GRM1 (glutamate metabotropic receptor 1)

Gene

• Entrez ID: 2911
• Gene name: Glutamate metabotropic receptor 1
• Gene symbol: GRM1
• Synonyms (NCBI Gene): GPRC1A, MGLU1, MGLUR1, PPP1R85, SCA44, SCAR13
• Chromosome: 6
• Chromosome location: 6q24.3
• Summary: This gene encodes a metabotropic glutamate receptor that functions by activating phospholipase C. L-glutamate is the major excitatory neurotransmitter in the central nervous system and activates both ionotropic and metabotropic glutamate receptors. Glutam

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs211694392	GAA>-	Pathogenic	Coding sequence variant, inframe deletion
rs211694393	T>C,G	Pathogenic	Splice donor variant
rs752403373	G>A	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, missense variant
rs758809498	T>-,TT	Pathogenic	Genic upstream transcript variant, coding sequence variant, frameshift variant
rs774214806	C>A,T	Pathogenic	Stop gained, synonymous variant, coding sequence variant, genic upstream transcript variant
rs1554274719	A>G	Pathogenic	Missense variant, coding sequence variant, genic upstream transcript variant
rs1554308513	A>G	Pathogenic	Missense variant, coding sequence variant
rs1554317158	->C	Pathogenic	3 prime UTR variant, coding sequence variant, frameshift variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT022650	hsa-miR-124-3p	Microarray	18668037
MIRT721806	hsa-miR-5196-3p	HITS-CLIP	19536157
MIRT721804	hsa-miR-5193	HITS-CLIP	19536157
MIRT721805	hsa-miR-660-3p	HITS-CLIP	19536157
MIRT721803	hsa-miR-1285-3p	HITS-CLIP	19536157
MIRT721801	hsa-miR-3187-5p	HITS-CLIP	19536157
MIRT721802	hsa-miR-5189-5p	HITS-CLIP	19536157
MIRT721800	hsa-miR-612	HITS-CLIP	19536157
MIRT721799	hsa-miR-6860	HITS-CLIP	19536157
MIRT721798	hsa-miR-4505	HITS-CLIP	19536157
MIRT721797	hsa-miR-5787	HITS-CLIP	19536157
MIRT721796	hsa-miR-3945	HITS-CLIP	19536157
MIRT721795	hsa-miR-4253	HITS-CLIP	19536157
MIRT721794	hsa-miR-6862-5p	HITS-CLIP	19536157
MIRT721793	hsa-miR-1281	HITS-CLIP	19536157
MIRT721806	hsa-miR-5196-3p	HITS-CLIP	19536157
MIRT721804	hsa-miR-5193	HITS-CLIP	19536157
MIRT721805	hsa-miR-660-3p	HITS-CLIP	19536157
MIRT721803	hsa-miR-1285-3p	HITS-CLIP	19536157
MIRT721801	hsa-miR-3187-5p	HITS-CLIP	19536157
MIRT721802	hsa-miR-5189-5p	HITS-CLIP	19536157
MIRT721800	hsa-miR-612	HITS-CLIP	19536157
MIRT721799	hsa-miR-6860	HITS-CLIP	19536157
MIRT721798	hsa-miR-4505	HITS-CLIP	19536157
MIRT721797	hsa-miR-5787	HITS-CLIP	19536157
MIRT721796	hsa-miR-3945	HITS-CLIP	19536157
MIRT721795	hsa-miR-4253	HITS-CLIP	19536157
MIRT721794	hsa-miR-6862-5p	HITS-CLIP	19536157
MIRT721793	hsa-miR-1281	HITS-CLIP	19536157
MIRT1035051	hsa-miR-101	CLIP-seq
MIRT1035052	hsa-miR-139-5p	CLIP-seq
MIRT1035053	hsa-miR-144	CLIP-seq
MIRT1035054	hsa-miR-15a	CLIP-seq
MIRT1035055	hsa-miR-15b	CLIP-seq
MIRT1035056	hsa-miR-16	CLIP-seq
MIRT1035057	hsa-miR-195	CLIP-seq
MIRT1035058	hsa-miR-221	CLIP-seq
MIRT1035059	hsa-miR-222	CLIP-seq
MIRT1035060	hsa-miR-3160-5p	CLIP-seq
MIRT1035061	hsa-miR-3190	CLIP-seq
MIRT1035062	hsa-miR-3650	CLIP-seq
MIRT1035063	hsa-miR-3911	CLIP-seq
MIRT1035064	hsa-miR-424	CLIP-seq
MIRT1035065	hsa-miR-4446-5p	CLIP-seq
MIRT1035066	hsa-miR-4678	CLIP-seq
MIRT1035067	hsa-miR-4755-5p	CLIP-seq
MIRT1035068	hsa-miR-4795-3p	CLIP-seq
MIRT1035069	hsa-miR-497	CLIP-seq
MIRT1035070	hsa-miR-548v	CLIP-seq
MIRT1035071	hsa-miR-642a	CLIP-seq
MIRT1035072	hsa-miR-1252	CLIP-seq
MIRT1035073	hsa-miR-1273e	CLIP-seq
MIRT1035074	hsa-miR-129-5p	CLIP-seq
MIRT1035075	hsa-miR-1587	CLIP-seq
MIRT1035076	hsa-miR-3189-3p	CLIP-seq
MIRT1035077	hsa-miR-3667-3p	CLIP-seq
MIRT1035078	hsa-miR-4326	CLIP-seq
MIRT1035079	hsa-miR-4417	CLIP-seq
MIRT1035080	hsa-miR-4444	CLIP-seq
MIRT1035081	hsa-miR-4492	CLIP-seq
MIRT1035082	hsa-miR-4498	CLIP-seq
MIRT1035083	hsa-miR-4517	CLIP-seq
MIRT1035084	hsa-miR-4656	CLIP-seq
MIRT1035085	hsa-miR-4675	CLIP-seq
MIRT1035086	hsa-miR-4687-3p	CLIP-seq
MIRT1035087	hsa-miR-4741	CLIP-seq
MIRT1035088	hsa-miR-4760-3p	CLIP-seq
MIRT1035089	hsa-miR-502-5p	CLIP-seq
MIRT1035090	hsa-miR-762	CLIP-seq
MIRT1035072	hsa-miR-1252	CLIP-seq
MIRT1035083	hsa-miR-4517	CLIP-seq
MIRT2006894	hsa-miR-3681	CLIP-seq
MIRT2239400	hsa-miR-124	CLIP-seq
MIRT1035054	hsa-miR-15a	CLIP-seq
MIRT1035055	hsa-miR-15b	CLIP-seq
MIRT1035056	hsa-miR-16	CLIP-seq
MIRT1035057	hsa-miR-195	CLIP-seq
MIRT2239401	hsa-miR-204	CLIP-seq
MIRT2239402	hsa-miR-211	CLIP-seq
MIRT2239403	hsa-miR-3688-3p	CLIP-seq
MIRT2239404	hsa-miR-3714	CLIP-seq
MIRT2239405	hsa-miR-3910	CLIP-seq
MIRT2239406	hsa-miR-3919	CLIP-seq
MIRT2239407	hsa-miR-3938	CLIP-seq
MIRT1035064	hsa-miR-424	CLIP-seq
MIRT2239408	hsa-miR-4659a-3p	CLIP-seq
MIRT2239409	hsa-miR-4659b-3p	CLIP-seq
MIRT1035067	hsa-miR-4755-5p	CLIP-seq
MIRT2239410	hsa-miR-4760-5p	CLIP-seq
MIRT1035069	hsa-miR-497	CLIP-seq
MIRT2239411	hsa-miR-506	CLIP-seq
MIRT2239412	hsa-miR-623	CLIP-seq
MIRT1035054	hsa-miR-15a	CLIP-seq
MIRT1035055	hsa-miR-15b	CLIP-seq
MIRT1035056	hsa-miR-16	CLIP-seq
MIRT1035057	hsa-miR-195	CLIP-seq
MIRT1035064	hsa-miR-424	CLIP-seq
MIRT1035069	hsa-miR-497	CLIP-seq
MIRT2450803	hsa-miR-4802-3p	CLIP-seq
MIRT2450804	hsa-miR-570	CLIP-seq
MIRT2450805	hsa-miR-600	CLIP-seq
MIRT2450803	hsa-miR-4802-3p	CLIP-seq
MIRT2450804	hsa-miR-570	CLIP-seq
MIRT2450805	hsa-miR-600	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	TAS	7476890
GO:0005515	Function	Protein binding	IPI	19084525
GO:0005634	Component	Nucleus	IEA
GO:0005886	Component	Plasma membrane	IBA
GO:0005886	Component	Plasma membrane	IEA
GO:0005886	Component	Plasma membrane	IMP	24603153
GO:0005886	Component	Plasma membrane	TAS	7476890
GO:0007165	Process	Signal transduction	IEA
GO:0007186	Process	G protein-coupled receptor signaling pathway	IEA
GO:0007186	Process	G protein-coupled receptor signaling pathway	IMP	28886343
GO:0007186	Process	G protein-coupled receptor signaling pathway	TAS	7476890
GO:0007196	Process	Adenylate cyclase-inhibiting G protein-coupled glutamate receptor signaling pathway	IEA
GO:0007200	Process	Phospholipase C-activating G protein-coupled receptor signaling pathway	IDA	20966218, 37991948
GO:0007200	Process	Phospholipase C-activating G protein-coupled receptor signaling pathway	IDA	27276689
GO:0007200	Process	Phospholipase C-activating G protein-coupled receptor signaling pathway	IEA
GO:0007206	Process	Phospholipase C-activating G protein-coupled glutamate receptor signaling pathway	IEA
GO:0007206	Process	Phospholipase C-activating G protein-coupled glutamate receptor signaling pathway	IMP	24603153
GO:0007216	Process	G protein-coupled glutamate receptor signaling pathway	IBA
GO:0007268	Process	Chemical synaptic transmission	IEA
GO:0007268	Process	Chemical synaptic transmission	TAS	9076744
GO:0007626	Process	Locomotory behavior	IEA
GO:0008066	Function	Glutamate receptor activity	IDA	10945991, 24603153
GO:0008066	Function	Glutamate receptor activity	IEA
GO:0008066	Function	Glutamate receptor activity	TAS	7476890
GO:0014069	Component	Postsynaptic density	IEA
GO:0016020	Component	Membrane	IEA
GO:0019233	Process	Sensory perception of pain	IEA
GO:0030425	Component	Dendrite	IEA
GO:0038037	Component	G protein-coupled receptor dimeric complex	IDA	24603153
GO:0038038	Component	G protein-coupled receptor homodimeric complex	IPI	10945991
GO:0042391	Process	Regulation of membrane potential	IEA
GO:0042995	Component	Cell projection	IEA
GO:0043005	Component	Neuron projection	IEA
GO:0043410	Process	Positive regulation of MAPK cascade	IEA
GO:0044293	Component	Dendriole	ISS
GO:0045202	Component	Synapse	IEA
GO:0045211	Component	Postsynaptic membrane	IEA
GO:0051930	Process	Regulation of sensory perception of pain	IEA
GO:0051966	Process	Regulation of synaptic transmission, glutamatergic	IBA
GO:0060078	Process	Regulation of postsynaptic membrane potential	IEA
GO:0071257	Process	Cellular response to electrical stimulus	IEA
GO:0098685	Component	Schaffer collateral - CA1 synapse	IEA
GO:0098712	Process	L-glutamate import across plasma membrane	IEA
GO:0098839	Component	Postsynaptic density membrane	IBA
GO:0098872	Function	G protein-coupled neurotransmitter receptor activity involved in regulation of postsynaptic cytosolic calcium ion concentration	IEA
GO:0098978	Component	Glutamatergic synapse	IEA
GO:0099530	Function	G protein-coupled receptor activity involved in regulation of postsynaptic membrane potential	IBA
GO:0099530	Function	G protein-coupled receptor activity involved in regulation of postsynaptic membrane potential	IDA	27276689
GO:0099530	Function	G protein-coupled receptor activity involved in regulation of postsynaptic membrane potential	IEA
GO:0099538	Process	Synaptic signaling via neuropeptide	IDA	27276689
GO:0099538	Process	Synaptic signaling via neuropeptide	IEA
GO:0099566	Process	Regulation of postsynaptic cytosolic calcium ion concentration	IEA
GO:0099583	Function	Neurotransmitter receptor activity involved in regulation of postsynaptic cytosolic calcium ion concentration	IBA

Other IDs

• MIM: 604473
• HGNC: 4593
• e!Ensembl: ENSG00000152822

Protein

• UniProt ID: Q13255
• Protein name: Metabotropic glutamate receptor 1 (mGluR1)
• 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 activates a phospha
• PDB: 3KS9, 4OR2, 7DGD, 7DGE
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF01094	ANF_receptor	77 → 488	Receptor family ligand binding region	Family
  PF07562	NCD3G	520 → 571	Nine Cysteines Domain of family 3 GPCR	Family
  PF00003	7tm_3	604 → 837	7 transmembrane sweet-taste receptor of 3 GCPR	Family
  PF10606	GluR_Homer-bdg	1144 → 1194	Homer-binding domain of metabotropic glutamate receptor	Domain

• Tissue specificity: TISSUE SPECIFICITY: Detected in brain. {ECO:0000269|PubMed:9076744}.
• Sequence:

  MVGLLLFFFPAIFLEVSLLPRSPGRKVLLAGASSQRSVARMDGDVIIGALFSVHHQPPAE
  KVPERKCGEIREQYGIQRVEAMFHTLDKINADPVLLPNITLGSEIRDSCWHSSVALEQSI
  EFIRDSLISIRDEKDGINRCLPDGQSLPPGRTKKPIAGVIGPGSSSVAIQVQNLLQLFDI
  PQIAYSATSIDLSDKTLYKYFLRVVPSDTLQARAMLDIVKRYNWTYVSAVHTEGNYGESG
  MDAFKELAAQEGLCIAHSDKIYSNAGEKSFDRLLRKLRERLPKARVVVCFCEGMTVRGLL
  SAMRRLGVVGEFSLIGSDGWADRDEVIEGYEVEANGGITIKLQSPEVRSFDDYFLKLRLD
  TNTRNPWFPEFWQHRFQCRLPGHLLENPNFKRICTGNESLEENYVQDSKMGFVINAIYAM
  AHGLQNMHHALCPGHVGLCDAMKPIDGSKLLDFLIKSSFIGVSGEEVWFDEKGDAPGRYD
  IMNLQYTEANRYDYVHVGTWHEGVLNIDDYKIQMNKSGVVRSVCSEPCLKGQIKVIRKGE
  VSCCWICTACKENEYVQDEFTCKACDLGWWPNADLTGCEPIPVRYLEWSNIESIIAIAFS
  CLGILVTLFVTLIFVLYRDTPVVKSSSRELCYIILAGIFLGYVCPFTLIAKPTTTSCYLQ
  RLLVGLSSAMCYSALVTKTNRIARILAGSKKKICTRKPRFMSAWAQVIIASILISVQLTL
  VVTLIIMEPPMPILSYPSIKEVYLICNTSNLGVVAPLGYNGLLIMSCTYYAFKTRNVPAN
  FNEAKYIAFTMYTTCIIWLAFVPIYFGSNYKIITTCFAVSLSVTVALGCMFTPKMYIIIA
  KPERNVRSAFTTSDVVRMHVGDGKLPCRSNTFLNIFRRKKAGAGNANSNGKSVSWSEPGG
  GQVPKGQHMWHRLSVHVKTNETACNQTAVIKPLTKSYQGSGKSLTFSDTSTKTLYNVEEE
  EDAQPIRFSPPGSPSMVVHRRVPSAATTPPLPSHLTAEETPLFLAEPALPKGLPPPLQQQ
  QQPPPQQKSLMDQLQGVVSNFSTAIPDFHAVLAGPGGPGNGLRSLYPPPPPPQHLQMLPL
  QLSTFGEELVSPPADDDDDSERFKLLQEYVYEHEREGNTEEDELEEEEEDLQAASKLTPD
  DSPALTPPSPFRDSVASGSSVPSSPVSESVLCTPPNVSYASVILRDYKQSSSTL

• Sequence length: 1194

Pathways

KEGG:

Calcium signaling pathway
FoxO signaling pathway
Phospholipase D signaling pathway
Neuroactive ligand-receptor interaction
Gap junction
Long-term potentiation
Retrograde endocannabinoid signaling
Glutamatergic synapse
Long-term depression
Taste transduction
Estrogen signaling pathway
Spinocerebellar ataxia
Pathways of neurodegeneration - multiple diseases

Reactome:

G alpha (q) signalling events
Class C/3 (Metabotropic glutamate/pheromone receptors)
Neurexins and neuroligins

Associated diseases

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Autosomal recessive spinocerebellar ataxia 13	Pathogenic; Likely pathogenic	rs2483930312, rs774214806, rs758809498, rs988699004	RCV003314345 RCV000768403 RCV001009623 RCV001265623
Cerebellar ataxia	Pathogenic	rs2484001104	RCV003159088
Global developmental delay	Pathogenic	rs774214806	RCV001255402
Spinocerebellar ataxia 44	Likely pathogenic; Pathogenic	rs1554308513, rs1554274719, rs1554317158	RCV000507901 RCV000506447 RCV000507391

Unknown
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
-	no classification for the single variant	rs211694393, rs211694392	-
GRM1-related disorder	Uncertain significance; Likely benign; Benign; Conflicting classifications of pathogenicity	rs757559798, rs145345975, rs376313056, rs147521426, rs7760248, rs112915383, rs143544032, rs201399008, rs1583495145, rs2941	RCV003401787 RCV003943650 RCV003905298 RCV003905299 RCV003972873 RCV003960745 RCV003958047 RCV003413777 RCV004754670 RCV003973188
Ovarian serous cystadenocarcinoma	Conflicting classifications of pathogenicity	rs143544032	RCV005907352
See cases	Conflicting classifications of pathogenicity	rs1227591846	RCV002252439

Associations from Text Mining
Disease Name	Relationship Type	References
Ataxia	Associate	22901947, 28886343
Attention Deficit Disorder with Hyperactivity	Associate	22138692, 24985920, 34233526
Bipolar Disorder	Associate	21559497, 28751646
Breast Neoplasms	Associate	23922822, 28591718, 33339858
Cerebellar Ataxia	Associate	28886343, 36675067
Congenital Abnormalities	Associate	26308914
Diabetes Gestational	Associate	40298873
Diffuse Intrinsic Pontine Glioma	Associate	30124166
Disease	Associate	36140834
Drug Resistant Epilepsy	Associate	28388656
Epilepsy	Associate	11051119
Esophageal Neoplasms	Associate	33357046
Fibroma	Associate	35650682, 36810795, 38303543
Huntington Disease	Associate	22741533
Insulinoma	Associate	29851790
Intellectual Disability	Associate	26308914, 28886343, 36675067
Lewy Body Disease	Associate	15605986
Lymphoma Primary Effusion	Stimulate	25299066
Melanoma	Associate	19458050, 20505744, 22771868, 24330389, 29453787
Neoplasm Metastasis	Associate	23922822
Neoplasms	Associate	20061814, 22771868, 23340843, 25062106, 29453787, 35086953, 37036756
Neuroblastoma	Associate	23620748
Osteosarcoma	Associate	24399291
Pain	Associate	38128761
Prostatic Neoplasms	Associate	23072969, 25062106
Prostatic Neoplasms	Stimulate	35086953
Sarcoma Kaposi	Associate	25299066
Schizophrenia	Associate	21559497
Sleep Wake Disorders	Associate	36137075
Smoke Inhalation Injury	Associate	31568004
Spinocerebellar ataxia 13	Associate	36140834
Spinocerebellar Ataxias	Associate	26308914, 28886343, 30367527, 36675067
Spinocerebellar Degenerations	Associate	22901947
Triple Negative Breast Neoplasms	Associate	33339858