GNA11 (guanine nucleotide binding protein (G protein), alpha 11 (Gq class))

2011-03-01   Klaus G Griewank , Swapna Vemula , Boris C Bastian 

Department of Pathology, Human Oncology, Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA (KGG, BCB); Department of Pathology, University of California, San Francisco, CA, USA (SV)




Atlas Image
Numbers pertain to amount of nucleotides in exons and introns of human GNA11. Untranscribed sequences are yellow, transcribed ones are blue. The arrows refer to the start and stop codon.


The GNA11 gene is composed of 7 exons spanning a region of 27044 bp.


The transcribed mRNA has ORF is 1080 nucleotides.


Processed pseudogene GNA11 is on chromosome 7, 65970152 to 65971210.


Atlas Image
The diagram shows the general functional domains of G alpha 11 in respect to the amino acid residues and the corresponding exons. The alpha helical domain is found in all G alpha family members. Switch regions (SR), the areas that change their conformation based on if GTP or GDP is bound, are shown in orange (SR1: 182-192, SR2: 204-224, SR3: 236-247). The location of the 183 and 209 mutations are shown and affect switch regions 1 and 2 respectively. The GTPase domain is both essential for hydrolyzing bound GTP as well as binding downstream effectors. Adapted from Mizuno and Itoh, 2009.


Aminoacids: 359. Molecular weight: 42123 daltons.
GNA11 is a proto-oncogene that belongs to the Gq family of the G alpha family of G protein coupled receptors. It is highly homologous to GNAQ.


GNA11 is generally expressed ubiquitously, an exception being platelets, where only GNAQ is expressed.


Cytoplasmic. Signaling occurs at the membrane, which requires N-terminal lipid modification (palmitoylation) of the protein.


GNA11 is a G protein alpha unit associating with a beta and a gamma subunit. Upon ligand binding to G protein coupled receptors, GNA11 binds GTP, which leads to activation and disassociation from the beta and gamma subunits. Known downstream signaling partners are phospholipase C (PLC) beta and RhoA. PLC beta upon activation releases inositol triphosphate (IP3) and diacylglycerol (DAG) from membrane phosphatidylinositol-3-phosphate. RhoA activation is mediated through proteins such as p63 RhoGef, Duet and Trio by GNAQ, and may thus also be mediating Rho activation by GNA11. GNA11 activation has been shown to induce MAP Kinase activation, possibly via DAG-mediated activation of protein kinase C isoforms. Many other proteins shown to bind GNAQ and or GNA11 have been reported, many with regulatory functions, thus named GRK (G Protein regulatory kinases) or RGS (regulator of G protein signaling) proteins.


GNA11 is part of the G q family of alpha proteins. This family consists of GNAQ, GNA11, GNA14 and GNA15. On an aminoacid level GNA11 is 90% homologous to GNAQ, 82% homologous to GNA14 and 55% homologous to GNA15.



The mutations that have been described in melanocytic neoplasia have previously been demonstrated to inhibit the GTPase function and lead to decreased (R183) or completely (Q209) abolished ability to hydrolyze GTP to GDP, locking the protein in the GTP bound, constitutively active state. Experimental in vitro and in vivo data has shown that fitting with the degree of GTPase inhibition Q209 mutations are more potent activators than R183 mutations.


No known germinal mutations.


Q209 mutations have been described in uveal melanomas (32% primary, 57% metastasis) and blue nevi (6.5%).

Implicated in

Entity name
Blue nevi (6.5%)
The mutations of GNA11 or its paralog GNAQ are expected to be early events in oncogenesis. A mutation in either gene alone is often found in benign proliferations of dermal melanocytes such as blue nevi. Segmental dermal melanocytic hyperplasia of the first trigeminal branch are called Nevi of Ota. In Caucasians Nevus of Ota is a risk factor for uveal melanoma. Similar segmental lesions in the shoulder area are termed Nevus of Ito. These proliferations of dermal melanocytes and blue nevi are benign, but can evolve into melanoma at a low frequency.
Blue nevi as well as segmental melanocytoses are typically harmless, with only a low probability of progressing to melanoma.
Entity name
Uveal melanoma
Primary uveal Melanoma (34%), Uveal melanoma metastases (62%).
Uveal melanoma is an aggressive form of eye cancer. It represents the most common eye cancer and has an incidence of about 2-8 people per million in Caucasians. It can originate in the ciliary body, the iris or most commonly the choroid.
Uveal melanoma is an aggressive cancer with a 10 year survival rate of approximately 50%. The primary tumor is often only recognized at a stage where it has already metastasized. Metastasis in uveal melanoma occurs predominantly to the liver. The prognosis of uveal melanomas is highly dependent on the presence of additional genetic alterations, loss of chromosome 3 in particular.
A frequent chromosomal aberration associated with poor prognosis is the loss of chromosome 3. A gene on this chromosome called BAP1, found to be mutated over 80% of metastasizing uveal melanomas, was recently identified.
Entity name
Other entities
Activating mutations of GNA11 have not been found in other malignancies although a recent publication screened a panel of 922 different tumor samples.
There is a reporting of reduced mRNA and protein levels of GNA11 in breast cancer. This indicates expression levels of GNA11 may be relevant in some settings.


