ATG4A
protein-codingautophagy related 4A cysteine peptidase, the group of Autophagy related
Gene summary
Autophagy is the process by which endogenous proteins and damaged organelles are destroyed intracellularly. Autophagy is postulated to be essential for cell homeostasis and cell remodeling during differentiation, metamorphosis, non-apoptotic cell death, and aging. Reduced levels of autophagy have been described in some malignant tumors, and a role for autophagy in controlling the unregulated cell growth linked to cancer has been proposed. This gene encodes a member of the autophagin protein family. The encoded protein is also designated as a member of the C-54 family of cysteine proteases. [provided by RefSeq, Mar 2016]
- AUTL2
- APG4A
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~63.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: XL
Disease ID:MONDO:0004796
Submitter: PanelApp Australia
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ATG4A variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_052936.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 20 | 3 | 23 | |||
| missense | 85 | 2 | 1 | 88 | ||
| nonsense | 8 | 8 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 30 | 30 | ||||
| Total | 0 | 0 | 144 | 2 | 4 | 150 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_443168.2 | 13 | MANE Select | |
| Ensembl | ENSP00000361306.3 | 13 | MANE Select | |
| RefSeq | NP_001308216.1 | 10 | Standard | |
| RefSeq | NP_001308217.1 | 10 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Autophagy - animal - Homo sapiens (human)
- Autophagy - other - Homo sapiens (human)
- Nanoparticle triggered autophagic cell death
- Macroautophagy
- Cellular responses to external stimuli
Biological Process
- autophagosome assembly
- proteolysis
- protein transport
- protein delipidation
Molecular Function
- cysteine-type endopeptidase activity
- protein binding
- cysteine-type peptidase activity
Cellular Component
- cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000372232
- Coding exons
- 13
- Length
- 63004
- Individuals with no LoFs
- 125736
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 3
- Defined
- 125740
- p
- 0.0000159
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.35 | 95 | 140 | 0.679 | 0.0000100 | 2612 |
| Missense (PolyPhen) | 41 | 68.305 | 0.60025 | 1273 | ||
| Synonymous | 1.19 | 39 | 49.6 | 0.786 | 0.00000365 | 711 |
| Loss of Function | 3.73 | 1 | 18.1 | 0.0552 | 0.00000122 | 335 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.00013 | 0.000092 | rare |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0.00011 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Cysteine protease required for the cytoplasm to vacuole transport (Cvt) and autophagy. Cleaves the C-terminal amino acid of ATG8 family proteins to reveal a C-terminal glycine. Exposure of the glycine at the C-terminus is essential for ATG8 proteins conjugation to phosphatidylethanolamine (PE) and insertion to membranes, which is necessary for autophagy. Preferred substrate is GABARAPL2 followed by MAP1LC3A and GABARAP. Has also an activity of delipidating enzyme for the PE-conjugated forms. {ECO:0000269|PubMed:12473658, ECO:0000269|PubMed:15169837, ECO:0000269|PubMed:17347651, ECO:0000269|PubMed:21177865, ECO:0000269|PubMed:21245471, ECO:0000269|PubMed:22302004}.;
Recessive Scores
- pRec
- 0.0981
Intolerance Scores
- LoFtool
- 0.545
- RVIS EVS
- 0.04
- RVIS percentile EVS
- 56.64
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.00970
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |