GRM3 (glutamate metabotropic receptor 3)

Gene

• Entrez ID: 2913
• Gene name: Glutamate metabotropic receptor 3
• Gene symbol: GRM3
• Synonyms (NCBI Gene): GLUR3, GPRC1C, MGLUR3, mGlu3
• Chromosome: 7
• Chromosome location: 7q21.11-q21.12
• 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 perturbe

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT018386	hsa-miR-335-5p	Microarray	18185580
MIRT2006895	hsa-miR-300	CLIP-seq
MIRT2006896	hsa-miR-381	CLIP-seq
MIRT2006897	hsa-miR-4633-3p	CLIP-seq
MIRT2006898	hsa-miR-4666-3p	CLIP-seq
MIRT2006899	hsa-miR-889	CLIP-seq
MIRT2239416	hsa-miR-30a	CLIP-seq
MIRT2239417	hsa-miR-30b	CLIP-seq
MIRT2239418	hsa-miR-30c	CLIP-seq
MIRT2239419	hsa-miR-30d	CLIP-seq
MIRT2239420	hsa-miR-30e	CLIP-seq
MIRT2239421	hsa-miR-3607-3p	CLIP-seq
MIRT2239422	hsa-miR-3686	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001641	Function	Group II metabotropic glutamate receptor activity	IBA
GO:0001641	Function	Group II metabotropic glutamate receptor activity	IEA
GO:0004930	Function	G protein-coupled receptor activity	IEA
GO:0004930	Function	G protein-coupled receptor activity	TAS	8840013
GO:0005246	Function	Calcium channel regulator activity	IEA
GO:0005515	Function	Protein binding	IPI	35512704
GO:0005886	Component	Plasma membrane	IBA
GO:0005886	Component	Plasma membrane	IDA	28655286
GO:0005886	Component	Plasma membrane	IEA
GO:0005886	Component	Plasma membrane	TAS	8840013
GO:0007165	Process	Signal transduction	IEA
GO:0007186	Process	G protein-coupled receptor signaling pathway	IEA
GO:0007193	Process	Adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	IDA	34239069
GO:0007194	Process	Negative regulation of adenylate cyclase activity	TAS	8840013
GO:0007196	Process	Adenylate cyclase-inhibiting G protein-coupled glutamate receptor signaling pathway	IEA
GO:0007216	Process	G protein-coupled glutamate receptor signaling pathway	IBA
GO:0007216	Process	G protein-coupled glutamate receptor signaling pathway	IDA	37286794
GO:0007216	Process	G protein-coupled glutamate receptor signaling pathway	IDA	37286794
GO:0007268	Process	Chemical synaptic transmission	TAS	8840013
GO:0008066	Function	Glutamate receptor activity	IEA
GO:0008066	Function	Glutamate receptor activity	TAS	8840013
GO:0010467	Process	Gene expression	IEA
GO:0014069	Component	Postsynaptic density	IEA
GO:0016020	Component	Membrane	IEA
GO:0030424	Component	Axon	IEA
GO:0030424	Component	Axon	ISS
GO:0033554	Process	Cellular response to stress	IEA
GO:0042734	Component	Presynaptic membrane	IEA
GO:0043005	Component	Neuron projection	IEA
GO:0043197	Component	Dendritic spine	IEA
GO:0045211	Component	Postsynaptic membrane	IEA
GO:0050804	Process	Modulation of chemical synaptic transmission	IEA
GO:0051966	Process	Regulation of synaptic transmission, glutamatergic	IBA
GO:0097110	Function	Scaffold protein binding	IEA
GO:0097110	Function	Scaffold protein binding	ISS
GO:0097449	Component	Astrocyte projection	IEA
GO:0097449	Component	Astrocyte projection	ISS
GO:0098978	Component	Glutamatergic synapse	IEA
GO:0099170	Process	Postsynaptic modulation of chemical synaptic transmission	IEA

Other IDs

• MIM: 601115
• HGNC: 4595
• e!Ensembl: ENSG00000198822

Protein

• UniProt ID: Q14832
• Protein name: Metabotropic glutamate receptor 3 (mGluR3)
• Protein 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
• PDB: 3SM9, 4XAR, 5CNK, 5CNM, 6B7H, 7WI6, 7WI8, 7WIH, 8JCU, 8JCV, 8JCW, 8JCX, 8JCY, 8JCZ, 8JD0, 8JD1, 8JD2, 8JD3, 9II2, 9II3
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF01094	ANF_receptor	67 → 475	Receptor family ligand binding region	Family
  PF07562	NCD3G	505 → 555	Nine Cysteines Domain of family 3 GPCR	Family
  PF00003	7tm_3	588 → 825	7 transmembrane sweet-taste receptor of 3 GCPR	Family

