INPP5D Gene

HGNC Family	SH2 domain containing
Name	inositol polyphosphate-5-phosphatase, 145kDa
Description	This gene is a member of the inositol polyphosphate-5-phosphatase (INPP5) family and encodes a protein with an N-terminal SH2 domain, an inositol phosphatase domain, and two C-terminal protein interaction domains. Expression of this protein is restricted to hematopoietic cells where its movement from the cytosol to the plasma membrane is mediated by tyrosine phosphorylation. At the plasma membrane, the protein hydrolyzes the 5' phosphate from phosphatidylinositol (3,4,5)-trisphosphate and inositol-1,3,4,5-tetrakisphosphate, thereby affecting multiple signaling pathways. The protein is also partly localized to the nucleus, where it may be involved in nuclear inositol phosphate signaling processes. Overall, the protein functions as a negative regulator of myeloid cell proliferation and survival. Mutations in this gene are associated with defects and cancers of the immune system. Deficiencies in the encoded protein, SHIP1, have been associated with Inflammatory Bowel Disease types such as Crohn's Disease and Ulcerative Colitis. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2020]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n INPP5D, which encodes the SH2‐containing inositol 5′‐phosphatase 1 (SHIP1), is emerging as a key negative regulator of immune receptor signaling. Acting primarily by dephosphorylating phosphatidylinositol‐(3,4,5)‐trisphosphate to generate phosphatidylinositol‐(3,4)‐bisphosphate, SHIP1 counterbalances phosphoinositide 3‐kinase (PI3K)–mediated pathways. In several immune cell types—including macrophages, natural killer (NK), and T cells—SHIP1 is recruited to activated inhibitory receptors (for instance, upon tyrosine phosphorylation of ITT‐like motifs in receptors such as TIGIT) to truncate downstream PI3K, Akt, and MAPK signaling, thereby dampening cellular activation and cytokine production."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition, its steady‐state expression is tightly modulated by microRNAs such as miR‑155; elevated miR‑155 levels decrease SHIP1 expression, which in turn enhances inflammatory responses by augmenting PI3K/Akt signaling in conditions like cystic fibrosis and certain lymphoid malignancies."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "2", "end_ref": "4"}]}, {"type": "t", "text": " Moreover, SHIP1 regulates Toll‑like receptor–dependent inflammatory responses through both phosphatase‐dependent and –independent mechanisms—for example, by inhibiting the assembly or signaling of proximal adaptor complexes—and contributes to the establishment of endotoxin tolerance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Differential expression of SHIP1 among leukemic and normal lymphocytes further highlights its pivotal role in tuning PI3K‐dependent signals to maintain immune homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Collectively, these studies underscore that INPP5D/SHIP1 functions as an essential “brake” within diverse signaling cascades to prevent overactivation, thereby safeguarding against excessive inflammation and malignant transformation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}, {"type": "fg_fs", "start_ref": "1", "end_ref": "3"}, {"type": "fg_f", "ref": "5"}, {"type": "fg_f", "ref": "7"}, {"type": "fg_f", "ref": "4"}, {"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "S Liu, H Zhang, M Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Recruitment of Grb2 and SHIP1 by the ITT-like motif of TIGIT suppresses granule polarization and cytotoxicity of NK cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Differ (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/cdd.2012.141"}], "href": "https://doi.org/10.1038/cdd.2012.141"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23154388"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23154388"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Sharmistha Bhattacharyya, Nagaraja S Balakathiresan, Clifton Dalgard, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Elevated miR-155 promotes inflammation in cystic fibrosis by driving hyperexpression of interleukin-8."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M110.198390"}], "href": "https://doi.org/10.1074/jbc.M110.198390"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21282106"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21282106"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Irene M Pedersen, Dennis Otero, Elaine Kao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Onco-miR-155 targets SHIP1 to promote TNFalpha-dependent growth of B cell lymphomas."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO Mol Med (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/emmm.200900028"}], "href": "https://doi.org/10.1002/emmm.200900028"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19890474"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19890474"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Rossana Trotta, Li Chen, David Ciarlariello, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-155 regulates IFN-γ production in natural killer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2011-12-398099"}], "href": "https://doi.org/10.1182/blood-2011-12-398099"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22378844"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22378844"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Huazhang An, Hongmei Xu, Minghui Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Src homology 2 domain-containing inositol-5-phosphatase 1 (SHIP1) negatively regulates TLR4-mediated LPS response primarily through a phosphatase activity- and PI-3K-independent mechanism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2005-01-0191"}], "href": "https://doi.org/10.1182/blood-2005-01-0191"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15701712"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15701712"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Wenji Piao, Chang Song, Haiyan Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Endotoxin tolerance dysregulates MyD88- and Toll/IL-1R domain-containing adapter inducing IFN-beta-dependent pathways and increases expression of negative regulators of TLR signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Leukoc Biol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1189/jlb.0309189"}], "href": "https://doi.org/10.1189/jlb.0309189"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19656901"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19656901"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Robin W Freeburn, Karen L Wright, Steven J Burgess, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Evidence that SHIP-1 contributes to phosphatidylinositol 3,4,5-trisphosphate metabolism in T lymphocytes and can regulate novel phosphoinositide 3-kinase effectors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.169.10.5441"}], "href": "https://doi.org/10.4049/jimmunol.169.10.5441"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12421919"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12421919"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Murugesan V S Rajaram, Bin Ni, Jessica D Morris, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mycobacterium tuberculosis lipomannan blocks TNF biosynthesis by regulating macrophage MAPK-activated protein kinase 2 (MK2) and microRNA miR-125b."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1112660108"}], "href": "https://doi.org/10.1073/pnas.1112660108"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21969554"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21969554"}]}]}]}
Synonyms	SHIP-1, P150SHIP, SHIP, SHIP1, SIP-145, HP51CN
Proteins	SHIP1_HUMAN
NCBI Gene ID	3635
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

INPP5D has 7,719 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 122 datasets.

Click the + buttons to view associations for INPP5D from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

INPP5D Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by INPP5D gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of INPP5D gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of INPP5D gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of INPP5D gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of INPP5D gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of INPP5D gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of INPP5D gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of INPP5D gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of INPP5D gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of INPP5D gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of INPP5D gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with INPP5D gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with INPP5D protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with INPP5D gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of INPP5D gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of INPP5D gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of INPP5D gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of INPP5D gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing INPP5D protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with INPP5D protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with INPP5D protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing INPP5D protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of INPP5D gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with INPP5D gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with INPP5D gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with INPP5D gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with INPP5D gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with INPP5D gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with INPP5D gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with INPP5D gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with INPP5D gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with INPP5D gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with INPP5D gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at INPP5D gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of INPP5D gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of INPP5D gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing INPP5D from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with INPP5D gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with INPP5D gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of INPP5D gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.