{"entity":{"id":"ptpn6","kind":"target","name":"PTPN6","aka":["protein tyrosine phosphatase non-receptor type 6","Tyrosine-protein phosphatase non-receptor type 6","PTP-1C","SHP-1","SHP1"],"tldr":"PTPN6 (Tyrosine-protein phosphatase non-receptor type 6) is an enzyme. The public catalogues list it as an oncogene driver, a tumour suppressor and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Hepatocellular carcinoma, Diffuse large B-cell lymphoma and Melanoma.","summary":"Tyrosine phosphatase enzyme that plays important roles in controlling immune signalling pathways and fundamental physiological processes such as haematopoiesis. Dephosphorylates and negatively regulate several receptor tyrosine kinases (RTKs) such as EGFR, PDGFR and FGFR, thereby modulating their signalling activities. When recruited to immunoreceptor tyrosine-based inhibitory motif (ITIM)-containing receptors such as immunoglobulin-like transcript 2/LILRB1, programmed cell death protein 1/PDCD1, CD3D, CD22, CLEC12A and other receptors involved in immune regulation, initiates their dephosphorylation and subsequently inhibits downstream signalling events.\n\nCIViC holds 1 clinical evidence item and 0 assertions across 1 variant. IntOGen calls it a driver in 3 cohorts (1 activating, 2 loss-of-function), covering Diffuse Large B-Cell Lymphoma, NOS, Melanoma.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:9658","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:9658"},{"label":"UniProt P29350","url":"https://www.uniprot.org/uniprotkb/P29350/entry"},{"label":"NCBI Gene 5777","url":"https://www.ncbi.nlm.nih.gov/gene/5777"},{"label":"Ensembl ENSG00000111679","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000111679"}],"tags":["cancer-genes-wave"],"related":["civic","intogen"],"cancers":["hcc","dlbcl","melanoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["cd47-sirpa"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: IntOGen calls it an activating (Act) driver in 1 cohort; IntOGen calls it a loss-of-function (LoF) driver in 2 cohorts; CIViC holds 1 clinical evidence items on its variants. Evidence tier \"clinical-evidence\" is the strongest of those signals.","Prevalence not recorded: none of the sources gives a positivity rate."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"PTPN6","role":["oncogene-driver","tumour-suppressor","biomarker"],"evidenceTier":"clinical-evidence","sources":[{"label":"HGNC HGNC:9658","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:9658","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt P29350","url":"https://www.uniprot.org/uniprotkb/P29350/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene PTPN6","url":"https://civicdb.org/features/4682","note":"1 evidence items, 0 assertions, 1 variants; diseases: Hepatocellular Carcinoma (GraphQL API, CC0)"},{"label":"IntOGen PTPN6","url":"https://www.intogen.org/search?gene=PTPN6","note":"driver in 3 cohorts (Act 1, LoF 2); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"specificity":"tumour-specific","distribution":"few-types","specificityNote":"Tumour-specific alteration: the catalogues call it an oncogene driver (IntOGen cohort analysis finds it activated more often than chance) and a tumour suppressor (IntOGen finds it knocked out more often than chance), so the direction differs between cohorts but the alteration is somatic either way; what a medicine would aim at or exploit is the altered form or its loss, absent from normal cells; no corpus medicine is aimed at it yet. HPA PTPN6: RNA tissue enhanced (bone marrow 125 nTPM, lymphoid tissue 144 nTPM); high antibody staining in 6 normal tissues; highest cancer staining lymphoma (12 of 12 high). Distribution: 3 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Hepatocellular carcinoma, Lymphoma, Skin cancer (all types)); Open Targets associates it with 0 specific cancer types at or above 0.5. (Rule 6 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"UniProt P29350","url":"https://www.uniprot.org/uniprotkb/P29350/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene PTPN6","url":"https://civicdb.org/features/4682","note":"1 evidence items, 0 assertions, 1 variants; diseases: Hepatocellular Carcinoma (GraphQL API, CC0)"},{"label":"IntOGen PTPN6","url":"https://www.intogen.org/search?gene=PTPN6","note":"driver in 3 cohorts (Act 1, LoF 2); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"},{"label":"Human Protein Atlas PTPN6 tissue","url":"https://www.proteinatlas.org/ENSG00000111679-PTPN6/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000111679 associations","url":"https://platform.opentargets.org/target/ENSG00000111679/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:9658","ensembl":"ENSG00000111679","uniprot":"P29350","entrez":"5777","firstDescribed":1991,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Shen S.H. et al, Nature, 1991, \"A protein-tyrosine phosphatase with sequence similarity to the SH2 domain of the protein-tyrosine kinases\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/1652101/","biology":"Tyrosine phosphatase enzyme that plays important roles in controlling immune signalling pathways and fundamental physiological processes such as haematopoiesis. Dephosphorylates and negatively regulate several receptor tyrosine kinases (RTKs) such as EGFR, PDGFR and FGFR, thereby modulating their signalling activities. When recruited to immunoreceptor tyrosine-based inhibitory motif (ITIM)-containing receptors such as immunoglobulin-like transcript 2/LILRB1, programmed cell death protein 1/PDCD1, CD3D, CD22, CLEC12A and other receptors involved in immune regulation, initiates their dephosphorylation and subsequently inhibits downstream signalling events. Modulates the signalling of several cytokine receptors including IL-4 receptor. Additionally, targets multiple cytoplasmic signalling molecules including STING1, LCK or STAT1 among others involved in diverse cellular processes including modulation of T-cell activation or cGAS-STING signalling. Within the nucleus, negatively regulates the activity of some transcription factors such as NFAT5 via direct dephosphorylation. Location: Cytoplasm; Nucleus (UniProt). Locus 12p13.31 (HGNC).","whereFound":["Hepatocellular carcinoma: CIViC evidence names this disease","Diffuse large B-cell lymphoma: IntOGen driver in 2 cohorts (DLBCLNOS)","Melanoma: IntOGen driver in 1 cohort (MEL)"],"targetClass":"enzyme","prevalence":[]},"route":"/targets/ptpn6/","neighbours":{"collection":[{"id":"civic","kind":"collection","name":"CIViC","route":"/collections/civic/"},{"id":"intogen","kind":"collection","name":"IntOGen","route":"/collections/intogen/"}],"cancer":[{"id":"dlbcl","kind":"cancer","name":"Diffuse large B-cell lymphoma","route":"/cancers/dlbcl/"},{"id":"hcc","kind":"cancer","name":"Hepatocellular carcinoma","route":"/cancers/hcc/"},{"id":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"}],"pathway":[{"id":"cd47-sirpa","kind":"pathway","name":"CD47 / SIRPα (the 'don't eat me' signal)","route":"/pathways/cd47-sirpa/"}]}}