Gene Detail

Gene Symbol GNA11
Synonyms FBH | FBH2 | FHH2 | GNA-11 | HHC2 | HYPOC2
Gene Description GNA11, G protein subunit alpha 11, is a guanine nucleotide-binding protein (G protein) subunit, which is activated following ligand binding to G-protein coupled receptors and functions in cell signaling (PMID: 27148356). GNA11 hotspot mutations impair intrinsic Gna11 GTPase activity, resulting in constitutive pathway activation and are common in uveal melanoma (PMID: 23640210, PMID: 27148356, PMID: 29209985).
Entrez Id 2767
Chromosome 19
Map Location 19p13.3
Canonical Transcript NM_002067

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Variant Impact Protein Effect Variant Description Associated with drug Resistance
L135P missense unknown GNA11 L135P does not lie within any known functional domains of the Gna11 protein (UniProt.org). L135P has not been characterized in the scientific literature and therefore, its effect on Gna11 protein function is unknown (PubMed, May 2018).
S18F missense unknown GNA11 S18F does not lie within any known functional domains of the Gna11 protein (UniProt.org). S18F has not been characterized in the scientific literature and therefore, its effect on Gna11 protein function is unknown (PubMed, May 2018).
Q209K missense unknown GNA11 Q209K lies within a GTP binding region of the Gna11 protein (UniProt.org). Q209K has been identified in sequencing studies (PMID: 22722839), but has not been biochemically characterized and therefore, its effect on Gna11 protein function is unknown (PubMed, Sep 2018).
R114W missense unknown GNA11 R114W does not lie within any known functional domains of the Gna11 protein (UniProt.org). R114W has not been characterized in the scientific literature and therefore, its effect on Gna11 protein function is unknown (PubMed, May 2018).
G66S missense unknown GNA11 G66S does not lie within any known functional domains of the Gna11 protein (UniProt.org). G66S has been identified in sequencing studies (PMID: 24755471), but has not been biochemically characterized and therefore, its effect on Gna11 protein function is unknown (PubMed, May 2018).
K275N missense unknown GNA11 K275N lies within the GTP binding region of the Gna11 protein (UniProt.org). K275N has not been characterized in the scientific literature and therefore, its effect on GNA11 protein function is unknown (PubMed, May 2018).
K57Q missense unknown GNA11 K57Q does not lie within any known functional domains of the Gna11 protein (UniProt.org). K57Q has not been characterized in the scientific literature and therefore, its effect on Gna11 protein function is unknown (PubMed, May 2018).
S130Vfs*32 frameshift loss of function - predicted GNA11 S130Vfs*32 indicates a shift in the reading frame starting at amino acid 130 and terminating 32 residues downstream causing a premature truncation of the 359 amino acid Gna11 protein (UniProt.org). Due to the loss of the majority of the GTP binding regions (UniProt.org), S130Vfs*32 is predicted to lead to a loss of Gna11 protein function.
V164G missense unknown GNA11 V164G does not lie within any known functional domains of the Gna11 protein (UniProt.org). V164G has not been characterized in the scientific literature and therefore, its effect on Gna11 protein function is unknown (PubMed, May 2018).
A110G missense unknown GNA11 A110G does not lie within any known functional domains of the Gna11 protein (UniProt.org). A110G has not been characterized and therefore, its effect on Gna11 protein function is unknown (PubMed, May 2018).
E294* nonsense loss of function - predicted GNA11 E294* results in a premature truncation of the Gna11 protein at amino acid 294 of 359 (UniProt.org). Due to disruption of the GTPase domain (PMID: 27647839) , E294* is predicted to lead to a loss of Gna11 protein function.
S268F missense unknown GNA11 S268F does not lie within any known functional domains of the Gna11 protein (UniProt.org). S268F has been identified in the scientific literature (PMID: 26994145), but not been biochemically characterized and therefore, its effect on Gna11 protein function is unknown (PubMed, May 2018).
V269I missense unknown GNA11 V269I does not lie within any known functional domains of the Gna11 protein (UniProt.org). V269I has not been characterized in the scientific literature and therefore, its effect on Gna11 protein function is unknown (PubMed, May 2018).
E245K missense unknown GNA11 E245K does not lie within any known functional domains of the Gna11 protein (UniProt.org). E245K has not been characterized in the scientific literature and therefore, its effect on Gna11 protein function is unknown (PubMed, May 2018).
R166H missense unknown GNA11 R166H does not lie within any known functional domains of the Gna11 protein (UniProt.org). R166H has not been characterized in the scientific literature and therefore, its effect on Gna11 protein function is unknown (PubMed, May 2018).
R181Q missense loss of function - predicted GNA11 R181Q lies within a GTP binding region of the Gna11 protein (UniProt.org). R181Q results in increased sensitivity to extracellular calcium in cells expressing calcium-sensitive receptors and calcium-dependent increase of Erk phosphorylation in cell culture (PMID: 23802516, PMID: 26994139), and therefore, is predicted to lead to a loss of Gna11 protein function.
A168T missense unknown GNA11 A168T does not lie within any known functional domains of the Gna11 protein (UniProt.org). A168T has not been characterized in the scientific literature and therefore, its effect on Gna11 protein function is unknown (PubMed, May 2018).
E4K missense unknown GNA11 E4K does not lie within any known functional domains of the Gna11 protein (UniProt.org). E4K has not been characterized in the scientific literature and therefore, its effect on Gna11 protein function is unknown (PubMed, May 2018).
D195N missense unknown GNA11 D195N does not lie within any known functional domains of the Gna11 protein (UniProt.org). D195N has not been characterized in the scientific literature and therefore, its effect on Gna11 protein function is unknown (PubMed, May 2018).
V344M missense unknown GNA11 V344M does not lie within any known functional domains of the Gna11 protein (UniProt.org). V344M has been identified in the scientific literature (PMID: 27756406), but has not been characterized and therefore, its effect on Gna11 protein function is unknown (PubMed, May 2018).
R183X missense unknown GNA11 R183X indicates any amino acid change at position 183 within a GTP binding region of the Gna11 protein (UniProt.org).
L351P missense unknown GNA11 L351P does not lie within any known functional domains of the Gna11 protein (UniProt.org). L351P has not been characterized in the scientific literature and therefore, its effect on Gna11 protein function is unknown (PubMed, May 2018).
S130G missense unknown GNA11 S130G does not lie within any known functional domains of the Gna11 protein (UniProt.org). S130G has not been characterized in the scientific literature and therefore, its effect on Gna11 protein function is unknown (PubMed, May 2018).
G208Afs*16 frameshift loss of function - predicted GNA11 G208Afs*16 indicates a shift in the reading frame starting at amino acid 208 and terminating 16 residues downstream causing a premature truncation of the 359 amino acid Gna11 protein (UniProt.org). Due to the disruption of the GTPase domain (PMID: 27647839), G208Afs*16 is predicted to lead to a loss of Gna11 protein function.
I56M missense unknown GNA11 I56M does not lie within any known functional domains of the Gna11 protein (UniProt.org). I56M has not been characterized in the scientific literature and therefore, its effect on Gna11 protein function is unknown (PubMed, May 2018).
Q209L missense loss of function GNA11 Q209L is a hotspot mutation that lies within a GTP binding region of the Gna11 protein (UniProt.org). Q209L results in a loss of Gna11 protein function as indicated by activation of downstream signaling in culture, and increased tumor growth in mouse models (PMID: 21083380, PMID: 24141786, PMID: 23640210).
Q209P missense unknown GNA11 Q209P lies within a GTP binding region of the Gna11 protein (UniProt.org). Q209P has been identified in the scientific literature (PMID: 26368812), but has not been biochemically characterized and therefore, its effect on Gna11 protein function is unknown (PubMed, Oct 2018.
Q209X missense unknown GNA11 Q209X indicates any amino acid change at position 209 within a GTP binding region of the Gnaq protein (UniProt.org).
D333N missense unknown GNA11 D333N does not lie within any known functional domains of the Gna11 protein (UniProt.org). D333N has not been characterized in the scientific literature and therefore, its effect on Gna11 protein function is unknown (PubMed, May 2018).
E221Q missense unknown GNA11 E221Q does not lie within any known functional domains of the Gna11 protein (UniProt.org). E221Q has not been characterized in the scientific literature and therefore, its effect on Gna11 protein function is unknown (PubMed, May 2018).
wild-type none no effect Wild-type GNA11 indicates that no mutation has been detected within the GNA11 gene.
R338C missense unknown GNA11 R338C does not lie within any known functional domains of the Gna11 protein (UniProt.org). R338C has not been characterized in the scientific literature and therefore, its effect on Gna11 protein function is unknown (PubMed, May 2018).
amp none no effect GNA11 amplification indicates an increased number of copies of the GNA11 gene. However, the mechanism causing the increase is unspecified.
P293S missense unknown GNA11 P293S does not lie within any known functional domains of the Gna11 protein (UniProt.org). P293S has not been characterized in the scientific literature and therefore, its effect on Gna11 protein function is unknown (PubMed, May 2018).
Y235* nonsense loss of function - predicted GNA11 Y235* results in a truncation of the Gna11 protein at aa 235 of 359 (UniProt.org). Due to disruption of the GTPase domain (PMID: 27647839) , Y235* is predicted to lead to a loss of Gna11 protein function.
I132V missense unknown GNA11 I132V does not lie within any known functional domains of the Gna11 protein (UniProt.org). I132V has not been characterized in the scientific literature and therefore, its effect on Gna11 protein function is unknown (PubMed, May 2018).
inact mut unknown loss of function GNA11 inact mut indicates that this variant results in a loss of function of the Gna11 protein. However, the specific amino acid change has not been identified.
R183H missense unknown GNA11 R183H lies within a GTP binding region of the Gna11 protein (UniProt.org). R183H has been identified in sequencing studies (PMID: 23640210) but has not been biochemically characterized and therefore, its effect on Gna11 protein function is unknown (PubMed, Oct 2018).
R183Q missense loss of function - predicted GNA11 R183Q lies within a GTP binding region of the Gna11 protein (UniProt.org). R183Q activates Yap signaling in cell culture in one study (PMID: 24882516), and therefore, is predicted to lead to a loss of Gna11 protein function.
R183C missense loss of function GNA11 R183C is a hotspot mutation that lies within a GTP binding region of the Gna11 protein (UniProt.org). R183Cresults in a loss of Gna11 protein function as indicated by activation of downstream signaling in culture, and increased tumor growth in mouse models (PMID: 21083380, PMID: 26778290, PMID: 23640210).
P318L missense unknown GNA11 P318L does not lie within any known functional domains of the Gna11 protein (UniProt.org). P318L has not been characterized in the scientific literature and therefore, its effect on Gna11 protein function is unknown (PubMed, May 2018).
I56V missense unknown GNA11 I56V does not lie within any known functional domains of the Gna11 protein (UniProt.org). I56V has not been characterized in the scientific literature and therefore, its effect on Gna11 protein function is unknown (PubMed, May 2018).
G171S missense unknown GNA11 G171S does not lie within any known functional domains of the Gna11 protein (UniProt.org). G171S has not been characterized in the scientific literature and therefore, its effect on Gna11 protein function is unknown (PubMed, May 2018).
S268A missense unknown GNA11 S268A does not lie within any known functional domains of the Gna11 protein (UniProt.org). S268A has not been characterized in the scientific literature and therefore, its effect on Gna11 protein function is unknown (PubMed, May 2018).
Q209* nonsense loss of function - predicted GNA11 Q209* results in a premature truncation of the Gna11 protein at amino acid 209 of 359 (UniProt.org). Due to disruption of the GTPase domain (PMID: 27647839), Q209* is predicted to lead to a loss of Gna11 protein function.
E294A missense unknown GNA11 E294A does not lie within any known functional domains of the Gna11 protein (UniProt.org). E294A has not been characterized in the scientific literature and therefore, its effect on Gna11 protein function is unknown (PubMed, May 2018).
mutant unknown unknown GNA11 mutant indicates an unspecified mutation in the GNA11 gene.
M203L missense unknown GNA11 M203L does not lie within any known functional domains of the Gna11 protein (UniProt.org). M203L has not been characterized in the scientific literature and therefore, its effect on Gna11 protein function is unknown (PubMed, May 2018).
R256Gfs*55 frameshift loss of function - predicted GNA11 R256Gfs*55 indicates a shift in the reading frame starting at amino acid 256 and terminating 55 residues downstream causing a premature truncation of the 359 amino acid Gna11 protein (UniProt.org). Due to disruption of the GTPase domain (PMID: 27647839), R256Gfs*55 is predicted to lead to a loss of Gna11 protein function.
H327R missense unknown GNA11 H327R does not lie within any known functional domains of the Gna11 protein (UniProt.org). H327R has not been characterized in the scientific literature and therefore, its effect on Gna11 protein function is unknown (PubMed, May 2018).
Q209R missense unknown GNA11 Q209R lies within a GTP binding region of the Gna11 protein (UniProt.org). Q209R has been identified in sequencing studies (PMID: 23778528), but has not been biochemically characterized and therefore, its effect on Gna11 protein function is unknown (PubMed, Oct 2018).
A342T missense unknown GNA11 A342T does not lie within any known functional domains of the Gna11 protein (UniProt.org). A342T has not been characterized in the scientific literature and therefore, its effect on Gna11 protein function is unknown (PubMed, May 2018).
F341L missense loss of function - predicted GNA11 F341L does not lie within any known functional domains of the Gna11 protein (UniProt.org). F341L results in increased sensitivity to extracellular calcium in cells expressing calcium-sensitive receptors and calcium-dependent increase of Erk phosphorylation in cell culture (PMID: 23802516, PMID: 26994139), and therefore, is predicted to lead to a loss of Gna11 protein function.
Molecular Profile Protein Effect Treatment Approaches
GNA11 L135P unknown
GNA11 S18F unknown
GNA11 Q209K unknown
GNA11 R114W unknown
GNA11 G66S unknown
GNA11 K275N unknown
GNA11 K57Q unknown
GNA11 S130Vfs*32 loss of function - predicted
GNA11 V164G unknown
GNA11 A110G unknown
GNA11 E294* loss of function - predicted
GNA11 S268F unknown
GNA11 V269I unknown
GNA11 E245K unknown
GNA11 R166H unknown
GNA11 R181Q loss of function - predicted MEK inhibitor (Pan) PKC Inhibitor (Pan)
GNA11 A168T unknown
GNA11 E4K unknown
GNA11 D195N unknown
GNA11 V344M unknown
GNA11 R183X unknown
GNA11 L351P unknown
GNA11 S130G unknown
GNA11 G208Afs*16 loss of function - predicted
GNA11 I56M unknown
GNA11 Q209L loss of function MEK inhibitor (Pan) PKC Inhibitor (Pan) Verteporfin
GNA11 Q209P unknown
GNA11 Q209X unknown
GNA11 D333N unknown
GNA11 E221Q unknown
GNA11 wild-type no effect
GNA11 R338C unknown
GNA11 amp no effect
GNA11 P293S unknown
GNA11 Y235* loss of function - predicted
GNA11 I132V unknown
GNA11 inact mut loss of function MEK inhibitor (Pan) PKC Inhibitor (Pan) Verteporfin
GNA11 R183H unknown
GNA11 R183Q loss of function - predicted MEK inhibitor (Pan) PKC Inhibitor (Pan) Verteporfin
GNA11 R183C loss of function MEK inhibitor (Pan) PKC Inhibitor (Pan) Verteporfin
GNA11 P318L unknown
GNA11 I56V unknown
GNA11 G171S unknown
GNA11 S268A unknown
GNA11 Q209* loss of function - predicted
GNA11 E294A unknown
GNA11 mutant unknown
GNA11 M203L unknown
GNA11 R256Gfs*55 loss of function - predicted
GNA11 H327R unknown
GNA11 Q209R unknown
GNA11 A342T unknown
GNA11 F341L loss of function - predicted MEK inhibitor (Pan) PKC Inhibitor (Pan)
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
GNA11 Q209L uveal melanoma sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, uveal melanoma cell lines harboring GNA11 Q209L demonstrated increased sensitivity to growth inhibition by Mekinist (trametinib) in culture, compared to cells with wild-type GNA11 (PMID: 22733540). 22733540
GNA11 Q209L uveal melanoma sensitive MEK162 + AEB071 Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Binimetinib (MEK162) and Sotrastaurin (AEB071) synergized to inhibit growth in a human uveal melanoma cancer cell line harboring a GNA11 Q209L mutation in culture and in xenograft models, and demonstrated improved efficacy over either agent alone (PMID: 24141786). 24141786
GNA11 Q209L uveal melanoma sensitive TAK-733 Preclinical - Cell culture Actionable In a preclinical study, TAK-733 inhibited growth of uveal melanoma cell lines harboring GNA11 Q209L in culture (PMID: 22515704). 22515704
GNA11 mutant uveal melanoma predicted - sensitive AEB071 + CGM097 Preclinical - Pdx & cell culture Actionable In a preclinical study, treatment with the combination of Sotrastaurin (AEB071) and CGM097 resulted in tumor regression or stasis in patient-derived xenograft (PDX) models of uveal melanoma harboring GNA11 mutations, and induced apoptosis and inhibited growth of GNA11-mutant uveal melanoma cell lines in culture (PMID: 27507190). 27507190
GNA11 mutant uveal melanoma predicted - sensitive AEB071 + Everolimus Preclinical - Pdx & cell culture Actionable In a preclinical study, treatment with the combination of Sotrastaurin (AEB071) and Afinitor (everolimus) inhibited tumor growth in patient-derived xenograft (PDX) models of uveal melanoma harboring GNA11 mutations, including tumor regression, and inhibited growth of GNA11-mutant uveal melanoma cell lines in culture (PMID: 27507190). 27507190
GNA11 mutant uveal melanoma predicted - sensitive MEK162 + AEB071 Preclinical - Pdx & cell culture Actionable In a preclinical study, the combination of Binimetinib (MEK162) and Sotrastaurin (AEB071) inhibited tumor growth in patient-derived xenograft (PDX) models of uveal melanoma harboring GNA11 mutations, and inhibited growth of GNA11-mutant uveal melanoma cell lines in culture (PMID: 27507190). 27507190