PSEN1

presenilin 1, the group of Peptidase family A22

Basic information

Region (hg38): 14:73136417-73223691

Previous symbols: [ "AD3" ]

Links

ENSG00000080815 ∙ NCBI:5663 ∙ OMIM:104311 ∙ HGNC:9508 ∙ Uniprot:P49768 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Alzheimer disease 3 (Strong), mode of inheritance: AD
• semantic dementia (Strong), mode of inheritance: AD
• Pick disease (Strong), mode of inheritance: AD
• Alzheimer disease 3 (Strong), mode of inheritance: AD
• early-onset autosomal dominant Alzheimer disease (Supportive), mode of inheritance: AD
• familial isolated dilated cardiomyopathy (Supportive), mode of inheritance: AD
• behavioral variant of frontotemporal dementia (Supportive), mode of inheritance: AD
• dilated cardiomyopathy 1U (Limited), mode of inheritance: AD
• acne inversa, familial, 3 (Limited), mode of inheritance: AD
• Alzheimer disease 3 (Strong), mode of inheritance: AD
• semantic dementia (Limited), mode of inheritance: AD
• dilated cardiomyopathy (Disputed Evidence), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cardiomyopathy, dilated 1U	AD	Cardiovascular	Surveillance (eg, with echocardiography), preventive measures and medical management may be helpful to decrease morbidity	Cardiovascular; Dermatologic; Neurologic	7550356; 7596406; 7585193; 9052708; 9384602; 9521418; 9544835; 11094121; 11389157; 11524469; 12891668; 12668610; 15122701; 16216949; 16033913; 17186461; 20194882; 20929727; 21495993; 21656036
The reported onset of heart failure has been in the adult period (including in young adults), but surveillance and early treatment may be indicated prior to adulthood

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PSEN1 gene.

• not provided (207 variants)
• Alzheimer disease 3 (169 variants)
• Dilated cardiomyopathy 1U (121 variants)
• Pick disease;Acne inversa, familial, 3;Frontotemporal dementia;Alzheimer disease 3 (36 variants)
• Alzheimer disease 3;Acne inversa, familial, 3;Frontotemporal dementia;Pick disease (26 variants)
• Alzheimer disease 3;Pick disease;Frontotemporal dementia;Acne inversa, familial, 3 (17 variants)
• not specified (14 variants)
• Alzheimer disease 3;Pick disease;Acne inversa, familial, 3;Frontotemporal dementia (14 variants)
• Alzheimer disease 3;Frontotemporal dementia;Acne inversa, familial, 3;Pick disease (10 variants)
• Pick disease;Frontotemporal dementia;Alzheimer disease 3;Acne inversa, familial, 3 (9 variants)
• Alzheimer disease (8 variants)
• Frontotemporal dementia (8 variants)
• PSEN1-related condition (8 variants)
• Pick disease;Frontotemporal dementia;Acne inversa, familial, 3;Alzheimer disease 3 (8 variants)
• Early-onset autosomal dominant Alzheimer disease (8 variants)
• Dilated Cardiomyopathy, Dominant (7 variants)
• Alzheimer disease 3;Acne inversa, familial, 3;Pick disease;Frontotemporal dementia (7 variants)
• Alzheimer disease 3;Frontotemporal dementia;Pick disease;Acne inversa, familial, 3 (6 variants)
• Acne inversa, familial, 3;Alzheimer disease 3;Frontotemporal dementia;Pick disease (5 variants)
• Frontotemporal dementia;Pick disease;Alzheimer disease 3;Acne inversa, familial, 3 (5 variants)
• Acne inversa, familial, 3;Frontotemporal dementia;Alzheimer disease 3;Pick disease (4 variants)
• Inborn genetic diseases (4 variants)
• Acne inversa, familial, 3;Alzheimer disease 3;Pick disease;Frontotemporal dementia (3 variants)
• Pick disease (3 variants)
• Frontotemporal dementia;Alzheimer disease 3;Pick disease;Acne inversa, familial, 3 (3 variants)
• Pick disease;Alzheimer disease 3;Acne inversa, familial, 3;Frontotemporal dementia (3 variants)
• Pick disease;Alzheimer disease 3;Frontotemporal dementia;Acne inversa, familial, 3 (3 variants)
• Alzheimer disease, familial, 3, with spastic paraparesis and apraxia (2 variants)
• Frontotemporal dementia;Alzheimer disease 3;Acne inversa, familial, 3;Pick disease (2 variants)
• Alzheimer disease, familial, 3, with unusual plaques (2 variants)
• Alzheimer disease, familial, with spastic paraparesis and unusual plaques (2 variants)
• Frontotemporal dementia;Pick disease;Acne inversa, familial, 3;Alzheimer disease 3 (1 variants)
• Alzheimer disease 4 (1 variants)
• Dementia;Mental deterioration (1 variants)
• Acne inversa, familial, 3;Frontotemporal dementia;Alzheimer disease 3;Dilated cardiomyopathy 1U;Pick disease (1 variants)
• Frontotemporal dementia;Acne inversa, familial, 3;Alzheimer disease 3;Pick disease (1 variants)
• Frontotemporal dementia;Primary degenerative dementia of the Alzheimer type, presenile onset (1 variants)
• Pick disease;Alzheimer disease 3;Frontotemporal dementia;Dilated cardiomyopathy 1U;Acne inversa, familial, 3 (1 variants)
• Alzheimer disease familial 3, with spastic paraparesis (1 variants)
• Frontotemporal dementia;Alzheimer disease 3;Dilated cardiomyopathy 1U;Acne inversa, familial, 3;Pick disease (1 variants)
• Pick disease;Acne inversa, familial, 3;Alzheimer disease 3;Frontotemporal dementia (1 variants)
• Acne inversa, familial, 3;Pick disease;Alzheimer disease 3;Frontotemporal dementia (1 variants)
• Abnormality of the nervous system (1 variants)
• Primary dilated cardiomyopathy;Heart failure (1 variants)
• Alzheimer disease 3;Spastic paraparesis (1 variants)
• Pick disease;Frontotemporal dementia;Acne inversa, familial, 3;Dilated cardiomyopathy 1U;Alzheimer disease 3 (1 variants)
• Pick disease;Frontotemporal dementia;Alzheimer disease 3;Dilated cardiomyopathy 1U;Acne inversa, familial, 3 (1 variants)
• Alzheimer disease 3;Acne inversa, familial, 3;Frontotemporal dementia;Pick disease;Dilated cardiomyopathy 1U (1 variants)
• Visual hallucination;Dementia;Auditory hallucination (1 variants)
• Familial Alzheimer disease (1 variants)
• Alzheimer disease 3;Frontotemporal dementia (1 variants)
• Mental deterioration;Dementia (1 variants)
• Acne inversa, familial, 3 (1 variants)
• Telangiectasia, hereditary hemorrhagic, type 1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PSEN1 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			5	27	4	36
missense	54	46	78	3	1	182
nonsense	1					1
start loss						0
frameshift						0
inframe indel	1	1	5			7
splice donor/acceptor (+/-2bp)	2	1	1			4
splice region		1	4	3	1	9
non coding			70	31	15	116
Total	58	48	159	61	20

Highest pathogenic variant AF is 0.000125

Variants in PSEN1

This is a list of pathogenic ClinVar variants found in the PSEN1 region.

