ATG4D

autophagy related 4D cysteine peptidase, the group of MicroRNA protein coding host genes|Autophagy related

Basic information

Region (hg38): 19:10543895-10553418

Previous symbols: [ "AUTL4", "APG4D" ]

Links

ENSG00000130734 ∙ NCBI:84971 ∙ OMIM:611340 ∙ HGNC:20789 ∙ Uniprot:Q86TL0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• complex neurodevelopmental disorder (Limited), mode of inheritance: AR

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ATG4D gene.

• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ATG4D 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				2	1	3
missense			34	2		36
nonsense						0
start loss						0
frameshift	1					1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	1	0	34	4	1

Variants in ATG4D

This is a list of pathogenic ClinVar variants found in the ATG4D region.

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

Position	Type	Phenotype	Significance	ClinVar
19-10544124-C-T		not specified	Uncertain significance (Dec 01, 2022)
19-10544154-C-T		not specified	Uncertain significance (Apr 22, 2024)
19-10544172-C-G		not specified	Uncertain significance (Dec 28, 2023)
19-10544175-C-G		not specified	Uncertain significance (Jun 16, 2023)
19-10544257-C-T		not specified	Uncertain significance (Nov 07, 2023)
19-10544266-C-T		not specified	Uncertain significance (Aug 28, 2023)
19-10544813-G-A		ASHER • not specified	Uncertain significance (Jul 13, 2021)
19-10544849-A-G		not specified	Uncertain significance (Nov 18, 2022)
19-10544852-G-C		not specified	Uncertain significance (Mar 18, 2024)
19-10544967-G-T		not specified	Uncertain significance (Oct 03, 2022)
19-10544968-C-A		not specified	Uncertain significance (Mar 04, 2024)
19-10545023-C-T		not specified	Uncertain significance (Sep 06, 2022)
19-10545099-A-G			Likely benign (Feb 01, 2023)
19-10546862-G-A		not specified	Uncertain significance (Oct 18, 2021)
19-10546871-C-T		not specified	Uncertain significance (Jul 07, 2022)
19-10546872-C-T		not specified	Uncertain significance (Apr 13, 2022)
19-10546881-T-C		not specified	Likely benign (Jul 14, 2021)
19-10546923-G-A		not specified	Uncertain significance (Dec 11, 2023)
19-10546938-G-A		not specified	Uncertain significance (Nov 30, 2022)
19-10546968-A-G		not specified	Uncertain significance (Jan 12, 2024)
19-10546974-G-A		not specified	Uncertain significance (Jun 06, 2023)
19-10546982-C-T		not specified	Uncertain significance (Jul 25, 2023)
19-10547036-C-T		not specified	Uncertain significance (Sep 12, 2023)
19-10547037-G-A		not specified	Uncertain significance (Jan 06, 2023)
19-10547094-C-T		not specified	Uncertain significance (Jul 26, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ATG4D	protein_coding	protein_coding	ENST00000309469	10	9524

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000268	0.997	125701	0	47	125748	0.000187

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.804	241	279	0.864	0.0000184	3015
Missense in Polyphen		84	97.537	0.86121		1073
Synonymous	0.496	104	111	0.940	0.00000680	992
Loss of Function	2.60	10	23.7	0.423	0.00000118	252

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000638	0.000637
Ashkenazi Jewish	0.00	0.00
East Asian	0.000327	0.000326
Finnish	0.0000469	0.0000462
European (Non-Finnish)	0.000221	0.000220
Middle Eastern	0.000327	0.000326
South Asian	0.0000684	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Cysteine protease ATG4D: Cysteine protease required for the cytoplasm to vacuole transport (Cvt) and autophagy. 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.
• Pathway: Autophagy - animal - Homo sapiens (human);Autophagy - other - Homo sapiens (human);Macroautophagy;Cellular responses to external stimuli (Consensus)

Recessive Scores

• pRec: 0.106

Intolerance Scores

• loftool: 0.348
• rvis_EVS: -0.58
• rvis_percentile_EVS: 18.72

Haploinsufficiency Scores

• pHI: 0.151
• hipred: N
• hipred_score: 0.379
• ghis: 0.537

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.470

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Atg4d

Zebrafish Information Network

• Gene name: atg4da
• Affected structure: Purkinje cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: proteolysis;autophagy;apoptotic process;protein transport
• Cellular component: cytoplasm;mitochondrial matrix
• Molecular function: cysteine-type peptidase activity