BACE2

beta-secretase 2, the group of Peptidase family A1

Basic information

Region (hg38): 21:41167800-41282530

Previous symbols: [ "AEPLC" ]

Links

ENSG00000182240 ∙ NCBI:25825 ∙ OMIM:605668 ∙ HGNC:934 ∙ Uniprot:Q9Y5Z0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the BACE2 gene.

• Inborn genetic diseases (19 variants)
• not provided (7 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the BACE2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				3		3
missense			17	3	1	21
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding					1	1
Total	0	0	17	6	2

Variants in BACE2

This is a list of pathogenic ClinVar variants found in the BACE2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
21-41168349-T-C		not specified	Uncertain significance (Jan 20, 2023)
21-41168358-C-A		not specified	Uncertain significance (Mar 11, 2024)
21-41168374-G-A		BACE2-related disorder	Benign (Jan 02, 2020)
21-41168402-C-T		not specified	Uncertain significance (Mar 06, 2023)
21-41168411-G-A		not specified	Uncertain significance (Feb 06, 2023)
21-41168429-C-T			Benign (Aug 20, 2018)
21-41168454-T-A		not specified	Uncertain significance (Jul 08, 2022)
21-41168527-T-A		BACE2-related disorder	Likely benign (Dec 03, 2019)
21-41168548-G-C		not specified	Uncertain significance (Nov 08, 2022)
21-41179613-G-A		PLAC4-related disorder	Likely benign (Jun 15, 2022)
21-41226315-C-T		not specified	Uncertain significance (Mar 29, 2023)
21-41237544-G-C		not specified	Uncertain significance (Aug 02, 2021)
21-41237600-C-T			Likely benign (Dec 31, 2019)
21-41237682-A-G		not specified	Uncertain significance (Sep 25, 2023)
21-41237710-C-G		not specified	Uncertain significance (Mar 14, 2023)
21-41241895-T-C		not specified	Uncertain significance (Dec 21, 2023)
21-41241931-C-T		not specified	Uncertain significance (Jul 14, 2021)
21-41243366-C-T		BACE2-related disorder	Benign (Oct 30, 2019)
21-41245968-G-A		not specified	Uncertain significance (Dec 07, 2021)
21-41246053-G-A		not specified	Uncertain significance (Sep 15, 2021)
21-41246055-G-A		not specified	Likely benign (Aug 11, 2022)
21-41246062-T-C		not specified	Uncertain significance (Apr 12, 2022)
21-41250859-C-T		BACE2-related disorder	Benign (Oct 30, 2019)
21-41250873-G-A		not specified	Uncertain significance (Dec 21, 2021)
21-41257148-C-T		BACE2-related disorder	Benign (Dec 31, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
BACE2	protein_coding	protein_coding	ENST00000330333	9	114718

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00676	0.990	125734	0	14	125748	0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.60	201	276	0.729	0.0000165	3305
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000872	0.0000872
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000792	0.0000791
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

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}.
• Pathway: Alzheimer,s disease - Homo sapiens (human) (Consensus)

Recessive Scores

• pRec: 0.355

Intolerance Scores

• loftool: 0.302
• rvis_EVS: -0.36
• rvis_percentile_EVS: 29.16

Haploinsufficiency Scores

• pHI: 0.242
• hipred: Y
• hipred_score: 0.768
• ghis: 0.511

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.637

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Bace2
• Phenotype: cellular phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; pigmentation phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Zebrafish Information Network

• Gene name: bace2
• Affected structure: myelinating Schwann cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: proteolysis;membrane protein ectodomain proteolysis;peptide hormone processing;protein catabolic process;glucose homeostasis;negative regulation of amyloid precursor protein biosynthetic process;astrocyte activation;amyloid-beta metabolic process
• Cellular component: endosome;endoplasmic reticulum;Golgi apparatus;trans-Golgi network;plasma membrane;cell surface;membrane;integral component of membrane;dense core granule
• Molecular function: amyloid-beta binding;aspartic-type endopeptidase activity