PTPN1
protein-codingprotein tyrosine phosphatase non-receptor type 1, the group of Protein tyrosine phosphatases non-receptor type
Gene summary
The protein encoded by this gene is the founding member of the protein tyrosine phosphatase (PTP) family, which was isolated and identified based on its enzymatic activity and amino acid sequence. PTPs catalyze the hydrolysis of the phosphate monoesters specifically on tyrosine residues. Members of the PTP family share a highly conserved catalytic motif, which is essential for the catalytic activity. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP has been shown to act as a negative regulator of insulin signaling by dephosphorylating the phosphotryosine residues of insulin receptor kinase. This PTP was also reported to dephosphorylate epidermal growth factor receptor kinase, as well as JAK2 and TYK2 kinases, which implicated the role of this PTP in cell growth control, and cell response to interferon stimulation. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2013]
- PTP1B
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~74.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0019751
Submitter: Ambry Genetics
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PTPN1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002827.4. 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 | 1 | 2 | 2 | 5 | ||
| missense | 1 | 32 | 4 | 37 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | 2 | |||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 2 | 1 | 34 | 6 | 2 | 45 |
Highest pathogenic variant AF is 0.0000027361878
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002818.1 | 10 | MANE Select | |
| Ensembl | ENSP00000360683.3 | 10 | MANE Select | |
| RefSeq | NP_001265547.1 | 8 | Standard | |
| Ensembl | ENSP00000437732.1 | 8 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Adherens junction - Homo sapiens (human)
- Insulin resistance - Homo sapiens (human)
- Insulin signaling pathway - Homo sapiens (human)
- IGF-Ncore
- JAK-STAT-Ncore
Biological Process
- protein dephosphorylation
- activation of JUN kinase activity
- insulin receptor signaling pathway
- regulation of signal transduction
- negative regulation of signal transduction
Molecular Function
- RNA binding
- protein tyrosine phosphatase activity
- insulin receptor binding
- protein binding
- zinc ion binding
Cellular Component
- early endosome
- endoplasmic reticulum
- cytosol
- plasma membrane
- protein-containing complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000371621
- Coding exons
- 10
- Length
- 74409
- Individuals with no LoFs
- 125735
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 13
- Defined
- 125748
- p
- 0.0000517
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.79 | 129 | 254 | 0.507 | 0.0000145 | 2883 |
| Missense (PolyPhen) | 22 | 83.316 | 0.26406 | 893 | ||
| Synonymous | 0.413 | 96 | 101 | 0.948 | 0.00000653 | 783 |
| Loss of Function | 3.98 | 5 | 27.5 | 0.182 | 0.00000166 | 287 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.000062 | 0.000062 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Tyrosine-protein phosphatase which acts as a regulator of endoplasmic reticulum unfolded protein response. Mediates dephosphorylation of EIF2AK3/PERK; inactivating the protein kinase activity of EIF2AK3/PERK. May play an important role in CKII- and p60c-src-induced signal transduction cascades. May regulate the EFNA5-EPHA3 signaling pathway which modulates cell reorganization and cell-cell repulsion. May also regulate the hepatocyte growth factor receptor signaling pathway through dephosphorylation of MET. {ECO:0000269|PubMed:18819921, ECO:0000269|PubMed:21135139, ECO:0000269|PubMed:22169477}.;
Recessive Scores
- pRec
- 0.425
Intolerance Scores
- LoFtool
- 0.380
- RVIS EVS
- -0.36
- RVIS percentile EVS
- 29.16
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.996
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |