GRM7

glutamate metabotropic receptor 7, the group of Glutamate metabotropic receptors|Protein phosphatase 1 regulatory subunits

Basic information

Region (hg38): 3:6770001-7741533

Links

ENSG00000196277 ∙ NCBI:2917 ∙ OMIM:604101 ∙ HGNC:4599 ∙ Uniprot:Q14831 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neurodevelopmental disorder with seizures, hypotonia, and brain imaging abnormalities (Moderate), mode of inheritance: AR
• neurodevelopmental disorder with seizures, hypotonia, and brain imaging abnormalities (Strong), mode of inheritance: AR
• neurodevelopmental disorder with seizures, hypotonia, and brain imaging abnormalities (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with seizures, hypotonia, and brain imaging abnormalities	AR	General	Among other findings, individuals have been described with endocrine abnormalities, including panhypopituitarism, hypothyroidism, and growth hormone deficiency, and awareness may allow early diagnosis and management of these sequelae	Craniofacial; Endocrine; Neurologic	27435318; 28097321; 32286009

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GRM7 gene.

• not_provided (201 variants)
• Inborn_genetic_diseases (98 variants)
• Neurodevelopmental_disorder_with_seizures,_hypotonia,_and_brain_imaging_abnormalities (16 variants)
• GRM7-related_disorder (6 variants)
• Global_developmental_delay (4 variants)
• Brain_atrophy (3 variants)
• Hypotonia (3 variants)
• Seizure (3 variants)
• CNS_hypomyelination (2 variants)
• Intellectual_disability (2 variants)
• Microcephaly (1 variants)
• Bilateral_multifocal_epileptiform_discharges (1 variants)
• Hypoplasia_of_the_corpus_callosum (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GRM7 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000844.4. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	94	12	108
missense	3	3	146	8	1	161
nonsense	3	1	1			5
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	6	4	149	102	13

Highest pathogenic variant AF is 0.000015489544

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GRM7	protein_coding	protein_coding	ENST00000357716	10	971528

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125739	0	9	125748	0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.05	402	536	0.750	0.0000305	5992
Missense in Polyphen		151	259.66	0.58154		2822
Synonymous	-1.39	240	214	1.12	0.0000131	1809
Loss of Function	5.07	4	37.6	0.107	0.00000193	428

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000165	0.000152
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000541	0.0000527
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
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, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity. {ECO:0000269|PubMed:9473604}.
• 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)

Recessive Scores

• pRec: 0.0937

Intolerance Scores

• loftool: 0.00124
• rvis_EVS: -1.62
• rvis_percentile_EVS: 2.94

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.341

Gene Damage Prediction

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

Gene ontology

• Biological process: behavioral fear response;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;sensory perception of sound;negative regulation of glutamate secretion;regulation of cyclase activity;regulation of synaptic transmission, glutamatergic
• Cellular component: plasma membrane;integral component of plasma membrane;cell cortex;integral component of membrane;axon;dendrite;asymmetric synapse;presynaptic membrane;dendritic shaft;receptor complex;postsynaptic membrane;presynaptic active zone
• Molecular function: group III metabotropic glutamate receptor activity;calcium channel regulator activity;glutamate receptor activity;adenylate cyclase inhibitor activity;serine binding