BAG4

Chr 8

BAG cochaperone 4

Also known as: BAG-4, SODD

NCBI Gene: 9530 ENSG00000156735 UniProt: O95429 OMIM: 603884

The protein encoded by this gene is a member of the BAG1-related protein family. BAG1 is an anti-apoptotic protein that functions through interactions with a variety of cell apoptosis and growth related proteins including BCL-2, Raf-protein kinase, steroid hormone receptors, growth factor receptors and members of the heat shock protein 70 kDa family. This protein contains a BAG domain near the C-terminus, which could bind and inhibit the chaperone activity of Hsc70/Hsp70. This protein was found to be associated with the death domain of tumor necrosis factor receptor type 1 (TNF-R1) and death receptor-3 (DR3), and thereby negatively regulates downstream cell death signaling. The regulatory role of this protein in cell death was demonstrated in epithelial cells which undergo apoptosis while integrin mediated matrix contacts are lost. Alternatively spliced transcript variants encoding distinct isoforms have been identified. [provided by RefSeq, Mar 2011]

OMIM Research

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.75

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.75LOEUF

pLI 0.000

Z-score 2.47

OE 0.44 (0.27–0.75)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.11Z-score

OE missense 1.02 (0.92–1.13)

258 obs / 253.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.44 (0.27–0.75)

0≤0.351.4

Missense OE?1.02 (0.92–1.13)

0≤0.61.4

Synonymous OE?0.79

0≤1.21.6

LoF obs/exp: 10 / 22.7Missense obs/exp: 258 / 253.3Syn Z: 1.62

Background carrier burden — how many people carry a rare variant somewhere in BAG4?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 150

569 rare PASS variants

Rare truncating (LoF)

1 in 1,500

54 rare PASS variants

Rare synonymous (reference)

1 in 360

229 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for BAG4. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 230	1 in 3,100
South Asian	~43k	1 in 73	1 in 6,200
Remaining (unassigned)	~30k	1 in 150	1 in 680
European (Finnish)	~27k	1 in 680	1 in 5,200
Admixed American	~22k	1 in 90	1 in 660
African / African American	~21k	1 in 92	1 in 1,200
East Asian	~20k	1 in 120	≈ 1 in 17,000
Ashkenazi Jewish	~13k	1 in 1,400	none seen
Middle Eastern	~2,884	1 in 100	≈ 1 in 2,800

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 5 coding exons well covered in gnomAD exomes and genomes.? see exons ↓