GRM6

glutamate metabotropic receptor 6, the group of Glutamate metabotropic receptors

Basic information

Region (hg38): 5:178977587-178996206

Links

ENSG00000113262 ∙ NCBI:2916 ∙ OMIM:604096 ∙ HGNC:4598 ∙ Uniprot:O15303 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital stationary night blindness 1B (Definitive), mode of inheritance: AR
• congenital stationary night blindness 1B (Definitive), mode of inheritance: AR
• congenital stationary night blindness 1B (Strong), mode of inheritance: AR
• congenital stationary night blindness (Supportive), mode of inheritance: AD
• congenital stationary night blindness 1B (Strong), mode of inheritance: AR
• GRM6-related retinopathy (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Night blindness, congenital stationary, type 1B	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Ophthalmologic	11874764; 15781871; 16249515; 16622103; 22008250

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GRM6 gene.

• not provided (39 variants)
• Congenital stationary night blindness 1B (5 variants)
• Congenital stationary night blindness (2 variants)
• Leber congenital amaurosis (1 variants)
• Retinal dystrophy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GRM6 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	202	24	229
missense	2	4	355	16	12	389
nonsense	17	2				19
start loss	1					1
frameshift	19	3				22
inframe indel			11	1		12
splice donor/acceptor (+/-2bp)	1	3				4
splice region			8	14	3	25
non coding				49	33	82
Total	40	12	369	268	69

Highest pathogenic variant AF is 0.000158

Variants in GRM6

This is a list of pathogenic ClinVar variants found in the GRM6 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
5-178981486-T-C			Likely benign (Aug 28, 2020)
5-178981529-C-T			Likely benign (Aug 28, 2020)
5-178981543-G-C			Likely benign (Aug 28, 2020)
5-178981663-G-A			Likely benign (Jul 10, 2023)
5-178981667-G-T		Retinal dystrophy • Inborn genetic diseases	Conflicting classifications of pathogenicity (Jan 18, 2024)
5-178981675-A-G			Likely benign (Mar 16, 2020)
5-178981680-C-T			Uncertain significance (Jul 10, 2023)
5-178981681-G-A			Conflicting classifications of pathogenicity (Jan 19, 2024)
5-178981682-C-T			Uncertain significance (Sep 13, 2022)
5-178981684-C-T			Likely benign (-)
5-178981688-G-C		Inborn genetic diseases	Uncertain significance (Jan 23, 2024)
5-178981690-T-C			Likely benign (Nov 11, 2022)
5-178981701-C-T			Uncertain significance (Jul 19, 2022)
5-178981702-C-T			Likely benign (Dec 02, 2022)
5-178981703-G-A		GRM6-related disorder	Likely benign (Nov 27, 2023)
5-178981705-G-A			Likely benign (Jan 15, 2024)
5-178981710-T-G			Uncertain significance (Mar 03, 2021)
5-178981711-G-A			Likely benign (Dec 16, 2022)
5-178981713-C-A			Uncertain significance (Jun 02, 2021)
5-178981717-G-A			Likely benign (Jan 07, 2024)
5-178981724-C-T			Uncertain significance (Sep 27, 2022)
5-178981725-G-A		Inborn genetic diseases	Uncertain significance (Feb 17, 2024)
5-178981730-C-T			Uncertain significance (Aug 16, 2022)
5-178981742-T-G			Uncertain significance (Aug 22, 2022)
5-178981761-G-C			Uncertain significance (Dec 20, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GRM6	protein_coding	protein_coding	ENST00000231188	10	17880

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.46e-17	0.0423	125557	1	190	125748	0.000760

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.512	534	502	1.06	0.0000340	5512
Missense in Polyphen		212	203.27	1.0429		2288
Synonymous	-0.887	236	219	1.08	0.0000161	1885
Loss of Function	0.778	28	32.8	0.853	0.00000173	332

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00101	0.00101
Ashkenazi Jewish	0.000299	0.000298
East Asian	0.000438	0.000435
Finnish	0.00130	0.00129
European (Non-Finnish)	0.000690	0.000686
Middle Eastern	0.000438	0.000435
South Asian	0.00141	0.00141
Other	0.000985	0.000978

dbNSFP

Source: dbNSFP

• Function: FUNCTION: G-protein coupled receptor for glutamate. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity (By similarity). Signaling stimulates TRPM1 channel activity and Ca(2+) uptake. Required for normal vision. {ECO:0000250, ECO:0000269|PubMed:23452348}.
• Pathway: Glutamatergic synapse - Homo sapiens (human);Phospholipase D signaling pathway - Homo sapiens (human);Neuroactive ligand-receptor interaction - Homo sapiens (human);GPCRs, Class C Metabotropic glutamate, pheromone;Signaling by GPCR;Signal Transduction;GPCR signaling-G alpha q;GPCR signaling-cholera toxin;GPCR signaling-pertussis toxin;Class C/3 (Metabotropic glutamate/pheromone receptors);GPCR ligand binding;GPCR signaling-G alpha s Epac and ERK;GPCR signaling-G alpha s PKA and ERK;G alpha (i) signalling events;GPCR signaling-G alpha i;GPCR downstream signalling (Consensus)

Intolerance Scores

• loftool: 0.0620
• rvis_EVS: -1.32
• rvis_percentile_EVS: 4.79

Haploinsufficiency Scores

• pHI: 0.285
• hipred: N
• hipred_score: 0.275
• ghis: 0.392

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.105

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Grm6
• Phenotype: vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: grm6b
• Affected structure: retina
• Phenotype tag: abnormal
• Phenotype quality: decreased functionality

Gene ontology

• Biological process: G protein-coupled receptor signaling pathway;adenylate cyclase-inhibiting G protein-coupled glutamate receptor signaling pathway;G protein-coupled glutamate receptor signaling pathway;detection of visible light;detection of light stimulus involved in visual perception;regulation of synaptic transmission, glutamatergic;positive regulation of calcium ion import
• Cellular component: Golgi membrane;endoplasmic reticulum membrane;plasma membrane;integral component of plasma membrane;dendrite;presynaptic membrane
• Molecular function: G protein-coupled receptor activity;protein binding;glutamate receptor activity;protein homodimerization activity