Pubmed IDLast YearTitleAuthors
127595362003Reduced expression of GNA11 and silencing of MCT1 in human breast cancers.Asada K et al
85506091996Functional importance of the amino terminus of Gq alpha.Hepler JR et al
161825152006Cell signalling diversity of the Gqalpha family of heterotrimeric G proteins.Hubbard KB et al
163655602006Metastatic uveal melanoma.Kivelä T et al
199367692010Activating mutations of the GNAQ gene: a frequent event in primary melanocytic neoplasms of the central nervous system.Küsters-Vandevelde HV et al
197184452009Mutational profile of GNAQQ209 in human tumors.Lamba S et al
180968062007Structure of Galphaq-p63RhoGEF-RhoA complex reveals a pathway for the activation of RhoA by GPCRs.Lutz S et al
192121392009Functions and regulatory mechanisms of Gq-signaling pathways.Mizuno N et al
193692092009Pasteurella multocida toxin activation of heterotrimeric G proteins by deamidation.Orth JH et al
86224521996Prognostic implications of monosomy 3 in uveal melanoma.Prescher G et al
157631932005Uveal melanoma: epidemiologic aspects.Singh AD et al
153399132004A novel Galphaq/11-selective inhibitor.Takasaki J et al
210833802010Mutations in GNA11 in uveal melanoma.Van Raamsdonk CD et al
209662182010Kinetic scaffolding mediated by a phospholipase C-beta and Gq signaling complex.Waldo GL et al
19464211991Characterization of G-protein alpha subunits in the Gq class: expression in murine tissues and in stromal and hematopoietic cell lines.Wilkie TM et al

Other Information

Locus ID:

NCBI: 2767
MIM: 139313
HGNC: 4379
Ensembl: ENSG00000088256


dbSNP: 2767
ClinVar: 2767
TCGA: ENSG00000088256


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Calcium signaling pathwayKEGGko04020
Gap junctionKEGGko04540
Long-term depressionKEGGko04730
GnRH signaling pathwayKEGGko04912
Calcium signaling pathwayKEGGhsa04020
Gap junctionKEGGhsa04540
Long-term depressionKEGGhsa04730
GnRH signaling pathwayKEGGhsa04912
Pathways in cancerKEGGhsa05200
Vascular smooth muscle contractionKEGGhsa04270
Vascular smooth muscle contractionKEGGko04270
Chagas disease (American trypanosomiasis)KEGGko05142
Chagas disease (American trypanosomiasis)KEGGhsa05142
Cholinergic synapseKEGGhsa04725
Insulin secretionKEGGhsa04911
cGMP-PKG signaling pathwayKEGGhsa04022
cGMP-PKG signaling pathwayKEGGko04022
Platelet activation, signaling and aggregationREACTOMER-HSA-76002
Signal amplificationREACTOMER-HSA-392518
ADP signalling through P2Y purinoceptor 1REACTOMER-HSA-418592
Thromboxane signalling through TP receptorREACTOMER-HSA-428930
Thrombin signalling through proteinase activated receptors (PARs)REACTOMER-HSA-456926
Signal TransductionREACTOMER-HSA-162582
Signaling by GPCRREACTOMER-HSA-372790
GPCR downstream signalingREACTOMER-HSA-388396
G alpha (q) signalling eventsREACTOMER-HSA-416476
Gastrin-CREB signalling pathway via PKC and MAPKREACTOMER-HSA-881907
Integration of energy metabolismREACTOMER-HSA-163685
Regulation of insulin secretionREACTOMER-HSA-422356
Acetylcholine regulates insulin secretionREACTOMER-HSA-399997
Free fatty acids regulate insulin secretionREACTOMER-HSA-400451
Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretionREACTOMER-HSA-434316
Aldosterone synthesis and secretionKEGGhsa04925
Aldosterone synthesis and secretionKEGGko04925

Protein levels (Protein atlas)

Not detected


Entity IDNameTypeEvidenceAssociationPKPDPMIDs


Pubmed IDYearTitleCitations
210833802010Mutations in GNA11 in uveal melanoma.396
210833802010Mutations in GNA11 in uveal melanoma.396
163653092005The cannabinoid agonist WIN55,212-2 increases intracellular calcium via CB1 receptor coupling to Gq/11 G proteins.80
156321742005The guanine nucleotide exchange factor p63RhoGEF, a specific link between Gq/11-coupled receptor signaling and RhoA.69
241417862014Combined PKC and MEK inhibition in uveal melanoma with GNAQ and GNA11 mutations.50
187137482008Protein kinase C-related kinase and ROCK are required for thrombin-induced endothelial cell permeability downstream from Galpha12/13 and Galpha11/q.37
249702622014Chromosome 3 status combined with BAP1 and EIF1AX mutation profiles are associated with metastasis in uveal melanoma.36
248234602014Autosomal dominant hypoparathyroidism caused by germline mutation in GNA11: phenotypic and molecular characterization.29
253042372014GNAQ and GNA11 mutations in uveal melanoma.26
267782902016Mosaic Activating Mutations in GNA11 and GNAQ Are Associated with Phakomatosis Pigmentovascularis and Extensive Dermal Melanocytosis.26


Klaus G Griewank ; Swapna Vemula ; Boris C Bastian

GNA11 (guanine nucleotide binding protein (G protein), alpha 11 (Gq class))

Atlas Genet Cytogenet Oncol Haematol. 2011-03-01

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