ATG4A

Chr X

autophagy related 4A cysteine peptidase

Also known as: APG4A, AUTL2, HsAPG4A

ATG4A encodes a cysteine protease that processes ATG8 family proteins for autophagy by cleaving their C-terminus and removing them from membranes, and also regulates mitochondrial autophagy through ATG9A trafficking. Mutations cause autosomal recessive spastic paraplegia with early childhood onset, characterized by progressive spasticity and intellectual disability. This gene is highly constrained against loss-of-function variants (pLI = 0.99, LOEUF = 0.26), indicating intolerance to protein-truncating mutations.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
8
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.26
LOEUF· LoF intol.
Mechanism
Clinical SummaryATG4A
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.26LOEUF
pLI 0.990
Z-score 3.73
OE 0.06 (0.020.26)
Highly constrained

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

Missense Constraint
1.35Z-score
OE missense 0.68 (0.570.81)
95 obs / 140.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.06 (0.020.26)
00.351.4
Missense OE0.68 (0.570.81)
00.61.4
Synonymous OE0.79
01.21.6
LoF obs/exp: 1 / 18.1Missense obs/exp: 95 / 140.0Syn Z: 1.19

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ATG4A · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

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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