GRM2

protein-coding

glutamate metabotropic receptor 2, the group of Glutamate metabotropic receptors

Gene summary

L-glutamate is the major excitatory neurotransmitter in the central nervous system and activates both ionotropic and metabotropic glutamate receptors. Glutamatergic neurotransmission is involved in most aspects of normal brain function and can be perturbed in many neuropathologic conditions. The metabotropic glutamate receptors are a family of G protein-coupled receptors, that have been divided into 3 groups on the basis of sequence homology, putative signal transduction mechanisms, and pharmacologic properties. Group I includes GRM1 and GRM5 and these receptors have been shown to activate phospholipase C. Group II includes GRM2 and GRM3 while Group III includes GRM4, GRM6, GRM7 and GRM8. Group II and III receptors are linked to the inhibition of the cyclic AMP cascade but differ in their agonist selectivities. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2017]

MANE transcript

NM_000839.5

Inheritance

—

ClinVar variants

U:111B:10

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.26

Max pathogenic AF

—

Genomic locus

chr3:51,707,068-51,718,613

External References & Databases

Ensembl (ENSG00000164082)

Transcript & Mutation Effects

hg38 • Region Span ~11.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GRM2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 106

not providedTotal: 10

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000839.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	4 clinvar	3 clinvar	8
missense			108 clinvar	2 clinvar	1 clinvar	111
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	111	6	4	121

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 25 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000839.5	RefSeq	NP_000830.2	5	MANE Select
ENST00000395052.8	Ensembl	ENSP00000378492.3	5	MANE Select
NM_001349116.2	RefSeq	NP_001336045.1	4	Standard
NM_001349117.2	RefSeq	NP_001336046.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Glutamatergic synapse - Homo sapiens (human)
Phospholipase D signaling pathway - Homo sapiens (human)
Neuroactive ligand-receptor interaction - Homo sapiens (human)
Cocaine addiction - Homo sapiens (human)
GPCRs, Class C Metabotropic glutamate, pheromone

Biological Process

G protein-coupled receptor signaling pathway
negative regulation of adenylate cyclase activity
adenylate cyclase-inhibiting G protein-coupled glutamate receptor signaling pathway
G protein-coupled glutamate receptor signaling pathway
chemical synaptic transmission

Molecular Function

group II metabotropic glutamate receptor activity
G protein-coupled receptor activity
calcium channel regulator activity
protein binding
glutamate receptor activity

Cellular Component

plasma membrane
integral component of plasma membrane
cell junction
axon
dendrite

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000395052
Coding exons: 5
Length: 11544
Individuals with no LoFs: 125727
Homozygous LoFs: 0
Heterozygous LoFs: 21
Defined: 125748
p: 0.0000835

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.37	423	584	0.724	0.0000398	5616
Missense (PolyPhen)		151	252.8	0.59732		2632
Synonymous	1.00	218	238	0.917	0.0000152	1909
Loss of Function	3.58	7	27.1	0.258	0.00000141	284

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.000098	0.000097	rare
South Asian	0.00013	0.00013	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

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. May mediate suppression of neurotransmission or may be involved in synaptogenesis or synaptic stabilization. {ECO:0000269|PubMed:18297054, ECO:0000269|PubMed:22300836, ECO:0000269|PubMed:23129762, ECO:0000269|PubMed:7620613}.;

Recessive Scores

pRec: 0.182

Intolerance Scores

LoFtool: 0.0683
RVIS EVS: -0.35
RVIS percentile EVS: 29.54

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.117

Gene Damage Prediction

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