PTPN11

protein tyrosine phosphatase non-receptor type 11, the group of Protein tyrosine phosphatases non-receptor type|SH2 domain containing

Basic information

Region (hg38): 12:112418350-112509918

Previous symbols: [ "NS1" ]

Links

ENSG00000179295 ∙ NCBI:5781 ∙ OMIM:176876 ∙ HGNC:9644 ∙ Uniprot:Q06124 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• LEOPARD syndrome 1 (Definitive), mode of inheritance: AD
• Noonan syndrome 1 (Definitive), mode of inheritance: AD
• LEOPARD syndrome 1 (Definitive), mode of inheritance: AD
• Noonan syndrome 1 (Definitive), mode of inheritance: AD
• metachondromatosis (Strong), mode of inheritance: AD
• Noonan syndrome 1 (Definitive), mode of inheritance: AD
• LEOPARD syndrome 1 (Strong), mode of inheritance: AD
• Noonan syndrome 1 (Strong), mode of inheritance: AD
• Noonan syndrome (Supportive), mode of inheritance: AD
• Noonan syndrome with multiple lentigines (Supportive), mode of inheritance: AD
• metachondromatosis (Supportive), mode of inheritance: AD
• Noonan syndrome 1 (Definitive), mode of inheritance: AD
• Noonan syndrome and Noonan-related syndrome (Definitive), mode of inheritance: AD
• metachondromatosis (Strong), mode of inheritance: AD
• LEOPARD syndrome 1 (Strong), mode of inheritance: AD
• Noonan syndrome 1 (Strong), mode of inheritance: AD
• Noonan syndrome (Definitive), mode of inheritance: AD
• Costello syndrome (Disputed Evidence), mode of inheritance: AD
• cardiofaciocutaneous syndrome (Disputed Evidence), mode of inheritance: AD
• Noonan syndrome with multiple lentigines (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Noonan syndrome 1; LEOPARD syndrome 1	AD	Cardiovascular; Hematologic; Oncologic; Renal	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Surveillance and treatment related to manifestations such as cardiac anomalies (which include pulmonic stenosis, hypertrophic cardiomyopathy, and arrhythmias) can be beneficial; The conditions can include bleeding diathesis, and recognition and preventive measures (eg, in surgical situations) can be beneficial; Individuals appear to be at increased risk for malignancy, and although specific surveillance may not be warranted, awareness may allow prompt detection and treatment; Awareness of increased risk of renal anomalies and hydronephrosis can allow prophylaxis and early and aggressive management of related manifestations (eg, infections)	Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Dermatologic; Genitourinary; Hematologic; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic; Renal	19994192; 5921856; 5638719; 5771505; 4672553; 4547387; 7193405; 6602353; 6539946; 345952; 9222968; 3232698; 11316696; 11344190; 11704759; 12058348; 11992261; 12634870; 12529711; 12717436; 15384080; 15240615; 15985475; 15956085; 15723289; 15690106; 16523510; 16263833; 16358218; 17497712; 18203203; 18678287; 18241070; 19273734; 19054014; 20602484; 20954246; 20979190; 20876176; 20577567; 20301303; 21533187; 20954246; 21407260; 21534355; 22315187; 23799168; 23813970; 23885229; 23918208; 24034393; 24444506

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PTPN11 gene.

• RASopathy (499 variants)
• not provided (327 variants)
• Noonan syndrome 1 (170 variants)
• Cardiovascular phenotype (165 variants)
• not specified (138 variants)
• LEOPARD syndrome 1 (122 variants)
• Metachondromatosis (115 variants)
• Noonan syndrome (100 variants)
• Noonan syndrome and Noonan-related syndrome (63 variants)
• Noonan syndrome 1;Juvenile myelomonocytic leukemia;LEOPARD syndrome 1;Metachondromatosis (24 variants)
• PTPN11-related condition (24 variants)
• Juvenile myelomonocytic leukemia (18 variants)
• Noonan syndrome with multiple lentigines (16 variants)
• Noonan syndrome 3 (15 variants)
• Inborn genetic diseases (14 variants)
• Juvenile myelomonocytic leukemia;Noonan syndrome 1;LEOPARD syndrome 1;Metachondromatosis (12 variants)
• Noonan syndrome 1;Juvenile myelomonocytic leukemia;Metachondromatosis;LEOPARD syndrome 1 (12 variants)
• PTPN11 Related Disorders (10 variants)
• Noonan syndrome 1;LEOPARD syndrome 1 (7 variants)
• Juvenile myelomonocytic leukemia;Noonan syndrome (6 variants)
• Noonan syndrome;Noonan syndrome with multiple lentigines (6 variants)
• See cases (5 variants)
• Neuroblastoma (5 variants)
• Metachondromatosis;Juvenile myelomonocytic leukemia;Noonan syndrome 1;LEOPARD syndrome 1 (5 variants)
• LEOPARD syndrome 1;Noonan syndrome 1;Juvenile myelomonocytic leukemia;Metachondromatosis (5 variants)
• Noonan syndrome 1;LEOPARD syndrome 1;Metachondromatosis (4 variants)
• Noonan syndrome 1;LEOPARD syndrome 1;Juvenile myelomonocytic leukemia;Metachondromatosis (4 variants)
• Juvenile myelomonocytic leukemia;Metachondromatosis;LEOPARD syndrome 1;Noonan syndrome 1 (4 variants)
• History of neurodevelopmental disorder (4 variants)
• Intellectual disability (3 variants)
• Neoplasm of the large intestine (3 variants)
• PTPN11-related disorder (3 variants)
• Juvenile myelomonocytic leukemia;Metachondromatosis;Noonan syndrome 1;LEOPARD syndrome 1 (3 variants)
• Multiple myeloma (3 variants)
• Non-immune hydrops fetalis (3 variants)
• Noonan syndrome;Juvenile myelomonocytic leukemia (3 variants)
• Astrocytoma (3 variants)
• Squamous cell lung carcinoma (3 variants)
• Noonan syndrome with multiple lentigines;Noonan syndrome (2 variants)
• Hypertrophic cardiomyopathy (2 variants)
• Acute myeloid leukemia (2 variants)
• B-cell chronic lymphocytic leukemia (2 variants)
• Neoplasm of brain (2 variants)
• Noonan syndrome 1;Metachondromatosis;Juvenile myelomonocytic leukemia;LEOPARD syndrome 1 (2 variants)
• Noonan syndrome 1;Metachondromatosis;LEOPARD syndrome 1;Juvenile myelomonocytic leukemia (2 variants)
• LEOPARD syndrome 1;Juvenile myelomonocytic leukemia;Noonan syndrome 1;Metachondromatosis (2 variants)
• Arrhythmogenic right ventricular cardiomyopathy (1 variants)
• 7 conditions (1 variants)
• Metachondromatosis;Juvenile myelomonocytic leukemia;LEOPARD syndrome 1;Noonan syndrome 1 (1 variants)
• Short stature;Abnormal cardiovascular system morphology (1 variants)
• LEOPARD syndrome 1;Juvenile myelomonocytic leukemia;Metachondromatosis;Noonan syndrome 1 (1 variants)
• Juvenile myelomonocytic leukemia;LEOPARD syndrome 1;Metachondromatosis;Noonan syndrome 1 (1 variants)
• Metachondromatosis;LEOPARD syndrome 1;Noonan syndrome 1;Juvenile myelomonocytic leukemia (1 variants)
• Thrombocytopenia;Abnormal bleeding (1 variants)
• Neurofibromatosis-Noonan syndrome (1 variants)
• Hereditary cancer-predisposing syndrome (1 variants)
• Premature ventricular contraction (1 variants)
• Primary dilated cardiomyopathy;Cardiomyopathy (1 variants)
• Metachondromatosis;Noonan syndrome 1;LEOPARD syndrome 1;Juvenile myelomonocytic leukemia (1 variants)
• Proportionate short stature (1 variants)
• Neurodevelopmental disorder (1 variants)
• CBL-related disorder (1 variants)
• Acute megakaryoblastic leukemia in down syndrome (1 variants)
• Pectus excavatum;Ptosis;Global developmental delay;Microcephaly;Brachycephaly (1 variants)
• Cardio-facio-cutaneous syndrome (1 variants)
• Neurodevelopmental abnormality (1 variants)
• Ventricular tachycardia (1 variants)
• Lymphoma;B lymphoblastic leukemia lymphoma, no ICD-O subtype (1 variants)
• Malignant neoplastic disease (1 variants)
• Autism spectrum disorder (1 variants)
• Metachondromatosis;LEOPARD syndrome 1;Juvenile myelomonocytic leukemia;Noonan syndrome 1 (1 variants)
• 6 conditions (1 variants)
• Scoliosis;Specific learning disability;Cafe-au-lait spot;Abnormal facial shape;Intellectual disability, mild (1 variants)
• Strabismus;Short stature;Abnormal facial shape (1 variants)
• Noonan syndrome 1;LEOPARD syndrome 1;Metachondromatosis;Juvenile myelomonocytic leukemia (1 variants)
• Early T cell progenitor acute lymphoblastic leukemia (1 variants)
• Werner syndrome (1 variants)
• Metachondromatosis;Noonan syndrome 1;Juvenile myelomonocytic leukemia;LEOPARD syndrome 1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PTPN11 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous		1	7	120	6	134
missense	67	60	240	3	5	375
nonsense	8	3				11
start loss						0
frameshift	9	1				10
inframe indel	2	2	2			6
splice donor/acceptor (+/-2bp)		6	2			8
splice region			14	20	1	35
non coding			56	95	45	196
Total	86	73	307	218	56

Highest pathogenic variant AF is 0.0000329

Variants in PTPN11

This is a list of pathogenic ClinVar variants found in the PTPN11 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
12-112418795-C-G		Noonan syndrome 1 • LEOPARD syndrome 1 • Metachondromatosis	Uncertain significance (Jan 13, 2018)
12-112418795-C-T		RASopathy	Benign/Likely benign (Jun 01, 2023)
12-112418821-G-A		Metachondromatosis • Noonan syndrome 1 • LEOPARD syndrome 1	Uncertain significance (Jan 13, 2018)
12-112418825-G-C		Metachondromatosis • LEOPARD syndrome 1 • Noonan syndrome 1	Benign/Likely benign (Jan 12, 2018)
12-112418839-G-A		Noonan syndrome 1 • Metachondromatosis • LEOPARD syndrome 1 • RASopathy • Noonan syndrome 1;Juvenile myelomonocytic leukemia;Metachondromatosis;LEOPARD syndrome 1	Benign (Jan 19, 2024)
12-112418867-C-G		LEOPARD syndrome 1 • Noonan syndrome 1 • Metachondromatosis	Uncertain significance (Jan 12, 2018)
12-112418933-G-C		Noonan syndrome 1 • Metachondromatosis • LEOPARD syndrome 1	Uncertain significance (Jan 12, 2018)
12-112418936-G-T		Noonan syndrome 1 • Metachondromatosis • LEOPARD syndrome 1	Uncertain significance (Jan 12, 2018)
12-112418951-T-A		Metachondromatosis • LEOPARD syndrome 1 • Noonan syndrome 1	Uncertain significance (Jan 13, 2018)
12-112418961-C-A		LEOPARD syndrome 1 • Noonan syndrome 1 • Metachondromatosis	Uncertain significance (Jan 12, 2018)
12-112418973-G-A		LEOPARD syndrome 1 • Noonan syndrome 1 • Metachondromatosis	Uncertain significance (Jan 12, 2018)
12-112419035-G-A		Metachondromatosis • LEOPARD syndrome 1 • Noonan syndrome 1	Uncertain significance (Jan 13, 2018)
12-112419041-C-T		Noonan syndrome 1 • Metachondromatosis • LEOPARD syndrome 1	Uncertain significance (Jan 13, 2018)
12-112419067-T-G		not specified	Benign (Aug 27, 2013)
12-112419079-G-A			Benign (Mar 03, 2015)
12-112419099-G-A		not specified	Conflicting classifications of pathogenicity (Jun 13, 2023)
12-112419105-G-A		not specified	Uncertain significance (Jul 09, 2023)
12-112419116-C-T		Noonan syndrome 1 • Noonan syndrome • Metachondromatosis • RASopathy • LEOPARD syndrome 1;Metachondromatosis;Juvenile myelomonocytic leukemia;Noonan syndrome 1 • See cases	Pathogenic/Likely pathogenic (Feb 13, 2024)
12-112419117-A-G		RASopathy • Cardiovascular phenotype	Likely benign (Sep 08, 2023)
12-112419121-C-A		RASopathy	Likely benign (Aug 23, 2022)
12-112419121-C-G			Conflicting classifications of pathogenicity (Sep 08, 2023)
12-112419122-G-A		RASopathy	Uncertain significance (May 13, 2023)
12-112419131-G-A		RASopathy	Uncertain significance (Sep 23, 2022)
12-112419131-G-T		RASopathy	Uncertain significance (Mar 19, 2022)
12-112419133-G-C		RASopathy	Likely benign (May 08, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PTPN11	protein_coding	protein_coding	ENST00000351677	15	91563

