ATF6 gene


Gene (OMIM No.)
Function of gene/protein
  • Protein: Activating transcription factor 6
  • Transcription factor of the endoplasmic reticulum (ER)
  • Activated upon ER stress resulting in recruitment of enzymes required to restore cellular homeostasis
  • May play a crucial role in cone development
Clinical phenotype
(OMIM phenotype no.)
  • Autosomal recessive
Ocular features
  • Nystagmus and photophobia from birth/early infancy
  • Absent foveal reflex
  • Variable central macular changes ranging from normal to well-demarcated atrophic areas
Visual function
  • Severely reduced visual acuity
  • Poor/absent colour vision
  • Bilateral central scotoma
  • Rarely progresses
Systemic features
  • May be associated with sensorineural hearing loss
Key investigations
  • Full field ERG — Normal rod responses with severely reduced/absent cone responses
  • FAF — Variable; parafoveal areas/rings of increased AF or a well-demarcated hypo-AF area corresponding to atrophy surrounded by a hyper-AF ring
  • OCT — Foveal hypoplasia with absence of foveal ellipsoid zone or presence of a foveal hyporeflective zone
Molecular diagnosisNext generation sequencing
  • Targeted gene panels (retinal)
  • Whole exome sequencing
  • Whole genome sequencing
Therapies under research
  • Oral glycerol phenylbutyrate (PBA) (NCT 04041232, early phase 1)
Further information

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  1.  Wu J, Rutkowski DT, Dubois M, et al. ATF6alpha optimizes long-term endoplasmic reticulum function to protect cells from chronic stress. Dev Cell. 2007;13(3):351-364
  2.  Kohl S, Zobor D, Chiang WC, et al. Mutations in the unfolded protein response regulator ATF6 cause the cone dysfunction disorder achromatopsia. Nat Genet. 2015;47(7):757-765
  3.  Ansar M, Santos-Cortez RL, Saqib MA, et al. Mutation of ATF6 causes autosomal recessive achromatopsia. Hum Genet. 2015;134(9):941-950.
  4.  Mastey RR, Georgiou M, Langlo CS, et al. Characterization of Retinal Structure in ATF6-Associated Achromatopsia. Invest Ophthalmol Vis Sci. 2019;60(7):2631-2640

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Updated on February 7, 2021
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