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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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PTPRF
protein tyrosine phosphatase receptor type F
Chromosome 1 · 1p34.2
NCBI Gene: 5792Ensembl: ENSG00000142949.19HGNC: HGNC:9670UniProt: G1UI20
138PubMed Papers
21Diseases
0Drugs
1Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedReceptor
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
cell migrationphosphoprotein phosphatase activityextracellular exosomeprotein bindingsmoking initiationbreasts and/or nipples, aplasia or hypoplasia of, 2attention deficit hyperactivity disorderrisk-taking behaviour
✦AI Summary

PTPRF (protein tyrosine phosphatase receptor type F) is a receptor-type protein tyrosine phosphatase with dual catalytic domains, where the first domain possesses enzymatic activity while the second modulates substrate specificity 1. The protein functions as a transmembrane signaling molecule involved in cell adhesion and cell-cell interactions, with roles in nervous system development and signal transduction 1. Mechanistically, PTPRF regulates phosphotyrosine levels through multiple pathways. It suppresses Wnt/β-catenin signaling in colorectal cancer by dephosphorylating LRP6 via clathrin-mediated endocytosis 2. PTPRF also negatively regulates EGFR phosphorylation in breast cancer, with its downregulation by miR-24 promoting tumor invasion and metastasis 3. In hepatocellular carcinoma, miR-647-mediated PTPRF inhibition activates ERK signaling, enhancing proliferation and invasion 4. Disease relevance encompasses both developmental and oncological contexts. PTPRF disruption causes syndromic amastia (breast aplasia/hypoplasia), implicating it in human mammary gland development 5. PTPRF variants are putatively causal for ADHD in fetal and adult cortical tissues 6 and are associated with reproductive-related disorders 7. Clinically, PTPRF functions as a tumor suppressor; PPARγ activation upregulates PTPRF to inhibit breast cancer progression, suggesting therapeutic potential through PTPRF restoration 8.

Sources cited
1
PTPRF structure with dual phosphatase domains, the second being evolutionarily conserved; its role in regulating phosphotyrosine levels through cell-cell/matrix interactions
PMID: 7665159
2
PTPRF suppresses Wnt signaling in colorectal cancer by dephosphorylating LRP6 via clathrin-mediated endocytosis
PMID: 32973331
3
miR-24 targets PTPRF to promote EGFR signaling and enhance breast cancer invasion, migration and metastasis
PMID: 23418360
4
miR-647 inhibits PTPRF to activate ERK signaling, promoting hepatocellular carcinoma cell proliferation, migration and invasion
PMID: 34969357
5
PTPRF disruption causes syndromic amastia (breast aplasia), indicating its role in human mammary gland development
PMID: 21453473
6
PTPRF is putatively causal for ADHD in fetal and adult cortical tissues
PMID: 40000109
7
PTPRF is linked to rare Mendelian reproductive-related disorders
PMID: 39672892
8
PPARγ upregulates PTPRF expression to inhibit breast cancer cell proliferation, migration, invasion and tumor growth
PMID: 31799666
Disease Associationsⓘ21
smoking initiationOpen Targets
0.46Moderate
breasts and/or nipples, aplasia or hypoplasia of, 2Open Targets
0.46Moderate
attention deficit hyperactivity disorderOpen Targets
0.44Moderate
risk-taking behaviourOpen Targets
0.40Weak
schizophreniaOpen Targets
0.39Weak
substance-related disorderOpen Targets
0.37Weak
isolated congenital breast hypoplasia/aplasiaOpen Targets
0.37Weak
intelligenceOpen Targets
0.35Weak
neurodegenerative diseaseOpen Targets
0.33Weak
smoking cessationOpen Targets
0.32Weak
HypermetropiaOpen Targets
0.31Weak
placenta praeviaOpen Targets
0.31Weak
balanoposthitisOpen Targets
0.30Weak
autism spectrum disorderOpen Targets
0.30Weak
Parkinson diseaseOpen Targets
0.29Weak
Alzheimer diseaseOpen Targets
0.28Weak
lysosomal storage diseaseOpen Targets
0.28Weak
multiple sclerosisOpen Targets
0.28Weak
health study participationOpen Targets
0.28Weak
Abnormality of refractionOpen Targets
0.27Weak
Aplasia or hypoplasia of the breasts and/or nipples 2UniProt
Pathogenic Variants1
NM_002840.5(PTPRF):c.1847_1848del (p.Val616fs)Pathogenic
Breasts and/or nipples, aplasia or hypoplasia of, 2
☆☆☆☆2014→ Residue 616
View on ClinVar ↗
Related Genes
IRS2Protein interaction100%PPFIA1Protein interaction100%IRS4Protein interaction98%LRRC4BProtein interaction98%CTNNB1Protein interaction98%INSRProtein interaction95%
Tissue Expression6 tissues
Liver
100%
Brain
36%
Ovary
23%
Lung
16%
Bone Marrow
7%
Heart
5%
Gene Interaction Network
Click a node to explore
PTPRFIRS2PPFIA1IRS4LRRC4BCTNNB1INSR
PROTEIN STRUCTURE
Preparing viewer…
PDB4N5U · 1.46 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.35Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.28 [0.22–0.35]
RankingsWhere PTPRF stands among ~20K protein-coding genes
  • #3,349of 20,598
    Most Researched138 · top quartile
  • #4,794of 5,498
    Most Pathogenic Variants1
  • #1,526of 17,882
    Most Constrained (LOEUF)0.35 · top 10%
Genes detectedPTPRF
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
The mouse gene Ptprf encoding the leukocyte common antigen-related molecule LAR: cloning, characterization, and chromosomal localization.
PMID: 7665159
Genomics · 1995
1.00
2
Unraveling ADHD: genes, co-occurring traits, and developmental dynamics.
PMID: 40000109
Life Sci Alliance · 2025
0.90
3
Genetics of female and male reproductive traits and their relationship with health, longevity and consequences for offspring.
PMID: 39672892
Nat Aging · 2024
0.80
4
Inhibition of protein tyrosine phosphatase receptor type F suppresses Wnt signaling in colorectal cancer.
PMID: 32973331
Oncogene · 2020
0.70
5
MicroRNA miR-24 enhances tumor invasion and metastasis by targeting PTPN9 and PTPRF to promote EGF signaling.
PMID: 23418360
J Cell Sci · 2013
0.60