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
neurodevelopmental disorder (Limited), mode of inheritance: AR

ClinVar

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

not_specified (70 variants)
SPERMATOGENIC_FAILURE_101 (5 variants)
not_provided (4 variants)
ASHER (3 variants)
ATG4D-related_neurodevelopmental_condition (2 variants)
Neurodevelopmental_disorder (1 variants)
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. These statistics are base on transcript: NM_000032885.6. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	3 clinvar		5
missense	5 clinvar	2 clinvar	66 clinvar	4 clinvar		77
nonsense						0
start loss						0
frameshift	1 clinvar					1
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	6	2	71	7	0

Highest pathogenic variant AF is 0.000989991

Loading clinvar variants...

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
Phenotype

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