GPER1

G protein-coupled estrogen receptor 1, the group of G protein-coupled estrogen receptor

Basic information

Region (hg38): 7:1082208-1093815

Previous symbols: [ "CMKRL2", "GPR30", "GPER" ]

Links

ENSG00000164850 ∙ NCBI:2852 ∙ OMIM:601805 ∙ HGNC:4485 ∙ Uniprot:Q99527 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GPER1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GPER1 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						0
missense			22	2	2	26
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	22	2	2

Variants in GPER1

This is a list of pathogenic ClinVar variants found in the GPER1 region.

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

Position	Type	Phenotype	Significance	ClinVar
7-1091742-C-T			Benign (May 10, 2018)
7-1091775-C-T			Benign (Apr 28, 2020)
7-1091816-G-A		not specified	Uncertain significance (Nov 07, 2022)
7-1091835-C-T		not specified	Uncertain significance (Sep 20, 2023)
7-1091861-G-A		not specified	Uncertain significance (Nov 14, 2023)
7-1091976-T-C		not specified	Uncertain significance (Apr 12, 2022)
7-1091999-A-T		not specified	Uncertain significance (Apr 12, 2022)
7-1092069-T-C		not specified	Uncertain significance (Mar 08, 2024)
7-1092089-G-A		not specified	Uncertain significance (Mar 26, 2024)
7-1092218-C-T		not specified	Uncertain significance (Sep 01, 2021)
7-1092294-C-T		not specified	Uncertain significance (Dec 19, 2022)
7-1092311-G-A		not specified	Uncertain significance (Jul 13, 2021)
7-1092401-G-A		not specified	Uncertain significance (Dec 01, 2022)
7-1092418-C-G		not specified	Uncertain significance (Jun 16, 2023)
7-1092423-T-C		not specified	Uncertain significance (Feb 28, 2023)
7-1092459-C-T		not specified	Uncertain significance (Sep 07, 2022)
7-1092470-C-T		not specified	Uncertain significance (Jun 06, 2023)
7-1092519-T-C		not specified	Uncertain significance (Apr 15, 2024)
7-1092536-G-A		not specified	Likely benign (Jul 09, 2021)
7-1092558-T-C		not specified	Uncertain significance (Jul 19, 2022)
7-1092584-C-T		not specified	Uncertain significance (May 13, 2022)
7-1092596-G-A		not specified	Uncertain significance (Apr 25, 2023)
7-1092618-C-A		not specified	Uncertain significance (Oct 12, 2021)
7-1092717-C-G		not specified	Uncertain significance (Nov 18, 2023)
7-1092781-C-G		not specified	Uncertain significance (Dec 02, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GPER1	protein_coding	protein_coding	ENST00000397092	1	11608

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.574	0.416	125689	0	4	125693	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.11	218	269	0.810	0.0000196	2433
Missense in Polyphen		68	112.99	0.6018		1109
Synonymous	-0.195	134	131	1.02	0.0000103	811
Loss of Function	2.07	1	6.83	0.147	2.94e-7	70

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000553	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000281	0.0000264
Middle Eastern	0.0000553	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: G-protein coupled estrogen receptor that binds to 17- beta-estradiol (E2) with high affinity, leading to rapid and transient activation of numerous intracellular signaling pathways. Stimulates cAMP production, calcium mobilization and tyrosine kinase Src inducing the release of heparin-bound epidermal growth factor (HB-EGF) and subsequent transactivation of the epidermal growth factor receptor (EGFR), activating downstream signaling pathways such as PI3K/Akt and ERK/MAPK. Mediates pleiotropic functions among others in the cardiovascular, endocrine, reproductive, immune and central nervous systems. Has a role in cardioprotection by reducing cardiac hypertrophy and perivascular fibrosis in a RAMP3-dependent manner. Regulates arterial blood pressure by stimulating vasodilation and reducing vascular smooth muscle and microvascular endothelial cell proliferation. Plays a role in blood glucose homeostasis contributing to the insulin secretion response by pancreatic beta cells. Triggers mitochondrial apoptosis during pachytene spermatocyte differentiation. Stimulates uterine epithelial cell proliferation. Enhances uterine contractility in response to oxytocin. Contributes to thymic atrophy by inducing apoptosis. Attenuates TNF-mediated endothelial expression of leukocyte adhesion molecules. Promotes neuritogenesis in developing hippocampal neurons. Plays a role in acute neuroprotection against NMDA- induced excitotoxic neuronal death. Increases firing activity and intracellular calcium oscillations in luteinizing hormone- releasing hormone (LHRH) neurons. Inhibits early osteoblast proliferation at growth plate during skeletal development. Inhibits mature adipocyte differentiation and lipid accumulation. Involved in the recruitment of beta-arrestin 2 ARRB2 at the plasma membrane in epithelial cells. Functions also as a receptor for aldosterone mediating rapid regulation of vascular contractibility through the PI3K/ERK signaling pathway. Involved in cancer progression regulation. Stimulates cancer-associated fibroblast (CAF) proliferation by a rapid genomic response through the EGFR/ERK transduction pathway. Associated with EGFR, may act as a transcription factor activating growth regulatory genes (c-fos, cyclin D1). Promotes integrin alpha-5/beta-1 and fibronectin (FN) matrix assembly in breast cancer cells. {ECO:0000269|PubMed:11043579, ECO:0000269|PubMed:15539556, ECO:0000269|PubMed:15705806, ECO:0000269|PubMed:19179659, ECO:0000269|PubMed:19342448, ECO:0000269|PubMed:20203690, ECO:0000269|PubMed:20551055, ECO:0000269|PubMed:21149639, ECO:0000269|PubMed:21242460, ECO:0000269|PubMed:21427217, ECO:0000269|PubMed:23135268, ECO:0000269|PubMed:23283935, ECO:0000269|PubMed:23285008, ECO:0000269|PubMed:23674134}.
• Pathway: Estrogen signaling pathway - Homo sapiens (human);GPCRs, Class A Rhodopsin-like;Estrogen signaling pathway;Signaling by GPCR;Signal Transduction;Peptide ligand-binding receptors;Class A/1 (Rhodopsin-like receptors);GPCR ligand binding;G alpha (i) signalling events;GPCR downstream signalling (Consensus)

Recessive Scores

• pRec: 0.134

Intolerance Scores

• rvis_EVS: -0.29
• rvis_percentile_EVS: 33.42

Haploinsufficiency Scores

• pHI: 0.0781
• hipred: Y
• hipred_score: 0.528
• ghis: 0.411

Essentials

• essential_gene_CRISPR: N
• essential_gene_gene_trap: N

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gper1
• Phenotype: cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; liver/biliary system phenotype; immune system phenotype; skeleton phenotype; limbs/digits/tail phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: gper1
• Affected structure: trunk
• Phenotype tag: abnormal
• Phenotype quality: decreased size

Gene ontology

• Biological process: positive regulation of protein phosphorylation;positive regulation of neurotransmitter secretion;negative regulation of leukocyte activation;inflammatory response;cell cycle;G protein-coupled receptor signaling pathway;adenylate cyclase-activating G protein-coupled receptor signaling pathway;positive regulation of cytosolic calcium ion concentration;positive regulation of cell population proliferation;negative regulation of cell population proliferation;positive regulation of gene expression;negative regulation of gene expression;negative regulation of cell cycle process;positive regulation of phosphatidylinositol 3-kinase signaling;neuronal action potential;apoptotic chromosome condensation;nuclear fragmentation involved in apoptotic nuclear change;positive regulation of cell migration;intracellular steroid hormone receptor signaling pathway;mineralocorticoid receptor signaling pathway;positive regulation of insulin secretion;positive regulation of inositol trisphosphate biosynthetic process;positive regulation of apoptotic process;positive regulation of cysteine-type endopeptidase activity involved in apoptotic process;steroid hormone mediated signaling pathway;positive regulation of MAPK cascade;innate immune response;negative regulation of fat cell differentiation;positive regulation of epidermal growth factor receptor signaling pathway;positive regulation of G protein-coupled receptor signaling pathway;positive regulation of transcription by RNA polymerase II;negative regulation of inflammatory response;positive regulation of neurogenesis;negative regulation of DNA metabolic process;negative regulation of lipid biosynthetic process;positive regulation of release of sequestered calcium ion into cytosol;regulation of cytosolic calcium ion concentration;negative regulation of protein kinase B signaling;negative regulation of ERK1 and ERK2 cascade;positive regulation of ERK1 and ERK2 cascade;positive regulation of uterine smooth muscle contraction;negative regulation of cell cycle arrest;cellular response to glucose stimulus;cellular response to tumor necrosis factor;cellular response to peptide hormone stimulus;cellular response to mineralocorticoid stimulus;cellular response to estradiol stimulus;positive regulation of release of cytochrome c from mitochondria;positive regulation of blood vessel diameter;positive regulation of protein localization to plasma membrane;negative regulation of vascular smooth muscle cell proliferation;positive regulation of endothelial cell apoptotic process;positive regulation of cardiac vascular smooth muscle cell differentiation;positive regulation of extrinsic apoptotic signaling pathway
• Cellular component: Golgi membrane;nucleus;nuclear envelope;cytoplasm;early endosome;endoplasmic reticulum;endoplasmic reticulum membrane;Golgi apparatus;trans-Golgi network;plasma membrane;integral component of plasma membrane;postsynaptic density;cell junction;axon;dendrite;cytoplasmic vesicle membrane;mitochondrial membrane;dendritic spine membrane;presynaptic membrane;dendritic shaft;axon terminus;dendritic spine head;keratin filament;perinuclear region of cytoplasm;presynaptic active zone;recycling endosome;hippocampal mossy fiber to CA3 synapse
• Molecular function: chromatin binding;G protein-coupled receptor activity;steroid binding;protein binding;mineralocorticoid receptor activity;estrogen receptor activity;steroid hormone binding