GABARAP

Chr 17

GABA type A receptor-associated protein

Also known as: ATG8A, GABARAP-a, MM46

NCBI Gene: 11337 ENSG00000170296 UniProt: O95166 OMIM: 605125

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.

OMIM ResearchSummary from RefSeq, UniProt

Gamma-aminobutyric acid A receptors [GABA(A) receptors] are ligand-gated chloride channels that mediate inhibitory neurotransmission. This gene encodes GABA(A) receptor-associated protein, which is highly positively charged in its N-terminus and shares sequence similarity with light chain-3 of microtubule-associated proteins 1A and 1B. This protein clusters neurotransmitter receptors by mediating interaction with the cytoskeleton. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.82

Clinical Summary— GABARAP

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.26) despite low pLI — interpret in context.

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.82LOEUF

pLI 0.261

Z-score 1.90

OE 0.26 (0.10–0.82)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.55Z-score

OE missense 0.47 (0.35–0.63)

31 obs / 66.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.26 (0.10–0.82)

0≤0.351.4

Missense OE?0.47 (0.35–0.63)

0≤0.61.4

Synonymous OE?0.56

0≤1.21.6

LoF obs/exp: 2 / 7.7Missense obs/exp: 31 / 66.6Syn Z: 1.71

This gene — mechanism propensity

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.