BACE1

protein-coding

beta-secretase 1, the group of Peptidase family A1

Gene summary

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]

Previous symbols:

BACE

MANE transcript

NM_012104.6

Inheritance

—

ClinVar variants

U:59B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.16

Max pathogenic AF

—

Genomic locus

chr11:117,285,232-117,316,259

External References & Databases

Ensembl (ENSG00000186318)

Transcript & Mutation Effects

hg38 • Region Span ~31.0 kb

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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 BACE1 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 56

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_012104.6. 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			1 clinvar			1
missense			55 clinvar	1 clinvar		56
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	59	1	0	60

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 31 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_012104.6	RefSeq	NP_036236.1	9	MANE Select
ENST00000313005.11	Ensembl	ENSP00000318585.6	9	MANE Select
NM_001207048.3	RefSeq	NP_001193977.1	8	Standard
NM_001207049.3	RefSeq	NP_001193978.1	8	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
bace1	Danio rerio	Structure: trunk Quality: increased amount abnormal

Gene / Model

Organism

Observed Phenotype

bace1

Danio rerio

Structure: trunk

Quality: increased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Alzheimer,s disease - Homo sapiens (human)
miR-targeted genes in epithelium - TarBase
miR-targeted genes in lymphocytes - TarBase
miR-targeted genes in muscle cell - TarBase
Alzheimers Disease

Biological Process

proteolysis
membrane protein ectodomain proteolysis
response to radiation
response to lead ion
protein catabolic process

Molecular Function

amyloid-beta binding
endopeptidase activity
aspartic-type endopeptidase activity
protein binding
peptidase activity

Cellular Component

lysosome
endosome
early endosome
late endosome
multivesicular body

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000313005
Coding exons: 9
Length: 30574
Individuals with no LoFs: 125724
Homozygous LoFs: 0
Heterozygous LoFs: 22
Defined: 125746
p: 0.0000875

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.24	186	294	0.632	0.0000166	3245
Missense (PolyPhen)		52	132.2	0.39335		1470
Synonymous	1.46	98	118	0.829	0.00000680	1030
Loss of Function	3.84	4	24.5	0.163	0.00000133	252

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.0017	0.0017	notable
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000037	0.000035	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Responsible for the proteolytic processing of the amyloid precursor protein (APP). Cleaves at the N-terminus of the A-beta peptide sequence, between residues 671 and 672 of APP, leads 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. {ECO:0000269|PubMed:10677483, ECO:0000269|PubMed:20354142}.;

Recessive Scores

pRec: 0.321

Intolerance Scores

LoFtool: 0.404
RVIS EVS: -0.76
RVIS percentile EVS: 13.33

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.420

Gene Damage Prediction

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