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.0000181	123755	0	1	123756	0.00000404

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.13	171	331	0.516	0.0000198	3938
Missense in Polyphen		50	129.77	0.38529		1662
Synonymous	0.824	112	124	0.906	0.00000824	1070
Loss of Function	5.34	1	35.2	0.0284	0.00000184	417

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000906	0.00000906
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acts downstream of various receptor and cytoplasmic protein tyrosine kinases to participate in the signal transduction from the cell surface to the nucleus. Positively regulates MAPK signal transduction pathway (PubMed:28074573). Dephosphorylates GAB1, ARHGAP35 and EGFR (PubMed:28074573). Dephosphorylates ROCK2 at 'Tyr-722' resulting in stimulatation of its RhoA binding activity. Dephosphorylates CDC73 (PubMed:26742426). {ECO:0000269|PubMed:10655584, ECO:0000269|PubMed:18559669, ECO:0000269|PubMed:18829466, ECO:0000269|PubMed:26742426, ECO:0000269|PubMed:28074573}.
• Disease: DISEASE: LEOPARD syndrome 1 (LPRD1) [MIM:151100]: A disorder characterized by lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormalities of genitalia, retardation of growth, and sensorineural deafness. {ECO:0000269|PubMed:12058348, ECO:0000269|PubMed:14961557, ECO:0000269|PubMed:15121796, ECO:0000269|PubMed:15389709, ECO:0000269|PubMed:15520399, ECO:0000269|PubMed:15690106, ECO:0000269|PubMed:16679933, ECO:0000269|PubMed:16733669, ECO:0000269|PubMed:24891296, ECO:0000269|PubMed:26742426}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Noonan syndrome 1 (NS1) [MIM:163950]: 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. {ECO:0000269|PubMed:11704759, ECO:0000269|PubMed:11992261, ECO:0000269|PubMed:12161469, ECO:0000269|PubMed:12325025, ECO:0000269|PubMed:12529711, ECO:0000269|PubMed:12634870, ECO:0000269|PubMed:12717436, ECO:0000269|PubMed:12739139, ECO:0000269|PubMed:12960218, ECO:0000269|PubMed:15384080, ECO:0000269|PubMed:15889278, ECO:0000269|PubMed:15948193, ECO:0000269|PubMed:19020799, ECO:0000269|PubMed:24891296, ECO:0000269|PubMed:28074573}. Note=The disease is caused by mutations affecting the gene represented in this entry. Mutations in PTPN11 account for more than 50% of the cases.; DISEASE: Leukemia, juvenile myelomonocytic (JMML) [MIM:607785]: 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. {ECO:0000269|PubMed:12717436, ECO:0000269|PubMed:26742426}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Metachondromatosis (MC) [MIM:156250]: 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. {ECO:0000269|PubMed:20577567}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Chronic myeloid leukemia - Homo sapiens (human);Adipocytokine signaling pathway - Homo sapiens (human);Renal cell carcinoma - Homo sapiens (human);Neurotrophin signaling pathway - Homo sapiens (human);Insulin resistance - Homo sapiens (human);Jak-STAT signaling pathway - Homo sapiens (human);Epithelial cell signaling in Helicobacter pylori infection - Homo sapiens (human);Axon guidance - Homo sapiens (human);C-type lectin receptor signaling pathway - Homo sapiens (human);Ras signaling pathway - Homo sapiens (human);Natural killer cell mediated cytotoxicity - Homo sapiens (human);Phospholipase D signaling pathway - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);Leukocyte transendothelial migration - Homo sapiens (human);Herpes simplex infection - Homo sapiens (human);IGF-Ncore;JAK-STAT-Ncore;EGF-Ncore;IL-5 Signaling Pathway;Heart Development;IL-1 signaling pathway;Angiogenesis overview;Leptin signaling pathway;Prolactin Signaling Pathway;Thymic Stromal LymphoPoietin (TSLP) Signaling Pathway;Pilocytic astrocytoma;Androgen Receptor Network in Prostate Cancer;B Cell Receptor Signaling Pathway;Interleukin-11 Signaling Pathway;Oncostatin M Signaling Pathway;Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;Alpha 6 Beta 4 signaling pathway;JAK-STAT;IL-3 Signaling Pathway;Kit receptor signaling pathway;Signaling of Hepatocyte Growth Factor Receptor;Rac1-Pak1-p38-MMP-2 pathway;IL-6 signaling pathway;Hepatitis C and Hepatocellular Carcinoma;IL-4 Signaling Pathway;VEGFA-VEGFR2 Signaling Pathway;ESC Pluripotency Pathways;MET in type 1 papillary renal cell carcinoma;Ras Signaling;EGF-EGFR Signaling Pathway;Insulin Signaling;IL-2 Signaling Pathway;Interferon type I signaling pathways;Type II interferon signaling (IFNG);T-Cell antigen Receptor (TCR) Signaling Pathway;Developmental Biology;FRS-mediated FGFR2 signaling;Negative regulation of FGFR2 signaling;Signaling by FGFR2;FRS-mediated FGFR3 signaling;PI-3K cascade:FGFR2;Downstream signaling of activated FGFR2;PI-3K cascade:FGFR4;PI-3K cascade:FGFR3;Downstream signaling of activated FGFR3;Disease;Negative regulation of FGFR3 signaling;Signaling by FGFR3;Signal Transduction;FRS-mediated FGFR4 signaling;Gene expression (Transcription);Downstream signaling of activated FGFR4;Signaling by Interleukins;Negative regulation of FGFR4 signaling;Signaling by FGFR4;Signaling by FGFR;Spry regulation of FGF signaling;the co-stimulatory signal during t-cell activation;il 6 signaling pathway;Prolactin receptor signaling;insulin signaling pathway;Generic Transcription Pathway;Prolactin;Cytokine Signaling in Immune system;Alpha6Beta4Integrin;Toll-Like Receptors Cascades;CTLA4 inhibitory signaling;PI3K Cascade;PD-1 signaling;Costimulation by the CD28 family;IRS-mediated signalling;Insulin receptor signalling cascade;Signaling by Insulin receptor;Signaling by PDGF;igf-1 signaling pathway;RNA Polymerase II Transcription;Growth hormone signaling;Regulation of IFNG signaling;HGF;Interleukin-20 family signaling;TCR;Innate Immune System;Immune System;IL5-mediated signaling events;Adaptive Immune System;KitReceptor;BCR;GPVI-mediated activation cascade;Signaling by EGFR;cell to cell adhesion signaling;MAPK1 (ERK2) activation;IL1;Platelet activation, signaling and aggregation;RAF-independent MAPK1/3 activation;Netrin mediated repulsion signals;Signaling by NTRK2 (TRKB);Signaling by NTRKs;BDNF;EGFR1;SHP2 signaling;Tie2 Signaling;PECAM1 interactions;CXCR4-mediated signaling events;Cell surface interactions at the vascular wall;Hemostasis;GAB1 signalosome;MAPK1/MAPK3 signaling;MAPK family signaling cascades;PIP3 activates AKT signaling;JAK STAT pathway and regulation;PDGF;IL2;Signaling by Leptin;Netrin-1 signaling;Signaling events regulated by Ret tyrosine kinase;IL3;IL2-mediated signaling events;Activated NTRK2 signals through FRS2 and FRS3;Downstream signal transduction;PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling;Negative regulation of the PI3K/AKT network;Interferon gamma signaling;IFN-gamma pathway;Angiopoietin receptor Tie2-mediated signaling;IL4;EPO signaling pathway;RET signaling;Axon guidance;Signaling by SCF-KIT;IL5;Leptin;Constitutive Signaling by Aberrant PI3K in Cancer;Regulation of RUNX1 Expression and Activity;PI3K/AKT Signaling in Cancer;IL6;IRS-related events triggered by IGF1R;IGF1R signaling cascade;TNFalpha;Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon;TRIF(TICAM1)-mediated TLR4 signaling ;MyD88-independent TLR4 cascade ;Toll Like Receptor 4 (TLR4) Cascade;Regulation of IFNA signaling;Interferon alpha/beta signaling;Signaling by MET;Signaling by Receptor Tyrosine Kinases;MAPK3 (ERK1) activation;Signal regulatory protein family interactions;Platelet sensitization by LDL;Platelet homeostasis;Cell-Cell communication;MET activates PTPN11;ErbB2/ErbB3 signaling events;Intracellular signaling by second messengers;Transcriptional regulation by RUNX1;GMCSF-mediated signaling events;IL2 signaling events mediated by STAT5;Insulin Pathway;Neurotrophic factor-mediated Trk receptor signaling;Diseases of signal transduction;Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met);Fc-epsilon receptor I signaling in mast cells;N-cadherin signaling events;Interferon Signaling;IL2 signaling events mediated by PI3K;IGF1 pathway;Signaling events mediated by Stem cell factor receptor (c-Kit);PDGFR-beta signaling pathway;Downstream signaling of activated FGFR1;Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R);Interleukin-6 signaling;Interleukin-6 family signaling;IL6-mediated signaling events;FGF signaling pathway;Signaling events mediated by VEGFR1 and VEGFR2;TCR signaling in naïve CD4+ T cells;IL3-mediated signaling events;Integrins in angiogenesis;VEGFR1 specific signals;FRS-mediated FGFR1 signaling;PI-3K cascade:FGFR1;Negative regulation of FGFR1 signaling;Signaling by FGFR1;Interleukin-3, 5 and GM-CSF signaling (Consensus)

