GRM4 (glutamate metabotropic receptor 4)

Gene

• Entrez ID: 2914
• Gene name: Glutamate metabotropic receptor 4
• Gene symbol: GRM4
• Synonyms (NCBI Gene): GPRC1D, MGLUR4, mGlu4
• Chromosome: 6
• Chromosome location: 6p21.31
• 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
MIRT054785	hsa-miR-1202	Immunocytochemistry, qRT-PCR, /Western blot	24908571
MIRT1035091	hsa-miR-1224-5p	CLIP-seq
MIRT1035092	hsa-miR-1321	CLIP-seq
MIRT1035093	hsa-miR-1324	CLIP-seq
MIRT1035094	hsa-miR-185	CLIP-seq
MIRT1035095	hsa-miR-28-5p	CLIP-seq
MIRT1035096	hsa-miR-3139	CLIP-seq
MIRT1035097	hsa-miR-3160-3p	CLIP-seq
MIRT1035098	hsa-miR-3605-5p	CLIP-seq
MIRT1035099	hsa-miR-4306	CLIP-seq
MIRT1035100	hsa-miR-4419a	CLIP-seq
MIRT1035101	hsa-miR-4459	CLIP-seq
MIRT1035102	hsa-miR-4510	CLIP-seq
MIRT1035103	hsa-miR-4644	CLIP-seq
MIRT1035104	hsa-miR-4728-5p	CLIP-seq
MIRT1035105	hsa-miR-4739	CLIP-seq
MIRT1035106	hsa-miR-4751	CLIP-seq
MIRT1035107	hsa-miR-4756-5p	CLIP-seq
MIRT1035108	hsa-miR-583	CLIP-seq
MIRT1035109	hsa-miR-708	CLIP-seq
MIRT1035110	hsa-miR-765	CLIP-seq
MIRT1035093	hsa-miR-1324	CLIP-seq
MIRT2006900	hsa-miR-31	CLIP-seq
MIRT1035101	hsa-miR-4459	CLIP-seq
MIRT2006901	hsa-miR-4539	CLIP-seq
MIRT2006902	hsa-miR-4680-5p	CLIP-seq
MIRT2006903	hsa-miR-4696	CLIP-seq
MIRT2006904	hsa-miR-4724-5p	CLIP-seq
MIRT1035091	hsa-miR-1224-5p	CLIP-seq
MIRT1035093	hsa-miR-1324	CLIP-seq
MIRT2239423	hsa-miR-182	CLIP-seq
MIRT1035095	hsa-miR-28-5p	CLIP-seq
MIRT2239424	hsa-miR-3117-5p	CLIP-seq
MIRT1035096	hsa-miR-3139	CLIP-seq
MIRT1035097	hsa-miR-3160-3p	CLIP-seq
MIRT2239425	hsa-miR-3614-5p	CLIP-seq
MIRT2239426	hsa-miR-3649	CLIP-seq
MIRT2239427	hsa-miR-4456	CLIP-seq
MIRT1035101	hsa-miR-4459	CLIP-seq
MIRT2239428	hsa-miR-4648	CLIP-seq
MIRT2239429	hsa-miR-4717-5p	CLIP-seq
MIRT2239430	hsa-miR-4722-5p	CLIP-seq
MIRT2239431	hsa-miR-4733-3p	CLIP-seq
MIRT1035106	hsa-miR-4751	CLIP-seq
MIRT2239432	hsa-miR-541	CLIP-seq
MIRT1035108	hsa-miR-583	CLIP-seq
MIRT2239433	hsa-miR-603	CLIP-seq
MIRT2239434	hsa-miR-654-5p	CLIP-seq
MIRT2239435	hsa-miR-665	CLIP-seq
MIRT1035109	hsa-miR-708	CLIP-seq
MIRT2239436	hsa-miR-711	CLIP-seq
MIRT1035110	hsa-miR-765	CLIP-seq
MIRT1035093	hsa-miR-1324	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001640	Function	Adenylate cyclase inhibiting G protein-coupled glutamate receptor activity	IBA
GO:0004930	Function	G protein-coupled receptor activity	IEA
GO:0004930	Function	G protein-coupled receptor activity	IMP	8738157, 9473604
GO:0005886	Component	Plasma membrane	IBA
GO:0005886	Component	Plasma membrane	IDA	15102938
GO:0005886	Component	Plasma membrane	IEA
GO:0005886	Component	Plasma membrane	TAS	8738157
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:0007196	Process	Adenylate cyclase-inhibiting G protein-coupled glutamate receptor signaling pathway	IEA
GO:0007196	Process	Adenylate cyclase-inhibiting G protein-coupled glutamate receptor signaling pathway	IMP	15102938
GO:0007216	Process	G protein-coupled glutamate receptor signaling pathway	IBA
GO:0007216	Process	G protein-coupled glutamate receptor signaling pathway	IDA	37286794
GO:0007268	Process	Chemical synaptic transmission	TAS	8738157
GO:0007269	Process	Neurotransmitter secretion	TAS	15102938
GO:0008066	Function	Glutamate receptor activity	IEA
GO:0008066	Function	Glutamate receptor activity	IMP	8738157, 9473604
GO:0016020	Component	Membrane	IEA
GO:0031410	Component	Cytoplasmic vesicle	IDA	15102938
GO:0043410	Process	Positive regulation of MAPK cascade	IDA	15102938
GO:0043523	Process	Regulation of neuron apoptotic process	TAS	15102938
GO:0045202	Component	Synapse	IEA
GO:0051966	Process	Regulation of synaptic transmission, glutamatergic	IBA
GO:0098793	Component	Presynapse	IEA

