BAG6

Chr 6

BAG cochaperone 6

Also known as: BAG-6, BAT3, D6S52E, G3

NCBI Gene: 7917ENSG00000204463UniProt: P46379

This gene was first characterized as part of a cluster of genes located within the human major histocompatibility complex class III region. This gene encodes a nuclear protein that is cleaved by caspase 3 and is implicated in the control of apoptosis. In addition, the protein forms a complex with E1A binding protein p300 and is required for the acetylation of p53 in response to DNA damage. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

121
ClinVar variants
7
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— BAG6
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
7 Pathogenic / Likely Pathogenic· 101 VUS of 121 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.17LOEUF
pLI 1.000
Z-score 6.21
OE 0.08 (0.04–0.17)
Highly constrained

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

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.72Z-score
OE missense 0.71 (0.66–0.76)
485 obs / 685.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.08 (0.04–0.17)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.71 (0.66–0.76)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.92
0≤1.21.6
LoF obs/exp: 4 / 52.6Missense obs/exp: 485 / 685.4Syn Z: 0.99

ClinVar Variant Classifications

121 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4
Likely Pathogenic3
VUS101
Likely Benign9
Benign4
4
Pathogenic
3
Likely Pathogenic
101
VUS
9
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
4
0
4
Likely Pathogenic
0
0
3
0
3
VUS
0
70
31
0
101
Likely Benign
0
0
1
8
9
Benign
0
0
0
4
4
Total0703912121

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

View in ClinVar →

Protein Context — Lollipop Plot

BAG6 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
BAG COCHAPERONE 6; BAG6
MIM #142590 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
BAG6 inhibits influenza A virus replication by inducing viral polymerase subunit PB2 degradation and perturbing RdRp complex assembly.
Zhou Y et al.·PLoS Pathog
2024
BAG6 restricts pancreatic cancer progression by suppressing the release of IL33-presenting extracellular vesicles and the activation of mast cells.
Alashkar Alhamwe B et al.·Cell Mol Immunol
2024
Genome-wide analysis of 53,400 people with irritable bowel syndrome highlights shared genetic pathways with mood and anxiety disorders.
Eijsbouts C et al.·Nat Genet
2021
BAG6 promotes hepatocellular carcinoma growth via enhancing PLK1-mediated aerobic glycolysis.
Zhang W et al.·Int J Biol Macromol
2026
Mechanism underlying CDC20 affecting epithelial ovarian cancer biological behavior by regulating BAG6 ubiquitination.
Zhang X et al.·Cell Signal
2025Functional
Retinitis pigmentosa 2 pathogenic mutants degrade through BAG6/HUWE1 complex.
Zhang J et al.·Exp Eye Res
2022
Senescent Tumoral HLA-E Reshapes Microenvironment through Impairing NK Cell-Dendritic Cell-T Cell Network in Malignant Pleural Effusion from Lung Cancer.
Tsai YM et al.·Int J Biol Sci
2025
Lysine deserts prevent adventitious ubiquitylation of ubiquitin-proteasome components.
Kampmeyer C et al.·Cell Mol Life Sci
2023
Circular SNX25 encoded radioresistance augmenter facilitates DNA damage repair in hepatocellular carcinoma by targeting BAG6-GET4 interaction.
Li S et al.·Cell Death Dis
2025
Regulation of Fibroblast Activation Protein-α Expression: Focus on Intracellular Protein Interactions.
Juillerat-Jeanneret L et al.·J Med Chem
2021Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools