ATG4C

Chr 1

autophagy related 4C cysteine peptidase

Also known as: APG4-C, APG4C, AUTL1, AUTL3, HsAPG4C

NCBI Gene: 84938 ENSG00000125703 UniProt: Q96DT6

ATG4C encodes a cysteine protease that mediates both proteolytic activation and delipidation of ATG8 family proteins, which are essential steps in the autophagy pathway for cellular homeostasis and organelle turnover. The gene shows very low constraint against loss-of-function variants (pLI near zero, LOEUF 1.4), and no definitive human disease associations have been established with ATG4C mutations to date.

ResearchSummary from RefSeq, UniProt

Autophagy is the process by which endogenous proteins and damaged organelles are destroyed intracellularly. Autophagy is postulated to be essential for cell homeostasis and cell remodeling during differentiation, metamorphosis, non-apoptotic cell death, and aging. Reduced levels of autophagy have been described in some malignant tumors, and a role for autophagy in controlling the unregulated cell growth linked to cancer has been proposed. This gene encodes a member of the autophagin protein family. The encoded protein is also designated as a member of the C-54 family of cysteine proteases. Alternate transcriptional splice variants, encoding the same protein, have been characterized. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

—

LOEUF

—

Mechanism

Some data sources returned errors (2)

gnomad: TimeoutError: The operation was aborted due to timeout

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Background carrier burden — how many people carry a rare variant somewhere in ATG4C?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 79

647 rare PASS variants

Rare truncating (LoF)

1 in 350

134 rare PASS variants

Rare synonymous (reference)

1 in 220

172 rare PASS variants

Rare missense and truncating variants are carried at similar rates in ATG4C; this gene does not show strong loss-of-function constraint by this measure. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 98	1 in 360
South Asian	~43k	1 in 53	1 in 600
Remaining (unassigned)	~30k	1 in 67	1 in 250
European (Finnish)	~27k	1 in 250	1 in 1,400
Admixed American	~22k	1 in 90	1 in 480
African / African American	~21k	1 in 93	1 in 320
East Asian	~20k	1 in 89	1 in 1,200
Ashkenazi Jewish	~13k	1 in 220	1 in 380
Middle Eastern	~2,883	1 in 81	1 in 290

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 7 of 10 coding exons well covered in gnomAD exomes; exons 2, 3, 6 marginal. Genomes: all 10.? see exons ↓