Review on GNA11 (guanine nucleotide binding protein (G protein), alpha 11 (Gq class)), with data on DNA, on the protein encoded, and where the gene is implicated

Bastian, BC

Griewank, KG

Vemula, S

Atlas of Genetics and Cytogenetics in Oncology and Haematology

KG Griewank

S Vemula

BC Bastian

Crossref

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

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Gene Section 
Mini Review 
 
Atlas Genet Cytogenet Oncol Haematol. 2010; 14(10)   828 
Atlas of Genetics and Cytogenetics 
in Oncology and Haematology 
OPEN ACCESS JOURNAL AT INIST-CNRS 
GNA11 (guanine nucleotide binding protein (G 
protein), alpha 11 (Gq class)) 
Klaus G Griewank, Swapna Vemula, Boris C Bastian 
Department of Pathology, University of California, San Francisco, CA, USA (SV); Department of Pathology 
and Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, 
USA (KG, BCB) 
 
Published in Atlas Database: March 2011 
Online updated version : http://AtlasGeneticsOncology.org/Genes/GNA11ID43272ch19p13.html 
DOI: 10.4267/2042/46046 
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence. 
© 2011 Atlas of Genetics and Cytogenetics in Oncology and Haematology 
 
Identity 
Other names: GNA-11; GA11 
HGNC (Hugo): GNA11 
Location: 19p13.3 
Local order: Between AES and AC0052641. 
DNA/RNA 
 
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. 
Description 
The GNA11 gene is composed of 7 exons spanning a 
region of 27044 bp. 
Transcription 
The transcribed mRNA has ORF is 1080 nucleotides. 
Pseudogene 
Processed pseudogene GNA11 is on chromosome 7, 
65970152 to 65971210. 
Protein 
Description 
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. 
Expression 
GNA11 is generally expressed ubiquitously, an 
exception being platelets, where only GNAQ is 
expressed. 
Localisation 
Cytoplasmic. Signaling occurs at the membrane, which 
requires N-terminal lipid modification (palmitoylation) 
of the protein. 
Function 
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.  
GNA11 (guanine nucleotide binding protein (G protein), alpha 11 (Gq class)) Griewank KG, et al. 
 
 
 
 
 
Atlas Genet Cytogenet Oncol Haematol. 2010; 14(10)   829 
 
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. 
 
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. 
Homology 
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. 
Mutations 
Note 
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. 
Germinal 
No known germinal mutations. 
Somatic 
Q209 mutations have been described in uveal 
melanomas (32% primary, 57% metastasis) and blue 
nevi (6.5%).  
R183 mutations have only been described in uveal 
melanoma (2% primary, 6% metastasis). Overall 
frequencies and distribution of GNA11 mutations as 
compared to GNAQ in uveal and cutaneous 
melanocytic tumors are listed in the table below. 
 
Categories n° GNA11 GNAQ Either 
Blue Nevi 139 7% 56% 63% 
Uveal melanoma, 
primary 
163 34% 48% 82% 
Uveal melanoma, 
metastasis 
23 62% 28% 90% 
Uveal nevus 1 0% 100% 100% 
Conjunctival 
melanoma 
9 0% 0% 0% 
Other nevi 105 0% 0% 0% 
Extra-ocular 
melanomas 
273 0% 1% 1% 
Total 713       
 
In the table, frequencies of mutations in GNAQ and 
GNA11 found in different melanocytic proliferations 
are listed. 
Implicated in 
Blue nevi (6.5%) 
Note 
The mutations of GNA11 or its paralog GNAQ are  
GNA11 (guanine nucleotide binding protein (G protein), alpha 11 (Gq class)) Griewank KG, et al. 
 
 
 
 
 
Atlas Genet Cytogenet Oncol Haematol. 2010; 14(10)   830 
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. 
Prognosis 
Blue nevi as well as segmental melanocytoses are 
typically harmless, with only a low probability of 
progressing to melanoma. 
Uveal melanoma 
Note 
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. 
Prognosis 
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. 
Cytogenetics 
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. 
Other entities 
Note 
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. 
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This article should be referenced as such: 
Griewank KG, Vemula S, Bastian BC. GNA11 (guanine 
nucleotide binding protein (G protein), alpha 11 (Gq class)). 
Atlas Genet Cytogenet Oncol Haematol. 2011; 15(10):828-830. 


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

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