GCGR (glucagon receptor)

Gene

• Entrez ID: 2642
• Gene name: Glucagon receptor
• Gene symbol: GCGR
• Synonyms (NCBI Gene): GGR, GL-R, MVAH
• Chromosome: 17
• Chromosome location: 17q25.3
• Summary: The protein encoded by this gene is a glucagon receptor that is important in controlling blood glucose levels. Defects in this gene are a cause of non-insulin-dependent diabetes mellitus (NIDDM).[provided by RefSeq, Jan 2010]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs1801483	G>A	Pathogenic, benign	Coding sequence variant, missense variant, 5 prime UTR variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT1014614	hsa-miR-1268	CLIP-seq
MIRT1014615	hsa-miR-1268b	CLIP-seq
MIRT1014616	hsa-miR-145	CLIP-seq
MIRT1014617	hsa-miR-198	CLIP-seq
MIRT1014618	hsa-miR-323b-5p	CLIP-seq
MIRT1014619	hsa-miR-3940-5p	CLIP-seq
MIRT1014620	hsa-miR-4277	CLIP-seq
MIRT1014621	hsa-miR-4314	CLIP-seq
MIRT1014622	hsa-miR-4447	CLIP-seq
MIRT1014623	hsa-miR-4472	CLIP-seq
MIRT1014624	hsa-miR-4488	CLIP-seq
MIRT1014625	hsa-miR-4507	CLIP-seq
MIRT1014626	hsa-miR-4651	CLIP-seq
MIRT1014627	hsa-miR-4697-5p	CLIP-seq
MIRT1014628	hsa-miR-585	CLIP-seq
MIRT1014629	hsa-miR-608	CLIP-seq
MIRT2233942	hsa-miR-3943	CLIP-seq
MIRT2233943	hsa-miR-4286	CLIP-seq
MIRT2388396	hsa-miR-361-3p	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
ECD	Repression	22908259

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004888	Function	Transmembrane signaling receptor activity	IEA
GO:0004930	Function	G protein-coupled receptor activity	IEA
GO:0004967	Function	Glucagon receptor activity	IBA
GO:0004967	Function	Glucagon receptor activity	IDA	9287038, 28514451
GO:0004967	Function	Glucagon receptor activity	IEA
GO:0004967	Function	Glucagon receptor activity	TAS	8144028
GO:0005085	Function	Guanyl-nucleotide exchange factor activity	TAS
GO:0005886	Component	Plasma membrane	IBA
GO:0005886	Component	Plasma membrane	IDA	9287038
GO:0005886	Component	Plasma membrane	IEA
GO:0005886	Component	Plasma membrane	IEA
GO:0005886	Component	Plasma membrane	IMP	28514451
GO:0005886	Component	Plasma membrane	TAS	8144028
GO:0006091	Process	Generation of precursor metabolites and energy	TAS	7773293
GO:0007165	Process	Signal transduction	IEA
GO:0007166	Process	Cell surface receptor signaling pathway	IEA
GO:0007186	Process	G protein-coupled receptor signaling pathway	IEA
GO:0007188	Process	Adenylate cyclase-modulating G protein-coupled receptor signaling pathway	IEA
GO:0007188	Process	Adenylate cyclase-modulating G protein-coupled receptor signaling pathway	IMP	9287038
GO:0007188	Process	Adenylate cyclase-modulating G protein-coupled receptor signaling pathway	TAS	8144028
GO:0007189	Process	Adenylate cyclase-activating G protein-coupled receptor signaling pathway	IBA
GO:0007189	Process	Adenylate cyclase-activating G protein-coupled receptor signaling pathway	IDA	28514451
GO:0007584	Process	Response to nutrient	TAS	7773293
GO:0008217	Process	Regulation of blood pressure	TAS	8563746
GO:0009267	Process	Cellular response to starvation	IEA
GO:0009267	Process	Cellular response to starvation	ISS
GO:0010628	Process	Positive regulation of gene expression	IEA
GO:0010628	Process	Positive regulation of gene expression	ISS
GO:0016020	Component	Membrane	IEA
GO:0016020	Component	Membrane	TAS	8144028
GO:0017046	Function	Peptide hormone binding	IBA
GO:0042593	Process	Glucose homeostasis	IEA
GO:0042593	Process	Glucose homeostasis	ISS
GO:0042594	Process	Response to starvation	IEA
GO:0042594	Process	Response to starvation	ISS
GO:0070873	Process	Regulation of glycogen metabolic process	IEA
GO:0070873	Process	Regulation of glycogen metabolic process	ISS
GO:0071377	Process	Cellular response to glucagon stimulus	IDA	9287038
GO:0071377	Process	Cellular response to glucagon stimulus	IEA
GO:0071377	Process	Cellular response to glucagon stimulus	TAS

Other IDs

• MIM: 138033
• HGNC: 4192
• e!Ensembl: ENSG00000215644

Protein

• UniProt ID: P47871
• Protein name: Glucagon receptor (GL-R)
• Protein function: G-protein coupled receptor for glucagon that plays a central role in the regulation of blood glucose levels and glucose homeostasis. Regulates the rate of hepatic glucose production by promoting glycogen hydrolysis and gluconeogenesis. Plays an
• PDB: 2A83, 3CZF, 4ERS, 4L6R, 4LF3, 5EE7, 5XEZ, 6LMK, 6LML, 6WHC, 6WPW, 7V35, 8FU6, 8JIQ, 8JIT, 8JIU, 8JRU, 8JRV, 8WG8, 8YW5
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF02793	HRM	55 → 124	Hormone receptor domain	Family
  PF00002	7tm_2	138 → 396	7 transmembrane receptor (Secretin family)	Family

• Sequence:

  MPPCQPQRPLLLLLLLLACQPQVPSAQVMDFLFEKWKLYGDQCHHNLSLLPPPTELVCNR
  TFDKYSCWPDTPANTTANISCPWYLPWHHKVQHRFVFKRCGPDGQWVRGPRGQPWRDASQ
  CQMDGEEIEVQKEVAKMYSSFQVMYTVGYSLSLGALLLALAILGGLSKLHCTRNAIHANL
  FASFVLKASSVLVIDGLLRTRYSQKIGDDLSVSTWLSDGAVAGCRVAAVFMQYGIVANYC
  WLLVEGLYLHNLLGLATLPERSFFSLYLGIGWGAPMLFVVPWAVVKCLFENVQCWTSNDN
  MGFWWILRFPVFLAILINFFIFVRIVQLLVAKLRARQMHHTDYKFRLAKSTLTLIPLLGV
  HEVVFAFVTDEHAQGTLRSAKLFFDLFLSSFQGLLVAVLYCFLNKEVQSELRRRWHRWRL
  GKVLWEERNTSNHRASSSPGHGPPSKELQFGRGGGSQDSSAETPLAGGLPRLAESPF

• Sequence length: 477

Pathways

KEGG:

Neuroactive ligand-receptor interaction
Hormone signaling
Glucagon signaling pathway

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)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
GCGR-related hyperglucagonemia	Pathogenic	rs2143128666, rs1598239171, rs1296378838, rs2509907102	RCV001374855 RCV001374860 RCV003994539 RCV003994540	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
DIABETES MELLITUS, NON-INSULIN-DEPENDENT	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GCGR-related disorder	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SYSTEMIC LUPUS ERYTHEMATOSUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Type 2 diabetes mellitus	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine carcinosarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Acth-Independent Macronodular Adrenal Hyperplasia	Cushing`s Syndrome	CTD_human_DG	20529775		★☆☆☆☆ Found in Text Mining only
Adrenal Gland Pheochromocytoma	Adrenal Gland Pheochromocytoma	BEFREE	11311729		★☆☆☆☆ Found in Text Mining only
Anxiety	Anxiety disorder	Pubtator	22908259	Associate	★☆☆☆☆ Found in Text Mining only
Arteriosclerosis	Arteriosclerosis	BEFREE	29325849		★☆☆☆☆ Found in Text Mining only
Atherosclerosis	Atherosclerosis	BEFREE	29325849		★☆☆☆☆ Found in Text Mining only
Carcinoma Pancreatic Ductal	Pancreatic ductal carcinoma	Pubtator	19657311	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Renal Cell	Renal cell carcinoma	Pubtator	26831905	Associate	★☆☆☆☆ Found in Text Mining only
Cholelithiasis	Cholelithiasis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Colon Carcinoma	Colon Carcinoma	BEFREE	29535833		★☆☆☆☆ Found in Text Mining only
Diabetes	Diabetes	BEFREE	23019069, 23562625, 28487437, 29031717, 29052441, 29879354, 29992313, 30170980, 8985646		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus	Diabetes Mellitus	BEFREE	23019069, 23562625, 28487437, 28775305, 29031717, 29052441, 29879354, 29992313, 30170980, 7589886, 8541847, 8985646		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus	Diabetes mellitus	Pubtator	35381520	Associate	★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus Type 2	Diabetes mellitus, type 2	Pubtator	25521597, 33097629	Associate	★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus, Insulin-Dependent	Diabetes Mellitus	BEFREE	28487437, 29283470, 30170980, 8541847, 9325468		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus, Non-Insulin-Dependent	Diabetes Mellitus	BEFREE	10090412, 10510728, 11961492, 15931615, 15948676, 25197025, 27501510, 28191913, 28237861, 28260721, 28371155, 28463898, 28514451, 28642113, 28654184, 28755409, 29052441, 29444429, 29535833, 29546411, 29923286, 29926478, 29945727, 30091218, 30203123, 30366787, 30391422, 30765435, 31068828, 31138472, 31443129, 31786794, 31808298, 7589886, 7773293, 8541847, 8635644, 8690179, 8712800, 8732719, 8858207, 8879960, 8931690, 9028723, 9059762, 9285210		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Diabetes Mellitus, Non-Insulin-Dependent	Diabetes Mellitus	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Diabetes Mellitus, Non-Insulin-Dependent	Diabetes Mellitus	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Dyslipidemias	Dyslipidemias	BEFREE	29275178, 29325849		★☆☆☆☆ Found in Text Mining only
Essential Hypertension	Hypertension	BEFREE	10090412, 10406817, 8977155, 9673441		★☆☆☆☆ Found in Text Mining only
Ewings sarcoma-primitive neuroectodermal tumor (PNET)	Ewing sarcoma	BEFREE	30294546		★☆☆☆☆ Found in Text Mining only
GCGR-related hyperglucagonemia	Hyperglucagonemia	Orphanet			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Glucagonoma	Glucagonoma	BEFREE	19657311, 28108603		★☆☆☆☆ Found in Text Mining only
Glucagonoma	Glucagonoma	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hyperglycemia	Hyperglycemia	BEFREE	15948676, 23305646, 25301258, 28463898, 28487437, 28775305, 30150304, 30170980, 30366787, 30920583		★☆☆☆☆ Found in Text Mining only
Hyperinsulinism	Hyperinsulinism	BEFREE	30650080		★☆☆☆☆ Found in Text Mining only
Hypertensive disease	Hypertension	BEFREE	11692154, 9673441		★☆☆☆☆ Found in Text Mining only
Hypertensive disease	Hypertension	LHGDN	11692154		★☆☆☆☆ Found in Text Mining only
Hypoglycemia	Hypoglycemia	BEFREE	26020795		★☆☆☆☆ Found in Text Mining only
Islet Cell Tumor	Islet Cell Tumor	BEFREE	19657311, 30294546		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	29535833		★☆☆☆☆ Found in Text Mining only
Malignant tumor of colon	Colonic Neoplasms	BEFREE	29535833		★☆☆☆☆ Found in Text Mining only
Metabolic Diseases	Metabolic Diseases	BEFREE	29412830, 29925501		★☆☆☆☆ Found in Text Mining only
Metabolic Syndrome X	Metabolic Syndrome	BEFREE	31405212		★☆☆☆☆ Found in Text Mining only
Myocardial Infarction	Myocardial Infarction	BEFREE	30626440		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	25695890, 28108603, 30294546, 31782107		★☆☆☆☆ Found in Text Mining only
Neuroectodermal Tumor, Primitive	Neuroectodermal Tumors	BEFREE	30294546		★☆☆☆☆ Found in Text Mining only
Neuroendocrine Tumors	Neuroendocrine Tumors	BEFREE	21853126, 22693263, 24285676		★☆☆☆☆ Found in Text Mining only
Non-alcoholic Fatty Liver Disease	Non-Alcoholic Fatty Liver Disease	BEFREE	30459715, 31386258		★☆☆☆☆ Found in Text Mining only
Nonalcoholic Steatohepatitis	Non-alcoholic Fatty Liver Disease	BEFREE	29926478		★☆☆☆☆ Found in Text Mining only
Obesity	Obesity	BEFREE	21294225, 23019069, 28733905, 29412829, 29879354, 31389463, 31786794, 9673441		★☆☆☆☆ Found in Text Mining only
Pancreatic Neoplasm	Pancreatic Neoplasm	HPO_DG			★☆☆☆☆ Found in Text Mining only
Papillary thyroid carcinoma	Papillary thyroid carcinoma	BEFREE	31782107		★☆☆☆☆ Found in Text Mining only
Pheochromocytoma	Pheochromocytoma	BEFREE	11311729		★☆☆☆☆ Found in Text Mining only
Sarcoma Endometrial Stromal	Endometrial stromal sarcoma	Pubtator	23178314	Associate	★☆☆☆☆ Found in Text Mining only
Skin lesion	Skin Lesion	BEFREE	28108603		★☆☆☆☆ Found in Text Mining only
Steatohepatitis	Fatty Liver	BEFREE	27880981		★☆☆☆☆ Found in Text Mining only