GRM1

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

Basic information

Region (hg38): 6:146027646-146437601

Links

ENSG00000152822 ∙ NCBI:2911 ∙ OMIM:604473 ∙ HGNC:4593 ∙ Uniprot:Q13255 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive spinocerebellar ataxia 13 (Strong), mode of inheritance: AR
• autosomal recessive spinocerebellar ataxia 13 (Supportive), mode of inheritance: AR
• autosomal recessive spinocerebellar ataxia 13 (Strong), mode of inheritance: AR
• spinocerebellar ataxia 44 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spinocerebellar ataxia 44; Spinocerebellar ataxia, autosomal recessive 13	AD/AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	22901947; 28886343

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GRM1 gene.

• Autosomal recessive spinocerebellar ataxia 13 (3 variants)
• Global developmental delay (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GRM1 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			5	89	15	109
missense			138	14	1	153
nonsense	1	1	1			3
start loss						0
frameshift	2	1	2			5
inframe indel			6			6
splice donor/acceptor (+/-2bp)						0
splice region			1	3		4
non coding			1	19	30	50
Total	3	2	153	122	46

Highest pathogenic variant AF is 0.0000263

Variants in GRM1

This is a list of pathogenic ClinVar variants found in the GRM1 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-146029012-A-G			Benign (May 12, 2021)
6-146029128-T-C			Benign (Sep 25, 2019)
6-146029523-C-G			Likely benign (Dec 09, 2022)
6-146029535-G-GT		Autosomal recessive spinocerebellar ataxia 13	Pathogenic (Jan 28, 2020)
6-146029543-T-C		not specified	Uncertain significance (Dec 27, 2023)
6-146029549-C-G			Uncertain significance (Jul 25, 2022)
6-146029550-G-C			Likely benign (Aug 21, 2022)
6-146029558-T-G			Uncertain significance (May 05, 2021)
6-146029567-C-T		not specified	Uncertain significance (Apr 14, 2017)
6-146029583-C-A			Uncertain significance (Jul 17, 2022)
6-146029590-A-C			Likely benign (Jun 20, 2023)
6-146029591-G-A			Uncertain significance (Jan 04, 2024)
6-146029598-G-C			Likely benign (Nov 28, 2022)
6-146029616-G-C			Likely benign (Aug 01, 2024)
6-146029630-T-C			Uncertain significance (Oct 08, 2019)
6-146029644-G-A			Uncertain significance (Jun 06, 2018)
6-146029661-A-G			Likely benign (Dec 20, 2022)
6-146029664-C-T			Likely benign (Apr 24, 2023)
6-146029709-G-A			Likely benign (Jul 16, 2023)
6-146029727-C-T			Likely benign (Jan 08, 2024)
6-146029729-G-C			Uncertain significance (Oct 17, 2022)
6-146029741-G-A			Uncertain significance (Sep 07, 2022)
6-146029781-G-A			Benign (Jun 09, 2022)
6-146029789-C-T		Inborn genetic diseases	Uncertain significance (Jul 13, 2021)
6-146029802-C-T			Likely benign (Jun 08, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GRM1	protein_coding	protein_coding	ENST00000361719	8	409953

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.143	0.857	125719	0	29	125748	0.000115

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.58	475	662	0.718	0.0000394	7798
Missense in Polyphen		95	249.51	0.38074		2954
Synonymous	-2.83	333	273	1.22	0.0000175	2449
Loss of Function	4.47	10	40.9	0.245	0.00000232	479

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000264	0.000264
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.000213	0.000185
European (Non-Finnish)	0.000115	0.000114
Middle Eastern	0.000109	0.000109
South Asian	0.0000329	0.0000327
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. May participate in the central action of glutamate in the CNS, such as long-term potentiation in the hippocampus and long-term depression in the cerebellum. {ECO:0000269|PubMed:24603153, ECO:0000269|PubMed:28886343, ECO:0000269|PubMed:7476890}.
• Disease: DISEASE: Spinocerebellar ataxia 44 (SCA44) [MIM:617691]: A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA44 is a slowly progressive, autosomal dominant form. {ECO:0000269|PubMed:28886343}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Long-term potentiation - Homo sapiens (human);Retrograde endocannabinoid signaling - Homo sapiens (human);Glutamatergic synapse - Homo sapiens (human);Long-term depression - Homo sapiens (human);Gap junction - Homo sapiens (human);FoxO signaling pathway - Homo sapiens (human);Calcium signaling pathway - Homo sapiens (human);Estrogen signaling pathway - Homo sapiens (human);Phospholipase D signaling pathway - Homo sapiens (human);Neuroactive ligand-receptor interaction - Homo sapiens (human);Taste transduction - Homo sapiens (human);GPCRs, Other;Common Pathways Underlying Drug Addiction;Serotonin and anxiety;ERK Pathway in Huntington,s Disease;GPCRs, Class C Metabotropic glutamate, pheromone;Signaling by GPCR;Signal Transduction;regulation of ck1/cdk5 by type 1 glutamate receptors;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: 0.186

Intolerance Scores

• loftool: 0.0173
• rvis_EVS: -0.15
• rvis_percentile_EVS: 42.34

Haploinsufficiency Scores

• pHI: 0.350
• hipred: Y
• hipred_score: 0.792
• ghis: 0.593

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.775

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Grm1
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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; neoplasm; pigmentation 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); vision/eye phenotype; renal/urinary system phenotype; skeleton 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); growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: activation of MAPKK activity;activation of MAPK activity;G protein-coupled receptor signaling pathway;G protein-coupled glutamate receptor signaling pathway;chemical synaptic transmission;locomotory behavior;sensory perception of pain;positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G protein-coupled signaling pathway;regulation of sensory perception of pain;regulation of synaptic transmission, glutamatergic;regulation of postsynaptic membrane potential;cellular response to electrical stimulus;regulation of postsynaptic cytosolic calcium ion concentration
• Cellular component: nucleus;plasma membrane;integral component of plasma membrane;dendrite;G protein-coupled receptor dimeric complex;G protein-coupled receptor homodimeric complex;Schaffer collateral - CA1 synapse;postsynaptic density membrane;glutamatergic synapse
• Molecular function: G protein-coupled receptor activity;protein binding;glutamate receptor activity;G protein-coupled neurotransmitter receptor activity involved in regulation of postsynaptic cytosolic calcium ion concentration;G protein-coupled receptor activity involved in regulation of postsynaptic membrane potential;neurotransmitter receptor activity involved in regulation of postsynaptic cytosolic calcium ion concentration