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

Position	Type	Phenotype	Significance	ClinVar
14-73136423-C-T		Early-onset autosomal dominant Alzheimer disease • Dilated Cardiomyopathy, Dominant • Alzheimer disease 3;Frontotemporal dementia;Pick disease;Acne inversa, familial, 3	Benign/Likely benign (Jan 08, 2024)
14-73136478-G-T		Dilated Cardiomyopathy, Dominant • Early-onset autosomal dominant Alzheimer disease	Uncertain significance (Jun 14, 2016)
14-73136493-C-A		Dilated Cardiomyopathy, Dominant • Early-onset autosomal dominant Alzheimer disease	Uncertain significance (Jun 14, 2016)
14-73136505-T-G		Dilated Cardiomyopathy, Dominant • Early-onset autosomal dominant Alzheimer disease	Uncertain significance (Jun 14, 2016)
14-73136518-A-C		Dilated cardiomyopathy 1U • Alzheimer disease 3	Uncertain significance (Jan 13, 2018)
14-73136528-C-T		Dilated cardiomyopathy 1U • Alzheimer disease 3	Uncertain significance (Jan 13, 2018)
14-73136539-C-T		Dilated cardiomyopathy 1U • Alzheimer disease 3	Uncertain significance (Jan 13, 2018)
14-73136796-G-A		Alzheimer disease 3;Acne inversa, familial, 3;Pick disease;Frontotemporal dementia	Likely benign (Feb 01, 2023)
14-73148040-G-A		Dilated cardiomyopathy 1U • Alzheimer disease 3	Uncertain significance (Jan 13, 2018)
14-73148061-A-C			Likely benign (Aug 01, 2022)
14-73148082-C-T			Likely benign (Jul 25, 2018)
14-73148098-C-T		Dilated cardiomyopathy 1U • Alzheimer disease 3 • Alzheimer disease 3;Frontotemporal dementia;Pick disease;Acne inversa, familial, 3	Uncertain significance (Feb 24, 2020)
14-73148099-G-A		Dilated cardiomyopathy 1U • Alzheimer disease 3	Uncertain significance (Jan 13, 2018)
14-73148113-T-TGTCA		Alzheimer disease 3;Pick disease;Frontotemporal dementia;Acne inversa, familial, 3	Likely benign (Jul 23, 2022)
14-73148358-G-A			Benign (Sep 23, 2018)
14-73170790-C-T		Alzheimer disease 3;Acne inversa, familial, 3;Pick disease;Frontotemporal dementia	Likely benign (Jul 09, 2018)
14-73170795-A-G			Uncertain significance (Mar 29, 2022)
14-73170804-A-G		not specified • Alzheimer disease 3;Pick disease;Frontotemporal dementia;Acne inversa, familial, 3	Conflicting classifications of pathogenicity (Jul 03, 2023)
14-73170805-T-C		not specified	Benign/Likely benign (Oct 01, 2023)
14-73170812-C-T		Frontotemporal dementia;Primary degenerative dementia of the Alzheimer type, presenile onset	Uncertain significance (Oct 28, 2019)
14-73170813-G-A		Alzheimer disease • Alzheimer disease 3;Frontotemporal dementia;Pick disease;Acne inversa, familial, 3 • Alzheimer disease 3 • Dilated cardiomyopathy 1U	Conflicting classifications of pathogenicity (Dec 04, 2023)
14-73170824-AACG-A		Alzheimer disease 3;Frontotemporal dementia;Pick disease;Acne inversa, familial, 3 • PSEN1-related disorder	Uncertain significance (Sep 27, 2023)
14-73170832-A-T		Alzheimer disease 3;Pick disease;Acne inversa, familial, 3;Frontotemporal dementia	Uncertain significance (Mar 06, 2022)
14-73170833-C-G		Pick disease;Acne inversa, familial, 3;Frontotemporal dementia;Alzheimer disease 3 • Inborn genetic diseases	Uncertain significance (Jul 26, 2023)
14-73170834-G-A		Alzheimer disease 3 • Dilated cardiomyopathy 1U • Alzheimer disease 3;Pick disease;Acne inversa, familial, 3;Frontotemporal dementia	Uncertain significance (Dec 03, 2020)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PSEN1	protein_coding	protein_coding	ENST00000324501	10	87274

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.973	0.0268	125736	0	12	125748	0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.16	159	256	0.621	0.0000138	3045
Missense in Polyphen		48	119.03	0.40325		1496
Synonymous	-0.441	103	97.5	1.06	0.00000540	918
Loss of Function	4.01	3	24.4	0.123	0.00000131	285

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000206	0.000206
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.000139	0.0000462
European (Non-Finnish)	0.0000532	0.0000527
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalytic subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid-beta precursor protein) (PubMed:15274632, PubMed:10545183, PubMed:10593990, PubMed:10206644, PubMed:10899933, PubMed:10811883, PubMed:12679784, PubMed:12740439, PubMed:25043039, PubMed:26280335). Requires the presence of the other members of the gamma-secretase complex for protease activity (PubMed:15274632, PubMed:25043039, PubMed:26280335). Plays a role in Notch and Wnt signaling cascades and regulation of downstream processes via its role in processing key regulatory proteins, and by regulating cytosolic CTNNB1 levels (PubMed:9738936, PubMed:10593990, PubMed:10899933, PubMed:10811883). Stimulates cell-cell adhesion via its interaction with CDH1; this stabilizes the complexes between CDH1 (E-cadherin) and its interaction partners CTNNB1 (beta-catenin), CTNND1 and JUP (gamma-catenin) (PubMed:11953314). Under conditions of apoptosis or calcium influx, cleaves CDH1 (PubMed:11953314). This promotes the disassembly of the complexes between CDH1 and CTNND1, JUP and CTNNB1, increases the pool of cytoplasmic CTNNB1, and thereby negatively regulates Wnt signaling (PubMed:9738936, PubMed:11953314). Required for normal embryonic brain and skeleton development, and for normal angiogenesis (By similarity). {ECO:0000250|UniProtKB:P49769, ECO:0000269|PubMed:10206644, ECO:0000269|PubMed:10545183, ECO:0000269|PubMed:10593990, ECO:0000269|PubMed:10811883, ECO:0000269|PubMed:10899933, ECO:0000269|PubMed:11953314, ECO:0000269|PubMed:12679784, ECO:0000269|PubMed:12740439, ECO:0000269|PubMed:15274632, ECO:0000269|PubMed:15341515, ECO:0000269|PubMed:16305624, ECO:0000269|PubMed:25043039, ECO:0000269|PubMed:26280335, ECO:0000269|PubMed:9738936}.
• Disease: DISEASE: Alzheimer disease 3 (AD3) [MIM:607822]: A familial early- onset form of Alzheimer disease. Alzheimer disease is a neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituents of these plaques are neurotoxic amyloid-beta protein 40 and amyloid-beta protein 42, that are produced by the proteolysis of the transmembrane APP protein. The cytotoxic C- terminal fragments (CTFs) and the caspase-cleaved products, such as C31, are also implicated in neuronal death. {ECO:0000269|PubMed:10025789, ECO:0000269|PubMed:10090481, ECO:0000269|PubMed:10200054, ECO:0000269|PubMed:10208579, ECO:0000269|PubMed:10439444, ECO:0000269|PubMed:10441572, ECO:0000269|PubMed:10447269, ECO:0000269|PubMed:10533070, ECO:0000269|PubMed:10631141, ECO:0000269|PubMed:10644793, ECO:0000269|PubMed:11027672, ECO:0000269|PubMed:11524469, ECO:0000269|PubMed:11710891, ECO:0000269|PubMed:11920851, ECO:0000269|PubMed:12048239, ECO:0000269|PubMed:12058025, ECO:0000269|PubMed:12484344, ECO:0000269|PubMed:12493737, ECO:0000269|PubMed:16305624, ECO:0000269|PubMed:20460383, ECO:0000269|PubMed:22503161, ECO:0000269|PubMed:26145164, ECO:0000269|PubMed:26280335, ECO:0000269|PubMed:26549787, ECO:0000269|PubMed:7550356, ECO:0000269|PubMed:7596406, ECO:0000269|PubMed:7651536, ECO:0000269|PubMed:8634711, ECO:0000269|PubMed:8634712, ECO:0000269|PubMed:8733303, ECO:0000269|PubMed:9172170, ECO:0000269|PubMed:9225696, ECO:0000269|PubMed:9298817, ECO:0000269|PubMed:9384602, ECO:0000269|PubMed:9507958, ECO:0000269|PubMed:9521423, ECO:0000269|PubMed:9719376, ECO:0000269|PubMed:9831473, ECO:0000269|PubMed:9833068, ECO:0000269|Ref.84}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Frontotemporal dementia (FTD) [MIM:600274]: A form of dementia characterized by pathologic finding of frontotemporal lobar degeneration, presenile dementia with behavioral changes, deterioration of cognitive capacities and loss of memory. In some cases, parkinsonian symptoms are prominent. Neuropathological changes include frontotemporal atrophy often associated with atrophy of the basal ganglia, substantia nigra, amygdala. In most cases, protein tau deposits are found in glial cells and/or neurons. {ECO:0000269|PubMed:11094121}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Cardiomyopathy, dilated 1U (CMD1U) [MIM:613694]: A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. {ECO:0000269|PubMed:17186461}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Acne inversa, familial, 3 (ACNINV3) [MIM:613737]: A chronic relapsing inflammatory disease of the hair follicles characterized by recurrent draining sinuses, painful skin abscesses, and disfiguring scars. Manifestations typically appear after puberty. {ECO:0000269|PubMed:20929727}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Neurotrophin signaling pathway - Homo sapiens (human);Alzheimer,s disease - Homo sapiens (human);Wnt signaling pathway - Homo sapiens (human);Notch signaling pathway - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);NOTCH-Core;Alzheimers Disease;Notch Signaling Pathway;Canonical and Non-canonical Notch signaling;Notch Signaling Pathway;Notch Signaling Pathway;Notch;Neutrophil degranulation;Disease;Signal Transduction;generation of amyloid b-peptide by ps1;proteolysis and signaling pathway of notch;segmentation clock;hiv-1 nef: negative effector of fas and tnf;g-secretase mediated erbb4 signaling pathway;Extracellular matrix organization;DroToll-like;Notch;Innate Immune System;Immune System;Signaling by NOTCH1;Signaling by NOTCH2;NOTCH3 Activation and Transmission of Signal to the Nucleus;Signaling by NOTCH3;Signaling by NOTCH4;Signaling by NOTCH;A third proteolytic cleavage releases NICD;NRIF signals cell death from the nucleus;NOTCH2 Activation and Transmission of Signal to the Nucleus;Degradation of the extracellular matrix;Death Receptor Signalling;Regulated proteolysis of p75NTR;p75 NTR receptor-mediated signalling;Notch signaling pathway;Nuclear signaling by ERBB4;Signaling by ERBB4;Constitutive Signaling by NOTCH1 PEST Domain Mutants;Signaling by NOTCH1 PEST Domain Mutants in Cancer;Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants;Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer;Signaling by NOTCH1 in Cancer;Signaling by Receptor Tyrosine Kinases;Diseases of signal transduction;p75(NTR)-mediated signaling;Cell death signalling via NRAGE, NRIF and NADE;Presenilin action in Notch and Wnt signaling;FGF signaling pathway;Syndecan-3-mediated signaling events;Activated NOTCH1 Transmits Signal to the Nucleus (Consensus)

