ATG12

protein-coding

autophagy related 12, the group of Autophagy related

Gene summary

Autophagy is a process of bulk protein degradation in which cytoplasmic components, including organelles, are enclosed in double-membrane structures called autophagosomes and delivered to lysosomes or vacuoles for degradation. ATG12 is the human homolog of a yeast protein involved in autophagy (Mizushima et al., 1998 [PubMed 9852036]).[supplied by OMIM, Mar 2008]

Previous symbols:

APG12L

MANE transcript

NM_004707.4

Inheritance

AD, AR

ClinVar variants

P:4U:27B:1

Top phenotype

NEURODEVELOPMENTAL DISORDER WITH SEIZURES AND CEREBELLAR HYPOPLASIA

gnomAD constraint

pLI —, LoF o/e 1.02

Max pathogenic AF

—

Genomic locus

chr5:115,828,200-115,841,837

External References & Databases

Ensembl (ENSG00000145782)

Transcript & Mutation Effects

hg38 • Region Span ~13.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

colorectal cancerLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0005575

Submitter: Ambry Genetics

neurodevelopmental disorderMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0700092

Submitter: G2P

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ATG12 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 25

NEURODEVELOPMENTAL DISORDER WITH SEIZURES AND CEREBELLAR HYPOPLASIATotal: 5

Mitochondrial diseaseTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004707.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar			1
missense		3 clinvar	23 clinvar	1 clinvar		27
nonsense		1 clinvar				1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	4	27	1	0	32

Highest pathogenic variant AF is 0.00023733662

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 22 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004707.4	RefSeq	NP_004698.3	4	MANE Select
ENST00000509910.2	Ensembl	ENSP00000425107.1	4	MANE Select
NM_001277783.2	RefSeq	NP_001264712.1	2	Standard
ENST00000379594.7	Ensembl	ENSP00000368913.3	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Autophagy - animal - Homo sapiens (human)
FoxO signaling pathway - Homo sapiens (human)
Autophagy - other - Homo sapiens (human)
NOD-like receptor signaling pathway - Homo sapiens (human)
RIG-I-like receptor signaling pathway - Homo sapiens (human)

Biological Process

autophagosome assembly
autophagy of mitochondrion
C-terminal protein lipidation
macroautophagy

Molecular Function

protein binding
Atg8 ligase activity

Cellular Component

autophagosome
cytosol
phagocytic vesicle membrane
phagophore assembly site membrane
Atg12-Atg5-Atg16 complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000509910
Coding exons: 4
Length: 13663
Individuals with no LoFs: 125721
Homozygous LoFs: 0
Heterozygous LoFs: 20
Defined: 125741
p: 0.0000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.37	106	73.1	1.45	0.00000334	885
Missense (PolyPhen)		16	19.631	0.81502		260
Synonymous	-1.97	42	28.6	1.47	0.00000135	290
Loss of Function	-0.0622	8	7.81	1.02	5.13e-7	81

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000059	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000055	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00012	0.00012	rare
South Asian	0.000098	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Ubiquitin-like protein involved in autophagy vesicles formation. Conjugation with ATG5 through a ubiquitin-like conjugating system involving also 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. {ECO:0000269|PubMed:12207896, ECO:0000269|PubMed:17999726, ECO:0000269|PubMed:19074260, ECO:0000269|PubMed:19164948, ECO:0000269|PubMed:23202584}.;

Recessive Scores

pRec: 0.106

Intolerance Scores

LoFtool: 0.436
RVIS EVS: 0.15
RVIS percentile EVS: 64.11

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.491

Gene Damage Prediction

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