ATG7

autophagy related 7, the group of Ubiquitin like modifier activating enzymes|Autophagy related

Basic information

Region (hg38): 3:11272309-11557665

Previous symbols: [ "APG7L" ]

Links

ENSG00000197548 ∙ NCBI:10533 ∙ OMIM:608760 ∙ HGNC:16935 ∙ Uniprot:O95352 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• spinocerebellar ataxia, autosomal recessive 31 (Strong), mode of inheritance: AR
• spinocerebellar ataxia, autosomal recessive 31 (Strong), mode of inheritance: AR
• spinocerebellar ataxia, autosomal recessive 31 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spinocerebellar ataxia, autosomal recessive 31	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Endocrine; Neurologic	34161705

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ATG7 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ATG7 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	2	5
missense			44	5	1	50
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1	2	3
non coding						0
Total	0	0	44	8	3

Variants in ATG7

This is a list of pathogenic ClinVar variants found in the ATG7 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-11298709-C-T		not specified	Likely benign (Apr 07, 2023)
3-11298726-T-A		not specified	Uncertain significance (May 29, 2024)
3-11298778-A-T		not specified	Uncertain significance (Dec 03, 2021)
3-11298797-G-T		not specified	Uncertain significance (May 05, 2023)
3-11298798-C-G		not specified	Uncertain significance (Mar 30, 2024)
3-11299385-C-T		not specified	Uncertain significance (Apr 01, 2022)
3-11299402-C-G		not specified	Uncertain significance (Dec 07, 2023)
3-11306951-C-A		not specified	Uncertain significance (Nov 08, 2022)
3-11306954-C-T		not specified	Uncertain significance (Apr 12, 2022)
3-11306960-C-T		not specified	Uncertain significance (Dec 27, 2023)
3-11307007-G-A		Spinocerebellar ataxia, autosomal recessive 31	Uncertain significance (Sep 22, 2024)
3-11307068-G-C		ATG7-related disorder	Likely benign (Aug 08, 2024)
3-11309006-G-C		not specified	Uncertain significance (Mar 28, 2024)
3-11313341-A-G		not specified	Uncertain significance (Dec 03, 2021)
3-11313383-G-A		not specified	Uncertain significance (Dec 14, 2023)
3-11313406-T-C		not specified	Uncertain significance (May 16, 2023)
3-11313411-A-G			Likely benign (Feb 01, 2023)
3-11315470-T-A		not specified	Uncertain significance (Nov 09, 2021)
3-11331346-A-G		not specified	Likely benign (Jun 21, 2023)
3-11331373-G-A		not specified	Uncertain significance (Mar 28, 2023)
3-11331420-C-T			Benign (Aug 22, 2018)
3-11332986-A-G		Spinocerebellar ataxia, autosomal recessive 31	Pathogenic (Jul 12, 2021)
3-11332989-C-G		not specified	Uncertain significance (Jan 23, 2024)
3-11333010-G-A		not specified	Uncertain significance (Dec 12, 2023)
3-11333013-A-C		not specified	Uncertain significance (Apr 04, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ATG7	protein_coding	protein_coding	ENST00000354449	18	285145

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.38e-12	0.860	125658	0	90	125748	0.000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.37	313	389	0.805	0.0000207	4612
Missense in Polyphen		77	104.71	0.73538		1192
Synonymous	0.114	143	145	0.988	0.00000794	1355
Loss of Function	1.86	23	34.8	0.660	0.00000156	455

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00110	0.00110
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000109	0.000109
Finnish	0.0000926	0.0000924
European (Non-Finnish)	0.000463	0.000457
Middle Eastern	0.000109	0.000109
South Asian	0.000263	0.000261
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: E1-like activating enzyme involved in the 2 ubiquitin- like systems required for cytoplasm to vacuole transport (Cvt) and autophagy. Activates ATG12 for its conjugation with ATG5 as well as the ATG8 family proteins for their conjugation with phosphatidylethanolamine. Both systems are needed for the ATG8 association to Cvt vesicles and autophagosomes membranes. Required for autophagic death induced by caspase-8 inhibition. Required for mitophagy which contributes to regulate mitochondrial quantity and quality by eliminating the mitochondria to a basal level to fulfill cellular energy requirements and preventing excess ROS production. Modulates p53/TP53 activity to regulate cell cycle and survival during metabolic stress. Plays also a key role in the maintenance of axonal homeostasis, the prevention of axonal degeneration, the maintenance of hematopoietic stem cells, the formation of Paneth cell granules, as well as in adipose differentiation. {ECO:0000269|PubMed:11096062, ECO:0000269|PubMed:16303767, ECO:0000269|PubMed:22170151}.
• Pathway: Autophagy - animal - Homo sapiens (human);Autophagy - other - Homo sapiens (human);Ferroptosis - Homo sapiens (human);Nanoparticle triggered autophagic cell death;Senescence and Autophagy in Cancer;Neutrophil degranulation;Disease;Innate Immune System;Immune System;Adaptive Immune System;Antigen processing: Ubiquitination & Proteasome degradation;Class I MHC mediated antigen processing & presentation;Macroautophagy;Cellular responses to external stimuli;Signaling by BRAF and RAF fusions;Oncogenic MAPK signaling;Diseases of signal transduction (Consensus)

Recessive Scores

• pRec: 0.173

Intolerance Scores

• loftool: 0.902
• rvis_EVS: -0.51
• rvis_percentile_EVS: 21.65

Haploinsufficiency Scores

• pHI: 0.102
• hipred: Y
• hipred_score: 0.652
• ghis: 0.573

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.448

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Atg7
• Phenotype: muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region 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); neoplasm; endocrine/exocrine gland phenotype; pigmentation phenotype; limbs/digits/tail 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); digestive/alimentary phenotype; immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system 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); hematopoietic system phenotype

Zebrafish Information Network

• Gene name: atg7
• Affected structure: cell
• Phenotype tag: abnormal
• Phenotype quality: decreased process quality

Gene ontology

• Biological process: autophagosome assembly;autophagy of mitochondrion;cellular protein modification process;protein lipidation;C-terminal protein lipidation;autophagy;cellular response to nitrogen starvation;aging;cellular response to starvation;response to glucose;positive regulation of autophagy;protein transport;macroautophagy;protein ubiquitination;positive regulation of protein modification process;protein modification by small protein conjugation;piecemeal microautophagy of the nucleus;suppression by virus of host autophagy;regulation of circadian rhythm;positive regulation of apoptotic process;neutrophil degranulation;late nucleophagy;positive regulation of protein catabolic process;defense response to virus;membrane fusion;chaperone-mediated autophagy;cellular response to morphine;cellular response to hyperoxia;autophagy of host cells involved in interaction with symbiont;negative regulation of mitochondrial DNA replication;response to fluoride;negative regulation of oxidative stress-induced neuron death
• Cellular component: phagophore assembly site;extracellular region;cytoplasm;cytosol;axoneme;axon;secretory granule lumen;ficolin-1-rich granule lumen
• Molecular function: ubiquitin activating enzyme activity;protein binding;transcription factor binding;Atg12 activating enzyme activity;Atg8 activating enzyme activity;protein homodimerization activity