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Gene Symbol | GNAQ | ||||||||||
Synonyms | CMC1 | G-ALPHA-q | GAQ | SWS | ||||||||||
Gene Description | GNAQ, G protein subunit alpha q, is a guanine-binding protein (G protein) subunit, which is activated following ligand binding to G-protein coupled receptors and functions in cell signaling (PMID: 27148356). GNAQ hotspot mutations impair intrinsic GTPase activity, resulting in constitutive pathway activation and are common in uveal melanoma (PMID: 23640210, PMID: 27148356) and have also been identified in nonuveal melanoma (PMID: 32064597), anastomosing hemangioma (PMID: 31707589), natural killer/T cell lymphoma (PMID: 31527657), and circumscribed choroidal hemangioma (PMID: 31336681). | ||||||||||
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Variant | Impact | Protein Effect | Variant Description | Associated with drug Resistance |
---|---|---|---|---|
A302G | missense | unknown | GNAQ A302G lies within the G-alpha domain of the Gnaq protein (UniProt.org). A302G has been identified in the scientific literature (PMID: 24755198), but has not been biochemically characterized and therefore, its effect on Gnaq protein function is unknown (PubMed, Feb 2021). | |
act mut | unknown | unknown | GNAQ act mut indicates that the variant results in activation of GNAQ downstream signaling. The mechanism causing the activation can include either loss of GTP hydrolysis activity (LOF) or increased nucleotide exchange rate (GOF). | |
D146H | missense | unknown | GNAQ D146H lies within the G-alpha domain of the Gnaq protein (UniProt.org). D146H has not been characterized and therefore, its effect on Gnaq protein function is unknown (PubMed, Feb 2021). | |
D205fs | frameshift | loss of function - predicted | GNAQ D205fs results in a change in the amino acid sequence of the Gnaq protein beginning at aa 205 of 359, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of GTP binding regions (UniProt.org), D205fs is predicted to result in a loss of Gnaq protein function. | |
D205G | missense | unknown | GNAQ D205G lies within the G-alpha domain of the Gnaq protein (UniProt.org). D205G has been identified in sequencing studies (PMID: 25583476), but has not been biochemically characterized and therefore, its effect on Gnaq protein function is unknown (PubMed, Aug 2020). | |
D205N | missense | unknown | GNAQ D205N lies within the G-alpha domain of the Gnaq protein (UniProt.org). D205N has not been characterized in the scientific literature and therefore, its effect on Gnaq protein function is unknown (PubMed, Aug 2020). | |
D290N | missense | unknown | GNAQ D290N lies within the G-alpha domain of the Gnaq protein (UniProt.org). D290N has been identified in sequencing studies (PMID: 28069802), but has not been biochemically characterized and therefore, its effect on Gnaq protein function is unknown (PubMed, Feb 2021). | |
D315N | missense | unknown | GNAQ D315N lies within the G-alpha domain of the Gnaq protein (UniProt.org). D315N has been identified in sequencing studies (PMID: 25589618), but has not been biochemically characterized and therefore, its effect on Gnaq protein function is unknown (PubMed, Feb 2021). | |
D319N | missense | unknown | GNAQ D319N lies within the G-alpha domain of the Gnaq protein (UniProt.org). D319N has been identified in sequencing studies (PMID: 27756406, PMID: 26010451), but has not been biochemically characterized and therefore, its effect on Gnaq protein function is unknown (PubMed, Feb 2021). | |
D333Afs*39 | frameshift | unknown | GNAQ D333Afs*39 indicates a shift in the reading frame starting at amino acid 333 and terminating 39 residues downstream, resulting in premature truncation of the functional protein and extension of the 359aa Gnaq protein length by 13 amino acids (UniProt.org). D333Afs*39 has not been characterized in the scientific literature and therefore, its effect on Gnaq protein function is unknown (PubMed, Oct 2020). | |
D71Y | missense | unknown | GNAQ D71Y lies within the G-alpha domain of the Gnaq protein (UniProt.org). D71Y has not been characterized in the scientific literature and therefore, its effect on Gnaq protein function is unknown (PubMed, Oct 2020). | |
E212_R213insERC | insertion | unknown | GNAQ E212_R213insERC results in the insertion of three amino acids in the G-alpha domain of the Gnaq protein between amino acids 212 and 213 (UniProt.org). E212_R213insERC has not been characterized in the scientific literature and therefore, its effect on Gnaq protein function is unknown (PubMed, Oct 2020). | |
E249K | missense | unknown | GNAQ E249K lies within the G-alpha domain of the Gnaq protein (UniProt.org). E249K has been identified in sequencing studies (PMID: 21720365), but has not been biochemically characterized and therefore, its effect on Gnaq protein function is unknown (PubMed, Feb 2021). | |
E307* | nonsense | unknown | GNAQ E307* results in a premature truncation of the Gnaq protein at amino acid 307 of 359 (UniProt.org). E307* has not been characterized and therefore, its effect on Gnaq protein function is unknown (PubMed, Feb 2021). | |
exon5 | unknown | unknown | GNAQ exon 5 indicates an unspecified mutation has occurred in exon 5 of the GNAQ gene. | |
G48* | nonsense | loss of function - predicted | GNAQ G48* results in a premature truncation of the Gnaq protein at amino acid 48 of 359 (UniProt.org). Due to the loss of the GTP binding regions (UniProt.org), G48* is predicted to lead to a loss of Gnaq protein function. | |
G48V | missense | unknown | GNAQ G48V lies within the G-alpha domain of the Gnaq protein (UniProt.org). G48V has been identified in the scientific literature (PMID: 31189994, PMID: 28594900), but has not been biochemically characterized and therefore, its effect on Gnaq protein function is unknown (PubMed, Aug 2020). | |
G64A | missense | unknown | GNAQ G64A lies within the G-alpha domain of the Gnaq protein (UniProt.org). G64A has been identified in sequencing studies (PMID: 24504448), but has not been biochemically characterized and therefore, its effect on Gnaq protein function is unknown (PubMed, Feb 2021). | |
G64V | missense | unknown | GNAQ G64V lies within the G-alpha domain of the Gnaq protein (UniProt.org). G64V has been identified in sequencing studies (PMID: 23640210), but has not been biochemically characterized and therefore, its effect on Gnaq protein function is unknown (PubMed, Feb 2021). | |
I217L | missense | unknown | GNAQ I217L lies within the G-alpha domain of the Gnaq protein (UniProt.org). I217L has been identified in sequencing studies (PMID: 26010451), but has not been biochemically characterized and therefore, its effect on Gnaq protein function is unknown (PubMed, Feb 2021). | |
I226V | missense | unknown | GNAQ I226V lies within the G-alpha domain of the Gnaq protein (UniProt.org). I226L has not been characterized and therefore, its effect on Gnaq protein function is unknown (PubMed, Feb 2021). | |
inact mut | unknown | loss of function | GNAQ inact mut indicates that this variant results in failure to activate GNAQ downstream signaling. However, the specific amino acid change has not been identified. | |
K133N | missense | unknown | GNAQ K133N lies within the G-alpha domain of the Gnaq protein (UniProt.org). K133N has not been characterized in the scientific literature and therefore, its effect on Gnaq protein function is unknown (PubMed, Feb 2021). | |
K276E | missense | unknown | GNAQ K276E lies within the G-alpha domain of the Gnaq protein (UniProt.org). K276E has not been characterized and therefore, its effect on Gnaq protein function is unknown (PubMed, Aug 2020). | |
K311T | missense | unknown | GNAQ K311T lies within the G-alpha domain of the Gnaq protein (UniProt.org). K311T has not been characterized and therefore, its effect on Gnaq protein function is unknown (PubMed, Feb 2021). | |
K345N | missense | unknown | GNAQ K345N lies within the G-alpha domain of the Gnaq protein (UniProt.org). K345N has not been characterized and therefore, its effect on Gnaq protein function is unknown (PubMed, Feb 2021). | |
K72E | missense | unknown | GNAQ K72E lies within the G-alpha domain of the Gnaq protein (UniProt.org). K72E has been identified in sequencing studies (PMID: 22941189), but has not been biochemically characterized and therefore, its effect on Gnaq protein function is unknown (PubMed, Feb 2021). | |
L135V | missense | unknown | GNAQ L135V lies within the G-alpha domain of the Gnaq protein (UniProt.org). L135V has been identified in sequencing studies (PMID: 22810696), but has not been biochemically characterized and therefore, its effect on Gnaq protein function is unknown (PubMed, Feb 2021). | |
L164F | missense | unknown | GNAQ L164F lies within the G-alpha domain of the Gnaq protein (UniProt.org). L164F has not been characterized in the scientific literature and therefore, its effect on Gnaq protein function is unknown (PubMed, Feb 2021). | |
M59L | missense | unknown | GNAQ M59L lies within the G-alpha domain of the Gnaq protein (UniProt.org). M59L has been identified in the scientific literature (PMID: 29191620, PMID: 30787173), but has not been biochemically characterized and therefore, its effect on Gnaq protein function is unknown (PubMed, Aug 2020). | |
mutant | unknown | unknown | GNAQ mutant indicates an unspecified mutation in the GNAQ gene. | |
N106I | missense | unknown | GNAQ N106I lies within the G-alpha domain of the Gnaq protein (UniProt.org). N106I has not been characterized in the scientific literature and therefore, its effect on Gnaq protein function is unknown (PubMed, Aug 2020). | |
P139R | missense | unknown | GNAQ P139R lies within the G-alpha domain of the Gnaq protein (UniProt.org). P139R has not been characterized in the scientific literature and therefore, its effect on Gnaq protein function is unknown (PubMed, Aug 2020). | |
P185S | missense | unknown | GNAQ P185S lies within the G-alpha domain of the Gnaq protein (UniProt.org). P185S has been identified in sequencing studies (PMID: 24755198), but has not been biochemically characterized and therefore, its effect on Gnaq protein function is unknown (PubMed, Aug 2020). | |
Q209H | missense | unknown | GNAQ Q209H is a hotspot mutation that lies within the GTPase domain of the Gnaq protein (PMID: 19936769). Q209H has been identified in sequencing studies (PMID: 30601876), but has not been biochemically characterized and therefore, its effect on Gnaq protein function is unknown (PubMed, Oct 2020). | |
Q209K | missense | unknown | GNAQ Q209K is a hotspot mutation that lies within the GTPase domain of the Gnaq protein (PMID: 19936769). Q209K has been identified in the scientific literature (PMID: 23640210), but has not been biochemically characterized and therefore, its effect on Gnaq protein function is unknown (PubMed, Dec 2020). | |
Q209L | missense | loss of function | GNAQ Q209L is a hotspot mutation that lies within the GTPase domain of the Gnaq protein (PMID: 19936769). Q209L confers a loss of function on Gnaq protein as indicated by activation of Erk signaling, transformation of cultured cells, and increased tumor growth in mouse models (PMID: 1328859, PMID: 19078957, PMID: 21083380). | |
Q209P | missense | loss of function - predicted | GNAQ Q209P lies within the G-alpha domain of the Gnaq protein (UniProt.org). Q209P results in similar effects on cell proliferation and apoptosis as wild-type Gnaq in culture (PMID: 23904987), however, results in increased Erk phosphorylation (PMID: 23904987, PMID: 30352874), decreased binding to effector proteins, G-protein beta gamma, and signaling proteins, and diminished GTPase activity (PMID: 30352874), and therefore, is predicted to result in a loss of Gnaq protein function. | |
Q209R | missense | unknown | GNAQ Q209R is a hotspot mutation that lies within the GTPase domain of the Gnaq protein (PMID: 19936769). Q209R has been identified in sequencing studies (PMID: 19654573, PMID: 31336681, PMID: 32064597), but has not been biochemically characterized and therefore, its effect on Gnaq protein function is unknown (PubMed, Aug 2020). | |
Q209X | missense | unknown | GNAQ Q209X indicates any amino acid change at position 209 within a GTP-binding region of the Gnaq protein (UniProt.org). | |
Q209Y | missense | unknown | GNAQ Q209Y is a hotspot mutation that lies within the GTPase domain of the Gnaq protein (PMID: 19936769). Q209Y has been identified in the scientific literature (PMID: 23640210), but has not been biochemically characterized and therefore, its effect on Gnaq protein function is unknown (PubMed, Dec 2020). | |
R114* | nonsense | loss of function - predicted | GNAQ R114* results in a premature truncation of the Gnaq protein at amino acid 114 of 359 (UniProt.org). Due to the loss of the majority of the GTP binding regions (UniProt.org), R114* is predicted to lead to a loss of Gnaq protein function. | |
R148* | nonsense | loss of function - predicted | GNAQ R148* results in a premature truncation of the Gnaq protein at amino acid 148 of 359 (UniProt.org). Due to the loss of the majority of the GTP binding regions (UniProt.org), R148* is predicted to lead to a loss of Gnaq protein function. | |
R166H | missense | unknown | GNAQ R166H lies within the G-alpha domain of the Gnaq protein (UniProt.org). R166H has been identified in sequencing studies (PMID: 28069802), but has not been biochemically characterized and therefore, its effect on Gnaq protein function is unknown (PubMed, Feb 2021). | |
R181T | missense | unknown | GNAQ R181T lies within the G-alpha domain of the Gnaq protein (UniProt.org). R181T has been identified in sequencing studies (PMID: 22810696), but has not been biochemically characterized and therefore, its effect on Gnaq protein function is unknown (PubMed, Aug 2020). | |
R183* | nonsense | loss of function - predicted | GNAQ R183* results in a premature truncation of the Gnaq protein at amino acid 183 of 359 (UniProt.org). Due to the loss of the majority of the GTP binding regions (UniProt.org), R183* is predicted to lead to a loss of Gnaq protein function. | |
R183C | missense | loss of function | GNAQ R183C lies within the G-alpha domain of the Gnaq protein (UniProt.org). R183C results in decreased GTP hydrolysis rate of Gnaq, leading to constitutive gene transcription in a reporter assay in cell culture (PMID: 10391901, PMID: 15339913). | |
R183G | missense | unknown | GNAQ R183G lies within the G-alpha domain of the Gnaq protein (UniProt.org). R183G has been identified in the scientific literature (PMID: 30601876), but has not been biochemically characterized and therefore, its effect on Gnaq protein function is unknown (PubMed, Aug 2020). | |
R183Q | missense | loss of function | GNAQ R183Q lies within the G-alpha domain of the Gnaq protein (UniProt.org). R183Q confers a loss of function on Gnaq as indicated by the activation of Erk and Yap signaling in culture (PMID: 23640210, PMID: 24882516, PMID: 23656586). | |
R183X | missense | unknown | GNAQ R183X indicates any amino acid change at position 183 within a GTP-binding region of the Gnaq protein (UniProt.org). | |
R214K | missense | unknown | GNAQ R214K lies within the G-alpha domain of the Gnaq protein (UniProt.org). R214K has been identified in the scientific literature (PMID: 23434405), but has not been biochemically characterized and therefore, its effect on Gnaq protein function is unknown (PubMed, Aug 2020). | |
R247L | missense | loss of function | GNAQ R247L lies within the G-alpha domain of the Gnaq protein (UniProt.org). R247L results in a loss of Gaip binding in an in vitro assay, and insensitivity to GAP-mediated deactivation of Gnaq in cultured cells (PMID: 32634377). | |
R247Q | missense | loss of function | GNAQ R247Q lies within the G-alpha domain of the Gnaq protein (UniProt.org). R247Q results in a loss of Gaip binding in an in vitro assay, and insensitivity to GAP-mediated deactivation of Gnaq in cultured cells (PMID: 32634377). | |
R300K | missense | unknown | GNAQ R300K lies within the G-alpha domain of the Gnaq protein (UniProt.org). R300K has not been characterized and therefore, its effect on Gnaq protein function is unknown (PubMed, Aug 2020). | |
R338H | missense | unknown | GNAQ R338H lies within the G-alpha domain of the Gnaq protein (UniProt.org). R338H has been identified in sequencing studies (PMID: 25790293), but has not been biochemically characterized and therefore, its effect on Gnaq protein function is unknown (PubMed, Aug 2020). | |
R37H | missense | unknown | GNAQ R37H does not lie within any known functional domains of the Gnaq protein (UniProt.org). R37H has been identified in sequencing studies (PMID: 29420467, PMID: 24755471), but has not been biochemically characterized and therefore, its effect on Gnaq protein function is unknown (PubMed, Oct 2020). | |
S122F | missense | unknown | GNAQ S122F lies within the G-alpha domain of the Gnaq protein (UniProt.org). S122F has not been characterized in the scientific literature and therefore, its effect on Gnaq protein function is unknown (PubMed, Aug 2020). | |
S211L | missense | unknown | GNAQ S211L lies within the G-alpha domain of the Gnaq protein (UniProt.org). S211L has been identified in sequencing studies (PMID: 24755198), but has not been biochemically characterized and therefore, its effect on Gnaq protein function is unknown (PubMed, Feb 2021). | |
S268L | missense | unknown | GNAQ S268L lies within the G-alpha domain of the Gnaq protein (UniProt.org). S268L has been identified in sequencing studies (PMID: 30057548, PMID: 24755471), but has not been biochemically characterized and therefore, its effect on Gnaq protein function is unknown (PubMed, Aug 2020). | |
S286F | missense | unknown | GNAQ S286F lies within the G-alpha domain of the Gnaq protein (UniProt.org). S286F has been identified in sequencing studies (PMID: 25589618), but has not been biochemically characterized and therefore, its effect on Gnaq protein function is unknown (PubMed, Aug 2020). | |
S50Wfs*19 | frameshift | loss of function - predicted | GNAQ S50Wfs*19 indicates a shift in the reading frame starting at amino acid 50 and terminating 19 residues downstream causing a premature truncation of the 359 amino acid Gnaq protein (UniProt.org). Due to the loss of the GTP binding regions (UniProt.org), S50Wfs*19 is predicted to lead to a loss of Gnaq protein function. | |
T329M | missense | unknown | GNAQ T329M lies within the G-alpha domain of the Gnaq protein (UniProt.org). T329M has not been characterized in the scientific literature and therefore, its effect on Gnaq protein function is unknown (PubMed, Aug 2020). | |
T54M | missense | unknown | GNAQ T54M lies within the G-alpha domain of the Gnaq protein (UniProt.org). T54M has been identified in sequencing studies (PMID: 30239046, PMID: 28179590), but has not been biochemically characterized and therefore, its effect on Gnaq protein function is unknown (PubMed, Aug 2020). | |
T96S | missense | loss of function | GNAQ T96S lies within the G-alpha domain of the Gnaq protein (UniProt.org). T96S confers a loss of function to the Gnaq protein as demonstrated by increased binding to G-protein beta gamma in cell culture, elevated Erk and Akt phosphorylation in cultured cells and xenograft tumors, and increased tumor growth in mouse models compared to wild-type Gnaq (PMID: 31527657). | |
V167I | missense | unknown | GNAQ V167I lies within the G-alpha domain of the Gnaq protein (UniProt.org). V167I has been identified in sequencing studies (PMID: 23525077), but has not been biochemically characterized and therefore, its effect on Gnaq protein function is unknown (PubMed, Aug 2020). | |
wild-type | none | no effect | Wild-type GNAQ indicates that no mutation has been detected within the GNAQ gene. | |
Y101* | nonsense | loss of function - predicted | GNAQ Y101* results in a premature truncation of the Gnaq protein at amino acid 101 of 359 (UniProt.org). Due to the loss of the majority of the GTP binding regions (UniProt.org), Y101* is predicted to lead to a loss of Gnaq protein function. | |
Y325F | missense | unknown | GNAQ Y325F lies within the G-alpha domain of the Gnaq protein (UniProt.org). Y325F has been identified in sequencing studies (PMID: 21798893), but has not been biochemically characterized and therefore, its effect on Gnaq protein function is unknown (PubMed, Aug 2020). | |
Y356C | missense | unknown | GNAQ Y356C lies within the G-alpha domain of the Gnaq protein (UniProt.org). Y356C has not been characterized and therefore, its effect on Gnaq protein function is unknown (PubMed, Aug 2020). | |
Y80* | nonsense | loss of function - predicted | GNAQ Y80* results in a premature truncation of the Gnaq protein at amino acid 80 of 359 (Uniprot.org). Due to the loss of the majority of the GTP binding regions (UniProt.org), Y80* is predicted to lead to a loss of Gnaq protein function. |