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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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PTPN4
protein tyrosine phosphatase non-receptor type 4
Chromosome 2 Β· 2q14.2
NCBI Gene: 5775Ensembl: ENSG00000088179.10HGNC: HGNC:9656UniProt: P29074
42PubMed Papers
20Diseases
0Drugs
12Pathogenic Variants
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
cytoplasmcytoplasmic side of plasma membraneprotein bindingprotein tyrosine phosphatase activityneurodegenerative diseasegenetic disorderIntellectual disabilityNeurodevelopmental disorder
✦AI Summary

PTPN4 (protein tyrosine phosphatase non-receptor type 4) is a non-receptor protein tyrosine phosphatase that functions primarily as an anti-apoptotic regulator and immunomodulatory protein. The protein consists of two globular domains - a PDZ domain and a phosphatase domain - connected by a flexible linker that regulates phosphatase activity 1. PTPN4 protects neurons against apoptosis by regulating neuronal cell homeostasis 1. In immune signaling, PTPN4 negatively regulates TLR4-induced interferon beta production by dephosphorylating adapter TICAM2, thereby inhibiting TRAM-TRIF interactions 1. The protein shows tumor suppressor activity in multiple cancers - it is inversely associated with multiple myeloma risk 2, and its degradation by E3 ubiquitin ligase MARCH8 promotes pancreatic cancer growth and metastasis through STAT3 activation 3. PTPN4 also serves as a target for high-risk HPV E6 oncoproteins, which bind to its PDZ domain potentially contributing to viral pathogenesis 4. Additionally, circRNA-PTPN4 regulates blood-brain barrier integrity and cognitive function in uremic encephalopathy by modulating FOXO3 and ZO-1 expression 5. These findings highlight PTPN4's diverse roles in neuroprotection, immune regulation, and cancer suppression.

Sources cited
1
PTPN4 structure consists of PDZ and phosphatase domains connected by a regulatory linker, and functions in preventing cell death and apoptosis
PMID: 28801650
2
PTPN4 is inversely associated with multiple myeloma risk
PMID: 37775746
3
PTPN4 degradation by MARCH8 promotes pancreatic cancer through STAT3 activation
PMID: 37747937
4
PTPN4 PDZ domain serves as a binding target for HPV E6 oncoproteins
PMID: 35089587
5
circRNA-PTPN4 regulates blood-brain barrier function and cognitive abilities in uremic encephalopathy
PMID: 38630149
Disease Associationsβ“˜20
neurodegenerative diseaseOpen Targets
0.54Moderate
genetic disorderOpen Targets
0.45Moderate
Intellectual disabilityOpen Targets
0.43Moderate
Neurodevelopmental disorderOpen Targets
0.42Moderate
Dupuytren ContractureOpen Targets
0.41Moderate
placenta praeviaOpen Targets
0.38Weak
Palmar FibromatosisOpen Targets
0.29Weak
smoking initiationOpen Targets
0.28Weak
fasciitisOpen Targets
0.28Weak
scoliosisOpen Targets
0.24Weak
severe acute respiratory syndromeOpen Targets
0.17Weak
COVID-19Open Targets
0.17Weak
rectum cancerOpen Targets
0.08Suggestive
posterior cortical atrophyOpen Targets
0.07Suggestive
neoplasmOpen Targets
0.06Suggestive
oral squamous cell carcinomaOpen Targets
0.05Suggestive