Recessive Scores

• pRec: 0.876

Intolerance Scores

• loftool: 0.00214
• rvis_EVS: -0.34
• rvis_percentile_EVS: 30.37

Haploinsufficiency Scores

• pHI: 0.949
• hipred: Y
• hipred_score: 0.729
• ghis: 0.652

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.964

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Psen1
• Phenotype: growth/size/body region 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); endocrine/exocrine gland phenotype; muscle phenotype; craniofacial phenotype; homeostasis/metabolism phenotype; cellular phenotype; skeleton phenotype; renal/urinary system phenotype; embryo phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; reproductive system phenotype; normal 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); digestive/alimentary phenotype; limbs/digits/tail 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; immune system phenotype

Zebrafish Information Network

• Gene name: psen1
• Affected structure: neuron
• Phenotype tag: abnormal
• Phenotype quality: increased amount

Gene ontology

• Biological process: autophagosome assembly;negative regulation of transcription by RNA polymerase II;activation of MAPKK activity;blood vessel development;cell fate specification;somitogenesis;neuron migration;positive regulation of receptor recycling;heart looping;positive regulation of L-glutamate import across plasma membrane;hematopoietic progenitor cell differentiation;astrocyte activation involved in immune response;T cell activation involved in immune response;neural retina development;protein glycosylation;membrane protein ectodomain proteolysis;mitochondrial transport;cellular response to DNA damage stimulus;response to oxidative stress;negative regulation of epidermal growth factor-activated receptor activity;Notch receptor processing;learning or memory;memory;post-embryonic development;protein transport;choline transport;synaptic vesicle targeting;protein processing;cerebral cortex cell migration;Cajal-Retzius cell differentiation;dorsal/ventral neural tube patterning;embryonic limb morphogenesis;positive regulation of protein binding;positive regulation of proteasomal ubiquitin-dependent protein catabolic process;endoplasmic reticulum calcium ion homeostasis;obsolete positive regulation of protein import into nucleus, translocation;amyloid-beta formation;Notch receptor processing, ligand-dependent;intracellular signal transduction;regulation of phosphorylation;positive regulation of phosphorylation;amyloid precursor protein metabolic process;amyloid precursor protein catabolic process;myeloid dendritic cell differentiation;positive regulation of apoptotic process;negative regulation of apoptotic process;positive regulation of catalytic activity;neutrophil degranulation;negative regulation of neuron apoptotic process;skin morphogenesis;positive regulation of transcription, DNA-templated;astrocyte activation;regulation of synaptic plasticity;thymus development;neuron development;skeletal system morphogenesis;brain morphogenesis;epithelial cell proliferation;negative regulation of axonogenesis;synapse organization;positive regulation of coagulation;T cell receptor signaling pathway;neuron apoptotic process;negative regulation of ubiquitin-protein transferase activity;smooth endoplasmic reticulum calcium ion homeostasis;regulation of synaptic transmission, glutamatergic;regulation of resting membrane potential;regulation of canonical Wnt signaling pathway;positive regulation of dendritic spine development;calcium ion transmembrane transport;modulation of age-related behavioral decline;cell-cell adhesion;cellular response to amyloid-beta;negative regulation of core promoter binding;negative regulation of low-density lipoprotein receptor activity;positive regulation of amyloid fibril formation;neuron projection maintenance;negative regulation of ubiquitin-dependent protein catabolic process;negative regulation of apoptotic signaling pathway
• Cellular component: Golgi membrane;kinetochore;nucleus;nuclear outer membrane;mitochondrion;mitochondrial inner membrane;endoplasmic reticulum;endoplasmic reticulum membrane;smooth endoplasmic reticulum;rough endoplasmic reticulum;Golgi apparatus;centrosome;plasma membrane;integral component of plasma membrane;cell cortex;cell surface;membrane;integral component of membrane;aggresome;cell junction;growth cone;neuromuscular junction;nuclear membrane;protein-containing complex;ciliary rootlet;azurophil granule membrane;neuronal cell body;dendritic shaft;membrane raft;gamma-secretase complex;integral component of presynaptic membrane
• Molecular function: endopeptidase activity;aspartic-type endopeptidase activity;calcium channel activity;protein binding;beta-catenin binding;PDZ domain binding;aspartic endopeptidase activity, intramembrane cleaving;cadherin binding