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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
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ABHD12
abhydrolase domain containing 12, lysophospholipase
Chromosome 20 Β· 20p11.21
NCBI Gene: 26090Ensembl: ENSG00000100997.20HGNC: HGNC:15868UniProt: A0A5F9ZH71
79PubMed Papers
21Diseases
0Drugs
55Pathogenic Variants
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
phosphatidylcholine lysophospholipase A1 activitymonoacylglycerol lipase activityglycerophospholipase activitymonoacylglycerol catabolic processPolyneuropathy - hearing loss - ataxia - retinitis pigmentosa - cataractPHARC syndromeRetinal dystrophyhearing loss
✦AI Summary

ABHD12 encodes a serine hydrolase with dual enzymatic functions critical for lipid signaling in the nervous system. The enzyme primarily functions as a lysophosphatidylserine (lyso-PS) lipase, mediating hydrolysis of lyso-PS, a signaling lipid that regulates immunological and neurological processes 1. ABHD12 also exhibits monoacylglycerol lipase activity, hydrolyzing 2-arachidonoylglycerol (2-AG) and thereby regulating endocannabinoid signaling pathways 1. The enzyme accounts for approximately 9% of total brain 2-AG hydrolysis and is highly expressed in microglia 1. Mechanistically, ABHD12 localizes to different cerebellar regions and cells compared to ABHD16A, with cerebellar lyso-PS levels being most affected by ABHD12 deletion 2. Loss-of-function mutations in ABHD12 cause PHARC syndrome (polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract), a rare neurodegenerative disorder characterized by lyso-PS accumulation in the brain 32. Clinical manifestations include demyelinating polyneuropathy (91% of patients), hearing loss (86%), retinitis pigmentosa (82%), cataracts (86%), and cerebellar ataxia (74%) 3. The variable clinical phenotype and age of onset make diagnosis challenging, emphasizing the need for multidisciplinary evaluation and genetic testing 3.

Sources cited
1
ABHD12 functions as both a lyso-PS lipase and 2-AG hydrolase, accounting for 9% of brain 2-AG hydrolysis
PMID: 21418147
2
ABHD12 has distinct cerebellar localization and its deletion increases cerebellar lyso-PS levels
PMID: 32462874
3
ABHD12 mutations cause PHARC syndrome with specific clinical manifestation frequencies and diagnostic challenges
PMID: 39501272
⚠Limited data available β€” This gene has 3 indexed publications. Summary and analysis may be incomplete.
Disease Associationsβ“˜21
Polyneuropathy - hearing loss - ataxia - retinitis pigmentosa - cataractOpen Targets
0.82Strong
PHARC syndromeOpen Targets
0.78Strong
Retinal dystrophyOpen Targets
0.47Moderate
hearing lossOpen Targets
0.46Moderate
hereditary ataxiaOpen Targets
0.46Moderate
neurodegeneration, childhood-onset, with cerebellar atrophyOpen Targets
0.46Moderate
Rare hereditary ataxiaOpen Targets
0.46Moderate
optic atrophyOpen Targets
0.40Weak
retinitis pigmentosaOpen Targets
0.37Weak
eye diseaseOpen Targets
0.37Weak
NystagmusOpen Targets
0.37Weak
Decreased nerve conduction velocityOpen Targets
0.37Weak
Distal sensory impairmentOpen Targets
0.37Weak
essential tremorOpen Targets
0.37Weak
HyporeflexiaOpen Targets
0.37Weak
methylmalonic acidemia with homocystinuria, type cblJOpen Targets
0.37Weak
pathologic nystagmusOpen Targets
0.37Weak
Sensorimotor neuropathyOpen Targets
0.37Weak
sensorineural hearing lossOpen Targets
0.37Weak
TremorOpen Targets
0.37Weak
Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataractUniProt
Pathogenic Variants55
NM_001042472.3(ABHD12):c.1054C>T (p.Arg352Ter)Pathogenic
PHARC syndrome|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 352
NM_001042472.3(ABHD12):c.1129A>T (p.Lys377Ter)Likely pathogenic
not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 377
NM_001042472.3(ABHD12):c.874C>T (p.Arg292Ter)Pathogenic
not provided|PHARC syndrome
β˜…β˜…β˜†β˜†2024β†’ Residue 292
NM_001042472.3(ABHD12):c.1029+1G>TLikely pathogenic
not provided
β˜…β˜…β˜†β˜†2023
NM_001042472.3(ABHD12):c.1075del (p.Val359fs)Pathogenic
not provided|See cases
β˜…β˜…β˜†β˜†2023β†’ Residue 359
NM_001042472.3(ABHD12):c.1063C>T (p.Arg355Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 355
NM_001042472.3(ABHD12):c.191+2T>ALikely pathogenic
not provided
β˜…β˜†β˜†β˜†2025
NM_001042472.3(ABHD12):c.787+1G>ALikely pathogenic
not provided
β˜…β˜†β˜†β˜†2025
NM_001042472.3(ABHD12):c.317-2A>GLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2025
NM_001042472.3(ABHD12):c.1122C>A (p.Tyr374Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 374
NM_001042472.3(ABHD12):c.337_338delinsTTT (p.Asp113fs)Pathogenic
PHARC syndrome|not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 113
NM_001042472.3(ABHD12):c.748_749+1delinsCTCLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2025
NM_001042472.3(ABHD12):c.120dup (p.Arg41fs)Pathogenic
PHARC syndrome
β˜…β˜†β˜†β˜†2025β†’ Residue 41
NM_001042472.3(ABHD12):c.605C>T (p.Thr202Ile)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 202
NM_001042472.3(ABHD12):c.690G>A (p.Trp230Ter)Pathogenic
PHARC syndrome
β˜…β˜†β˜†β˜†2025β†’ Residue 230
NM_001042472.3(ABHD12):c.784C>T (p.Arg262Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 262
NM_001042472.3(ABHD12):c.749+1G>ALikely pathogenic
not provided
β˜…β˜†β˜†β˜†2024
NM_001042472.3(ABHD12):c.134_137dup (p.Ala47fs)Pathogenic
PHARC syndrome
β˜…β˜†β˜†β˜†2024β†’ Residue 47
NC_000020.11:g.25302218_25320318delLikely pathogenic
PHARC syndrome
β˜…β˜†β˜†β˜†2024
NM_001042472.3(ABHD12):c.477G>A (p.Trp159Ter)Pathogenic
PHARC syndrome
β˜…β˜†β˜†β˜†2024β†’ Residue 159
View on ClinVar β†—
Related Genes
NAPEPLDProtein interaction93%DAGLBProtein interaction85%DAGLAProtein interaction83%MGLLProtein interaction73%ABHD4Protein interaction72%ABHD6Protein interaction63%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
83%
Heart
57%
Ovary
56%
Liver
55%
Lung
50%
Gene Interaction Network
Click a node to explore
ABHD12NAPEPLDDAGLBDAGLAMGLLABHD4ABHD6
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q8N2K0
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.97LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.74 [0.56–0.97]
RankingsWhere ABHD12 stands among ~20K protein-coding genes
  • #5,977of 20,598
    Most Researched79
  • #1,242of 5,498
    Most Pathogenic Variants55 Β· top quartile
  • #9,166of 17,882
    Most Constrained (LOEUF)0.97
Genes detectedABHD12
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Comprehensive Molecular Screening in Chinese Usher Syndrome Patients.
PMID: 29625443
Invest Ophthalmol Vis Sci Β· 2018
1.00
2
A 20-year Clinical and Genetic Neuromuscular Cohort Analysis in Lebanon: An International Effort.
PMID: 34602496
J Neuromuscul Dis Β· 2022
0.90
3
Pharmacogenetics of Cannabinoids.
PMID: 28534260
Eur J Drug Metab Pharmacokinet Β· 2018
0.80
4
Structural properties and role of the endocannabinoid lipases ABHD6 and ABHD12 in lipid signalling and disease.
PMID: 30564946
Amino Acids Β· 2019
0.70
5
PHARC syndrome: an overview.
PMID: 39501272
Orphanet J Rare Dis Β· 2024
0.60