colorectal cancerOpen Targets
0.04Suggestive
colorectal carcinomaOpen Targets
0.03Suggestive
Rett syndromeOpen Targets
0.03Suggestive
liver cancerOpen Targets
0.03Suggestive
Pathogenic Variants12
NM_002830.4(PTPN4):c.745C>T (p.Arg249Ter)Pathogenic
Inborn genetic diseases|PTPN4-related disorder
β˜…β˜…β˜†β˜†2024β†’ Residue 249
NM_002830.4(PTPN4):c.191T>A (p.Leu64Ter)Pathogenic
Inborn genetic diseases
β˜…β˜†β˜†β˜†2025β†’ Residue 64
NM_002830.4(PTPN4):c.16C>T (p.Arg6Ter)Likely pathogenic
Inborn genetic diseases
β˜…β˜†β˜†β˜†2025β†’ Residue 6
NM_002830.4(PTPN4):c.64C>T (p.Arg22Ter)Likely pathogenic
Inborn genetic diseases
β˜…β˜†β˜†β˜†2025β†’ Residue 22
NM_002830.4(PTPN4):c.538C>T (p.Gln180Ter)Likely pathogenic
PTPN4-related aberrant neurodevelopment and growth
β˜…β˜†β˜†β˜†2024β†’ Residue 180
NM_002830.4(PTPN4):c.629del (p.Thr210fs)Likely pathogenic
PTPN4-related Neurodevelopmental Disorder
β˜…β˜†β˜†β˜†2023β†’ Residue 210
NM_002830.4(PTPN4):c.149del (p.Gln50fs)Likely pathogenic
Neurodevelopmental disorder
β˜…β˜†β˜†β˜†2023β†’ Residue 50
NM_002830.4(PTPN4):c.2338C>T (p.Gln780Ter)Pathogenic
Neurodevelopmental disorder
β˜…β˜†β˜†β˜†2023β†’ Residue 780
NM_002830.4(PTPN4):c.246+1G>TLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2022
NM_002830.4(PTPN4):c.138+2T>CLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2022
NM_002830.4(PTPN4):c.1355+1G>ALikely pathogenic
not provided|Papillary renal cell carcinoma type 1
β˜…β˜†β˜†β˜†2022
NM_002830.4(PTPN4):c.1738G>T (p.Asp580Tyr)Likely pathogenic
Intellectual disability
β˜†β˜†β˜†β˜†β†’ Residue 580
View on ClinVar β†—
Related Genes
PPM1MShared pathway100%PTPN5Shared pathway100%CTDSP1Shared pathway100%DAPP1Shared pathway100%PTPN18Shared pathway100%CTDSP2Shared pathway100%
Tissue Expression6 tissues
Brain
100%
Heart
84%
Bone Marrow
47%
Ovary
46%
Lung
36%
Liver
36%
Gene Interaction Network
Click a node to explore
PTPN4PPM1MPTPN5CTDSP1DAPP1PTPN18CTDSP2
PROTEIN STRUCTURE
Preparing viewer…
PDB3NFK Β· 1.43 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.50Moderately Constrained
pLIβ“˜
0.95Intolerant
Observed/Expected LoF0.38 [0.29–0.50]
RankingsWhere PTPN4 stands among ~20K protein-coding genes
  • #9,933of 20,598
    Most Researched42
  • #2,700of 5,498
    Most Pathogenic Variants12
  • #2,955of 17,882
    Most Constrained (LOEUF)0.50 Β· top quartile
Genes detectedPTPN4
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Recent advances in adipose-derived mesenchymal stem cell-derived exosomes for regulating macrophage polarization.
PMID: 39963133
Front Immunol Β· 2025
1.00
2
Regulation of the Human Phosphatase PTPN4 by the inter-domain linker connecting the PDZ and the phosphatase domains.
PMID: 28801650
Sci Rep Β· 2017
0.90
3
Structural and biochemical analysis of the PTPN4 PDZ domain bound to the C-terminal tail of the human papillomavirus E6 oncoprotein.
PMID: 35089587
J Microbiol Β· 2022
0.80
4
PTPN3 and PTPN4 tyrosine phosphatase expression in human gastric adenocarcinoma.
PMID: 16619586
Anticancer Res Β· 2006
0.70
5
Integrating plasma proteomes with genome-wide association data for causal protein identification in multiple myeloma.
PMID: 37775746
BMC Med Β· 2023
0.60