PTPRF
protein-codingprotein tyrosine phosphatase receptor type F, the group of Fibronectin type III domain containing|I-set domain containing|Protein tyrosine phosphatases 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, mitotic cycle, and oncogenic transformation. This PTP possesses an extracellular region, a single transmembrane region, and two tandem intracytoplasmic catalytic domains, and thus represents a receptor-type PTP. The extracellular region contains three Ig-like domains, and nine non-Ig like domains similar to that of neural-cell adhesion molecule. This PTP was shown to function in the regulation of epithelial cell-cell contacts at adherents junctions, as well as in the control of beta-catenin signaling. An increased expression level of this protein was found in the insulin-responsive tissue of obese, insulin-resistant individuals, and may contribute to the pathogenesis of insulin resistance. Two alternatively spliced transcript variants of this gene, which encode distinct proteins, have been reported. [provided by RefSeq, Jul 2008]
- LAR
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~98.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0014450
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0014450
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Dermatologic; Endocrine
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PTPRF variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002840.5. 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 | 6 | 46 | 6 | 58 | ||
| missense | 269 | 15 | 4 | 288 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | 1 | 3 | ||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 1 | 1 | 281 | 61 | 10 | 354 |
Highest pathogenic variant AF is 7.758012e-7
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002831.2 | 32 | MANE Select | |
| Ensembl | ENSP00000353030.4 | 32 | MANE Select | |
| RefSeq | NP_001316066.1 | 32 | Standard | |
| RefSeq | NP_001316067.1 | 34 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| ptprfb | Danio rerio | Structure: Rohon-Beard neuron Quality: subdermal abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Cell adhesion molecules (CAMs) - Homo sapiens (human)
- Adherens junction - Homo sapiens (human)
- Insulin resistance - Homo sapiens (human)
- Insulin signaling pathway - Homo sapiens (human)
- miR-targeted genes in epithelium - TarBase
Biological Process
- cell adhesion
- transmembrane receptor protein tyrosine phosphatase signaling pathway
- cell migration
- neuron projection regeneration
- peptidyl-tyrosine dephosphorylation
Molecular Function
- protein tyrosine phosphatase activity
- transmembrane receptor protein tyrosine phosphatase activity
- heparin binding
- chondroitin sulfate proteoglycan binding
- protein-containing complex binding
Cellular Component
- plasma membrane
- integral component of plasma membrane
- neuron projection
- neuronal cell body
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000359947
- Coding exons
- 32
- Length
- 98486
- Individuals with no LoFs
- 125728
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 20
- Defined
- 125748
- p
- 0.0000795
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.80 | 990 | 1.27e+3 | 0.779 | 0.0000882 | 12310 |
| Missense (PolyPhen) | 343 | 572.93 | 0.59868 | 5540 | ||
| Synonymous | -0.596 | 555 | 537 | 1.03 | 0.0000401 | 3928 |
| Loss of Function | 7.86 | 10 | 90.8 | 0.110 | 0.00000458 | 955 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00018 | 0.00018 | rare |
| Latino/Admixed American | 0.00014 | 0.00012 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000062 | 0.000062 | rare |
| South Asian | 0.00020 | 0.00020 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Possible cell adhesion receptor. It possesses an intrinsic protein tyrosine phosphatase activity (PTPase) and dephosphorylates EPHA2 regulating its activity.;
- Disease
- DISEASE: Aplasia or hypoplasia of the breasts and/or nipples 2 (BNAH2) [MIM:616001]: A group of congenital deformities encompassing total absence of breasts and nipple (amastia), absence of the nipple (athelia), and absence of the mammary gland (amazia). {ECO:0000269|PubMed:24781087}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.142
Intolerance Scores
- LoFtool
- 0.330
- RVIS EVS
- -3.92
- RVIS percentile EVS
- 0.2
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.977
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |