PTPN13
protein-codingprotein tyrosine phosphatase non-receptor type 13, the group of Protein tyrosine phosphatases non-receptor type|PDZ domain containing|FERM domain containing
Gene summary
The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP is a large intracellular protein. It has a catalytic PTP domain at its C-terminus and two major structural domains: a region with five PDZ domains and a FERM domain that binds to plasma membrane and cytoskeletal elements. This PTP was found to interact with, and dephosphorylate, Fas receptor and IkappaBalpha through the PDZ domains. This suggests it has a role in Fas mediated programmed cell death. This PTP was also shown to interact with GTPase-activating protein, and thus may function as a regulator of Rho signaling pathways. Four alternatively spliced transcript variants, which encode distinct proteins, have been reported. [provided by RefSeq, Oct 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~220.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0000159
Submitter: PanelApp Australia
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PTPN13 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_080683.3. 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 | 6 | 4 | 1 | 11 | ||
| missense | 366 | 22 | 4 | 392 | ||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 9 | 9 | ||||
| Total | 0 | 0 | 384 | 26 | 5 | 415 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_542414.1 | 47 | MANE Select | |
| Ensembl | ENSP00000407249.2 | 47 | MANE Select | |
| RefSeq | NP_006255.1 | 46 | Standard | |
| RefSeq | NP_542415.1 | 44 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Apoptosis - Homo sapiens (human)
- Apoptosis Modulation and Signaling
- Ectoderm Differentiation
- Metabolism of lipids
- Metabolism
Biological Process
- protein dephosphorylation
- phosphatidylinositol biosynthetic process
- regulation of phosphatidylinositol 3-kinase signaling
- peptidyl-tyrosine dephosphorylation
- cellular response to cytokine stimulus
Molecular Function
- protein tyrosine phosphatase activity
- protein binding
- phosphatidylinositol 3-kinase regulatory subunit binding
Cellular Component
- nucleus
- nucleoplasm
- cytoplasm
- cytoskeleton
- plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000436978
- Coding exons
- 47
- Length
- 220857
- Individuals with no LoFs
- 124574
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 115
- Defined
- 124689
- p
- 0.000461
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.576 | 1174 | 1.23e+3 | 0.954 | 0.0000619 | 16206 |
| Missense (PolyPhen) | 453 | 510.83 | 0.8868 | 6731 | ||
| Synonymous | 0.461 | 431 | 443 | 0.972 | 0.0000225 | 4743 |
| Loss of Function | 4.83 | 61 | 118 | 0.519 | 0.00000617 | 1570 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00013 | 0.00013 | rare |
| Latino/Admixed American | 0.00077 | 0.00075 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00062 | 0.00061 | rare |
| Finnish | 0.00047 | 0.00046 | rare |
| European (Non-Finnish) | 0.00050 | 0.00049 | rare |
| South Asian | 0.00027 | 0.00026 | rare |
| Other | 0.00050 | 0.00050 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Tyrosine phosphatase which regulates negatively FAS- induced apoptosis and NGFR-mediated pro-apoptotic signaling (PubMed:15611135). May regulate phosphoinositide 3-kinase (PI3K) signaling through dephosphorylation of PIK3R2 (PubMed:23604317). {ECO:0000269|PubMed:15611135, ECO:0000269|PubMed:23604317}.;
Recessive Scores
- pRec
- 0.176
Intolerance Scores
- LoFtool
- 0.839
- RVIS EVS
- 1.3
- RVIS percentile EVS
- 93.89
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.804
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |