ABHD12

Chr 20AR

abhydrolase domain containing 12, lysophospholipase

Also known as: ABHD12A, BEM46L2, C20orf22, PHARC, dJ965G21.2, hABHD12

NCBI Gene: 26090 ENSG00000100997 UniProt: Q8N2K0 OMIM: 613599

The protein encoded by this gene is a lysophosphatidylserine lipase that hydrolyzes signaling lipids regulating neurological processes and also degrades the endocannabinoid 2-arachidonoylglycerol. Mutations cause PHARC syndrome (polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract), a multisystem neurodegenerative disorder with autosomal recessive inheritance. The gene shows relatively high tolerance to loss-of-function variants (LOEUF 0.763), suggesting complete loss of function may be required for disease manifestation.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes an enzyme that catalyzes the hydrolysis of 2-arachidonoyl glycerol (2-AG), the main endocannabinoid lipid transmitter that acts on cannabinoid receptors, CB1 and CB2. The endocannabinoid system is involved in a wide range of physiological processes, including neurotransmission, mood, appetite, pain appreciation, addiction behavior, and inflammation. Mutations in this gene are associated with the neurodegenerative disease, PHARC (polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract), resulting from an inborn error of endocannabinoid metabolism. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene.[provided by RefSeq, Jan 2011]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataractMIM #612674

Clinical highlights

Gene-disease validity (ClinGen)

PHARC syndrome · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.76

LOEUF

LOF

Mechanism· G2P

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GeneReview available — ABHD12