PTPRN2
protein-codingprotein tyrosine phosphatase receptor type N2, the group of MicroRNA protein coding host genes|Protein tyrosine phosphatases receptor type
Gene summary
This gene encodes a protein with sequence similarity to receptor-like protein tyrosine phosphatases. However, tyrosine phosphatase activity has not been experimentally validated for this protein. Studies of the rat ortholog suggest that the encoded protein may instead function as a phosphatidylinositol phosphatase with the ability to dephosphorylate phosphatidylinositol 3-phosphate and phosphatidylinositol 4,5-diphosphate, and this function may be involved in the regulation of insulin secretion. This protein has been identified as an autoantigen in insulin-dependent diabetes mellitus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2015]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~1,048.8 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 PTPRN2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002847.5. 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 | 1 | 18 | 16 | 35 | ||
| missense | 186 | 20 | 9 | 215 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 3 | 1 | 4 | |||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 188 | 42 | 26 | 256 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002838.2 | 23 | MANE Select | |
| Ensembl | ENSP00000374069.4 | 23 | MANE Select | |
| RefSeq | NP_001295196.1 | 22 | Standard | |
| RefSeq | NP_001295197.1 | 23 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Type I diabetes mellitus - Homo sapiens (human)
- Neutrophil degranulation
- Innate Immune System
- Immune System
Biological Process
- protein dephosphorylation
- lipid metabolic process
- neurotransmitter secretion
- negative regulation of GTPase activity
- peptidyl-tyrosine dephosphorylation
Molecular Function
- transmembrane receptor protein tyrosine phosphatase activity
Cellular Component
- endoplasmic reticulum lumen
- plasma membrane
- integral component of plasma membrane
- cell junction
- integral component of synaptic vesicle membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000389418
- Coding exons
- 23
- Length
- 1048731
- Individuals with no LoFs
- 125706
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 41
- Defined
- 125748
- p
- 0.000167
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.0573 | 630 | 634 | 0.994 | 0.0000423 | 6455 |
| Missense (PolyPhen) | 182 | 233.28 | 0.78018 | 2470 | ||
| Synonymous | 0.242 | 292 | 297 | 0.982 | 0.0000229 | 2106 |
| Loss of Function | 4.04 | 20 | 51.1 | 0.391 | 0.00000258 | 569 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00013 | 0.00012 | rare |
| Latino/Admixed American | 0.00029 | 0.00029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00017 | 0.00017 | rare |
| South Asian | 0.00027 | 0.00023 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Plays a role in vesicle-mediated secretory processes. Required for normal accumulation of secretory vesicles in hippocampus, pituitary and pancreatic islets. Required for the accumulation of normal levels of insulin-containing vesicles and preventing their degradation. Plays a role in insulin secretion in response to glucose stimuli. Required for normal accumulation of the neurotransmitters norepinephrine, dopamine and serotonin in the brain. In females, but not in males, required for normal accumulation and secretion of pituitary hormones, such as luteinizing hormone (LH) and follicle-stimulating hormone (FSH) (By similarity). Required to maintain normal levels of renin expression and renin release (By similarity). May regulate catalytic active protein-tyrosine phosphatases such as PTPRA through dimerization (By similarity). Has phosphatidylinositol phosphatase activity; the PIPase activity is involved in its ability to regulate insulin secretion. Can dephosphorylate phosphatidylinositol 4,5-biphosphate (PI(4,5)P2), phosphatidylinositol 5-phosphate and phosphatidylinositol 3- phosphate (By similarity). Regulates PI(4,5)P2 level in the plasma membrane and localization of cofilin at the plasma membrane and thus is indirectly involved in regulation of actin dynamics related to cell migration and metastasis; upon hydrolyzation of PI(4,5)P2 cofilin is released from the plasma membrane and acts in the cytoplasm in severing F-actin filaments (PubMed:26620550). {ECO:0000250|UniProtKB:P80560, ECO:0000250|UniProtKB:Q63475, ECO:0000269|PubMed:26620550}.;
- Disease
- DISEASE: Note=Autoantigen in insulin-dependent diabetes mellitus (IDDM). {ECO:0000269|PubMed:8637868, ECO:0000269|PubMed:8798755, ECO:0000269|PubMed:8878534}.;
Recessive Scores
- pRec
- 0.0998
Intolerance Scores
- LoFtool
- 0.730
- RVIS EVS
- 0.89
- RVIS percentile EVS
- 89.2
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.780
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | High | Medium | Medium |
| Primary Immunodeficiency | High | High | High |
| Cancer | High | High | High |