Molecule Information

General Information of the Molecule (ID: Mol01835)

• Name: Guanine nucleotide-binding protein subunit alpha-11 (GNA11) ,Homo sapiens
• Synonyms: Guanine nucleotide-binding protein subunit alpha-11; G alpha-11; G-protein subunit alpha-11; Guanine nucleotide-binding protein G(y) subunit alpha; GNA11; GA11
• Molecule Type: Protein
• Gene Name: GNA11
• Gene ID: 2767
• Location: chr19:3,094,362-3,123,999[+]
• Sequence:
  MTLESMMACC LSDEVKESKR INAEIEKQLR RDKRDARREL KLLLLGTGES GKSTF
  IKQMR IIHGAGYSEE DKRGFTKLVY QNIFTAMQAM IRAMETLKIL YKYEQNKANA
  LLIREVDVEK VTTFEHQYVS AIKTLWEDPG IQECYDRRRE YQLSDSAKYY LTDV
  DRIATL GYLPTQQDVL RVRVPTTGII EYPFDLENII FRMVDVGGQR SERRKWIHC
  F ENVTSIMFLV ALSEYDQVLV ESDNENRMEE SKALFRTIIT YPWFQNSSVI LFL
  NKKDLLE DKILYSHLVD YFPEFDGPQR DAQAAREFIL KMFVDLNPDS DKIIYSHF
  TC ATDTENIRFV FAAVKDTILQ LNLKEYNLV
• Function: Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. Acts as an activator of phospholipase C. Transduces FFAR4 signaling in response to long-chain fatty acids (LCFAs).
• Uniprot ID: GNA11_HUMAN
• Ensembl ID: ENSG00000088256
• HGNC ID: HGNC:4379

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  ADTT: Aberration of the Drug's Therapeutic Target

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Trametinib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Uveal melanoma [1]

• Sensitive Disease: Uveal melanoma [ICD-11: 2D0Y.0]
• Sensitive Drug: Trametinib
• Molecule Alteration: Missense mutation; p.Q209L (c.626A>T)
• Experimental Note: Revealed Based on the Cell Line Data
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Cell Titer-blue assay
• Mechanism Description: The missense mutation p.Q209L (c.626A>T) in gene GNA11 cause the sensitivity of Trametinib by unusual activation of pro-survival pathway

Clinical Trial Drug(s) 1 drug(s) in total

Selumetinib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Melanoma [2]

• Sensitive Disease: Melanoma [ICD-11: 2C30.0]
• Sensitive Drug: Selumetinib
• Molecule Alteration: Missense mutation; p.Q209P (c.626A>C)
• Experimental Note: Identified from the Human Clinical Data

Disease Class: Melanoma [2]

• Sensitive Disease: Melanoma [ICD-11: 2C30.0]
• Sensitive Drug: Selumetinib
• Molecule Alteration: Missense mutation; p.Q209L (c.626A>T)
• Experimental Note: Identified from the Human Clinical Data

Disease Class: Melanoma [2]

• Sensitive Disease: Melanoma [ICD-11: 2C30.0]
• Sensitive Drug: Selumetinib
• Molecule Alteration: Missense mutation; p.Q209P (c.626A>C)
• Experimental Note: Identified from the Human Clinical Data

Disease Class: Melanoma [2]

• Sensitive Disease: Melanoma [ICD-11: 2C30.0]
• Sensitive Drug: Selumetinib
• Molecule Alteration: Missense mutation; p.Q209L (c.626A>T)
• Experimental Note: Identified from the Human Clinical Data

Preclinical Drug(s) 2 drug(s) in total

AEB071/Binimetinib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Uveal melanoma [3]

• Sensitive Disease: Uveal melanoma [ICD-11: 2D0Y.0]
• Sensitive Drug: AEB071/Binimetinib
• Molecule Alteration: Missense mutation; p.Q209L (c.626A>T)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: OMM-GN11; N.A.; Mus musculus (Mouse); N.A.
• In Vitro Model: OMM13; N.A.; .; N.A.
• In Vitro Model: Mel202; Eye; Homo sapiens (Human); CVCL_C301
• In Vitro Model: GNAQ cells; N.A.; .; N.A.
• In Vitro Model: Mel270 cells; Skin; Homo sapiens (Human); CVCL_C302
• In Vitro Model: GNA11 cells; N.A.; .; N.A.
• In Vitro Model: UPMD-1 cells; Skin; Homo sapiens (Human); CVCL_C297
• In Vitro Model: 92-1 cells; Bladder; Homo sapiens (Human); CVCL_W909
• In Vitro Model: Mel202; Eye; Homo sapiens (Human); CVCL_C301
• In Vivo Model: C57/BL6 mouse model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Cell proliferation assay

FR900359

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Uveal melanoma [4]

• Sensitive Disease: Uveal melanoma [ICD-11: 2D0Y.0]
• Sensitive Drug: FR900359
• Molecule Alteration: Missense mutation; p.Q209L (c.626A>T)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: UM002B cells; Brain; Homo sapiens (Human); N.A.
• In Vitro Model: Omm13 cells; N.A.; .; N.A.
• In Vitro Model: Ocm3 cells; Skin; Homo sapiens (Human); CVCL_6937
• In Vitro Model: 92-1 cells; Bladder; Homo sapiens (Human); CVCL_W909
• Experiment for Molecule Alteration: Sanger sequencing assay; Western blotting analysis

Investigative Drug(s) 1 drug(s) in total

TAK-733

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Uveal melanoma [5]

• Sensitive Disease: Uveal melanoma [ICD-11: 2D0Y.0]
• Sensitive Drug: TAK-733
• Molecule Alteration: Missense mutation; p.Q209L (c.626A>T)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Wn1366 cells; Skin; Homo sapiens (Human); CVCL_6789
• In Vitro Model: SkMEL28 cells; Skin; Homo sapiens (Human); CVCL_0526
• In Vitro Model: SBCL2 cells; Skin; Homo sapiens (Human); CVCL_D732
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: The missense mutation p.Q209L (c.626A>T) in gene GNA11 cause the sensitivity of TAK-733 by unusual activation of pro-survival pathway

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Melanoma [ICD-11: 2C30]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Skin
• The Specified Disease: Melanoma
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 5.69E-01; Fold-change: 3.82E-01; Z-score: 2.99E-01

References

• Ref 1: Combination small molecule MEK and PI3K inhibition enhances uveal melanoma cell death in a mutant GNAQ- and GNA11-dependent mannerClin Cancer Res. 2012 Aug 15;18(16):4345-55. doi: 10.1158/1078-0432.CCR-11-3227. Epub 2012 Jun 25.
• Ref 2: Turk J Haematol. 2016 Mar 5;33(1):41-7. doi: 10.4274/tjh.2014.0010. Epub 2014 May 21.
• Ref 3: Combined PKC and MEK inhibition in uveal melanoma with GNAQ and GNA11 mutationsOncogene. 2014 Sep 25;33(39):4724-34. doi: 10.1038/onc.2013.418. Epub 2013 Oct 21.
• Ref 4: Effects of Oncogenic GAlpha(q) and GAlpha(11) Inhibition by FR900359 in Uveal MelanomaMol Cancer Res. 2019 Apr;17(4):963-973. doi: 10.1158/1541-7786.MCR-18-0574. Epub 2018 Dec 19.
• Ref 5: Antitumor effects of the investigational selective MEK inhibitor TAK733 against cutaneous and uveal melanoma cell linesMol Cancer. 2012 Apr 19;11:22. doi: 10.1186/1476-4598-11-22.