BAG1

Chr 9

BAG cochaperone 1

Also known as: BAG-1, HAP, RAP46

NCBI Gene: 573 ENSG00000107262 UniProt: Q99933 OMIM: 601497

BAG1 encodes a co-chaperone protein that facilitates HSP70/HSC70 chaperone function by promoting nucleotide exchange and client protein release, while also enhancing the anti-apoptotic effects of BCL2. Mutations in BAG1 cause autosomal dominant myofibrillar myopathy with early adult onset, characterized by progressive muscle weakness and cardiac involvement. The gene shows very low constraint against loss-of-function variants (pLI near 0), suggesting tolerance to such mutations.

OMIM ResearchSummary from RefSeq, UniProt

The oncogene BCL2 is a membrane protein that blocks a step in a pathway leading to apoptosis or programmed cell death. The protein encoded by this gene binds to BCL2 and is referred to as BCL2-associated athanogene. It enhances the anti-apoptotic effects of BCL2 and represents a link between growth factor receptors and anti-apoptotic mechanisms. Multiple protein isoforms are encoded by this mRNA through the use of a non-AUG (CUG) initiation codon, and three alternative downstream AUG initiation codons. A related pseudogene has been defined on chromosome X. [provided by RefSeq, Feb 2010]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.16

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.16LOEUF

pLI 0.000

Z-score 1.11

OE 0.69 (0.42–1.16)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.52Z-score

OE missense 1.11 (0.99–1.25)

198 obs / 178.4 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.69 (0.42–1.16)

0≤0.351.4

Missense OE?1.11 (0.99–1.25)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 10 / 14.6Missense obs/exp: 198 / 178.4Syn Z: -0.04

Background carrier burden — how many people carry a rare variant somewhere in BAG1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

528 rare PASS variants

Rare truncating (LoF)

1 in 680

93 rare PASS variants

Rare synonymous (reference)

1 in 220

192 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for BAG1. 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 180	1 in 1,200
South Asian	~43k	1 in 76	1 in 540
Remaining (unassigned)	~30k	1 in 90	1 in 590
European (Finnish)	~27k	1 in 230	1 in 880
Admixed American	~22k	1 in 74	1 in 1,100
African / African American	~21k	1 in 59	1 in 1,200
East Asian	~20k	1 in 120	1 in 930
Ashkenazi Jewish	~13k	1 in 330	none seen
Middle Eastern	~2,884	1 in 73	≈ 1 in 2,200

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 7 coding exons well covered in gnomAD exomes and genomes.? see exons ↓