PTPN11

protein tyrosine phosphatase non-receptor type 11

5 disorders 3 untyped 1 biomarker 1 unknown 12q24.13 gene with protein product

HGNC:9644 Monarch NCBI Gene 5781 ENSG00000179295 UniProt Q06124 OMIM 176876

Previous symbols: NS1. Aliases: BPTP3, SH-PTP2, SHP-2, PTP2C, SHP2.

Normal function · from ai-gene-review (Q06124, commit 79fe13b38970) · AI-generated, not KB evidence

PTPN11 encodes SHP2, a widely expressed soluble non-receptor protein tyrosine phosphatase. Its tandem N-terminal SH2 domains both autoinhibit the catalytic PTP domain and recruit SHP2 to phosphotyrosine-containing receptors and adaptors, where ligand binding activates tyrosine dephosphorylation. SHP2 also has phosphotyrosine-dependent molecular-adaptor and scaffolding activities. These coupled functions commonly promote RAS-ERK output downstream of receptor tyrosine kinases, while producing inhibitory effects in selected immune-receptor pathways. PTPN11 is required in many developmental and homeostatic contexts, and altered catalytic regulation causes RASopathy syndromes and contributes to malignancy.

SH2-recruited non-receptor protein tyrosine phosphatase activity that dephosphorylates receptor-proximal proteins and frequently promotes RAS-ERK output by removing inhibitory phosphotyrosines.

molecular function: non-membrane spanning protein tyrosine phosphatase activity · directly involved in: peptidyl-tyrosine dephosphorylation; positive regulation of ERK1 and ERK2 cascade · locations: cytosol

Tandem-SH2-domain phosphotyrosine binding that relieves autoinhibition and recruits SHP2 to activated receptors and docking proteins.

molecular function: phosphotyrosine residue binding · directly involved in: positive regulation of ERK1 and ERK2 cascade · locations: cytosol

Phosphotyrosine-dependent molecular-adaptor and scaffolding activity that assembles receptor-proximal signaling proteins independently of direct substrate dephosphorylation.

molecular function: molecular adaptor activity · locations: cytosol

In the knowledge base · computed from kb/ at build time

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.

Disorder	Relationship	Where the gene appears
Acute Megakaryoblastic Leukemia	biomarker somatic	mechanism: Adult Adverse Genomic Landscape and Therapy Resistance scoped to subtype: Adult AMKL
Vein of Galen malformation	unknown	mechanism: Dysregulated Endothelial Developmental Signaling
Juvenile Myelomonocytic Leukemia	untyped Somatic activating mutation	scoped to subtype: PTPN11-mutated
Noonan Syndrome	untyped Pathogenic Variants	mechanism: Neural Crest Cell Developmental Dysregulation; SHP2 Gain-of-Function Activation subtype: NS1; Noonan Syndrome with Multiple Lentigines animal model: Chick neural tube electroporation of PTPN11 variants; Mouse scoped to subtype: NS1
Noonan Syndrome with Multiple Lentigines	untyped Pathogenic Variants	mechanism: Catalytically-Impaired SHP2 Phosphatase (Dominant-Negative) subtype: LPRD1

ClinGen gene–disease validity · snapshot 2026-10-03 · matched to entries by MONDO

An entry matches when ClinGen's MONDO disease is the entry's own disease term, a subtype term, or an exact-match mapping. An amber status marks an entry ClinGen supports the gene for (Definitive, Strong or Moderate) whose own record does not type it. A Limited, Disputed or Refuted tier on such an entry is not a gap.

ClinGen disease	MOI	Classification	dismech entry
Noonan syndrome with multiple lentigines MONDO:0007893	AD	Definitive 2018-07-25	Noonan Syndrome untyped Noonan Syndrome with Multiple Lentigines untyped
Costello syndrome MONDO:0009026	AD	Disputed 2018-05-31	Costello Syndrome not named
cardiofaciocutaneous syndrome MONDO:0015280	AD	Disputed 2018-05-30	Cardiofaciocutaneous Syndrome not named
Noonan syndrome MONDO:0018997	AD	Definitive 2018-07-24	Noonan Syndrome untyped

Identity from HGNC (snapshot 2026-10-01). Page layers are described in the gene pages documentation.