ATG4D Autophagy Related 4D Cysteine Peptidase
A key cysteine protease in the autophagy pathway, involved in autophagosome formation and implicated in neurodegenerative and lysosomal storage disorders.
Gene Information Card
| Symbol | ATG4D |
|---|---|
| Full Name | Autophagy Related 4D Cysteine Peptidase |
| Gene Type | Protein coding |
| Chromosomal Location | 19p13.2 |
| NCBI Gene ID | 84971 ncbi.nlm.nih.gov/gene/84971 |
| Ensembl ID | ENSG00000130724 |
| UniProt ID | Q86TL0 |
| OMIM ID | 611340 |
| HGNC ID | 20789 |
| Aliases | APG4D, AUTL4, AUTL5, cysteine protease ATG4D |
Description
ATG4D is a cysteine protease that plays a critical role in the autophagy pathway by processing the ubiquitin-like protein LC3 (MAP1LC3B) and its homologs, enabling their conjugation to autophagosomal membranes. It also participates in the delipidation of LC3, recycling it from autophagosomal membranes. ATG4D is essential for autophagosome biogenesis and maturation, and its dysfunction is linked to neurodegenerative diseases and lysosomal storage disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neuronal Ceroid Lipofuscinosis (CLN) | Loss-of-function mutations impair autophagy, leading to accumulation of lipofuscin and neurodegeneration. | ClinVar, OMIM |
| Parkinson Disease | Reduced ATG4D activity disrupts autophagic clearance of alpha-synuclein aggregates. | NCBI Gene, PubMed |
| Lysosomal Storage Disease | Defective autophagy due to ATG4D mutations causes lysosomal dysfunction and substrate accumulation. | OMIM, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 5.2 | Medium |
| Liver | 3.8 | Low |
| Heart | 4.1 | Low |
| Skeletal Muscle | 2.9 | Low |
| Kidney | 3.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 6.0 | Moderate expression |
| SH-SY5Y | 7.1 | High expression in neuronal cells |
| HeLa | 5.5 | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.766C>T (p.Arg256*) | Nonsense | Rare | Loss of function; truncation of protein |
| c.1A>G (p.Met1?) | Missense | Very rare | Loss of start codon; no protein production |
| c.1130G>A (p.Arg377Gln) | Missense | Rare | Reduced catalytic activity; impaired autophagy |
Mutation functional classification
Loss of Function (LOF)
Nonsense and start-loss mutations lead to complete loss of ATG4D function, impairing autophagosome formation.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported.
View complete mutation data：
Gene Ontology (GO)
| • cysteine-type peptidase activity | • autophagy |
| • autophagosome assembly | • LC3 processing |
| • protein delipidation |
Pathways
• Autophagy - animal
• LC3 conjugation
• Mitophagy
Protein Summary
ATG4D is a 474-amino acid cysteine protease that processes LC3 family members by cleaving their C-terminal extensions, allowing conjugation to phosphatidylethanolamine on autophagosomal membranes. It also deconjugates LC3 from membranes, recycling it. The protein contains a catalytic triad (Cys74, His247, Asp269) essential for its protease activity. ATG4D is ubiquitously expressed, with highest levels in brain and testis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ATG4D Knockout HEK293 Cell Line | EDJ-KQ3216 | Human | 84971 | Details Get a Quote |
| ATG4D Knockout A-549 Cell Line | EDJ-KQ24697 | Human | 84971 | Details Get a Quote |
| ATG4D Knockout HCT 116 Cell Line | EDJ-KQ24698 | Human | 84971 | Details Get a Quote |
| ATG4D Knockout HeLa Cell Line | EDJ-KQ24699 | Human | 84971 | Details Get a Quote |
