Gene Symbol: GNAT2
Description: G protein subunit alpha transducin 2
Alias: ACHM4, GNATC, guanine nucleotide-binding protein G(t) subunit alpha-2, cone-type transducin alpha subunit, guanine nucleotide binding protein (G protein), alpha transducing activity polypeptide 2, transducin alpha-2 chain, transducin, cone-specific, alpha polypeptide
Species: human
Products:     GNAT2

Top Publications

  1. Hollborn M, Ulbricht E, Rillich K, Dukic Stefanovic S, Wurm A, Wagner L, et al. The human Müller cell line MIO-M1 expresses opsins. Mol Vis. 2011;17:2738-50 pubmed
    ..protein [GNAZ], alpha transducing activity polypeptide 1 [GNAT1], alpha transducing activity polypeptide 2 [GNAT2]). The presence of blue opsin and melanopsin was confirmed with immunocytochemistry and western blotting...
  2. Chakraborty R, Yang V, Park H, Landis E, Dhakal S, Motz C, et al. Lack of cone mediated retinal function increases susceptibility to form-deprivation myopia in mice. Exp Eye Res. 2019;180:226-230 pubmed publisher
    Retinal photoreceptors are important in visual signaling for normal eye growth in animals. We used Gnat2cplf3/cplf3 (Gnat2-/-) mice, a genetic mouse model of cone dysfunction to investigate the influence of cone ..
  3. Lotfi P, Tse D, di Ronza A, Seymour M, Martano G, Cooper J, et al. Trehalose reduces retinal degeneration, neuroinflammation and storage burden caused by a lysosomal hydrolase deficiency. Autophagy. 2018;14:1419-1434 pubmed publisher
    ..replacement therapy; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GFAP: glial fibrillary acidic protein; GNAT2: guanine nucleotide binding protein, alpha transducing 2; HSCT: hematopoietic stem cell transplantation; INL: ..
  4. Yang F, Ma H, Boye S, Hauswirth W, Ding X. Overexpression of Type 3 Iodothyronine Deiodinase Reduces Cone Death in the Leber Congenital Amaurosis Model Mice. Adv Exp Med Biol. 2018;1074:125-131 pubmed publisher
    ..Subretinal delivery of AAV5-IRBP/GNAT2-hDIO3 induced robust expression of DIO3 in the mouse retina and significantly reduced the number of TUNEL-positive ..
  5. Wawrocka A, Kohl S, Baumann B, Walczak Sztulpa J, Wicher K, Skorczyk Werner A, et al. Five novel CNGB3 gene mutations in Polish patients with achromatopsia. Mol Vis. 2014;20:1732-9 pubmed
    ..Direct DNA sequencing encompassing the entire coding region of the CNGB3 gene, eight exons of the GNAT2 gene, and exons 5-7 of the CNGA3 gene was performed...
  6. Lagman D, Callado Pérez A, Franzén I, Larhammar D, Abalo X. Transducin duplicates in the zebrafish retina and pineal complex: differential specialisation after the teleost tetraploidisation. PLoS ONE. 2015;10:e0121330 pubmed publisher
    ..Early vertebrate tetraploidisations resulted in separate transducin heterotrimers: gnat1/gnb1/gngt1 for rods, and gnat2/gnb3/gngt2 for cones...
  7. Yao K, Qiu S, Wang Y, Park S, Mohns E, Mehta B, et al. Restoration of vision after de novo genesis of rod photoreceptors in mammalian retinas. Nature. 2018;560:484-488 pubmed publisher
    ..MG-derived rods restored visual responses in Gnat1rd17Gnat2cpfl3 double mutant mice, a model of congenital blindness9,10, throughout the visual pathway ..
  8. Pascual Camps I, Barranco González H, Aviñó Martínez J, Silva E, Harto Castaño M. Diagnosis and Treatment Options for Achromatopsia: A Review of the Literature. J Pediatr Ophthalmol Strabismus. 2018;55:85-92 pubmed publisher
    ..CNGA3, CNGB3, GNAT2, PDE6C, PDE6H, and ATF6 gene mutations have been identified as associated with this disease...
  9. Liang X, Dong F, Li H, Li H, Yang L, Sui R. Novel CNGA3 mutations in Chinese patients with achromatopsia. Br J Ophthalmol. 2015;99:571-6 pubmed publisher
    ..All exons of CNGA3, CNGB3, GNAT2, PDE6C and PDE6H were amplified by a PCR and screened for mutation by direct Sanger sequencing...

More Information


  1. Ansar M, Santos Cortez R, Saqib M, Zulfiqar F, Lee K, Ashraf N, et al. Mutation of ATF6 causes autosomal recessive achromatopsia. Hum Genet. 2015;134:941-50 pubmed publisher
    ..Currently mutations in five genes CNGA3, CNGB3, GNAT2, PDE6C and PDE6H have been implicated in ACHM...
  2. Wang W, Hsu H, Li Y, Wu C. Retinoic Acid Protects and Rescues the Development of Zebrafish Embryonic Retinal Photoreceptor Cells from Exposure to Paclobutrazol. Int J Mol Sci. 2017;18: pubmed publisher
    ..Eye size and histology were examined. Expression levels of gnat1 (rod photoreceptor marker), gnat2 (cone photoreceptor marker), aldehyde dehydrogenases (encoding key enzymes for RA synthesis), and ..
  3. Rainy N, Etzion T, Alon S, Pomeranz A, Nisgav Y, Livnat T, et al. Knockdown of unc119c results in visual impairment and early-onset retinal dystrophy in zebrafish. Biochem Biophys Res Commun. 2016;473:1211-1217 pubmed publisher
    ..morphology was analyzed using immunohistochemistry with anti-cone arrestin (zpr-1) and anti-cone transducin-? (GNAT2) antibodies. The zebrafish genome contains four genes encoding unc119 paralogs located on different chromosomes...
  4. Allen A, Cameron M, Brown T, Vugler A, Lucas R. Visual responses in mice lacking critical components of all known retinal phototransduction cascades. PLoS ONE. 2010;5:e15063 pubmed publisher
    ..of U73122 (a phospholipase C antagonist), but is inhibited by a missense mutation of cone α transducin (Gnat2(cpfl3)), suggesting Gnat2-dependence...
  5. Li W, Zhou L, Li Z, Wang Y, Shi J, Yang Y, et al. Zebrafish Lbh-like Is Required for Otx2-mediated Photoreceptor Differentiation. Int J Biol Sci. 2015;11:688-700 pubmed publisher morpholinos specifically inhibits expression of multiple photoreceptor-specific genes, such as opsins, gnat1, gnat2 and irbp...
  6. Sundaram V, Wilde C, Aboshiha J, Cowing J, Han C, Langlo C, et al. Retinal structure and function in achromatopsia: implications for gene therapy. Ophthalmology. 2014;121:234-245 pubmed publisher
    ..9 years (range, 6-52 years) were included. Disease-causing variants were found in CNGA3 (n = 18), CNGB3 (n = 15), GNAT2 (n = 4), and PDE6C (n = 1). No variants were found in 2 individuals. In all, 22...
  7. Ueno S, Nakanishi A, Kominami T, Ito Y, Hayashi T, Yoshitake K, et al. In vivo imaging of a cone mosaic in a patient with achromatopsia associated with a GNAT2 variant. Jpn J Ophthalmol. 2017;61:92-98 pubmed publisher
    The 2 most common causative genes for achromatopsia (ACHM) are CNGA3 and CNGB3; other genes including GNAT2 account for only a small portion of ACHM cases...
  8. Ronning K, Allina G, Miller E, Zawadzki R, Pugh E, Herrmann R, et al. Loss of cone function without degeneration in a novel Gnat2 knock-out mouse. Exp Eye Res. 2018;171:111-118 pubmed publisher
    ..Here we describe a novel Gnat2 knockout mouse line (Gnat2-/-) ideal for dissecting rod and cone function...
  9. Kohl S, Baumann B, Rosenberg T, Kellner U, Lorenz B, Vadalà M, et al. Mutations in the cone photoreceptor G-protein alpha-subunit gene GNAT2 in patients with achromatopsia. Am J Hum Genet. 2002;71:422-5 pubmed
    ..identification of five independent families with achromatopsia that segregate protein-truncation mutations in the GNAT2 gene, located on chromosome 1p13...
  10. Pina A, Baumert U, Loyer M, Koenekoop R. A three base pair deletion encoding the amino acid (lysine-270) in the alpha-cone transducin gene. Mol Vis. 2004;10:265-71 pubmed
    ..The human gene for the alpha-subunit of cone transducin (GNAT2) has been cloned and characterized. Recently achromatopsia has been associated with mutations in this gene...
  11. Mazzoni M, Malinski J, Hamm H. Structural analysis of rod GTP-binding protein, Gt. Limited proteolytic digestion pattern of Gt with four proteases defines monoclonal antibody epitope. J Biol Chem. 1991;266:14072-81 pubmed
    ..Additionally, the antibody did not bind the 38- and 36-kDa or other fragments containing the carboxyl terminus, showing that the amino-terminal residues from Met1 to Lys17 were essential for antibody binding to alpha t. ..
  12. Caricasole A, Sala C, Roncarati R, Formenti E, Terstappen G. Cloning and characterization of the human phosphoinositide-specific phospholipase C-beta 1 (PLC beta 1). Biochim Biophys Acta. 2000;1517:63-72 pubmed
    ..Finally, we characterized the structure of the PLC beta 1 locus and confirmed its mapping to human chromosome 20. ..
  13. Yang F, Ma H, Belcher J, Butler M, Redmond T, Boye S, et al. Targeting iodothyronine deiodinases locally in the retina is a therapeutic strategy for retinal degeneration. FASEB J. 2016;30:4313-4325 pubmed
    ..Subretinal delivery of AAV5-IRBP/GNAT2-DIO3, which directs expression of human DIO3 specifically in cones, increased cone density by 30-40% in a Rpe65<..
  14. Morris T, Fong S. Characterization of the gene encoding human cone transducin alpha-subunit (GNAT2). Genomics. 1993;17:442-8 pubmed
    The human cone transducin alpha-subunit (GNAT2) gene has been completely characterized. The human GNAT2 transcription unit is 9967-bp in length and consists of eight exons with seven introns...
  15. Lambright D, Noel J, Hamm H, Sigler P. Structural determinants for activation of the alpha-subunit of a heterotrimeric G protein. Nature. 1994;369:621-8 pubmed
    ..The changes are distinct from those observed in other members of the GTPase superfamily. ..
  16. Chen C, Woodruff M, Chen F, Shim H, Cilluffo M, Fain G. Replacing the rod with the cone transducin subunit decreases sensitivity and accelerates response decay. J Physiol. 2010;588:3231-41 pubmed publisher
    ..They also indicate more generally that the molecular nature of G-protein alpha may play an important role in the kinetics of G-protein cascades for metabotropic receptors throughout the body. ..
  17. Ouechtati F, Merdassi A, Bouyacoub Y, Largueche L, Derouiche K, Ouragini H, et al. Clinical and genetic investigation of a large Tunisian family with complete achromatopsia: identification of a new nonsense mutation in GNAT2 gene. J Hum Genet. 2011;56:22-8 pubmed publisher
    Complete achromatopsia is a rare autosomal recessive disease associated with CNGA3, CNGB3, GNAT2 and PDE6C mutations...
  18. Berstein G, Blank J, Jhon D, Exton J, Rhee S, Ross E. Phospholipase C-beta 1 is a GTPase-activating protein for Gq/11, its physiologic regulator. Cell. 1992;70:411-8 pubmed
    ..Such GAP activity by an effector coupled to a trimeric G protein can reconcile slow GTP hydrolysis by pure G proteins in vitro with fast physiologic deactivation of G protein-mediated signaling. ..
  19. Thiadens A, Slingerland N, Roosing S, van Schooneveld M, van Lith Verhoeven J, van Moll Ramirez N, et al. Genetic etiology and clinical consequences of complete and incomplete achromatopsia. Ophthalmology. 2009;116:1984-9.e1 pubmed publisher
    ..To investigate the genetic causes of complete and incomplete achromatopsia (ACHM) and assess the association between disease-causing mutations, phenotype at diagnosis, and visual prognosis...
  20. Oldham W, Van Eps N, Preininger A, Hubbell W, Hamm H. Mechanism of the receptor-catalyzed activation of heterotrimeric G proteins. Nat Struct Mol Biol. 2006;13:772-7 pubmed
    ..These data provide the first direct observation of R*-mediated conformational changes in G proteins and define the structural basis for GDP release from G alpha. ..
  21. Rosenberg T, Baumann B, Kohl S, Zrenner E, Jorgensen A, Wissinger B. Variant phenotypes of incomplete achromatopsia in two cousins with GNAT2 gene mutations. Invest Ophthalmol Vis Sci. 2004;45:4256-62 pubmed
    ..Molecular genetic analysis of the X-linked cone opsin genes, mutation screening of the CNGA3, CNGB3, and GNAT2 genes, and heterologous splicing experiments...
  22. Aligianis I, Forshew T, Johnson S, Michaelides M, Johnson C, Trembath R, et al. Mapping of a novel locus for achromatopsia (ACHM4) to 1p and identification of a germline mutation in the alpha subunit of cone transducin (GNAT2). J Med Genet. 2002;39:656-60 pubmed
    ..Direct sequence analysis of the candidate gene GNAT2 located within this interval identified a frameshift mutation in exon 7 (c842_843insTCAG; M280fsX291) that ..
