ATG5

autophagy related 5, the group of Autophagy related

Basic information

Region (hg38): 6:106045422-106325791

Previous symbols: [ "APG5L" ]

Links

ENSG00000057663 ∙ NCBI:9474 ∙ OMIM:604261 ∙ HGNC:589 ∙ Uniprot:Q9H1Y0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• spinocerebellar ataxia, autosomal recessive 25 (Limited), mode of inheritance: AR
• spinocerebellar ataxia, autosomal recessive 25 (Limited), mode of inheritance: AR

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ATG5 gene.

• not provided (5 variants)
• Inborn genetic diseases (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ATG5 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			3	1	2	6
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding					1	1
Total	0	0	3	1	3

Variants in ATG5

This is a list of pathogenic ClinVar variants found in the ATG5 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-106086581-G-A		not specified	Uncertain significance (Dec 19, 2022)
6-106088205-C-T		not specified	Uncertain significance (Mar 20, 2023)
6-106088211-A-G		not specified	Uncertain significance (Mar 20, 2023)
6-106088231-A-G		not specified	Uncertain significance (Oct 12, 2022)
6-106088233-G-C		not specified	Uncertain significance (Jun 06, 2023)
6-106088378-G-A		not specified	not provided (Sep 19, 2013)
6-106088388-T-C		not specified	Uncertain significance (Apr 25, 2023)
6-106088397-A-T		PRDM1-related disorder	Likely benign (Jul 20, 2022)
6-106088408-C-G		not specified	Uncertain significance (Jun 03, 2022)
6-106088437-CA-C		not specified	Uncertain significance (Feb 19, 2019)
6-106095710-C-T			Benign (Dec 31, 2019)
6-106099336-G-A		not specified	not provided (Sep 19, 2013)
6-106099390-C-G		not specified	not provided (Sep 19, 2013)
6-106099493-G-A		not specified	Uncertain significance (Jan 29, 2024)
6-106099497-C-G		not specified	Benign (Feb 18, 2020)
6-106099540-A-G		not specified	Uncertain significance (Jan 30, 2024)
6-106104834-A-G		not specified	Uncertain significance (Jun 24, 2022)
6-106104900-A-G		not specified	Uncertain significance (Dec 01, 2022)
6-106104944-A-G		not specified	Uncertain significance (Dec 14, 2022)
6-106104971-A-G		not specified	Benign (Dec 31, 2019)
6-106105001-G-A		not specified	Uncertain significance (May 13, 2022)
6-106105017-G-C		not specified	Benign (Dec 31, 2019)
6-106105091-A-C		not specified	Uncertain significance (Feb 15, 2023)
6-106105170-C-A		not specified	Uncertain significance (Jun 22, 2023)
6-106105221-G-A		not specified	not provided (Sep 19, 2013)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ATG5	protein_coding	protein_coding	ENST00000369076	7	141316

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.978	0.0224	125630	0	2	125632	0.00000796

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.82	81	142	0.570	0.00000689	1842
Missense in Polyphen		21	52.425	0.40057		681
Synonymous	0.891	38	45.7	0.832	0.00000228	475
Loss of Function	3.48	1	16.1	0.0623	8.24e-7	194

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000374	0.0000374
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000880	0.00000880
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in autophagic vesicle formation. Conjugation with ATG12, through a ubiquitin-like conjugating system involving ATG7 as an E1-like activating enzyme and ATG10 as an E2-like conjugating enzyme, is essential for its function. The ATG12-ATG5 conjugate acts as an E3-like enzyme which is required for lipidation of ATG8 family proteins and their association to the vesicle membranes. Involved in mitochondrial quality control after oxidative damage, and in subsequent cellular longevity. Plays a critical role in multiple aspects of lymphocyte development and is essential for both B and T lymphocyte survival and proliferation. Required for optimal processing and presentation of antigens for MHC II. Involved in the maintenance of axon morphology and membrane structures, as well as in normal adipocyte differentiation. Promotes primary ciliogenesis through removal of OFD1 from centriolar satellites and degradation of IFT20 via the autophagic pathway. {ECO:0000250|UniProtKB:Q99J83, ECO:0000269|PubMed:12207896, ECO:0000269|PubMed:20580051, ECO:0000269|PubMed:22170153, ECO:0000269|PubMed:26812546}.; FUNCTION: (Microbial infection) May act as a proviral factor. In association with ATG12, negatively regulates the innate antiviral immune response by impairing the type I IFN production pathway upon vesicular stomatitis virus (VSV) infection (PubMed:17709747). Required for the translation of incoming hepatitis C virus (HCV) RNA and, thereby, for initiation of HCV replication, but not required once infection is established (PubMed:19666601). {ECO:0000269|PubMed:17709747, ECO:0000269|PubMed:19666601}.
• Disease: DISEASE: Spinocerebellar ataxia, autosomal recessive, 25 (SCAR25) [MIM:617584]: A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR25 patients manifest delayed psychomotor development with delayed walking, truncal ataxia, dysmetria, and nystagmus, Cerebellar hypoplasia is seen on brain imaging. {ECO:0000269|PubMed:26812546}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Longevity regulating pathway - multiple species - Homo sapiens (human);Autophagy - animal - Homo sapiens (human);Autophagy - other - Homo sapiens (human);Mitophagy - animal - Homo sapiens (human);Longevity regulating pathway - Homo sapiens (human);NOD-like receptor signaling pathway - Homo sapiens (human);Shigellosis - Homo sapiens (human);Ferroptosis - Homo sapiens (human);RIG-I-like receptor signaling pathway - Homo sapiens (human);Nanoparticle triggered autophagic cell death;RIG-I-like Receptor Signaling;Senescence and Autophagy in Cancer;DDX58/IFIH1-mediated induction of interferon-alpha/beta;Innate Immune System;Immune System;Pink/Parkin Mediated Mitophagy;Receptor Mediated Mitophagy;Mitophagy;Macroautophagy;Cellular responses to external stimuli;Negative regulators of DDX58/IFIH1 signaling (Consensus)

Recessive Scores

• pRec: 0.171

Intolerance Scores

• loftool: 0.0998
• rvis_EVS: 0.1
• rvis_percentile_EVS: 61.28

Haploinsufficiency Scores

• pHI: 0.361
• hipred: Y
• hipred_score: 0.853
• ghis: 0.603

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.741

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Atg5
• Phenotype: homeostasis/metabolism phenotype; cellular phenotype; muscle phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); renal/urinary system phenotype; immune system phenotype; vision/eye phenotype; digestive/alimentary phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); liver/biliary system phenotype; respiratory system phenotype

Zebrafish Information Network

• Gene name: atg5
• Affected structure: dopaminergic neuron
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: autophagosome assembly;autophagy of mitochondrion;blood vessel remodeling;regulation of cytokine secretion involved in immune response;C-terminal protein lipidation;autophagy;apoptotic process;cellular response to nitrogen starvation;response to fungus;macroautophagy;cellular homeostasis;antigen processing and presentation of endogenous antigen;negative regulation of protein ubiquitination;aggrephagy;negative stranded viral RNA replication;vasodilation;response to drug;negative regulation of apoptotic process;post-translational protein modification;negative thymic T cell selection;otolith development;negative regulation of phagocytosis;regulation of release of sequestered calcium ion into cytosol;ventricular cardiac muscle cell development;heart contraction;negative regulation of cell death;protein lipidation involved in autophagosome assembly;positive regulation of mucus secretion;cellular response to nitrosative stress;autophagy of host cells involved in interaction with symbiont;regulation of cilium assembly;negative regulation of reactive oxygen species metabolic process;negative regulation of histone H4-K16 acetylation
• Cellular component: cytoplasm;autophagosome;cytosol;axoneme;membrane;phagocytic vesicle membrane;phagophore assembly site membrane;Atg12-Atg5-Atg16 complex;mitochondria-associated endoplasmic reticulum membrane
• Molecular function: protein binding;Atg8 ligase activity