GRM4

glutamate metabotropic receptor 4, the group of Glutamate metabotropic receptors

Basic information

Region (hg38): 6:34018643-34155622

Links

ENSG00000124493 ∙ NCBI:2914 ∙ OMIM:604100 ∙ HGNC:4596 ∙ Uniprot:Q14833 ∙ 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 GRM4 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GRM4 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				1	7	8
missense			37		1	38
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				1		1
Total	0	0	37	2	8

Variants in GRM4

This is a list of pathogenic ClinVar variants found in the GRM4 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-34022847-C-T		not specified	Uncertain significance (Apr 08, 2024)
6-34022848-G-A			Benign (Dec 31, 2019)
6-34022870-G-A		not specified	Uncertain significance (Dec 12, 2023)
6-34028125-G-A		not specified	Uncertain significance (Nov 14, 2023)
6-34028138-C-G		not specified	Uncertain significance (Oct 26, 2021)
6-34028243-G-A		not specified	Uncertain significance (May 06, 2024)
6-34028277-G-T			Benign (Dec 21, 2017)
6-34028303-T-C		not specified	Uncertain significance (Aug 02, 2021)
6-34028350-G-A		not specified	Uncertain significance (Dec 20, 2023)
6-34028353-G-A		not specified	Uncertain significance (Dec 20, 2023)
6-34035669-T-A			Uncertain significance (Dec 17, 2020)
6-34035681-T-C		not specified	Uncertain significance (Nov 16, 2021)
6-34035765-T-C		not specified	Uncertain significance (Dec 11, 2023)
6-34035806-G-A			Benign (Dec 31, 2019)
6-34035855-G-A		not specified	Uncertain significance (May 24, 2024)
6-34035905-G-A			Benign (Apr 20, 2018)
6-34036133-C-T			Benign (Dec 28, 2018)
6-34036151-C-T			Benign (Dec 31, 2019)
6-34036168-C-T		not specified	Uncertain significance (Mar 06, 2023)
6-34036169-G-A			Likely benign (Dec 13, 2017)
6-34036179-A-G		not specified	Uncertain significance (Sep 12, 2023)
6-34036270-C-T		not specified	Uncertain significance (Apr 08, 2022)
6-34036271-G-T		not specified	Uncertain significance (Jun 23, 2023)
6-34036278-C-T		not specified	Uncertain significance (Nov 07, 2022)
6-34036397-C-T			Benign (Dec 31, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GRM4	protein_coding	protein_coding	ENST00000538487	10	133772

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.993	0.00693	125720	0	26	125746	0.000103

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.68	447	638	0.701	0.0000443	5933
Missense in Polyphen		179	296.3	0.60412		2805
Synonymous	1.03	251	273	0.921	0.0000204	1892
Loss of Function	4.86	5	36.9	0.136	0.00000194	380

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000630	0.0000615
Middle Eastern	0.000109	0.000109
South Asian	0.000523	0.000523
Other	0.00	0.00

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 inhibits adenylate cyclase activity. {ECO:0000269|PubMed:7617140, ECO:0000269|PubMed:8738157, ECO:0000269|PubMed:9473604}.
• Pathway: Glutamatergic synapse - Homo sapiens (human);Phospholipase D signaling pathway - Homo sapiens (human);Neuroactive ligand-receptor interaction - Homo sapiens (human);Taste transduction - 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)

Recessive Scores

• pRec: 0.198

Intolerance Scores

• loftool: 0.0353
• rvis_EVS: -2.48
• rvis_percentile_EVS: 0.96

Haploinsufficiency Scores

• pHI: 0.270
• hipred: Y
• hipred_score: 0.755
• ghis: 0.691

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.453

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Grm4
• 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: activation of MAPK activity;G protein-coupled receptor signaling pathway;adenylate cyclase-inhibiting G protein-coupled glutamate receptor signaling pathway;G protein-coupled glutamate receptor signaling pathway;chemical synaptic transmission;neurotransmitter secretion;positive regulation of MAPK cascade;regulation of neuron apoptotic process;regulation of synaptic transmission, glutamatergic
• Cellular component: plasma membrane;integral component of plasma membrane;cytoplasmic vesicle;presynaptic membrane
• Molecular function: G protein-coupled receptor activity;glutamate receptor activity