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

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 (1 variants)
• Bilateral multifocal epileptiform discharges;Microcephaly;Global developmental delay (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.

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				78	16	94
missense	1	1	85	5	2	94
nonsense	1					1
start loss						0
frameshift						0
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region			2	5	1	8
non coding				8	2	10
Total	2	1	86	91	20

Highest pathogenic variant AF is 0.0000132

Variants in GRM7

This is a list of pathogenic ClinVar variants found in the GRM7 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-6861414-G-A		Inborn genetic diseases	Uncertain significance (Nov 08, 2022)
3-6861430-G-C			Uncertain significance (Jan 12, 2022)
3-6861439-C-T			Likely benign (Jun 25, 2023)
3-6861455-G-A			Benign (Dec 02, 2021)
3-6861466-C-T			Likely benign (Jun 05, 2018)
3-6861469-G-C			Benign (Jan 08, 2024)
3-6861471-TGGC-T			Uncertain significance (Mar 04, 2022)
3-6861473-G-A			Uncertain significance (Dec 27, 2022)
3-6861487-C-A			Benign (Jan 25, 2024)
3-6861488-G-T			Uncertain significance (May 13, 2022)
3-6861502-C-T			Benign (Jan 13, 2024)
3-6861507-C-T			Uncertain significance (Dec 26, 2023)
3-6861508-G-T			Likely benign (Jun 28, 2022)
3-6861518-C-A			Likely benign (Jun 01, 2023)
3-6861532-C-T			Benign/Likely benign (Jun 01, 2024)
3-6861547-G-T			Likely benign (Sep 13, 2022)
3-6861582-T-A			Uncertain significance (Aug 21, 2022)
3-6861584-C-T		Inborn genetic diseases	Uncertain significance (Oct 12, 2022)
3-6861599-A-G		Inborn genetic diseases	Uncertain significance (Mar 02, 2023)
3-6861610-C-T		GRM7-related disorder	Benign (Jan 30, 2024)
3-6861611-G-A		Inborn genetic diseases	Uncertain significance (Apr 13, 2022)
3-6861616-C-T			Likely benign (May 01, 2022)
3-6861641-G-T		Neurodevelopmental disorder with seizures, hypotonia, and brain imaging abnormalities	Uncertain significance (May 02, 2024)
3-6861673-A-G			Likely benign (Nov 03, 2021)
3-6861682-C-A		Inborn genetic diseases	Uncertain significance (Nov 08, 2022)

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
0.999	0.00104	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

Haploinsufficiency Scores

• pHI: 0.684
• hipred: Y
• hipred_score: 0.765
• ghis: 0.607

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

Mouse Genome Informatics

• Gene name: Grm7
• 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); muscle phenotype; homeostasis/metabolism phenotype; cellular phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; 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); normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; limbs/digits/tail 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); skeleton phenotype

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