BAG2

Chr 6

BAG cochaperone 2

Also known as: BAG-2, dJ417I1.2

BAG proteins compete with Hip for binding to the Hsc70/Hsp70 ATPase domain and promote substrate release. All the BAG proteins have an approximately 45-amino acid BAG domain near the C terminus but differ markedly in their N-terminal regions. The predicted BAG2 protein contains 211 amino acids. The BAG domains of BAG1, BAG2, and BAG3 interact specifically with the Hsc70 ATPase domain in vitro and in mammalian cells. All 3 proteins bind with high affinity to the ATPase domain of Hsc70 and inhibit its chaperone activity in a Hip-repressible manner. [provided by RefSeq, Jul 2008]

0
Active trials
0
Pathogenic / LP
0
ClinVar variants
19
Pubs (1 yr)
1.3
Missense Z
1.15
LOEUF
Clinical SummaryBAG2
Population Constraint (gnomAD)
Low constraint (pLI 0.04) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.15LOEUF
pLI 0.042
Z-score 1.33
OE 0.45 (0.201.15)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
1.28Z-score
OE missense 0.65 (0.530.79)
68 obs / 104.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.45 (0.201.15)
00.351.4
Missense OE0.65 (0.530.79)
00.61.4
Synonymous OE0.83
01.21.6
LoF obs/exp: 3 / 6.7Missense obs/exp: 68 / 104.9Syn Z: 0.81
GOFDN
DN
0.6356th %ile
GOF
0.6542th %ile
LOF
0.3745th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
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

0 submitted variants in ClinVar

BAG2 · 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
Landmark / reviewRecent case evidence