ATG4C

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

Basic information

Region (hg38): 1:62784131-62865516

Previous symbols: [ "AUTL1", "APG4C" ]

Links

ENSG00000125703 ∙ NCBI:84938 ∙ OMIM:611339 ∙ HGNC:16040 ∙ Uniprot:Q96DT6 ∙ 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 ATG4C gene.

• Inborn genetic diseases (16 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ATG4C 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						0
missense			16			16
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	16	0	0

Variants in ATG4C

This is a list of pathogenic ClinVar variants found in the ATG4C region.

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

Position	Type	Phenotype	Significance	ClinVar
1-62805225-C-A		not specified	Uncertain significance (Sep 22, 2022)
1-62805241-A-C		not specified	Uncertain significance (Mar 24, 2023)
1-62816592-C-T		not specified	Uncertain significance (Mar 23, 2022)
1-62816613-A-G		not specified	Uncertain significance (Nov 10, 2022)
1-62816652-C-T		not specified	Uncertain significance (May 01, 2022)
1-62816689-G-A		not specified	Uncertain significance (Nov 15, 2023)
1-62816765-G-T		not specified	Uncertain significance (Feb 05, 2024)
1-62816803-G-A		not specified	Uncertain significance (Jan 04, 2022)
1-62819021-T-G		not specified	Uncertain significance (Jan 26, 2022)
1-62819200-A-T		not specified	Uncertain significance (May 30, 2022)
1-62819206-A-G		not specified	Uncertain significance (Aug 11, 2021)
1-62819227-A-T		not specified	Uncertain significance (Feb 03, 2022)
1-62819230-C-T		not specified	Uncertain significance (Oct 22, 2021)
1-62819263-T-C		not specified	Uncertain significance (Oct 05, 2021)
1-62819267-A-C		not specified	Uncertain significance (Aug 02, 2021)
1-62819328-A-G		not specified	Uncertain significance (Jun 11, 2021)
1-62829099-G-A		not specified	Uncertain significance (Aug 26, 2022)
1-62834039-G-T		not specified	Uncertain significance (Aug 02, 2022)
1-62834084-C-G		not specified	Uncertain significance (Dec 06, 2023)
1-62834800-C-T		not specified	Uncertain significance (Feb 28, 2024)
1-62841465-G-A		not specified	Uncertain significance (Aug 08, 2022)
1-62841483-G-C		not specified	Uncertain significance (Oct 27, 2023)
1-62841491-G-A		not specified	Uncertain significance (Oct 13, 2023)
1-62864083-A-G		not specified	Uncertain significance (Jul 06, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ATG4C	protein_coding	protein_coding	ENST00000317868	10	81379

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.67e-17	0.00617	124969	3	773	125745	0.00309

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.437	244	226	1.08	0.0000106	3008
Missense in Polyphen		97	92.422	1.0495		1265
Synonymous	-0.0610	77	76.3	1.01	0.00000383	817
Loss of Function	-0.0278	25	24.9	1.01	0.00000134	319

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00383	0.00383
Ashkenazi Jewish	0.000796	0.000794
East Asian	0.000560	0.000544
Finnish	0.0110	0.0110
European (Non-Finnish)	0.00329	0.00325
Middle Eastern	0.000560	0.000544
South Asian	0.000685	0.000621
Other	0.00361	0.00359

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Cysteine protease required for the cytoplasm to vacuole transport (Cvt) and autophagy. Is not essential for autophagy development under normal conditions but is required for a proper autophagic response under stressful conditions such as prolonged starvation (By similarity). Cleaves the C-terminal amino acid of ATG8 family proteins MAP1LC3 and GABARAPL2, 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. Has also an activity of delipidating enzyme for the PE-conjugated forms. {ECO:0000250, ECO:0000269|PubMed:21177865}.
• Pathway: Autophagy - animal - Homo sapiens (human);Autophagy - other - Homo sapiens (human);Macroautophagy;Cellular responses to external stimuli (Consensus)

Recessive Scores

• pRec: 0.0969

Intolerance Scores

• loftool: 0.576
• rvis_EVS: 0
• rvis_percentile_EVS: 53.73

Haploinsufficiency Scores

• pHI: 0.129
• hipred: N
• hipred_score: 0.292
• ghis: 0.533

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.892

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Atg4c
• Phenotype: neoplasm; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cellular phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: autophagosome assembly;proteolysis;protein targeting to membrane;autophagy
• Cellular component: extracellular region;cytoplasm;cytosol
• Molecular function: cysteine-type endopeptidase activity;peptidase activity