BCL2A1

Chr 15

BCL2 related protein A1

Also known as: ACC-1, ACC-2, ACC1, ACC2, BCL2L5, BFL1, GRS, HBPA1

NCBI Gene: 597 ENSG00000140379 UniProt: Q16548

This gene encodes a member of the BCL-2 protein family. The proteins of this family form hetero- or homodimers and act as anti- and pro-apoptotic regulators that are involved in a wide variety of cellular activities such as embryonic development, homeostasis and tumorigenesis. The protein encoded by this gene is able to reduce the release of pro-apoptotic cytochrome c from mitochondria and block caspase activation. This gene is a direct transcription target of NF-kappa B in response to inflammatory mediators, and is up-regulated by different extracellular signals, such as granulocyte-macrophage colony-stimulating factor (GM-CSF), CD40, phorbol ester and inflammatory cytokine TNF and IL-1, which suggests a cytoprotective function that is essential for lymphocyte activation as well as cell survival. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Research

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.91

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.91LOEUF

pLI 0.208

Z-score 1.73

OE 0.29 (0.12–0.91)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.13Z-score

OE missense 0.67 (0.55–0.83)

62 obs / 92.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.29 (0.12–0.91)

0≤0.351.4

Missense OE?0.67 (0.55–0.83)

0≤0.61.4

Synonymous OE?1.14

0≤1.21.6

LoF obs/exp: 2 / 6.9Missense obs/exp: 62 / 92.6Syn Z: -0.68

Background carrier burden — how many people carry a rare variant somewhere in BCL2A1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 270

222 rare PASS variants

Rare truncating (LoF)

1 in 4,300

34 rare PASS variants

Rare synonymous (reference)

1 in 230

86 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for BCL2A1. 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 220	1 in 4,300
South Asian	~43k	1 in 320	1 in 4,300
Remaining (unassigned)	~30k	1 in 310	≈ 1 in 7,500
European (Finnish)	~27k	1 in 1,000	none seen
Admixed American	~22k	1 in 550	≈ 1 in 5,600
African / African American	~21k	1 in 410	≈ 1 in 9,200
East Asian	~20k	1 in 510	1 in 1,000
Ashkenazi Jewish	~13k	1 in 980	none seen
Middle Eastern	~2,884	1 in 410	≈ 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 2 coding exons well covered in gnomAD exomes and genomes.? see exons ↓