GRM5

glutamate metabotropic receptor 5, the group of Glutamate metabotropic receptors|Protein phosphatase 1 regulatory subunits

Basic information

Region (hg38): 11:88504575-89065982

Links

ENSG00000168959 ∙ NCBI:2915 ∙ OMIM:604102 ∙ HGNC:4597 ∙ Uniprot:P41594 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GRM5 gene.

• not provided (45 variants)
• Inborn genetic diseases (31 variants)
• Normal pregnancy (1 variants)
• not specified (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GRM5 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				24	12	36
missense			33	2	2	37
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				2	1	3
non coding						0
Total	0	0	33	26	14

Variants in GRM5

This is a list of pathogenic ClinVar variants found in the GRM5 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-88508776-G-A		not specified	Uncertain significance (Feb 28, 2024)
11-88508785-T-G		not specified	Uncertain significance (Nov 15, 2021)
11-88508795-C-A			Likely benign (Jan 17, 2018)
11-88508809-C-T		not specified	Uncertain significance (Mar 08, 2024)
11-88508813-C-T		not specified	Uncertain significance (Jul 05, 2022)
11-88508815-G-A		not specified	Uncertain significance (Mar 17, 2023)
11-88508825-C-A		not specified	Uncertain significance (Sep 27, 2022)
11-88508859-C-G			Benign (Dec 31, 2019)
11-88508867-C-T		not specified	Uncertain significance (Apr 12, 2022)
11-88508877-C-T			Likely benign (Mar 28, 2018)
11-88508898-G-A			Likely benign (Jul 25, 2017)
11-88508912-T-C		not specified	Uncertain significance (Jan 05, 2022)
11-88508975-T-G		not specified	Uncertain significance (Oct 22, 2021)
11-88508978-G-A		not specified	Uncertain significance (Aug 02, 2021)
11-88508985-G-A			Likely benign (May 09, 2018)
11-88509031-C-T			Uncertain significance (Jan 04, 2021)
11-88509081-G-A			Likely benign (Apr 13, 2018)
11-88509103-T-G			Likely benign (Dec 07, 2019)
11-88509108-C-G			Likely benign (Feb 01, 2023)
11-88509112-G-A		not specified	Uncertain significance (Jan 07, 2022)
11-88509122-C-T		not specified	Uncertain significance (Mar 28, 2023)
11-88509167-T-C		not specified	Uncertain significance (Jan 05, 2022)
11-88509261-G-C			Likely benign (Dec 31, 2019)
11-88509273-G-T			Likely benign (Jan 17, 2018)
11-88509293-C-T		not specified	Uncertain significance (Mar 28, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GRM5	protein_coding	protein_coding	ENST00000418177	9	561370

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.00128	125738	0	10	125748	0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.21	425	656	0.648	0.0000341	7885
Missense in Polyphen		150	356.73	0.42049		4316
Synonymous	-2.25	308	262	1.18	0.0000140	2432
Loss of Function	5.24	5	41.4	0.121	0.00000223	504

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.000199	0.000198
East Asian	0.000114	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000457	0.0000439
Middle Eastern	0.000114	0.000109
South Asian	0.00	0.00
Other	0.000163	0.000163

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. Signaling activates a phosphatidylinositol-calcium second messenger system and generates a calcium-activated chloride current. Plays an important role in the regulation of synaptic plasticity and the modulation of the neural network activity. {ECO:0000269|PubMed:25042998, ECO:0000269|PubMed:7908515}.
• Pathway: Long-term potentiation - Homo sapiens (human);Retrograde endocannabinoid signaling - Homo sapiens (human);Glutamatergic synapse - Homo sapiens (human);Huntington,s disease - Homo sapiens (human);Gap junction - Homo sapiens (human);Calcium signaling pathway - Homo sapiens (human);Phospholipase D signaling pathway - Homo sapiens (human);Neuroactive ligand-receptor interaction - Homo sapiens (human);Common Pathways Underlying Drug Addiction;GPCRs, Class C Metabotropic glutamate, pheromone;Signaling by GPCR;Signal Transduction;GPCR GroupI metabotropic glutamate receptor;GPCR signaling-G alpha q;GPCR signaling-cholera toxin;GPCR signaling-pertussis toxin;Neuronal System;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;Neurexins and neuroligins;GPCR signaling-G alpha i;Protein-protein interactions at synapses;G alpha (q) signalling events;GPCR downstream signalling (Consensus)

Recessive Scores

• pRec: 0.187

Intolerance Scores

• loftool: 0.00978
• rvis_EVS: -1.26
• rvis_percentile_EVS: 5.26

Haploinsufficiency Scores

• pHI: 0.343
• hipred: Y
• hipred_score: 0.846
• ghis: 0.631

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.327

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Grm5
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); reproductive system 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); adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan)

Gene ontology

• Biological process: regulation of protein phosphorylation;regulation of translation;regulation of translational elongation;G protein-coupled receptor signaling pathway;phospholipase C-activating G protein-coupled glutamate receptor signaling pathway;G protein-coupled glutamate receptor signaling pathway;chemical synaptic transmission;learning or memory;learning;locomotory behavior;calcium-mediated signaling using intracellular calcium source;regulation of long-term neuronal synaptic plasticity;synapse organization;cognition;regulation of synaptic transmission, glutamatergic;regulation of postsynaptic membrane potential;positive regulation of protein tyrosine kinase activity;modulation of age-related behavioral decline;postsynaptic modulation of chemical synaptic transmission;trans-synaptic signaling by endocannabinoid, modulating synaptic transmission;regulation of postsynaptic cytosolic calcium ion concentration;regulation of intracellular calcium activated chloride channel activity;cellular response to amyloid-beta
• Cellular component: cytoplasm;plasma membrane;integral component of plasma membrane;neuron projection;Schaffer collateral - CA1 synapse;postsynaptic density membrane
• Molecular function: G protein-coupled receptor activity;protein binding;glutamate receptor activity;protein tyrosine kinase activator activity;G protein-coupled receptor activity involved in regulation of postsynaptic membrane potential;neurotransmitter receptor activity involved in regulation of postsynaptic cytosolic calcium ion concentration;protein tyrosine kinase binding