ABHD5 Gene: Structure, Function, and Clinical Significance
A comprehensive overview of the ABHD5 gene, its protein product, associated diseases, and molecular mechanisms.
Gene Information Card
| Symbol | ABHD5 |
|---|---|
| Full Name | abhydrolase domain containing 5 |
| Gene Type | protein-coding |
| Chromosomal Location | 3p21.33 |
| NCBI Gene ID | 51099 ncbi.nlm.nih.gov/gene/51099 |
| Ensembl ID | ENSG00000104213 |
| UniProt ID | Q8WTS1 |
| OMIM ID | 604780 |
| HGNC ID | 21396 |
| Aliases | CGI-58, NCIE2, ABHD5 |
Description
The ABHD5 gene encodes a protein belonging to the alpha/beta hydrolase domain-containing family. It is a co-activator of adipose triglyceride lipase (PNPLA2), playing a critical role in the hydrolysis of triglycerides in lipid droplets. Mutations in ABHD5 cause Chanarin-Dorfman syndrome, a rare autosomal recessive disorder characterized by ichthyosis and accumulation of lipid droplets in various tissues.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Chanarin-Dorfman syndrome | Loss-of-function mutations in ABHD5 impair activation of PNPLA2, leading to defective triglyceride hydrolysis and lipid droplet accumulation in multiple tissues. | OMIM #275630; ClinVar |
| Neutral lipid storage disease with ichthyosis | Same as above; ABHD5 mutations cause the ichthyosiform erythroderma and systemic lipid storage. | OMIM #275630; ClinVar |
| Non-alcoholic fatty liver disease (NAFLD) | Reduced ABHD5 expression or function may contribute to hepatic steatosis, though direct causal mutations are not established. | PubMed studies; not listed in ClinVar as a disease-causing gene for NAFLD |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 10.2 | Medium |
| Adipose tissue | 8.5 | Medium |
| Skin | 5.1 | Low |
| Muscle | 4.3 | Low |
| Brain | 2.0 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 12.5 | Liver cancer cell line; high expression |
| A549 | 7.8 | Lung carcinoma; moderate expression |
| HeLa | 5.3 | Cervical adenocarcinoma; low expression |
| MCF7 | 4.1 | Breast cancer; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.175C>T (p.Arg59Ter) | Nonsense | Rare | Premature stop codon; loss of function |
| c.589G>A (p.Gly197Arg) | Missense | Rare | Impaired protein stability and function |
| c.773C>T (p.Pro258Leu) | Missense | Rare | Reduced co-activation of PNPLA2 |
| c.1118delA (p.Asn373ThrfsTer2) | Frameshift | Rare | Truncated protein; loss of function |
Mutation functional classification
Loss of Function (LOF)
Most ABHD5 mutations are loss-of-function, leading to Chanarin-Dorfman syndrome due to impaired triglyceride hydrolysis.
Gain of Function (GOF)
No gain-of-function mutations have been reported for ABHD5.
Dominant Negative (DN)
No dominant-negative effects have been described; the disease is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • triglyceride lipase activity (GO:0004806) | • cytoplasm (GO:0005737) |
| • lipid droplet (GO:0005811) | • lipid catabolic process (GO:0016042) |
| • triglyceride metabolic process (GO:0006641) |
Pathways
• Triglyceride metabolism
• Lipid droplet degradation
• Fatty acid oxidation
Protein Summary
The ABHD5 protein (also known as CGI-58) is a 349-amino acid protein that localizes to lipid droplets. It lacks intrinsic hydrolase activity but acts as a co-activator of adipose triglyceride lipase (PNPLA2), enhancing its activity to hydrolyze triglycerides. It also interacts with other proteins involved in lipid metabolism and signaling.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ABHD5 Knockout HEK293 Cell Line | EDJ-KQ10916 | Human | 51099 | Details Get a Quote |
| ABHD5 Knockout A-549 Cell Line | EDJ-KQ38658 | Human | 51099 | Details Get a Quote |
| ABHD5 Knockout HCT 116 Cell Line | EDJ-KQ38659 | Human | 51099 | Details Get a Quote |
| ABHD5 Knockout HeLa Cell Line | EDJ-KQ38660 | Human | 51099 | Details Get a Quote |
