BACE2

Chr 21

beta-secretase 2

Also known as: AEPLC, ALP56, ASP1, ASP21, BAE2, CDA13, CEAP1, DRAP

NCBI Gene: 25825ENSG00000182240UniProt: Q9Y5Z0

The protein functions as an aspartic protease that cleaves amyloid precursor protein to generate amyloid beta peptide and processes other substrates including PMEL in melanosomes and collectrin in pancreatic beta cells. Mutations cause Alzheimer disease type 4 with autosomal dominant inheritance. The gene shows relatively low constraint to loss-of-function variants (pLI = 0.007, LOEUF = 0.689).

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
25
Pubs (1 yr)
79
P/LP submissions
0%
P/LP missense
0.69
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— BACE2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
74 unique Pathogenic / Likely Pathogenic· 65 VUS of 172 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.69LOEUF
pLI 0.007
Z-score 2.56
OE 0.37 (0.21–0.69)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.60Z-score
OE missense 0.73 (0.65–0.82)
201 obs / 275.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.37 (0.21–0.69)
0≤0.351.4
Missense OE0.73 (0.65–0.82)
0≤0.61.4
Synonymous OE0.89
0≤1.21.6
LoF obs/exp: 7 / 19.1Missense obs/exp: 201 / 275.9Syn Z: 0.91
DN
0.75top 25%
GOF
0.74top 25%
LOF
0.2287th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

172 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic72
Likely Pathogenic2
VUS65
Likely Benign13
Benign6
72
Pathogenic
2
Likely Pathogenic
65
VUS
13
Likely Benign
6
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
72
0
72
Likely Pathogenic
0
0
2
0
2
VUS
0
62
3
0
65
Likely Benign
0
9
0
4
13
Benign
0
1
3
2
6
Total072806158

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

View in ClinVar →

Protein Context — Lollipop Plot

BACE2 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients