ABHD12

Last update 08 May 2025

Basic Info

Synonyms

2-arachidonoylglycerol hydrolase ABHD12, ABHD12, ABHD12A

+ [12]

Introduction

Lysophosphatidylserine (LPS) lipase that mediates the hydrolysis of lysophosphatidylserine, a class of signaling lipids that regulates immunological and neurological processes (PubMed:25290914, PubMed:30237167, PubMed:30420694, PubMed:30643283, PubMed:30720278). Represents a major lysophosphatidylserine lipase in the brain, thereby playing a key role in the central nervous system (By similarity). Also able to hydrolyze oxidized phosphatidylserine; oxidized phosphatidylserine is produced in response to severe inflammatory stress and constitutes a proapoptotic 'eat me' signal (PubMed:30643283). Also has monoacylglycerol (MAG) lipase activity: hydrolyzes 2-arachidonoylglycerol (2-AG), thereby acting as a regulator of endocannabinoid signaling pathways (PubMed:22969151, PubMed:24027063). Has a strong preference for very-long-chain lipid substrates; substrate specificity is likely due to improved catalysis and not improved substrate binding (PubMed:30237167).

100 Clinical Results associated with ABHD12

100 Translational Medicine associated with ABHD12

0 Patents (Medical) associated with ABHD12

Literatures (Medical) associated with ABHD12

15 Apr 2025·Biochemistry

Bioinformatics Analysis Identifies Sequence Determinants of Enzymatic Activity for the PHARC-Associated Lipase ABHD12

Article

Author: Devarajan, Archit ; Ratnaparkhi, Girish S. ; Kamat, Siddhesh S. ; C. S., Rohith ; Chakraborty, Arnab ; Kumar, Kundan ; Madhusudhan, M. S.

In humans, PHARC (polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract) is an early onset autosomal recessive neurological disorder caused by deleterious mutations to ABHD12 (α/β-hydrolase domain protein # 12). Biochemically, ABHD12 functions as a lipase and catalyzes the hydrolysis of lysophosphatidylserine (lyso-PS) (lyso-PS lipase). By doing so, it controls the concentrations and signaling pathways regulated by this potent signaling lysophospholipid in the mammalian brain. While genetic mapping efforts have identified over 30 mutations in ABHD12 from human PHARC subjects, the biochemical activity of these pathogenic mutants remains unknown. To understand this, here, we performed an exhaustive bioinformatics survey and collated ABHD12 protein sequences from various organisms across evolution. Next, based on sequence alignments and structural modeling, we identified functionally relevant conserved residues in the ABHD12 protein sequence that are potentially important for its enzymatic activity. To validate these in silico findings, we generated numerous mutants of murine ABHD12, including those associated with human PHARC subjects, and assayed them for their enzymatic activity. Taken together, these complementary in silico and biochemical studies provide the first thorough sequence-function relationship for mammalian ABHD12, especially relevant in the context of PHARC. Finally, our evolutionary analysis identified CG15111 as an ABHD12 ortholog in the fruit fly (Drosophila melanogaster), and enzymatic assays indeed confirmed that recombinant CG15111 has robust lyso-PS lipase activity. Flies serve as an excellent animal system to model various human neurological diseases, and the identification of CG15111 as a Drosophila melanogaster ABHD12 ortholog opens new avenues to study PHARC in fly models.

01 Mar 2025·Stem Cell Research

Generation of a human iPSC line (UCLi025-A) from a patient with PHARC syndrome harbouring biallelic variants in ABHD12

Article

Author: Houlden, Henry ; Linkens, Katy ; Jackson, Daniel ; Méjécase, Cécile ; Romero-Vázquez, Sara ; Moosajee, Mariya ; Toualbi, Lyes

A human induced pluripotent stem cell (hiPSC) line (UCLi025-A) was generated from dermal fibroblast cells from a 42-year-old female donor with polyneuropathy, hearing loss, retinitis pigmentosa and early-onset cataract (PHARC) syndrome carrying a homozygous nonsense variant in ABHD12 c.193C>T, p.(Arg65*). Fibroblasts were confirmed to carry the variant by Sanger sequencing and subsequently reprogrammed using non-integrating episomal plasmids generating a hiPSC line (UCLi025-A). This established cell line was validated for pluripotency markers expression, in vitro differentiation potential and normal karyotype. The utilization of this cell line will serve as a valuable resource for modelling PHARC syndrome and identification of therapeutic targets.

01 Feb 2025·Molecular Genetics & Genomic Medicine

A Novel Compound Heterozygous Variant in the ABHD12 Gene Cause PHARC Syndrome in a Chinese Family: The Proband Presenting New Genotype and Phenotype

Article

Author: Ma, Meijiao ; Rong, Weining ; Wang, Wenming ; Sheng, Xunlun ; Wu, Xueli ; Ma, Jinhai ; Lian, Yuanyuan

ABSTRACTBackgroundPHARC syndrome, a rare autosomal recessive neurodegenerative disorder caused by mutations in the ABHD12 gene, is characterized by demyelinating polyneuropathy, hearing loss, ataxia, retinitis pigmentosa (RP), and early‐onset cataracts. If patients are first diagnosed in the ophthalmology department, they are easily misdiagnosed as having RP or Usher syndrome. This study aimed to identify the genetic etiology and determine the clinical diagnosis of a Chinese family with suspected PHARC syndrome.MethodComprehensive ophthalmic examinations and systemic evaluations were conducted to confirm the phenotype. The genotype was identified through Whole Exome Sequencing (WES), and the current literature was reviewed understand better manifestations of PHARC syndrome related to pathogenic variants.ResultsThe principal symptoms of the proband comprised profound sensorineural hearing loss since childhood, severe visual impairment, congenital cataracts, cone‐rod dystrophy, and ataxia. WES revealed that the proband carried a compound heterozygous variant in the ABHD12 gene: M1, a known nonsense variation c.477G > A (p.Trp159Ter); and M2, a novel copy number variant with a deletion of approximately 18.10 Kbp in chromosome 20p11.21 (seq[GRCh38]del(20) (p11.21)chr20:g. 25302218_25320318del), covering exons 4–12 of the ABHD12 gene. The literature review indicated that there were 65 patients with PHARC from 30 different families. All clinical information of the described patients with PHARC syndrome and all known mutations associated with the disease to date were compiled.ConclusionThis study expands the spectrum of pathogenic variants and phenotype for PHARC syndrome and suggests genetic testing is necessary for a definitive diagnosis of PHARC syndrome.

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ABHD12

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