  23. Morris T, Fong W, Ward M, Hu H, Fong S. Localization of upstream silencer elements involved in the expression of cone transducin alpha-subunit (GNAT2). Invest Ophthalmol Vis Sci. 1997;38:196-206 pubmed
    ..cis-acting elements involved in the expression of the cone-specific G-protein, cone transducin alpha-subunit (GNAT2)...
  24. Buss J, Mumby S, Casey P, Gilman A, Sefton B. Myristoylated alpha subunits of guanine nucleotide-binding regulatory proteins. Proc Natl Acad Sci U S A. 1987;84:7493-7 pubmed
    ..Myristate may play an important role in stabilizing interactions of G proteins with phospholipid or with membrane-bound proteins. ..
  25. Doucette L, Green J, Black C, Schwartzentruber J, Johnson G, Galutira D, et al. Molecular genetics of achromatopsia in Newfoundland reveal genetic heterogeneity, founder effects and the first cases of Jalili syndrome in North America. Ophthalmic Genet. 2013;34:119-29 pubmed publisher
    ..from Newfoundland, Canada were sequenced for mutations in the four known achromatopsia genes CNGA3, CNGB3, GNAT2, and PDE6C...
  26. Fawzi A, Fay D, Murphy E, Tamir H, Erdos J, Northup J. Rhodopsin and the retinal G-protein distinguish among G-protein beta gamma subunit forms. J Biol Chem. 1991;266:12194-200 pubmed
    ..These results may indicate that the recently uncovered diversity in the expression of beta gamma subunit forms may complement the diversity of G alpha subunits in providing for specific receptor recognition of G-proteins. ..
  27. Lerea C, Bunt Milam A, Hurley J. Alpha transducin is present in blue-, green-, and red-sensitive cone photoreceptors in the human retina. Neuron. 1989;3:367-76 pubmed
    ..The multiple Tc alpha genes could be closely related genes or different Tc alpha alleles, or one could be a pseudogene. ..
  28. Blatt C, Eversole Cire P, Cohn V, Zollman S, Fournier R, Mohandas L, et al. Chromosomal localization of genes encoding guanine nucleotide-binding protein subunits in mouse and human. Proc Natl Acad Sci U S A. 1988;85:7642-6 pubmed
    ..The retinal-specific transducin subunit genes GNAT1 and GNAT2 were on chromosomes 3 and 1; GNAI1, GNAI2, and GNAI3 were assigned to chromosomes 7, 3, and 1, respectively; GNAZ ..
  29. Hirano T. [Analysis of cell specific transcription of the human cone transducin alpha subunit gene]. Hokkaido Igaku Zasshi. 1993;68:885-93 pubmed
    ..By further study utilizing genomic sequencing, HeLa DNA was methylated in contrast to Y79, suggesting methylation as one of the transcription-regulating factors of this region. ..
  30. Wall M, Coleman D, Lee E, Iñiguez Lluhí J, Posner B, Gilman A, et al. The structure of the G protein heterotrimer Gi alpha 1 beta 1 gamma 2. Cell. 1995;83:1047-58 pubmed
    ..Repeated WD motifs in beta form a circularized sevenfold beta propeller. The conserved cores of these motifs are a scaffold for display of their more variable linkers on the exterior face of each propeller blade. ..
  31. Shi J, Potash J, Knowles J, Weissman M, Coryell W, Scheftner W, et al. Genome-wide association study of recurrent early-onset major depressive disorder. Mol Psychiatry. 2011;16:193-201 pubmed publisher
    ..Larger samples will be required to confirm the hypothesis of association between MDD (and particularly the recurrent early-onset subtype) and common SNPs. ..
  32. Berndt S, Gustafsson S, Magi R, Ganna A, Wheeler E, Feitosa M, et al. Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture. Nat Genet. 2013;45:501-12 pubmed publisher
    ..H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity...
  33. Kubo M, Hirano T, Kakinuma M. Molecular cloning and sequence analysis of cDNA and genomic DNA for the human cone transducin alpha subunit. FEBS Lett. 1991;291:245-8 pubmed
    ..In Jurkat, however, the message was detectable only by reverse transcription/PCR. Taken together, this novel G protein alpha subunit must be human Tc. ..
  34. Kohl S, Hamel C. Clinical utility gene card for: achromatopsia. Eur J Hum Genet. 2011;19: pubmed publisher
  35. Arshavsky VYu -, Gray Keller M, Bownds M. cGMP suppresses GTPase activity of a portion of transducin equimolar to phosphodiesterase in frog rod outer segments. Light-induced cGMP decreases as a putative feedback mechanism of the photoresponse. J Biol Chem. 1991;266:18530-7 pubmed