Recessive Scores

• pRec: 0.729

Intolerance Scores

• loftool: 0.0482
• rvis_EVS: -0.43
• rvis_percentile_EVS: 25.15

Haploinsufficiency Scores

• pHI: 0.262
• hipred: Y
• hipred_score: 0.783
• ghis: 0.674

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.991

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Ptpn11
• Phenotype: neoplasm; pigmentation phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; reproductive system phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; liver/biliary system phenotype; embryo phenotype; skeleton phenotype; immune system phenotype; vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; limbs/digits/tail phenotype; muscle phenotype; digestive/alimentary phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype; craniofacial phenotype

Zebrafish Information Network

• Gene name: ptpn11a
• Affected structure: melanocyte
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: DNA damage checkpoint;activation of MAPK activity;triglyceride metabolic process;epidermal growth factor receptor signaling pathway;integrin-mediated signaling pathway;axon guidance;brain development;heart development;fibroblast growth factor receptor signaling pathway;hormone-mediated signaling pathway;cytokine-mediated signaling pathway;cerebellar cortex formation;platelet activation;platelet formation;T cell costimulation;microvillus organization;positive regulation of interferon-beta production;positive regulation of interleukin-6 production;positive regulation of tumor necrosis factor production;abortive mitotic cell cycle;regulation of cell adhesion mediated by integrin;negative regulation of cell adhesion mediated by integrin;multicellular organism growth;organ growth;peptidyl-tyrosine dephosphorylation;megakaryocyte development;phosphatidylinositol-3-phosphate biosynthetic process;atrioventricular canal development;ERBB signaling pathway;regulation of multicellular organism growth;hormone metabolic process;glucose homeostasis;regulation of protein complex assembly;positive regulation of mitotic cell cycle;positive regulation of glucose import;positive regulation of insulin receptor signaling pathway;negative regulation of insulin secretion;regulation of protein export from nucleus;phosphatidylinositol phosphorylation;positive regulation of hormone secretion;platelet-derived growth factor receptor signaling pathway;neurotrophin TRK receptor signaling pathway;ephrin receptor signaling pathway;multicellular organismal reproductive process;genitalia development;inner ear development;homeostasis of number of cells within a tissue;leukocyte migration;negative regulation of cortisol secretion;positive regulation of protein kinase B signaling;Bergmann glial cell differentiation;negative regulation of growth hormone secretion;face morphogenesis;regulation of type I interferon-mediated signaling pathway;intestinal epithelial cell migration;interleukin-6-mediated signaling pathway;positive regulation of ERK1 and ERK2 cascade;cellular response to mechanical stimulus;cellular response to cytokine stimulus;cellular response to epidermal growth factor stimulus
• Cellular component: nucleus;nucleoplasm;cytoplasm;mitochondrion;cytosol;protein-containing complex
• Molecular function: phosphotyrosine residue binding;phosphoprotein phosphatase activity;protein tyrosine phosphatase activity;non-membrane spanning protein tyrosine phosphatase activity;SH3/SH2 adaptor activity;insulin receptor binding;protein binding;1-phosphatidylinositol-3-kinase activity;protein kinase binding;protein domain specific binding;receptor tyrosine kinase binding;D1 dopamine receptor binding;phospholipase binding;insulin receptor substrate binding;phosphatidylinositol-4,5-bisphosphate 3-kinase activity;cell adhesion molecule binding;peptide hormone receptor binding