PTBP2
protein-codingpolypyrimidine tract binding protein 2, the group of Heterogeneous nuclear ribonucleoproteins|RNA binding motif containing
Gene summary
The protein encoded by this gene binds to intronic polypyrimidine clusters in pre-mRNA molecules and is implicated in controlling the assembly of other splicing-regulatory proteins. This protein is very similar to the polypyrimidine tract binding protein (PTB) but most of its isoforms are expressed primarily in the brain. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~102.1 kbGenCC 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 PTBP2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_021190.4. 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 | 4 | 2 | 6 | |||
| missense | 1 | 40 | 41 | |||
| nonsense | 0 | |||||
| start loss | 1 | 1 | ||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 2 | 0 | 46 | 0 | 2 | 50 |
Highest pathogenic variant AF is 7.0311523e-7
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_067013.1 | 14 | MANE Select | |
| Ensembl | ENSP00000502818.1 | 14 | MANE Select | |
| RefSeq | NP_001287914.1 | 14 | Standard | |
| RefSeq | NP_001287915.1 | 14 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- TarBasePathway
- miR-targeted genes in lymphocytes - TarBase
- miR-targeted genes in muscle cell - TarBase
- mRNA Processing
- internal ribosome entry pathway
Biological Process
- mRNA splice site selection
- spinal cord development
- cerebellum development
- negative regulation of RNA splicing
- regulation of neural precursor cell proliferation
Molecular Function
- RNA binding
- mRNA binding
Cellular Component
- spliceosomal complex
- growth cone
- neuronal cell body
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000426398
- Coding exons
- 14
- Length
- 102074
- Individuals with no LoFs
- 125186
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 2
- Defined
- 125188
- p
- 0.00000799
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.20 | 134 | 287 | 0.468 | 0.0000145 | 3481 |
| Missense (PolyPhen) | 32 | 121.23 | 0.26395 | 1499 | ||
| Synonymous | 0.172 | 97 | 99.2 | 0.978 | 0.00000505 | 1053 |
| Loss of Function | 4.59 | 2 | 28.4 | 0.0704 | 0.00000168 | 314 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.0000089 | 0.0000088 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: RNA-binding protein which binds to intronic polypyrimidine tracts and mediates negative regulation of exons splicing. May antagonize in a tissue-specific manner the ability of NOVA1 to activate exon selection. In addition to its function in pre-mRNA splicing, plays also a role in the regulation of translation. Isoform 5 has a reduced affinity for RNA. {ECO:0000269|PubMed:11003644, ECO:0000269|PubMed:12667457}.;
Recessive Scores
- pRec
- 0.124
Intolerance Scores
- LoFtool
- 0.290
- RVIS EVS
- -0.52
- RVIS percentile EVS
- 21.2
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.696
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |