PTPN3
protein-codingprotein tyrosine phosphatase non-receptor type 3, the group of Protein tyrosine phosphatases non-receptor type|FERM domain containing|PDZ domain containing|MicroRNA protein coding host genes
Gene summary
The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This protein contains a C-terminal PTP domain and an N-terminal domain homologous to the band 4.1 superfamily of cytoskeletal-associated proteins. P97, a cell cycle regulator involved in a variety of membrane related functions, has been shown to be a substrate of this PTP. This PTP was also found to interact with, and be regulated by adaptor protein 14-3-3 beta. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2009]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~122.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: Unknown
Disease ID:MONDO:0005090
Submitter: Labcorp Genetics (formerly Invitae)
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PTPN3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002829.4. 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 | 3 | 3 | 1 | 7 | ||
| missense | 143 | 3 | 146 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 7 | 7 | ||||
| Total | 0 | 0 | 154 | 6 | 1 | 161 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002820.3 | 25 | MANE Select | |
| Ensembl | ENSP00000363667.1 | 25 | MANE Select | |
| RefSeq | NP_001138840.1 | 24 | Standard | |
| RefSeq | NP_001138841.1 | 21 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Signal Transduction
- TCR
- EGFR downregulation
- Signaling by EGFR
- Signaling by Receptor Tyrosine Kinases
Biological Process
- protein dephosphorylation
- peptidyl-tyrosine dephosphorylation
- negative regulation of epidermal growth factor receptor signaling pathway
- negative regulation of mitotic cell cycle
- negative regulation of membrane protein ectodomain proteolysis
Molecular Function
- phosphotyrosine residue binding
- protein tyrosine phosphatase activity
- protein binding
- cytoskeletal protein binding
- sodium channel regulator activity
Cellular Component
- cytoplasm
- cytoskeleton
- plasma membrane
- cytoplasmic side of plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000374541
- Coding exons
- 25
- Length
- 122845
- Individuals with no LoFs
- 125680
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 68
- Defined
- 125748
- p
- 0.000270
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.706 | 495 | 541 | 0.915 | 0.0000322 | 5999 |
| Missense (PolyPhen) | 188 | 221.52 | 0.84867 | 2398 | ||
| Synonymous | -0.259 | 214 | 209 | 1.02 | 0.0000135 | 1716 |
| Loss of Function | 4.31 | 25 | 61.5 | 0.407 | 0.00000369 | 649 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00043 | 0.00043 | rare |
| Latino/Admixed American | 0.00032 | 0.00032 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0.00040 | 0.00038 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00026 | 0.00026 | rare |
| South Asian | 0.00027 | 0.00026 | rare |
| Other | 0.00050 | 0.00049 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May act at junctions between the membrane and the cytoskeleton. Possesses tyrosine phosphatase activity.;
Recessive Scores
- pRec
- 0.609
Intolerance Scores
- LoFtool
- 0.286
- RVIS EVS
- -1.17
- RVIS percentile EVS
- 6.07
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.851
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |