ABHD12: Abhydrolase Domain Containing 12, Lysophosphatidylserine Lipase
A key enzyme in lipid metabolism implicated in PHARC syndrome and potential cancer biology
Gene Information Card
| Symbol | ABHD12 |
|---|---|
| Full Name | Abhydrolase Domain Containing 12, Lysophosphatidylserine Lipase |
| Gene Type | Protein coding |
| Chromosomal Location | 20p11.21 |
| NCBI Gene ID | 26090 ncbi.nlm.nih.gov/gene/26090 |
| Ensembl ID | ENSG00000100997 |
| UniProt ID | Q8N2K0 |
| OMIM ID | 613599 |
| HGNC ID | 15868 |
| Aliases | BEM46L2, C20orf22, dJ966C24.1.1, PHARC |
Description
ABHD12 encodes a member of the serine hydrolase family that functions as a lysophosphatidylserine (lyso-PS) lipase. The enzyme is involved in the degradation of bioactive lysophospholipids, particularly lyso-PS, which modulates immune and neurological signaling. Loss-of-function mutations in ABHD12 cause PHARC syndrome (polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract), a progressive neurodegenerative disorder. The gene is also implicated in cancer through its role in lipid metabolism and immune modulation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| PHARC syndrome | Loss-of-function mutations in ABHD12 impair lyso-PS degradation, leading to accumulation of bioactive lipids that disrupt neuronal and glial function, resulting in progressive neurodegeneration. | ClinVar, OMIM |
| Hereditary spastic paraplegia (rare) | Missense variants in ABHD12 may alter enzyme activity, contributing to axonal degeneration in motor pathways. | ClinVar |
| Cancer (potential) | ABHD12 expression changes in tumors may alter lyso-PS levels, affecting tumor microenvironment and immune evasion. | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Cerebellum | 15.2 | Medium |
| Retina | 18.0 | Medium-High |
| Cochlea | 10.1 | Medium |
| Testis | 8.3 | Low-Medium |
| Lung | 6.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 14.5 | Neuronal model |
| HEK293 (embryonic kidney) | 9.2 | Common expression system |
| HepG2 (hepatocellular carcinoma) | 7.8 | Liver cancer line |
| MCF7 (breast cancer) | 5.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.337C>T (p.Arg113*) | Nonsense | Rare (found in PHARC families) | Loss of function; premature stop codon |
| c.349G>A (p.Gly117Arg) | Missense | Rare | Impaired catalytic activity |
| c.442_443del (p.Leu148Valfs*2) | Frameshift | Rare | Loss of function |
| c.1031T>C (p.Leu344Pro) | Missense | Rare | Structural disruption |
Mutation functional classification
Loss of Function (LOF)
Majority of PHARC-associated mutations are loss-of-function (nonsense, frameshift, missense affecting catalytic site), leading to reduced lyso-PS lipase activity.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported; PHARC is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004622 – lysophospholipase activity | • GO:0016787 – hydrolase activity |
| • GO:0006629 – lipid metabolic process | • GO:0005886 – plasma membrane |
| • GO:0016021 – integral component of membrane | • GO:0046470 – phosphatidylcholine metabolic process |
Pathways
• Lysophospholipid metabolism (Reactome: R-HSA-1483206)
• Glycerophospholipid biosynthesis (Reactome: R-HSA-1483257)
Protein Summary
ABHD12 is a 398-amino acid integral membrane protein with an alpha/beta hydrolase fold. It localizes to the endoplasmic reticulum and plasma membrane. The enzyme specifically hydrolyzes lysophosphatidylserine to produce free fatty acid and serine, regulating levels of this immunomodulatory lipid. Structural studies reveal a catalytic triad (Ser246, Asp319, His349) essential for activity. In the nervous system, ABHD12 is expressed in microglia and neurons, where its dysfunction leads to neuroinflammation and myelin abnormalities.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ABHD12 Knockout HEK293 Cell Line | EDJ-KQ8394 | Human | 26090 | Details Get a Quote |
| ABHD12B Knockout HEK293 Cell Line | EDJ-KQ10441 | Human | 145447 | Details Get a Quote |
| ABHD12 Knockout HeLa Cell Line | EDJ-KQ33130 | Human | 26090 | Details Get a Quote |
| ABHD12 Knockout A-549 Cell Line | EDJ-KQ34462 | Human | 26090 | Details Get a Quote |
| ABHD12 Knockout HCT 116 Cell Line | EDJ-KQ34463 | Human | 26090 | Details Get a Quote |
| ABHD12B Knockout HeLa Cell Line | EDJ-KQ37819 | Human | 145447 | Details Get a Quote |
| ABHD12B Knockout A-549 Cell Line | EDJ-KQ67011 | Human | 145447 | Details Get a Quote |
| ABHD12B Knockout HCT 116 Cell Line | EDJ-KQ75411 | Human | 145447 | Details Get a Quote |
Displaying Records 1 To 8 Of 8 Records
