PPFIA2
protein-codingPTPRF interacting protein alpha 2, the group of Sterile alpha motif domain containing
Gene summary
The protein encoded by this gene is a member of the LAR protein-tyrosine phosphatase-interacting protein (liprin) family. Liprins interact with members of LAR family of transmembrane protein tyrosine phosphatases, which are known to be important for axon guidance and mammary gland development. It has been proposed that liprins are multivalent proteins that form complex structures and act as scaffolds for the recruitment and anchoring of LAR family of tyrosine phosphatases. This protein has been shown to bind the calcium/calmodulin-dependent serine protein kinase (MAGUK family) protein (also known as CASK) and proposed to regulate higher-order brain functions in mammals. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~501.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0700092
Submitter: Ambry Genetics
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PPFIA2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003625.5. 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 | 3 | 1 | 4 | |||
| missense | 114 | 1 | 1 | 116 | ||
| nonsense | 3 | 3 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 117 | 4 | 2 | 123 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003616.2 | 30 | MANE Select | |
| Ensembl | ENSP00000450337.1 | 30 | MANE Select | |
| RefSeq | NP_001207402.1 | 30 | Standard | |
| RefSeq | NP_001207403.1 | 30 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Neuronal System
- Glutamate Neurotransmitter Release Cycle
- Dopamine Neurotransmitter Release Cycle
- Acetylcholine Neurotransmitter Release Cycle
- Neurotransmitter release cycle
Biological Process
- cell-matrix adhesion
- presynapse organization
- regulation of synaptic vesicle exocytosis
Molecular Function
- protein binding
- structural constituent of presynapse
Cellular Component
- cytoplasm
- cytosol
- cell surface
- presynaptic active zone
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000549396
- Coding exons
- 30
- Length
- 501288
- Individuals with no LoFs
- 124187
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 359
- Defined
- 124546
- p
- 0.00144
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.26 | 406 | 638 | 0.637 | 0.0000334 | 8109 |
| Missense (PolyPhen) | 91 | 234.33 | 0.38834 | 2948 | ||
| Synonymous | -0.505 | 230 | 220 | 1.04 | 0.0000112 | 2350 |
| Loss of Function | 7.51 | 5 | 75.4 | 0.0663 | 0.00000435 | 916 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00095 | 0.00090 | rare |
| Latino/Admixed American | 0.00033 | 0.00032 | rare |
| Ashkenazi Jewish | 0.00020 | 0.00020 | rare |
| East Asian | 0.00035 | 0.00033 | rare |
| Finnish | 0.0092 | 0.0090 | notable |
| European (Non-Finnish) | 0.0012 | 0.0011 | notable |
| South Asian | 0 | 0.0 | absent |
| Other | 0.00068 | 0.00066 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Alters PTPRF cellular localization and induces PTPRF clustering. May regulate the disassembly of focal adhesions. May localize receptor-like tyrosine phosphatases type 2A at specific sites on the plasma membrane, possibly regulating their interaction with the extracellular environment and their association with substrates. {ECO:0000269|PubMed:9624153}.;
Recessive Scores
- pRec
- 0.117
Intolerance Scores
- LoFtool
- 0.158
- RVIS EVS
- -1.04
- RVIS percentile EVS
- 7.77
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.586
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |