ABHD12 gene


Gene (OMIM No.)
Function of gene/protein
  • Protein: Lysophosphatidylserine lipase ABHD12
  • Hydrolyses 2-arachidonoyl glycerol (2-AG) to arachidonate and glycerol in the brain
  • Highly expressed in microglia
Clinical phenotype
(OMIM phenotype no.)
  • Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa and cataract; PHARC (#612674)
  • Autosomal recessive
  • Cataract (posterior sub-capsular type predominantly)
  • Retinitis pigmentosa
  • Some have macular involvement ranging from RPE alterations to perifoveal atrophy
Visual function
  • Nyctalopia from the 3rd decade
  • Progressive visual field loss eventually affecting central vision
Systemic features
  • Progressive neurodegenerative disorder
  • Variable age of onset and neurological features
  • Sensorineural hearing loss and ocular signs seem to be constant features
  • Ataxic and/or spastic gait disturbances
  • Sensorimotor neuropathy in upper and lower limbs
  • High arched feet, Achilles tendon contractures
Key investigations
  • ERG: severe rod-cone dystrophy/extinguished responses
  • OCT and FAF
  • Neurological assessment (audiology, MRI brain)
  • Systemic assessment with a paediatrician and other relevant specialists
Molecular diagnosisNext generation sequencing
  • Targeted gene panels (retinal)
  • Whole exome sequencing
  • Whole genome sequencing
  • Multidisciplinary approach
Therapies under research
  • None at present
Further information

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Additional information

Homozygous or complex heterozygous null variants are associated with the complete PHARC phenotype while the presence of one missense variant may be associated with a milder phenotype, ranging from having some neurological features of PHARC to non-syndromic RP.[3] 

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  1.  Fiskerstrand, T., H’mida-Ben Brahim, D., Johansson, S., M’zahem, A., Haukanes, B. I., Drouot, N., Zimmermann, J., Cole, A. J., Vedeler, C., Bredrup, C., Assoum, M., Tazir, M., Klockgether, T., Hamri, A., Steen, V. M., Boman, H., Bindoff, L. A., Koenig, M., Knappskog, P. M. Mutations in ABHD12 cause the neurodegenerative disease PHARC: an inborn error of endocannabinoid metabolism. Am. J. Hum. Genet. 87: 410-417, 2010
  2.  Navia-Paldanius, D., Savinainen, J. R., Laitinen, J. T. Biochemical and pharmacological characterization of human alpha/beta-hydrolase domain containing 6 (ABHD6) and 12 (ABHD12). J. Lipid Res. 53: 2413-2424, 2012
  3.  Nishiguchi KM, Avila-Fernandez A, van Huet RA, et al. Exome sequencing extends the phenotypic spectrum for ABHD12 mutations: from syndromic to nonsyndromic retinal degeneration [published correction appears in Ophthalmology. 2017 Feb;124(2):273-274]. Ophthalmology. 2014;121(8):1620‐1627

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Updated on November 30, 2020

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