APLP2

protein-coding

amyloid beta precursor like protein 2

Gene summary

This gene encodes amyloid precursor- like protein 2 (APLP2), which is a member of the APP (amyloid precursor protein) family including APP, APLP1 and APLP2. This protein is ubiquitously expressed. It contains heparin-, copper- and zinc- binding domains at the N-terminus, BPTI/Kunitz inhibitor and E2 domains in the middle region, and transmembrane and intracellular domains at the C-terminus. This protein interacts with major histocompatibility complex (MHC) class I molecules. The synergy of this protein and the APP is required to mediate neuromuscular transmission, spatial learning and synaptic plasticity. This protein has been implicated in the pathogenesis of Alzheimer's disease. Multiple alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Aug 2011]

Previous symbols:

APPL2

MANE transcript

NM_001142276.2

Inheritance

—

ClinVar variants

U:133B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.23

Max pathogenic AF

—

Genomic locus

chr11:130,068,147-130,144,811

External References & Databases

Ensembl (ENSG00000084234)

Transcript & Mutation Effects

hg38 • Region Span ~76.7 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 APLP2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 133

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001142276.2. 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 clinvar		2
missense			126 clinvar	3 clinvar		129
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	133	4	0	137

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 123 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001142276.2	RefSeq	NP_001135748.1	17	MANE Select
ENST00000338167.10	Ensembl	ENSP00000345444.5	17	MANE Select
NM_001142277.2	RefSeq	NP_001135749.1	16	Standard
NM_001142278.2	RefSeq	NP_001135750.1	13	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Splicing factor NOVA regulated synaptic proteins
Post-translational protein phosphorylation
Post-translational protein modification
Metabolism of proteins
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)

Biological Process

platelet degranulation
G protein-coupled receptor signaling pathway
negative regulation of endopeptidase activity
post-translational protein modification
cellular protein metabolic process

Molecular Function

DNA binding
serine-type endopeptidase inhibitor activity
protein binding
heparin binding
identical protein binding

Cellular Component

nucleus
endoplasmic reticulum lumen
plasma membrane
membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000263574
Coding exons: 18
Length: 74968
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	-0.00417	455	455	1.00	0.0000268	5068
Missense (PolyPhen)		193	206.92	0.93271		2229
Synonymous	0.0466	165	166	0.995	0.0000101	1394
Loss of Function	4.54	9	39.9	0.225	0.00000195	480

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.000054	0.000054	rare
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.000044	0.000044	rare
South Asian	0.000065	0.000065	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May play a role in the regulation of hemostasis. The soluble form may have inhibitory properties towards coagulation factors. May interact with cellular G-protein signaling pathways. May bind to the DNA 5'-GTCACATG-3'(CDEI box). Inhibits trypsin, chymotrypsin, plasmin, factor XIA and plasma and glandular kallikrein. Modulates the Cu/Zn nitric oxide-catalyzed autodegradation of GPC1 heparan sulfate side chains in fibroblasts (By similarity). {ECO:0000250, ECO:0000269|PubMed:8307156}.;

Recessive Scores

pRec: 0.200

Intolerance Scores

LoFtool: 0.0205
RVIS EVS: -0.71
RVIS percentile EVS: 14.67

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.887

Gene Damage Prediction

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