Overview
GRM6 encodes a metabotropic glutamate receptor (mGluR6) expressed in the ON-bipolar cells of the retina. This receptor is the primary glutamate receptor in these cells and initiates the signaling cascade for bright-light responses. Mutations in GRM6 lead to congenital stationary night blindness type 1B (CSNB1B).
5q35.3 (Chromosome 5)
Hereditary Diseases
Autosomal recessive
Rare
Function & Significance
GRM6 (mGluR6) is a G-protein-coupled receptor located at the synapse between photoreceptors and ON-bipolar cells. In the dark, photoreceptors continuously release glutamate, which binds to mGluR6 and keeps the bipolar cell hyperpolarized. In the light, glutamate release is reduced, mGluR6 becomes inactive, and the bipolar cell depolarizes.
In mutations in GRM6, this signaling cascade is interrupted. The ON-bipolar cells cannot respond to light stimuli, leading to night blindness. GRM6 is upstream of TRPM1 in the same signaling cascade.
🔬 mGluR6 Signaling Cascade
The mGluR6 signaling cascade in ON-bipolar cells: Glutamate binds to mGluR6 → activates G-protein (Gαo) → activates effectors → closes TRPM1 channels → hyperpolarization. In light: less glutamate → mGluR6 inactive → TRPM1 channels open → depolarization. Defects in GRM6, TRPM1, or other components of this cascade lead to CSNB1.
Associated Diseases
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🌙 Congenital Stationary Night Blindness Type 1B (CSNB1B)
Night blindness from birth, normal or slightly reduced day vision, myopia, nystagmus
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👁️ Autosomal Recessive Night Blindness
Affects both sexes equally
🧬 Relevant SNPs
Various mutations in GRM6 have been described, including missense, nonsense, and splice-site mutations. Most are private mutations. There is no single common mutation.
⚕️ Clinical Significance
Diagnosis: Electroretinogram (ERG) shows a missing b-wave (negative ERG), characteristic of CSNB1. Clinical examination reveals night blindness. Genetic tests differentiate between GRM6, TRPM1, NYX, and other CSNB genes.
Management: No causal therapy available. Symptomatic treatment:
- Glasses/Contact Lenses: For myopia correction
- Lighting: Bright lighting at night
- Fitness to Drive: Night driving ban recommended
Prognose: Stationary, no worsening. Normal life expectancy. Day vision is usually sufficient for normal activities.
📚 Data Sources
The information on this page is based on the following scientific sources:
- OMIM: #613216 (Night Blindness, Congenital Stationary, Type 1B)
- ClinVar: Pathogenic GRM6 variants
- PubMed: Literature on GRM6 and night blindness
- Orphanet: ORPHA216816 (Autosomal recessive congenital stationary night blindness)
Last Update: February 2026