BACE2

protein-coding

beta-secretase 2, the group of Peptidase family A1

Gene summary

This gene encodes an integral membrane glycoprotein that functions as an aspartic protease. The encoded protein cleaves amyloid precursor protein into amyloid beta peptide, which is a critical step in the etiology of Alzheimer's disease and Down syndrome. The protein precursor is further processed into an active mature peptide. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

Previous symbols:

AEPLC

MANE transcript

NM_012105.5

Inheritance

—

ClinVar variants

U:68B:14

Top phenotype

BACE2-related disorder

gnomAD constraint

pLI —, LoF o/e 0.37

Max pathogenic AF

—

Genomic locus

chr21:41,167,801-41,282,530

External References & Databases

Ensembl (ENSG00000182240)

Transcript & Mutation Effects

hg38 • Region Span ~114.7 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to BACE2 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 70

not providedTotal: 7

BACE2-related disorderTotal: 6

PLAC4-related disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_012105.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				5 clinvar	1 clinvar	6
missense			65 clinvar	7 clinvar	1 clinvar	73
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	68	12	2	82

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 33 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_012105.5	RefSeq	NP_036237.2	9	MANE Select
ENST00000330333.11	Ensembl	ENSP00000332979.6	9	MANE Select
NM_138991.3	RefSeq	NP_620476.1	8	Standard
NM_138992.3	RefSeq	NP_620477.1	8	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
bace2	Danio rerio	Structure: myelinating Schwann cell Quality: decreased amount abnormal

Gene / Model

Organism

Observed Phenotype

bace2

Danio rerio

Structure: myelinating Schwann cell

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Alzheimer,s disease - Homo sapiens (human)

Biological Process

proteolysis
membrane protein ectodomain proteolysis
peptide hormone processing
protein catabolic process
glucose homeostasis

Molecular Function

amyloid-beta binding
aspartic-type endopeptidase activity

Cellular Component

endosome
endoplasmic reticulum
Golgi apparatus
trans-Golgi network
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000330333
Coding exons: 9
Length: 114718
Individuals with no LoFs: 125734
Homozygous LoFs: 0
Heterozygous LoFs: 14
Defined: 125748
p: 0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.60	201	276	0.729	0.0000165	3305
Missense (PolyPhen)		73	129.88	0.56207		1535
Synonymous	0.914	106	119	0.893	0.00000822	1104
Loss of Function	2.56	7	19.1	0.367	8.97e-7	233

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000079	0.000079	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Responsible for the proteolytic processing of the amyloid precursor protein (APP). Cleaves APP, between residues 690 and 691, leading to the generation and extracellular release of beta-cleaved soluble APP, and a corresponding cell-associated C- terminal fragment which is later released by gamma-secretase. It has also been shown that it can cleave APP between residues 671 and 672. {ECO:0000269|PubMed:10591213, ECO:0000269|PubMed:11083922, ECO:0000269|PubMed:11423558, ECO:0000269|PubMed:15857888, ECO:0000269|PubMed:16816112}.;

Recessive Scores

pRec: 0.355

Intolerance Scores

LoFtool: 0.302
RVIS EVS: -0.36
RVIS percentile EVS: 29.16

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.637

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium