PTPN18
protein-codingprotein tyrosine phosphatase non-receptor type 18, the group of Protein tyrosine phosphatases non-receptor type
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, the mitotic cycle, and oncogenic transformation. This PTP contains a PEST motif, which often serves as a protein-protein interaction domain, and may be related to protein intracellular half-live. This protein can differentially dephosphorylate autophosphorylated tyrosine kinases that are overexpressed in tumor tissues, and it appears to regulate HER2, a member of the epidermal growth factor receptor family of receptor tyrosine kinases. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~19.4 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 PTPN18 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_014369.4. 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 | 5 | 5 | ||||
| missense | 96 | 1 | 97 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 8 | 8 | ||||
| Total | 0 | 0 | 109 | 1 | 0 | 110 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_055184.2 | 15 | MANE Select | |
| Ensembl | ENSP00000175756.5 | 15 | MANE Select | |
| RefSeq | NP_001135842.1 | 11 | Standard | |
| Ensembl | ENSP00000310092.5 | 11 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- B Cell Receptor Signaling Pathway
- Signal Transduction
- Fibroblast growth factor-1
- BCR
- Downregulation of ERBB2 signaling
Biological Process
- blastocyst formation
- protein dephosphorylation
- peptidyl-tyrosine dephosphorylation
- ERBB2 signaling pathway
- cellular response to cytokine stimulus
Molecular Function
- protein tyrosine phosphatase activity
- non-membrane spanning protein tyrosine phosphatase activity
- protein binding
Cellular Component
- nucleoplasm
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000175756
- Coding exons
- 15
- Length
- 19403
- Individuals with no LoFs
- 125632
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 116
- Defined
- 125748
- p
- 0.000461
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.332 | 241 | 256 | 0.942 | 0.0000160 | 2934 |
| Missense (PolyPhen) | 85 | 94.173 | 0.90259 | 1040 | ||
| Synonymous | 0.497 | 96 | 102 | 0.937 | 0.00000644 | 928 |
| Loss of Function | 1.62 | 18 | 27.1 | 0.664 | 0.00000141 | 298 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00037 | 0.00037 | rare |
| Latino/Admixed American | 0.00055 | 0.00055 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.00023 | 0.00023 | rare |
| European (Non-Finnish) | 0.00017 | 0.00017 | rare |
| South Asian | 0.0021 | 0.0021 | notable |
| Other | 0.00049 | 0.00049 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Differentially dephosphorylate autophosphorylated tyrosine kinases which are known to be overexpressed in tumor tissues.;
Recessive Scores
- pRec
- 0.116
Intolerance Scores
- LoFtool
- 0.414
- RVIS EVS
- -0.22
- RVIS percentile EVS
- 37.43
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.0457
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |