GCGR

glucagon receptor, the group of Glucagon receptor family

Basic information

Region (hg38): 17:81804132-81814008

Links

ENSG00000215644 ∙ NCBI:2642 ∙ OMIM:138033 ∙ HGNC:4192 ∙ Uniprot:P47871 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• GCGR-related hyperglucagonemia (Supportive), mode of inheritance: AR
• GCGR-related hyperglucagonemia (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mahvash disease	AR	Endocrine; Oncologic	The condition can involve alpha-cell hyperplasia with glucagonemia, and can lead to glucagonomas and/or primitive neuroectodermal tumors, and awareness may allow early diagnosis and management of medical manifestations and neoplasms	Endocrine; Oncologic	19657311; 29702528; 30032256; 30294546; 32677665

ClinVar

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

• GCGR-related hyperglucagonemia (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GCGR 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			1	23	11	35
missense			60	6	2	68
nonsense			1			1
start loss						0
frameshift	2					2
inframe indel			2			2
splice donor/acceptor (+/-2bp)						0
splice region			2	4	3	9
non coding				18	8	26
Total	2	0	64	47	21

Highest pathogenic variant AF is 0.0000200

Variants in GCGR

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

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

Position	Type	Phenotype	Significance	ClinVar
17-81809026-C-T		not specified	Uncertain significance (Nov 10, 2022)
17-81809032-A-C			Uncertain significance (Feb 13, 2023)
17-81809063-G-A			Likely benign (May 14, 2022)
17-81809064-C-T			Likely benign (Sep 01, 2022)
17-81809071-C-A		not specified	Uncertain significance (May 25, 2022)
17-81809086-C-T			Likely benign (Oct 19, 2023)
17-81809773-G-A			Benign (Oct 13, 2023)
17-81809779-C-A			Uncertain significance (Nov 01, 2022)
17-81809839-G-A		Type 2 diabetes mellitus	Benign/Likely benign (Jan 07, 2024)
17-81809865-C-T		GCGR-related disorder	Likely benign (Feb 21, 2019)
17-81809875-C-A			Uncertain significance (Dec 12, 2022)
17-81809882-C-T		not specified	Uncertain significance (Sep 16, 2021)
17-81809889-GC-G			Benign (Oct 17, 2022)
17-81809903-G-A			Likely benign (Jan 12, 2023)
17-81810847-C-T			Benign (Dec 25, 2021)
17-81810848-G-A		GCGR-related hyperglucagonemia	Uncertain significance (Nov 19, 2023)
17-81810875-C-G		not specified	Uncertain significance (Jan 06, 2023)
17-81810878-G-A			Uncertain significance (Aug 04, 2023)
17-81810888-C-T		not specified	Conflicting classifications of pathogenicity (Dec 25, 2023)
17-81810896-A-G		not specified	Uncertain significance (Nov 18, 2022)
17-81810904-C-T			Likely benign (Jun 23, 2023)
17-81810906-C-T			Uncertain significance (Nov 28, 2023)
17-81810907-CT-C		GCGR-related hyperglucagonemia	Pathogenic (Jun 29, 2023)
17-81810917-C-T		GCGR-related hyperglucagonemia	Pathogenic (Apr 22, 2021)
17-81810923-C-A		not specified	Uncertain significance (Feb 10, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GCGR	protein_coding	protein_coding	ENST00000400723	13	9882

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000222	0.977	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.66	220	301	0.730	0.0000198	3058
Missense in Polyphen		62	108.38	0.57204		1169
Synonymous	0.314	128	133	0.965	0.00000940	941
Loss of Function	2.10	13	24.1	0.539	0.00000108	249

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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 important role in mediating the responses to fasting. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Promotes activation of adenylate cyclase. Besides, plays a role in signaling via a phosphatidylinositol-calcium second messenger system. {ECO:0000269|PubMed:19657311, ECO:0000269|PubMed:22908259, ECO:0000269|PubMed:23863937, ECO:0000269|PubMed:27111510, ECO:0000269|PubMed:28514451, ECO:0000269|PubMed:7507321, ECO:0000269|PubMed:9287038}.
• Pathway: Glucagon signaling pathway - Homo sapiens (human);Neuroactive ligand-receptor interaction - Homo sapiens (human);GPCRs, Class B Secretin-like;Signaling by GPCR;Signal Transduction;Glucagon signaling in metabolic regulation;Metabolism;G alpha (s) signalling events;Glucagon-type ligand receptors;Class B/2 (Secretin family receptors);GPCR ligand binding;Integration of energy metabolism;G alpha (q) signalling events;GPCR downstream signalling (Consensus)

Intolerance Scores

• rvis_EVS: 0.19
• rvis_percentile_EVS: 67.03

Haploinsufficiency Scores

• pHI: 0.314
• hipred: N
• hipred_score: 0.378
• ghis: 0.391

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.577

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gcgr
• Phenotype: homeostasis/metabolism phenotype; cellular phenotype; growth/size/body region 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); adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); neoplasm; endocrine/exocrine gland phenotype; digestive/alimentary phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; 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); normal phenotype; reproductive system phenotype

Zebrafish Information Network

• Gene name: gcgrb
• Affected structure: pancreatic A cell
• Phenotype tag: abnormal
• Phenotype quality: hyperplastic

Gene ontology

• Biological process: generation of precursor metabolites and energy;exocytosis;cell surface receptor signaling pathway;G protein-coupled receptor signaling pathway;adenylate cyclase-modulating G protein-coupled receptor signaling pathway;adenylate cyclase-activating G protein-coupled receptor signaling pathway;response to nutrient;regulation of blood pressure;hormone-mediated signaling pathway;glucose homeostasis;response to starvation;regulation of glycogen metabolic process;cellular response to glucagon stimulus
• Cellular component: endosome;plasma membrane;integral component of plasma membrane;integral component of membrane
• Molecular function: glucagon receptor activity;guanyl-nucleotide exchange factor activity;G protein-coupled peptide receptor activity;peptide hormone binding