GNAT2 gene


Gene (OMIM No.)
Function of gene/protein
  • Protein: G protein subunit alpha transducin 2
  • Expressed in cones and involved in the cone phototransduction cascade
  • Light-activated opsins interact with transducin, which in turn activates cyclic guanosine monophosphate (cGMP)-phosphodiesterase
  • Activated cGMP-phosphodiesterase closes the cGMP-gated ion channels which in turn causes hyperpolarisation of the photoreceptor plasma membrane
Clinical phenotype
(OMIM phenotype no.)
  • Autosomal recessive
Ocular features
  • Nystagmus from birth/early infancy
  • Photophobia
  • Normal appearing fundus is common but some may display macular RPE mottling
  • Adaptive optics scanning light ophthalmoscopy shows relatively well-preserved cone mosaic compared to other causative genes of achromatopsia
Visual function
  • Complete and incomplete achromats with GNAT2 variants have been reported
  • Visual impairment evident from birth/early infancy
  • Variable severity of colour vision impairment and reduced visual acuity
  • Affected individuals may be seen to favour dimly-lit environment
Systemic features
  • No specific extraocular features
Key investigations
  • Full-field ERG (ffERG): Severely reduced cone response with normal/subnormal rod response
  • FAF: Usually appears normal
  • OCT: Usually normal appearing with a continuous EZ; some may display a hyporeflective zone at the fovea
Molecular diagnosisNext generation sequencing
  • Targeted gene panels (retinal)
  • Whole exome sequencing
  • Whole genome sequencing
Therapies under research
Further information

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Multimodal imaging

Different images of the retina of a patient with achromatopsia due to mutations in the GNAT2 gene. No abnormalities in the retina was found in all imaging protocols.
Multimodal imaging of a patient with GNAT2-achromatopsia. Both wide field colour fundus photograph (A) and FAF imaging (B) are unremarkable. The OCT scan of the macula (C) looks normal.


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  2.  Müller F, Kaupp U. Signaltransduktion in Sehzellen. Naturwissenschaften. 1998;85(2):49-61
  3.  Kohl S, Baumann B, Rosenberg T et al. Mutations in the Cone Photoreceptor G-Protein α-Subunit Gene GNAT2 in Patients with Achromatopsia. The American Journal of Human Genetics. 2002;71(2):422-425
  4.  Kohl S, Marx T, Giddings I et al. Total colourblindness is caused by mutations in the gene encoding the α-subunit of the cone photoreceptor cGMP-gated cation channel. Nat Genet. 1998;19(3):257-259
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  6.  Michaelides M, Aligianis IA, Holder GE, et al. Cone dystrophy phenotype associated with a frameshift mutation (M280fsX291) in the alpha-subunit of cone specific transducin (GNAT2) [published correction appears in Br J Ophthalmol. 2004 Feb;88(2):314]. Br J Ophthalmol. 2003;87(11):1317-1320
  7.  Bidaut Garnier M, Flores M, Debellemanière G et al. Reliability of cone counts using an adaptive optics retinal camera. Clin Exp Ophthalmol. 2014;42(9):833-840
  8.  Felden J, Baumann B, Ali M, et al. Mutation spectrum and clinical investigation of achromatopsia patients with mutations in the GNAT2 gene. Hum Mutat. 2019;40(8):1145-1155
  9.  Georgiou M, Singh N, Kane T, et al. Photoreceptor Structure in GNAT2-Associated Achromatopsia. Invest Ophthalmol Vis Sci. 2020;61(3):40

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Updated on November 30, 2020
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