ATG4B

Chr 2

autophagy related 4B cysteine peptidase

Also known as: APG4B, AUTL1, HsAPG4B

ATG4B encodes a cysteine protease essential for autophagy, mediating both proteolytic activation and delipidation of ATG8 family proteins required for cellular degradation of damaged organelles and proteins. The gene is highly constrained against loss-of-function variants (pLI 0.96, LOEUF 0.34), but no specific human disease has been definitively associated with ATG4B mutations to date. Any potential disorders would likely follow autosomal recessive inheritance given the gene's essential cellular function.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
52
Pubs (1 yr)
106
P/LP submissions
0%
P/LP missense
0.34
LOEUF· LoF intol.
Mechanism
Clinical SummaryATG4B
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.96). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
104 unique Pathogenic / Likely Pathogenic· 87 VUS of 220 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.34LOEUF
pLI 0.956
Z-score 3.87
OE 0.13 (0.060.34)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
1.41Z-score
OE missense 0.74 (0.650.84)
170 obs / 230.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.13 (0.060.34)
00.351.4
Missense OE0.74 (0.650.84)
00.61.4
Synonymous OE1.00
01.21.6
LoF obs/exp: 3 / 23.0Missense obs/exp: 170 / 230.4Syn Z: 0.01

ClinVar Variant Classifications

220 submitted variants in ClinVar

Classification Summary

Pathogenic92
Likely Pathogenic12
VUS87
Likely Benign4
Benign1
92
Pathogenic
12
Likely Pathogenic
87
VUS
4
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
92
0
92
Likely Pathogenic
0
0
12
0
12
VUS
1
63
23
0
87
Likely Benign
0
1
1
2
4
Benign
0
0
1
0
1
Total1641292196

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ATG4B · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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