APBA2
protein-codingamyloid beta precursor protein binding family A member 2, the group of PDZ domain containing
Gene summary
The protein encoded by this gene is a member of the X11 protein family. It is a neuronal adapter protein that interacts with the Alzheimer's disease amyloid precursor protein (APP). It stabilizes APP and inhibits production of proteolytic APP fragments including the A beta peptide that is deposited in the brains of Alzheimer's disease patients. This gene product is believed to be involved in signal transduction processes. It is also regarded as a putative vesicular trafficking protein in the brain that can form a complex with the potential to couple synaptic vesicle exocytosis to neuronal cell adhesion. [provided by RefSeq, Jul 2017]
- X11L
- MINT2
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~233.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0005027
Submitter: Ambry Genetics
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to APBA2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001353788.2. 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 | 2 | 23 | 10 | 35 | ||
| missense | 112 | 6 | 3 | 121 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 116 | 29 | 13 | 158 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001340717.1 | 12 | MANE Select | |
| Ensembl | ENSP00000507394.1 | 12 | MANE Select | |
| RefSeq | NP_001123886.1 | 11 | Standard | |
| RefSeq | NP_001340718.1 | 12 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Neuronal System
- Neurexins and neuroligins
- Protein-protein interactions at synapses
Biological Process
- in utero embryonic development
- chemical synaptic transmission
- nervous system development
- locomotory behavior
- regulation of gene expression
Molecular Function
- amyloid-beta binding
- protein binding
Cellular Component
- cytoplasm
- plasma membrane
- synaptic vesicle
- dendritic spine
- synapse
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000558402
- Coding exons
- 12
- Length
- 280890
- Individuals with no LoFs
- 125738
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 10
- Defined
- 125748
- p
- 0.0000398
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.46 | 363 | 450 | 0.806 | 0.0000301 | 4958 |
| Missense (PolyPhen) | 71 | 125.4 | 0.5662 | 1350 | ||
| Synonymous | -1.53 | 223 | 196 | 1.14 | 0.0000158 | 1419 |
| Loss of Function | 4.15 | 6 | 30.8 | 0.195 | 0.00000145 | 366 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0.000092 | 0.000092 | rare |
| European (Non-Finnish) | 0.000035 | 0.000035 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Putative function in synaptic vesicle exocytosis by binding to STXBP1, an essential component of the synaptic vesicle exocytotic machinery. May modulate processing of the amyloid-beta precursor protein (APP) and hence formation of APP-beta.;
Recessive Scores
- pRec
- 0.205
Intolerance Scores
- LoFtool
- 0.451
- RVIS EVS
- -1.39
- RVIS percentile EVS
- 4.31
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.804
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |