BACE1

Chr 11

beta-secretase 1

Also known as: ASP2, BACE, HSPC104

NCBI Gene: 23621 ENSG00000186318 UniProt: P56817

This gene encodes a member of the peptidase A1 family of aspartic proteases. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate the mature protease. This transmembrane protease catalyzes the first step in the formation of amyloid beta peptide from amyloid precursor protein. Amyloid beta peptides are the main constituent of amyloid beta plaques, which accumulate in the brains of human Alzheimer's disease patients. [provided by RefSeq, Nov 2015]

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

458

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.37

LOEUF

—

Mechanism

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.37LOEUF

pLI 0.879

Z-score 3.84

OE 0.16 (0.08–0.37)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.24Z-score

OE missense 0.63 (0.56–0.71)

186 obs / 294.3 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.16 (0.08–0.37)

0≤0.351.4

Missense OE?0.63 (0.56–0.71)

0≤0.61.4

Synonymous OE?0.83

0≤1.21.6

LoF obs/exp: 4 / 24.5Missense obs/exp: 186 / 294.3Syn Z: 1.46

Background carrier burden — how many people carry a rare variant somewhere in BACE1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 150

591 rare PASS variants

Rare truncating (LoF)

1 in 2,100

72 rare PASS variants

Rare synonymous (reference)

1 in 240

260 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for BACE1. 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 170	1 in 2,900
South Asian	~43k	1 in 100	1 in 910
Remaining (unassigned)	~30k	1 in 120	1 in 1,400
European (Finnish)	~27k	1 in 180	1 in 4,700
Admixed American	~22k	1 in 110	≈ 1 in 20,000
African / African American	~21k	1 in 130	1 in 2,600
East Asian	~20k	1 in 100	1 in 2,000
Ashkenazi Jewish	~13k	1 in 760	≈ 1 in 6,200
Middle Eastern	~2,884	1 in 140	≈ 1 in 1,400

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