protein
Tyrosine-protein phosphatase non-receptor type 11
Gene
PTPN11
Organism
Homo sapiens(9606)
Length
593 aa
Mass
68,011 Da
PTPN11 encodes tyrosine-protein phosphatase non-receptor type 11, a protein that acts downstream of receptor and cytoplasmic tyrosine kinases to regulate signal transduction from the cell surface to the nucleus (UniProt: Q06124). It positively regulates MAPK signaling and dephosphorylates multiple substrates including GAB1, EGFR, ROCK2, and components of T-cell receptor signaling pathways, thereby modulating immune responses and developmental processes.
PTPN11 is implicated in several syndromic developmental disorders. Mutations cause Noonan syndrome 1, characterized by short stature, facial dysmorphic features, congenital heart defects, and variable intellectual deficits; LEOPARD syndrome 1, featuring lentigines and sensorineural deafness; and predisposition to juvenile myelomonocytic leukemia (UniProt: Q06124). The protein also associates with metachondromatosis, a skeletal disorder combining exostoses and enchondromas.
PTPN11 carries SFARI classification as a syndromic autism-associated gene (SFARI Cat S). This designation reflects its role in neurodevelopmental pathology, though the primary clinical manifestations in PTPN11-related disorders span cardiac, skeletal, hematologic, and intellectual domains alongside autism spectrum features in affected individuals.
Generated from the curated entity record below. May contain errors — verify against source links.
Proteomics Evidence · AD
↑ Up in ADP3
+0.819
P2
not detected
S2
not detected
S3
not detected
Mean log₂FC across detected fractions: +0.8189 (1 of 4 fractions detected)
Human post-mortem AD brain vs age-matched controls, TMT-labeled, 4 subcellular fractions (P2, P3, S2, S3), DDA proteomics.
Genetic Evidence · ASD
Source: SFARI Gene database · gene.sfari.org
This protein is implicated in both ASD and Alzheimer's Disease. View all cross-disease proteins →
Related Publications
Browse all →Tau molecular diversity contributes to clinical heterogeneity in Alzheimer's disease.
Dujardin Simon et al.Nature medicine2020PMID 32572268Deep Multilayer Brain Proteomics Identifies Molecular Networks in Alzheimer's Disease Progression.
Bai Bing et al.Neuron2020PMID 31926610A Multi-network Approach Identifies Protein-Specific Co-expression in Asymptomatic and Symptomatic Alzheimer's Disease.
Seyfried Nicholas T et al.Cell systems2017PMID 27989508Large-scale deep multi-layer analysis of Alzheimer's disease brain reveals strong proteomic disease-related changes not observed at the RNA level.
Johnson Erik C B et al.Nature neuroscience2022PMID 35115731Organization and regulation of gene transcription.
Cramer PatrickNature2019PMID 31462772Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.
Ruzzo Elizabeth K et al.Cell2019PMID 31398340Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model.
Guo Hui et al.Molecular autism2018PMID 30564305Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder.
C Yuen Ryan K et al.Nature neuroscience2017PMID 28263302Identification of common genetic risk variants for autism spectrum disorder.
Grove Jakob et al.Nature genetics2019PMID 30804558Synaptic, transcriptional and chromatin genes disrupted in autism.
De Rubeis Silvia et al.Nature2014PMID 25363760
Function
Acts downstream of various receptor and cytoplasmic protein tyrosine kinases to participate in the signal transduction from the cell surface to the nucleus (PubMed:10655584, PubMed:14739280, PubMed:18559669, PubMed:18829466, PubMed:26742426, PubMed:28074573, PubMed:32184441). Positively regulates MAPK signal transduction pathway (PubMed:28074573). Dephosphorylates GAB1, ARHGAP35 and EGFR (PubMed:28074573). Dephosphorylates ROCK2 at 'Tyr-722' resulting in stimulation of its RhoA binding activity (PubMed:18559669). Dephosphorylates CDC73 (PubMed:26742426). Dephosphorylates SOX9 on tyrosine residues, leading to inactivate SOX9 and promote ossification (By similarity). Dephosphorylates tyrosine-phosphorylated NEDD9/CAS-L (PubMed:19275884). Acts as an effector of PDCD1-mediated inhibition of T-cell response: recruited by phosphorylated PDCD1, mediating dephosphorylation of key T-cell receptor (TCR) proximal signaling molecules, leading to TCR signaling inhibition (PubMed:32184441)
Disease associations
LEOPARD syndrome 1LPRD1
A disorder characterized by lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormalities of genitalia, retardation of growth, and sensorineural deafness.
Noonan syndrome 1NS1
A form of Noonan syndrome, a disease characterized by short stature, facial dysmorphic features such as hypertelorism, a downward eyeslant and low-set posteriorly rotated ears, and a high incidence of congenital heart defects and hypertrophic cardiomyopathy. Other features can include a short neck with webbing or redundancy of skin, deafness, motor delay, variable intellectual deficits, multiple skeletal defects, cryptorchidism, and bleeding diathesis. Individuals with Noonan syndrome are at risk of juvenile myelomonocytic leukemia, a myeloproliferative disorder characterized by excessive production of myelomonocytic cells. Some patients with NS1 develop multiple giant cell lesions of the jaw or other bony or soft tissues, which are classified as pigmented villonodular synovitis (PVNS) when occurring in the jaw or joints.
Leukemia, juvenile myelomonocyticJMML
An aggressive pediatric myelodysplastic syndrome/myeloproliferative disorder characterized by malignant transformation in the hematopoietic stem cell compartment with proliferation of differentiated progeny. Patients have splenomegaly, enlarged lymph nodes, rashes, and hemorrhages.
MetachondromatosisMC
A skeletal disorder with radiologic features of both multiple exostoses and Ollier disease, characterized by the presence of exostoses, commonly of the bones of the hands and feet, and enchondromas of the metaphyses of long bones and iliac crest.
Sources
Last updated 5/8/2026, 1:11:04 AM