Publication date: 2026/04/27
Bahmani LeilaGalvan PatriciaHosseini HiradBai JinlunBharathan Sumitha PChen MichaelStepanian KaylaThornton Matthew EGrubbs Brendan HNagiel Aaron - Scotopic vision impairment as an early event is found in diabetic retinopathy. However, the underlying mechanisms behind hyperglycemia-induced scotopic vision impairment remain unclear. This study aims to identify that Grm6 is associated with glutamate accumulation-induced scotopic vision impairment under hyperglycemia. - Source: PubMed
Publication date: 2025/11/10
Lian YingZhao YanpuYang XiaoyuHe HongjieYang ZhanyiZhang HuanhuanYan GuigangLu LuMi JiaTian GengZhu Yanping - Inherited retinal diseases (IRDs) are a clinically and genetically heterogeneous group of disorders, with ~30% of cases remaining genetically unsolved. Complete congenital stationary night blindness (cCSNB) is a subtype of IRD, usually associated with reduced visual acuity, nystagmus and high myopia. Most cases are caused by variants in NYX, TRPM1, GRM6, GPR179 or LRIT3. This study aimed to identify the genetic defect in a subject with clinically diagnosed cCSNB lacking coding variants in known associated genes. - Source: PubMed
Publication date: 2026/02/23
Spanic FilipMichiels ChristelleNavarro JulienAntonio AlineCondroyer ChristelAndrieu CamilleGipsy BillyBerthémy-Pellet SylvieGallice MathildeAudo IsabelleZeitz Christina - Optogenetic vision restoration has progressed from proof-of-concept to early clinical testing, yet most programmes rely on microbial channels that demand high irradiance and offer limited adaptation. This review synthesizes preclinical and clinical evidence comparing microbial actuators with human opsins (rhodopsin, cone opsins, melanopsin) and outlines vector and safety considerations for translation. Human opsins activate G-protein-coupled cascades, providing intrinsic signal amplification and operation at room-light levels (∼10-10 photons⋅cm⋅s), in contrast to the ≥1015 photons⋅cm⋅s typically needed for channelrhodopsins. Rhodopsin and MW cone opsin preserve photopic-range sensitivity (rhodopsin > cone opsin) while delivering millisecond-scale kinetics and adaptation across backgrounds, enabling patterned retinal responses without optical intensification devices; clinical validation without external intensification is pending. Such mammalian pigments also confer bleaching-based light adaptation, whereas microbial tools are photocyclic and can desensitize under steady illumination, limiting sustained contrast encoding. Bistable melanopsin enables durable irradiance coding but with slow dynamics; chimeric designs (e.g., melanopsin-mGluR6, Gloeobacter-human rhodopsin) aim to combine amplification with favorable reset properties. In contrast to human opsins, microbial channels warrant safety considerations including light-dose budgeting (particularly at short wavelengths), potential cytotoxicity from proton or calcium loads, and vector-related ocular inflammation; red-shifted actuators improve photochemical safety margins. Targeting opsins to ON bipolar (ON-BP) cells retains inner-retinal computations (center-surround, ON/OFF segregation, temporal filtering). Engineered adeno-associated virus (AAV) capsids (e.g., AAV2-7m8 intravitreally; AAV8.BP2 subretinally) paired with GRM6 or L7 promoters achieve broad ON-BP expression in rodents but a much more limited expression profile in non-human primates. First clinical studies report acceptable early ocular safety with emerging efficacy signals. We propose accelerating phase I safety human trials of human-opsin vectors with prospectively defined light-exposure budgets and low vision functional endpoints such as navigation, face and object recognition, temporal contrast sensitivity, alongside work on chromophore support, cascade integrity in late degeneration, and scalable vector-promoter solutions. Pharmacological noise suppression in degenerating retinas (e.g., gap-junction blockers or retinoic-acid pathway modulators) may further enhance signal-to-noise without altering opsin biochemistry. Together, these steps can move human-opsin optogenetics from experimental promise to clinically meaningful restoration of light sensitivity. - Source: PubMed
Publication date: 2025/11/28
Bica Mihai TeodorCehajic-Kapetanovic Jasmina - Focal Cortical Dysplasia Type II (FCDII) is a subtype of cortical malfunction and is the primary cause of drug-resistant epilepsy in children. Although somatic mosaicism and clonal expansion of brain cells have been identified as crucial factors in FCD cases, the overall genetic landscape and clinical implications of FCDII remain largely unclear due to a significant gap in translating genetic data to inform surgical approaches and prognostic evaluations of individual cases. We carried out deep exome sequencing and deep amplicon validation of surgical biopsies and matched blood samples from 14 FCDII patients with confirmed neuropathology. We further performed multiscale pathogenic validations and took advantage of existing single-nucleus RNA sequencing and spatial maps from developing human cortices to explore the functionality of potential pathogenic somatic variants. We identified novel somatic variants in several functional categories, like neurotransmission (), structural regulation (), cellular maintenance (), and RNA processing (), mapping the expression of these genes back to the developing human brain demonstrated significant enrichment in neuronal cell types, especially excitatory neurons, further confirming their contributions in early brain development and phenotypic functions in dysmorphic neurons. Combining these genetic findings with clinical phenotypes, we found brain-specific mosaic variants with very high mosaic fractions (fraction of mosaic cells, MF, up to 99.5% on ) associated with different clinical phenotypes. FCDIIB, a more severe subtype that contains balloon cells, had higher MFs (>40%) for variants within resectable cortical layers (excitatory neurons in Layers 5 and 6). This allows potentially targeted resection and achieves better clinical outcome (87.5 % with Engel score I). FCDIIA subtype, on the other hand, displayed lower MFs (<5%) with diffuse distribution, and required hemispherectomy, with poor surgical outcomes (Engel score II/III). Our results suggest MF thresholds are high-definition biomarkers of surgical outcome estimate, with MF > 40% predicting viable focal resection and MF < 5% indicating network dysfunction that necessitates broad-spectrum resection. Combining genetic mapping with cellular localization thus offers a coherent solution to precision surgery in FCDII, translating molecular diagnosis to clinical practice. - Source: PubMed
Publication date: 2025/10/07
Bernardino Garcia Camila AraújoZubair MuhammadXi XincenGraham Ian AlfredLee Sang HyunPatarlapalli Sai BabuSantos Marcelo VolponMachado Hélio RubensYang Xiaoxu