ATG4A

autophagy related 4A cysteine peptidase, the group of Autophagy related

Basic information

Region (hg38): X:108091668-108154671

Previous symbols: [ "AUTL2", "APG4A" ]

Links

ENSG00000101844 ∙ NCBI:115201 ∙ OMIM:300663 ∙ HGNC:16489 ∙ Uniprot:Q8WYN0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ATG4A gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ATG4A gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous					3	3
missense			12	1	1	14
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding					2	2
Total	0	0	12	1	6

Variants in ATG4A

This is a list of pathogenic ClinVar variants found in the ATG4A region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
X-108131266-C-T		not specified	Uncertain significance (Nov 17, 2022)
X-108131267-G-T			Benign (Apr 04, 2018)
X-108131283-G-A		not specified	Uncertain significance (Dec 06, 2022)
X-108134063-G-A		not specified	Likely benign (Aug 15, 2023)
X-108134092-G-A		not specified	Uncertain significance (Jul 13, 2022)
X-108134368-A-G		not specified	Uncertain significance (Jan 10, 2023)
X-108134380-T-C		not specified	Uncertain significance (Feb 28, 2024)
X-108137109-C-T			Benign (May 14, 2018)
X-108137134-G-A		not specified	Uncertain significance (Aug 21, 2023)
X-108137163-A-C			Benign (May 30, 2018)
X-108137806-A-C		not specified	Uncertain significance (Sep 29, 2022)
X-108137816-G-A		not specified	Uncertain significance (Dec 06, 2022)
X-108137978-T-C		not specified	Uncertain significance (Dec 28, 2022)
X-108138110-C-T			Likely benign (Jan 01, 2023)
X-108138159-C-T		not specified	Uncertain significance (May 15, 2024)
X-108150100-T-TG		not specified	Benign (Jan 24, 2024)
X-108150219-G-A			Benign (Feb 25, 2018)
X-108152983-T-C		not specified	Uncertain significance (Jan 10, 2022)
X-108153066-G-C		not specified	Uncertain significance (Jan 10, 2022)
X-108153135-G-A		not specified	Benign (Jan 24, 2024)
X-108153670-G-T		not specified	Uncertain significance (Oct 06, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ATG4A	protein_coding	protein_coding	ENST00000372232	13	63004

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.990	0.0105	125736	1	3	125740	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.35	95	140	0.679	0.0000100	2612
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.000128	0.0000924
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.000107	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• 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}.
• Pathway: Autophagy - animal - Homo sapiens (human);Autophagy - other - Homo sapiens (human);Nanoparticle triggered autophagic cell death;Macroautophagy;Cellular responses to external stimuli (Consensus)

Recessive Scores

• pRec: 0.0981

Intolerance Scores

• loftool: 0.545
• rvis_EVS: 0.04
• rvis_percentile_EVS: 56.64

Haploinsufficiency Scores

• pHI: 0.233
• hipred: Y
• hipred_score: 0.749
• ghis: 0.517

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.00970

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Atg4a

Gene ontology

• Biological process: autophagosome assembly;proteolysis;protein transport;protein delipidation
• Cellular component: cytoplasm
• Molecular function: cysteine-type endopeptidase activity;protein binding;cysteine-type peptidase activity