Gene Symbol: GNB4
Description: G protein subunit beta 4
Alias: CMTD1F, guanine nucleotide-binding protein subunit beta-4, G protein beta-4 subunit, guanine nucleotide binding protein (G protein), beta polypeptide 4, transducin beta chain 4
Species: human
Products:     GNB4

Top Publications

  1. Hu W, Zeng Y, Zuo Y, Zhang J. Identification of novel candidate genes involved in the progression of emphysema by bioinformatic methods. Int J Chron Obstruct Pulmon Dis. 2018;13:3733-3747 pubmed publisher
    ..Direct PPi suggested that GPR65, GNB4, P2RY13, NPSR1, BCR, BAG4, and IMPDH2 were potential pathogenic genes...
  2. Saddala M, Lennikov A, Grab D, Liu G, Tang S, Huang H. Proteomics reveals ablation of PlGF increases antioxidant and neuroprotective proteins in the diabetic mouse retina. Sci Rep. 2018;8:16728 pubmed publisher interaction analysis suggested that several proteins involved in insulin resistance pathways (Gnb1, Gnb2, Gnb4, Gnai2, Gnao1, Snap2, and Gngt1) were significantly down-regulated in PlGF ablated Akita diabetic mice (Akita...
  3. Wang B, Li D, Rodriguez Juarez R, Farfus A, Storozynsky Q, Malach M, et al. A suppressive role of guanine nucleotide-binding protein subunit beta-4 inhibited by DNA methylation in the growth of anti-estrogen resistant breast cancer cells. BMC Cancer. 2018;18:817 pubmed publisher
    ..and cell cycle analyses were performed to examine the effect of either guanine nucleotide-binding protein beta-4 (GNB4) overexpression or knockdown on cell proliferation, apoptosis and cell cycle...
  4. Baets J, De Jonghe P, Timmerman V. Recent advances in Charcot-Marie-Tooth disease. Curr Opin Neurol. 2014;27:532-40 pubmed publisher
    ..diversity and phenotypic variability, including: SBF1, DHTKD1, TFG, MARS, HARS, HINT1, TRIM1, AIFM1, PDK3 and GNB4. The increasing availability and affordability of next-generation sequencing technologies has ramped up gene ..
  5. Lee C, Ahn H, Lee S, Shin J, Park W, Kim J, et al. Integrated analysis of omics data using microRNA-target mRNA network and PPI network reveals regulation of Gnai1 function in the spinal cord of Ews/Ewsr1 KO mice. BMC Med Genomics. 2016;9 Suppl 1:33 pubmed publisher
    ..Neighbor proteins of Gnai1, G-protein complex subunits Gnb1, Gnb2 and Gnb4 were also down-regulated at their gene expression level...
  6. Laššuthová P, Šafka Brožková D, Neupauerová J, Krůtová M, Mazanec R, Seeman P. Confirmation of the GNB4 gene as causal for Charcot-Marie-Tooth disease by a novel de novo mutation in a Czech patient. Neuromuscul Disord. 2017;27:57-60 pubmed publisher
    The association of GNB4 with Charcot-Marie-Tooth (CMT) has recently been described in a publication by Soong et al. (Soong, et al., 2013). Here we present a patient with CMT in whom whole exome sequencing identified the mutation p...
  7. Li X, Carreria M, Witonsky K, Zeric T, Lofaro O, Bossert J, et al. Role of Dorsal Striatum Histone Deacetylase 5 in Incubation of Methamphetamine Craving. Biol Psychiatry. 2018;84:213-222 pubmed publisher 30 but not on day 2; this manipulation also altered other HDACs (Hdac1 and Hdac4) and potential HDAC5 targets (Gnb4 and Suv39h1). Results demonstrate a novel role of dorsal striatum HDAC5 in incubation of meth craving...
  8. Block H, Stadtmann A, Riad D, Rossaint J, Sohlbach C, Germena G, et al. Gnb isoforms control a signaling pathway comprising Rac1, Plcβ2, and Plcβ3 leading to LFA-1 activation and neutrophil arrest in vivo. Blood. 2016;127:314-24 pubmed publisher
    ..knockout mice and short hairpin RNA to knock down guanine nucleotide binding protein (GNB) isoforms (GNB1, GNB2, GNB4, and GNB5) in HL60 cells and primary murine hematopoietic cells...
  9. Sprague R, Bowles E, Olearczyk J, Stephenson A, Lonigro A. The role of G protein beta subunits in the release of ATP from human erythrocytes. J Physiol Pharmacol. 2002;53:667-74 pubmed
    ..Activation of the heterotrimeric G protein, Gi, results in ATP release from erythrocytes. This effect is may be related to the activity of beta subunits associated with this G protein in the human erythrocyte. ..

More Information


  1. Riemann K, Struwe H, Eisenhardt A, Obermaier B, Schmid K, Siffert W. Characterization of intron-1 haplotypes of the G protein beta 4 subunit gene--association with survival and progression in patients with urothelial bladder carcinoma. Pharmacogenet Genomics. 2008;18:999-1008 pubmed publisher be involved in proliferation and invasion processes, we analyzed genetic variations in regulatory regions of GNB4, which encodes the G beta 4 subunit, for their potential influence on cancer progression...
  2. Gibson S, Gilman A. Gialpha and Gbeta subunits both define selectivity of G protein activation by alpha2-adrenergic receptors. Proc Natl Acad Sci U S A. 2006;103:212-7 pubmed
    ..The molecular properties of each Gialpha, Gbeta, and alpha2-adrenergic receptor subtype influence signaling efficiency for the alpha2-adrenergic receptor-mediated signaling pathway. ..
  3. Soong B, Huang Y, Tsai P, Huang C, Pan H, Lu Y, et al. Exome sequencing identifies GNB4 mutations as a cause of dominant intermediate Charcot-Marie-Tooth disease. Am J Hum Genet. 2013;92:422-30 pubmed publisher
    ..158G>A (p.Gly53Asp) in GNB4, encoding guanine-nucleotide-binding protein subunit beta-4 (G?4), to cosegregate with the CMT phenotype in the ..
  4. Huang L, Shanker Y, Dubauskaite J, Zheng J, Yan W, Rosenzweig S, et al. Ggamma13 colocalizes with gustducin in taste receptor cells and mediates IP3 responses to bitter denatonium. Nat Neurosci. 1999;2:1055-62 pubmed
    ..We conclude that gustducin heterotrimers transduce responses to bitter and sweet compounds via alpha-gustducin's regulation of phosphodiesterase (PDE) and Gbetagamma's activation of phospholipase C (PLC). ..
  5. Zha Z, Han X, Smith M, Liu Y, Giguère P, Kopanja D, et al. A Non-Canonical Function of Gβ as a Subunit of E3 Ligase in Targeting GRK2 Ubiquitylation. Mol Cell. 2015;58:794-803 pubmed publisher
    ..These results reveal a non-canonical function of the Gβ protein as a ubiquitin ligase component and a mechanism of feedback regulation of GPCR signaling. ..
  6. Ruiz Velasco V, Ikeda S, Puhl H. Cloning, tissue distribution, and functional expression of the human G protein beta 4-subunit. Physiol Genomics. 2002;8:41-50 pubmed
    ..Furthermore, coexpression of Gbeta4gamma2 and Galpha(oA) resulted in heterotrimer formation. These results show that the newly cloned Gbeta subunit shares several properties with other human Gbeta family members. ..
  7. Cuello F, Schulze R, Heemeyer F, Meyer H, Lutz S, Jakobs K, et al. Activation of heterotrimeric G proteins by a high energy phosphate transfer via nucleoside diphosphate kinase (NDPK) B and Gbeta subunits. Complex formation of NDPK B with Gbeta gamma dimers and phosphorylation of His-266 IN Gbeta. J Biol Chem. 2003;278:7220-6 pubmed
    ..We conclude that NDPK B forms complexes with Gbetagamma dimers and contributes to G protein activation by increasing the high energetic phosphate transfer onto GDP via intermediately phosphorylated His-266 in Gbeta(1) subunits. ..
  8. Evanko D, Thiyagarajan M, Siderovski D, Wedegaertner P. Gbeta gamma isoforms selectively rescue plasma membrane localization and palmitoylation of mutant Galphas and Galphaq. J Biol Chem. 2001;276:23945-53 pubmed
  9. Riemann K, Struwe H, Alakus H, Obermaier B, Schmitz K, Schmid K, et al. Association of GNB4 intron-1 haplotypes with survival in patients with UICC stage III and IV colorectal carcinoma. Anticancer Res. 2009;29:1271-4 pubmed
    ..As previously shown, intron 1 of GNB4 harbours distinct haplotype blocks and block 1 is associated with survival and disease progression in urothelial ..
  10. Liu L, Zhang R. Intermediate Charcot-Marie-Tooth disease. Neurosci Bull. 2014;30:999-1009 pubmed publisher
    ..GJB1 is currently considered to be associated with X-linked DI-CMT, and MPZ, INF2, DNM2, YARS, GNB4, NEFL, and MFN2 are associated with autosomal DI-CMT. Moreover, GDAP1, KARS, and PLEKHG5 are associated with RI-CMT...
  11. Snow B, Betts L, Mangion J, Sondek J, Siderovski D. Fidelity of G protein beta-subunit association by the G protein gamma-subunit-like domains of RGS6, RGS7, and RGS11. Proc Natl Acad Sci U S A. 1999;96:6489-94 pubmed
  12. Yan K, Kalyanaraman V, Gautam N. Differential ability to form the G protein betagamma complex among members of the beta and gamma subunit families. J Biol Chem. 1996;271:7141-6 pubmed
    ..The strong preference of all gamma subunit types for the beta1 subunit type explains the preponderence of this subunit type in most G proteins. ..
  13. Pietruck F, Moritz A, Montemurro M, Sell A, Busch S, Rosskopf D, et al. Selectively enhanced cellular signaling by Gi proteins in essential hypertension. G alpha i2, G alpha i3, G beta 1, and G beta 2 are not mutated. Circ Res. 1996;79:974-83 pubmed
    ..Although the molecular mechanisms remain to be defined, these data support the concept of a selective enhancement of signal transduction via PTX-sensitive G proteins in essential hypertension. ..
  14. Miura S, Morikawa T, Fujioka R, Noda K, Kosaka K, Taniwaki T, et al. A novel missense variant (Gln220Arg) of GNB4 encoding guanine nucleotide-binding protein, subunit beta-4 in a Japanese family with autosomal dominant motor and sensory neuropathy. Eur J Med Genet. 2017;60:474-478 pubmed publisher
    ..disease (CMT) caused by variations in the guanine nucleotide-binding protein, subunit beta-4 gene (GNB4). We examined two Japanese familial cases with CMT...
  15. Khan S, Min A, Gora S, Houranieh G, Campden R, Robitaille M, et al. Gβ4γ1 as a modulator of M3 muscarinic receptor signalling and novel roles of Gβ1 subunits in the modulation of cellular signalling. Cell Signal. 2015;27:1597-608 pubmed publisher
    ..We noted that Gβ(1) occupies the promoter of Gβ(4) and may participate in maturation of its mRNA. This highlights a new role for Gβγ signalling beyond their canonical roles in cellular signalling. ..
  16. Goddard A, Ladds G, Forfar R, Davey J. Identification of Gnr1p, a negative regulator of G alpha signalling in Schizosaccharomyces pombe, and its complementation by human G beta subunits. Fungal Genet Biol. 2006;43:840-51 pubmed
    ..Human G beta subunits complement the loss of Gnr1p, functioning as negative regulators of G alpha signalling in fission yeast. ..
  17. Rosskopf D, Nikula C, Manthey I, Joisten M, Frey U, Kohnen S, et al. The human G protein beta4 subunit: gene structure, expression, Ggamma and effector interaction. FEBS Lett. 2003;544:27-32 pubmed
  18. Downes G, Gautam N. The G protein subunit gene families. Genomics. 1999;62:544-52 pubmed
  19. Asano T, Morishita R, Ueda H, Kato K. Selective association of G protein beta(4) with gamma(5) and gamma(12) subunits in bovine tissues. J Biol Chem. 1999;274:21425-9 pubmed
    ..Particular combinations of beta and gamma subunit isoforms may contribute to maintaining efficient and specific signal transduction mediated by G proteins. ..
  20. Howlett A, Gray A, Hunter J, Willardson B. Role of molecular chaperones in G protein beta5/regulator of G protein signaling dimer assembly and G protein betagamma dimer specificity. J Biol Chem. 2009;284:16386-99 pubmed publisher
    ..These findings point to a general role for PhLP1 in the assembly of all Gbetagamma combinations and suggest a CCT-dependent mechanism for Gbeta5-RGS7 assembly that utilizes the co-chaperone activity of PhLP1 in a unique way. ..
  21. Pol S, Polanco J, Seidman R, O Bara M, Shayya H, Dietz K, et al. Network-Based Genomic Analysis of Human Oligodendrocyte Progenitor Differentiation. Stem Cell Reports. 2017;9:710-723 pubmed publisher
    ..These analyses identified G-protein β4 (GNB4), which was associated with hOPC commitment...
  22. Huang L, Max M, Margolskee R, Su H, Masland R, Euler T. G protein subunit G gamma 13 is coexpressed with G alpha o, G beta 3, and G beta 4 in retinal ON bipolar cells. J Comp Neurol. 2003;455:1-10 pubmed
    ..Gbeta1, 2, and 5 are expressed in partially overlapping subpopulations of cone bipolar cells. Ggamma13 and Gbeta3 and/or Gbeta4, thus, seem selectively to participate in signal transduction by ON bipolar cells. ..