ARHGEF18 gene


Gene (OMIM No.)
Function of gene/protein
  • Protein: Rho guanine nucleotide exchange factor 18
  • Nucleotide exchange factor for Rho GTPases
  • Required for tight junction assembly and barrier formation in epithelial cells
  • Important role in shaping cell morphology
Clinical phenotype
(OMIM phenotype no.)
  • Autosomal recessive
  • Shares features with CRB1-retinopathy
  • Vessel attenuation
  • Nummular pigment clumping with RPE atrophy
  • Optic disc pallor
  • Cystoid macular oedema may be present
  • Irregular mid-peripheral intraretinal pigment migration
Visual function
  • Onset in 3rd to 4th decade of life
  • Mild nyctalopia
  • Central visual disturbance
  • Visual field defects
  • BCVA 0.18 to 1.8 logMAR
Systemic features
  • No extraocular features reported
Key investigations
  • Full field ERG: rod-cone dystrophy
  • Pattern ERG: subnormal in one patient and undetectable in the other two patients
  • FAF: widespread irregular peripheral hypo-AF
  • OCT: intraretinal cysts; preserved ellipsoid zone (EZ) throughout the macula but this was only retained in the fovea in one patient
Molecular diagnosisNext generation sequencing
  • Targeted gene panels (retinal)
  • Whole exome sequencing
  • Whole genome sequencing
Therapies under research
  • None at present
Further information

Jump to top


  1.  Loosli, F. (2013) ArhGEF18regulated Rho signalling in vertebrate retina development. Small GTPases, 4 (4), pg.242–246
  2.  Arno, G., Carss, K. J., Hull, S., Zihni, C., Robson, A. G., Fiorentino, A., UK Inherited Retinal Disease Consortium, Hardcastle, A. J., Holder, G. E., Cheetham, M. E., Plagnol, V., NIHR Bioresource-Rare Diseases Consortium, Moore, A. T., Raymond, F. L., Matter, K., Balda, M., Webster, A. R. (2017) Biallelic mutation of ARHGEF18, involved in the determination of epithelial apicobasal polarity, causes adult-onset retinal degeneration. Am. J. Hum. Genet. 100: pg.334-342

Jump to top

Updated on November 30, 2020
Was this article helpful?