Other IDs

• MIM: 604100
• HGNC: 4596
• e!Ensembl: ENSG00000124493

Protein

• UniProt ID: Q14833
• Protein name: Metabotropic glutamate receptor 4 (mGluR4)
• 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: 7E9H, 8JD4, 8JD5, 8JD6, 8WG9, 8WGB, 8WGC, 8WGD
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF01094	ANF_receptor	77 → 484	Receptor family ligand binding region	Family
  PF07562	NCD3G	516 → 566	Nine Cysteines Domain of family 3 GPCR	Family
  PF00003	7tm_3	599 → 844	7 transmembrane sweet-taste receptor of 3 GCPR	Family

• Tissue specificity: TISSUE SPECIFICITY: Strongly expressed in the cerebellum. Expressed at low levels in hippocampus, hypothalamus and thalamus. No expression detected in liver. {ECO:0000269|PubMed:7617140, ECO:0000269|PubMed:8738157}.
• Sequence:

  MPGKRGLGWWWARLPLCLLLSLYGPWMPSSLGKPKGHPHMNSIRIDGDITLGGLFPVHGR
  GSEGKPCGELKKEKGIHRLEAMLFALDRINNDPDLLPNITLGARILDTCSRDTHALEQSL
  TFVQALIEKDGTEVRCGSGGPPIITKPERVVGVIGASGSSVSIMVANILRLFKIPQISYA
  STAPDLSDNSRYDFFSRVVPSDTYQAQAMVDIVRALKWNYVSTVASEGSYGESGVEAFIQ
  KSREDGGVCIAQSVKIPREPKAGEFDKIIRRLLETSNARAVIIFANEDDIRRVLEAARRA
  NQTGHFFWMGSDSWGSKIAPVLHLEEVAEGAVTILPKRMSVRGFDRYFSSRTLDNNRRNI
  WFAEFWEDNFHCKLSRHALKKGSHVKKCTNRERIGQDSAYEQEGKVQFVIDAVYAMGHAL
  HAMHRDLCPGRVGLCPRMDPVDGTQLLKYIRNVNFSGIAGNPVTFNENGDAPGRYDIYQY
  QLRNDSAEYKVIGSWTDHLHLRIERMHWPGSGQQLPRSICSLPCQPGERKKTVKGMPCCW
  HCEPCTGYQYQVDRYTCKTCPYDMRPTENRTGCRPIPIIKLEWGSPWAVLPLFLAVVGIA
  ATLFVVITFVRYNDTPIVKASGRELSYVLLAGIFLCYATTFLMIAEPDLGTCSLRRIFLG
  LGMSISYAALLTKTNRIYRIFEQGKRSVSAPRFISPASQLAITFSLISLQLLGICVWFVV
  DPSHSVVDFQDQRTLDPRFARGVLKCDISDLSLICLLGYSMLLMVTCTVYAIKTRGVPET
  FNEAKPIGFTMYTTCIVWLAFIPIFFGTSQSADKLYIQTTTLTVSVSLSASVSLGMLYMP
  KVYIILFHPEQNVPKRKRSLKAVVTAATMSNKFTQKGNFRPNGEAKSELCENLEAPALAT
  KQTYVTYTNHAI

• Sequence length: 912

Pathways

KEGG:

Phospholipase D signaling pathway
Neuroactive ligand-receptor interaction
Glutamatergic synapse
Taste transduction

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
ASTHMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATOPIC ECZEMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BIPOLAR DISORDER	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHILDHOOD ONSET ASTHMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
EPILEPSY, TEMPORAL LOBE	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
INFLAMMATORY SKIN DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OSTEONECROSIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OSTEOSARCOMA	—	CTD, GWAS catalog CTD, GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PSORIASIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SARCOIDOSIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCHIZOPHRENIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Adult Medulloblastoma	Medulloblastoma	BEFREE	29525720		★☆☆☆☆ Found in Text Mining only
Bipolar Disorder	Bipolar Disorder	PSYGENET_DG	16380905, 17239033		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Bipolar Disorder	Bipolar disorder	Pubtator	16380905	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Bladder Neoplasm	Bladder Neoplasm	BEFREE	30145816		★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	31492116		★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	31492116	Associate	★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	33318294	Stimulate	★☆☆☆☆ Found in Text Mining only
Carcinoma of bladder	Bladder carcinoma	BEFREE	30145816		★☆☆☆☆ Found in Text Mining only
Carcinoma Renal Cell	Renal cell carcinoma	Pubtator	30488581, 32788609	Associate	★☆☆☆☆ Found in Text Mining only
Catalepsy	Catalepsy	BEFREE	28902994		★☆☆☆☆ Found in Text Mining only
Childhood Medulloblastoma	Medulloblastoma	BEFREE	29525720		★☆☆☆☆ Found in Text Mining only
CNS disorder	CNS Disorder	BEFREE	29486616		★☆☆☆☆ Found in Text Mining only
Colonic Neoplasms	Colonic Neoplasms	LHGDN	15217955		★☆☆☆☆ Found in Text Mining only
Conventional (Clear Cell) Renal Cell Carcinoma	Renal Carcinoma	BEFREE	30488581		★☆☆☆☆ Found in Text Mining only
Depressive disorder	Mental Depression	BEFREE	27792966		★☆☆☆☆ Found in Text Mining only
Dyskinetic syndrome	Dyskinetic Syndrome	BEFREE	30066121		★☆☆☆☆ Found in Text Mining only
Epilepsy	Epilepsy	BEFREE	11223165, 18463015		★☆☆☆☆ Found in Text Mining only
Epilepsy, Benign Psychomotor, Childhood	Epilepsy	CTD_human_DG	15694259		★☆☆☆☆ Found in Text Mining only
Epilepsy, Generalized	Epilepsy	BEFREE	20338729		★☆☆☆☆ Found in Text Mining only
Epilepsy, Lateral Temporal	Epilepsy	CTD_human_DG	15694259		★☆☆☆☆ Found in Text Mining only
Epilepsy, Temporal Lobe	Epilepsy	CTD_human_DG	15694259		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Glioblastoma Multiforme	Glioblastoma	BEFREE	29867331		★☆☆☆☆ Found in Text Mining only
Glioma	Glioma	Pubtator	38164693	Associate	★☆☆☆☆ Found in Text Mining only
Idiopathic generalized epilepsy	Epilepsy	BEFREE	14582146, 20338729		★☆☆☆☆ Found in Text Mining only
Juvenile Myoclonic Epilepsy	Myoclonic Epilepsy	BEFREE	11223165, 14582146, 20338729, 28636645		★☆☆☆☆ Found in Text Mining only
Major Depressive Disorder	Mental Depression	BEFREE	27792966		★☆☆☆☆ Found in Text Mining only
Malignant Glioma	Glioma	BEFREE	29525720		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	31492116		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of urinary bladder	Urinary bladder cancer	BEFREE	30145816		★☆☆☆☆ Found in Text Mining only
Medulloblastoma	Medulloblastoma	LHGDN	16899734		★☆☆☆☆ Found in Text Mining only
Medulloblastoma	Medulloblastoma	BEFREE	29525720		★☆☆☆☆ Found in Text Mining only
Mental Depression	Mental Depression	BEFREE	27792966		★☆☆☆☆ Found in Text Mining only
Metabolic Diseases	Metabolic Diseases	BEFREE	29486616		★☆☆☆☆ Found in Text Mining only
Mitral Valve Stenosis	Mitral Valve Stenosis	BEFREE	15589052		★☆☆☆☆ Found in Text Mining only
Multiple Sclerosis	Multiple Sclerosis	BEFREE	15589052		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	24399291, 30145816, 31492116, 31581881		★☆☆☆☆ Found in Text Mining only
Neurodegenerative Disorders	Neurodegenerative Disorders	BEFREE	30483053		★☆☆☆☆ Found in Text Mining only
Osteosarcoma	Osteosarcoma	GWASDB_DG	23727862		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Osteosarcoma	Osteosarcoma	GWASCAT_DG	23727862		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Osteosarcoma	Osteosarcoma	CTD_human_DG	23727862		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Osteosarcoma	Osteosarcoma	Pubtator	23727862, 24399291, 24984297, 26276359, 29339716	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Osteosarcoma	Osteosarcoma	BEFREE	24399291, 24984297, 26276359, 31527131, 31581881		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Parkinson Disease	Parkinson disease	BEFREE	22088953, 27441572, 28694498, 28902994, 29625424, 30066121		★☆☆☆☆ Found in Text Mining only
Parkinsonian Disorders	Parkinson Disease	BEFREE	30216534		★☆☆☆☆ Found in Text Mining only
Psychotic Disorders	Psychotic disorders	Pubtator	16380905	Associate	★☆☆☆☆ Found in Text Mining only
Renal Cell Carcinoma	Renal Carcinoma	BEFREE	30488581		★☆☆☆☆ Found in Text Mining only
Schizophrenia	Schizophrenia	BEFREE	11525421, 19351574		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Schizophrenia	Schizophrenia	PSYGENET_DG	11525421, 19351574, 23714430		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Schizophrenia	Schizophrenia	Pubtator	16380905	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uncinate Epilepsy	Epilepsy	CTD_human_DG	15694259		★☆☆☆☆ Found in Text Mining only
Unipolar Depression	Mental Depression	BEFREE	27792966		★☆☆☆☆ Found in Text Mining only