GABARAP

Chr 17

GABA type A receptor-associated protein

Also known as: ATG8A, GABARAP-a, MM46

GABARAP encodes a ubiquitin-like modifier protein that facilitates intracellular transport of GABA(A) receptors and plays essential roles in autophagosome maturation and endoplasmic reticulum turnover. Based on current databases, no definitive human diseases have been established from pathogenic mutations in this gene. The gene shows moderate tolerance to loss-of-function variants (pLI=0.26, LOEUF=0.82), suggesting that complete loss of function may be compatible with normal development.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.82
Clinical SummaryGABARAP
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.26) despite low pLI — interpret in context.
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ClinVar Variants
29 unique Pathogenic / Likely Pathogenic· 13 VUS of 46 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.82LOEUF
pLI 0.261
Z-score 1.90
OE 0.26 (0.100.82)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.55Z-score
OE missense 0.47 (0.350.63)
31 obs / 66.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.26 (0.100.82)
00.351.4
Missense OE0.47 (0.350.63)
00.61.4
Synonymous OE0.56
01.21.6
LoF obs/exp: 2 / 7.7Missense obs/exp: 31 / 66.6Syn Z: 1.71
DN
0.6648th %ile
GOF
0.5071th %ile
LOF
0.3551th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

46 submitted variants in ClinVar

Classification Summary

Pathogenic26
Likely Pathogenic3
VUS13
26
Pathogenic
3
Likely Pathogenic
13
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
26
Likely Pathogenic
3
VUS
13
Likely Benign
0
Benign
0
Total42

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

GABARAP · 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.

Search ClinicalTrials.gov →
Clinical Literature
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