• Tissue specificity: TISSUE SPECIFICITY: Detected in brain cortex, thalamus, subthalamic nucleus, substantia nigra, hypothalamus, hippocampus, corpus callosum, caudate nucleus and amygdala. {ECO:0000269|PubMed:8840013}.
• Sequence:

  MKMLTRLQVLTLALFSKGFLLSLGDHNFLRREIKIEGDLVLGGLFPINEKGTGTEECGRI
  NEDRGIQRLEAMLFAIDEINKDDYLLPGVKLGVHILDTCSRDTYALEQSLEFVRASLTKV
  DEAEYMCPDGSYAIQENIPLLIAGVIGGSYSSVSIQVANLLRLFQIPQISYASTSAKLSD
  KSRYDYFARTVPPDFYQAKAMAEILRFFNWTYVSTVASEGDYGETGIEAFEQEARLRNIC
  IATAEKVGRSNIRKSYDSVIRELLQKPNARVVVLFMRSDDSRELIAAASRANASFTWVAS
  DGWGAQESIIKGSEHVAYGAITLELASQPVRQFDRYFQSLNPYNNHRNPWFRDFWEQKFQ
  CSLQNKRNHRRVCDKHLAIDSSNYEQESKIMFVVNAVYAMAHALHKMQRTLCPNTTKLCD
  AMKILDGKKLYKDYLLKINFTAPFNPNKDADSIVKFDTFGDGMGRYNVFNFQNVGGKYSY
  LKVGHWAETLSLDVNSIHWSRNSVPTSQCSDPCAPNEMKNMQPGDVCCWICIPCEPYEYL
  ADEFTCMDCGSGQWPTADLTGCYDLPEDYIRWEDAWAIGPVTIACLGFMCTCMVVTVFIK
  HNNTPLVKASGRELCYILLFGVGLSYCMTFFFIAKPSPVICALRRLGLGSSFAICYSALL
  TKTNCIARIFDGVKNGAQRPKFISPSSQVFICLGLILVQIVMVSVWLILEAPGTRRYTLA
  EKRETVILKCNVKDSSMLISLTYDVILVILCTVYAFKTRKCPENFNEAKFIGFTMYTTCI
  IWLAFLPIFYVTSSDYRVQTTTMCISVSLSGFVVLGCLFAPKVHIILFQPQKNVVTHRLH
  LNRFSVSGTGTTYSQSSASTYVPTVCNGREVLDSTTSSL

• Sequence length: 879

Pathways

KEGG:

Phospholipase D signaling pathway
Neuroactive ligand-receptor interaction
Glutamatergic synapse
Cocaine addiction

Reactome:

G alpha (i) signalling events
Class C/3 (Metabotropic glutamate/pheromone receptors)

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ALZHEIMER DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ANOREXIA NERVOSA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ASTHMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATTENTION DEFICIT HYPERACTIVITY DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTISM SPECTRUM DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BIPOLAR DISORDER	—	Disgenet, GWAS catalog Disgenet, GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BREAST CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BREAST CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
EBV-positive nodal T- and NK-cell lymphoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
EPILEPSY	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
EPILEPSY, TEMPORAL LOBE	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GASTROESOPHAGEAL REFLUX DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GENERALISED EPILEPSY	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
INSOMNIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
INTERNET ADDICTION DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
IRON METABOLISM DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MAJOR DEPRESSIVE DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MELANOMA	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
METABOLIC DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MOOD DISORDERS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NEUROTIC DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OBSESSIVE-COMPULSIVE DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PARTIAL EPILEPSY	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PERIPHERAL ARTERIAL DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCHIZOPHRENIA	—	CTD, Disgenet, GWAS catalog CTD, Disgenet, GWAS catalog CTD, Disgenet, GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SEBORRHEIC DERMATITIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SQUAMOUS CELL LUNG CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TOURETTE SYNDROME	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Adenocarcinoma	Adenocarcinoma	BEFREE	28114282		★☆☆☆☆ Found in Text Mining only
Alzheimer Disease	Alzheimer disease	Pubtator	34981809	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Amnesia	Amnesia	BEFREE	28285415		★☆☆☆☆ Found in Text Mining only
Amyloidosis	Amyloidosis	BEFREE	28495373		★☆☆☆☆ Found in Text Mining only
Amyotrophic Lateral Sclerosis	Amyotrophic Lateral Sclerosis	BEFREE	25434487		★☆☆☆☆ Found in Text Mining only
Amyotrophic Lateral Sclerosis	Amyotrophic lateral sclerosis	Pubtator	31925813	Associate	★☆☆☆☆ Found in Text Mining only
Amyotrophic lateral sclerosis 1	Amyotrophic lateral sclerosis	Pubtator	31925813	Associate	★☆☆☆☆ Found in Text Mining only
Astrocytoma	Astrocytoma	BEFREE	11500049		★☆☆☆☆ Found in Text Mining only
Attention Deficit Disorder with Hyperactivity	Attention deficit hyperactivity disorder	Pubtator	28452824	Associate	★☆☆☆☆ Found in Text Mining only
Autism Spectrum Disorder	Autism	Pubtator	21996756	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Autoimmune Diseases	Autoimmune Diseases	BEFREE	10441170		★☆☆☆☆ Found in Text Mining only
Bipolar Disorder	Bipolar Disorder	BEFREE	11840505, 19386277, 20226637, 23575746, 28800512		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Bipolar Disorder	Bipolar disorder	Pubtator	16380905, 27063557	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Bipolar Disorder	Bipolar Disorder	PSYGENET_DG	19386277, 20226637, 20957330, 23575746, 25583490		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Breast Neoplasms	Breast neoplasm	Pubtator	28615627, 34623384, 34920184	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Renal Cell	Renal cell carcinoma	Pubtator	30488581	Associate	★☆☆☆☆ Found in Text Mining only
Child Development Disorders, Pervasive	Development Disorder	GWASCAT_DG	28540026		★☆☆☆☆ Found in Text Mining only
Chronic Lymphocytic Leukemia	Lymphocytic Leukemia	BEFREE	27431857		★☆☆☆☆ Found in Text Mining only
CNS disorder	CNS Disorder	BEFREE	25583490		★☆☆☆☆ Found in Text Mining only
Cognition Disorders	Cognitive disorder	BEFREE	18197082, 28108498, 28213064		★☆☆☆☆ Found in Text Mining only
Cognition Disorders	Cognition disorder	Pubtator	21281445	Associate	★☆☆☆☆ Found in Text Mining only
Colon Carcinoma	Colon Carcinoma	BEFREE	28114282		★☆☆☆☆ Found in Text Mining only
Depressive disorder	Mental Depression	BEFREE	24498053		★☆☆☆☆ Found in Text Mining only
Distal Myopathies	Distal myopathy	Pubtator	28615627	Associate	★☆☆☆☆ Found in Text Mining only
Epilepsy	Epilepsy	BEFREE	10441169, 31247287, 31837458		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Epilepsy, Benign Psychomotor, Childhood	Epilepsy	CTD_human_DG	18804094		★☆☆☆☆ Found in Text Mining only
Epilepsy, Lateral Temporal	Epilepsy	CTD_human_DG	18804094		★☆☆☆☆ Found in Text Mining only
Epilepsy, Temporal Lobe	Epilepsy	CTD_human_DG	18804094		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Esophageal Neoplasms	Esophageal neoplasm	Pubtator	19360286	Associate	★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	BEFREE	28212543		★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	Pubtator	34290229	Associate	★☆☆☆☆ Found in Text Mining only
Glioblastoma Multiforme	Glioblastoma	BEFREE	23175182		★☆☆☆☆ Found in Text Mining only
Glioma	Glioma	Pubtator	12614329	Associate	★☆☆☆☆ Found in Text Mining only
Glioma	Glioma	BEFREE	24482010, 28212543, 31073373		★☆☆☆☆ Found in Text Mining only
Impaired cognition	Impaired Cognition	BEFREE	18197082, 18541626, 28108498, 28213064		★☆☆☆☆ Found in Text Mining only
leukemia	Leukemia	BEFREE	19391040		★☆☆☆☆ Found in Text Mining only
Lymphoma	Lymphoma	BEFREE	19391040		★☆☆☆☆ Found in Text Mining only
MAJOR AFFECTIVE DISORDER 1	Major Affective Disorder	BEFREE	11840505, 23575746		★☆☆☆☆ Found in Text Mining only
MAJOR AFFECTIVE DISORDER 2	Major Affective Disorder	BEFREE	11840505, 23575746		★☆☆☆☆ Found in Text Mining only
MAJOR AFFECTIVE DISORDER 4	Major Affective Disorder	BEFREE	11840505, 23575746		★☆☆☆☆ Found in Text Mining only
MAJOR AFFECTIVE DISORDER 6	Major Affective Disorder	BEFREE	11840505, 23575746		★☆☆☆☆ Found in Text Mining only
MAJOR AFFECTIVE DISORDER 7	Major Affective Disorder	BEFREE	11840505, 23575746		★☆☆☆☆ Found in Text Mining only
MAJOR AFFECTIVE DISORDER 8	Major Affective Disorder	BEFREE	11840505, 23575746		★☆☆☆☆ Found in Text Mining only
MAJOR AFFECTIVE DISORDER 9	Major Affective Disorder	BEFREE	11840505, 23575746		★☆☆☆☆ Found in Text Mining only
Major Depressive Disorder	Mental Depression	BEFREE	16983646, 19386277, 29020418, 30326345		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant Glioma	Glioma	BEFREE	29525720		★☆☆☆☆ Found in Text Mining only
Malignant tumor of colon	Colonic Neoplasms	BEFREE	28114282		★☆☆☆☆ Found in Text Mining only
melanoma	Melanoma	BEFREE	21946352, 28646617		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
melanoma	Melanoma	CTD_human_DG	21946352, 22842228		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Melanoma	Melanoma	Pubtator	21946352	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Mental Depression	Mental Depression	BEFREE	24498053		★☆☆☆☆ Found in Text Mining only
Mental disorders	Mental Disorders	BEFREE	30005976, 31665922		★☆☆☆☆ Found in Text Mining only
Mood Disorders	Mood Disorder	BEFREE	19386277, 23575746		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Mood Disorders	Mood Disorder	PSYGENET_DG	19386277, 23575746		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Multiple Myeloma	Multiple myeloma	BEFREE	27431857		★☆☆☆☆ Found in Text Mining only
Multiple Sclerosis	Multiple Sclerosis	BEFREE	28236206		★☆☆☆☆ Found in Text Mining only
Muscular Dystrophy Duchenne	Duchenne muscular dystrophy	Pubtator	28615627	Associate	★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	23175182, 27431857, 28114282, 28212543, 28646617		★☆☆☆☆ Found in Text Mining only
Neuroblastoma	Neuroblastoma	BEFREE	11500049		★☆☆☆☆ Found in Text Mining only
Neurodegenerative Disorders	Neurodegenerative Disorders	BEFREE	30483053		★☆☆☆☆ Found in Text Mining only
Nonorganic psychosis	Nonorganic Psychosis	BEFREE	18541626, 21344500		★☆☆☆☆ Found in Text Mining only
Olivopontocerebellar Atrophies	Olivopontocerebellar Atrophies	BEFREE	12083339		★☆☆☆☆ Found in Text Mining only
Parkinson Disease	Parkinson disease	BEFREE	31632264		★☆☆☆☆ Found in Text Mining only
Psychotic Disorders	Psychosis	BEFREE	18541626, 21344500, 24682224		★☆☆☆☆ Found in Text Mining only
Psychotic Disorders	Psychotic disorders	Pubtator	24682224	Associate	★☆☆☆☆ Found in Text Mining only
Rasmussen Syndrome	Rasmussen`s Syndrome	BEFREE	10441170, 15249609, 7718238, 9892506		★☆☆☆☆ Found in Text Mining only
Schizophrenia	Schizophrenia	BEFREE	11840505, 12782962, 15310849, 15567072, 15892884, 15913960, 16365481, 16417579, 16585454, 16904291, 17006672, 17531207, 17726000, 17948896, 17982252, 18197082, 18256595, 18541626, 18614340, 18853337, 19403271, 19439994, 19482054, 19707855, 20638435, 21281445, 21344500, 22728822, 24498053, 24680030, 25096017, 25209194, 25583490, 25914064, 26187343, 27130562, 27296644, 28655286, 28786982, 30040841, 30890967, 31340894, 31665922		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Schizophrenia	Schizophrenia	LHGDN	11840505, 12782962, 15310849, 15913960, 16417579, 17531207, 17636131, 18614340, 18853337		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Schizophrenia	Schizophrenia	CTD_human_DG	18256595		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Schizophrenia	Schizophrenia	Pubtator	21281445	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Schizophrenia	Schizophrenia	GWASCAT_DG	25056061, 26198764, 28540026, 28991256, 29483656, 30285260, 31268507, 31374203		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Seborrheic dermatitis	Seborrheic dermatitis	GWASCAT_DG	29203360		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uncinate Epilepsy	Epilepsy	CTD_human_DG	18804094		★☆☆☆☆ Found in Text Mining only
Unipolar Depression	Mental Depression	BEFREE	16983646, 29020418		★☆☆☆☆ Found in Text Mining only