INPP4A Gene

HGNC Family	C2 domain containing
Name	inositol polyphosphate-4-phosphatase, type I, 107kDa
Description	This gene encodes an Mg++ independent enzyme that hydrolyzes the 4-position phosphate from the inositol ring of phosphatidylinositol 3,4-bisphosphate, inositol 1,3,4-trisphosphate, and inositol 3,4-bisphosphate. Multiple transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Aug 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Inositol polyphosphate 4‐phosphatase type I (INPP4A) is a lipid phosphatase that dephosphorylates phosphatidylinositol (3,4)‐bisphosphate, thereby functioning as a key negative regulator of phosphoinositide 3‐kinase/Akt (PI3K/Akt) signaling. In the central nervous system, INPP4A localizes at the postsynaptic density where it modulates NMDA receptor distribution and excitatory postsynaptic currents, consequently protecting neurons against glutamate‐mediated excitotoxicity. Loss‐of‐function mutations in INPP4A lead to cerebellar neurodegeneration, resulting in progressive ataxia, epileptic encephalopathy, and intellectual disability (see."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the pulmonary system, INPP4A contributes to the control of inflammatory responses. Reduced expression or destabilizing genetic variants of INPP4A are associated with allergic airway inflammation, where diminished INPP4A activity leads to exaggerated PI3K/Akt signaling, enhanced calpain activity, and subsequent airway remodeling and hyperresponsiveness. Moreover, extracellular INPP4A secreted by airway epithelial cells appears to act in a paracrine fashion to limit inflammatory cell responses and fibroblast proliferation (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In cancer, several studies reveal that INPP4A behaves as a contextual tumor suppressor by dampening PI3K/Akt pathway activation. In various malignancies—including esophageal, colorectal, non‐small cell lung, and oral squamous cell carcinomas—aberrantly elevated levels of specific microRNAs (such as miR‑508, miR‑4443, and miR‑935) target and suppress INPP4A expression. This downregulation releases the inhibitory brake on PI3K/Akt signaling, promoting increased cell proliferation, migration, invasion, and therapy resistance (see."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "7"}]}, {"type": "t", "text": " \n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies underscore the multifaceted and context‐dependent roles of INPP4A. By tightly regulating levels of phosphoinositide intermediates, INPP4A supports neuronal integrity, constrains aberrant pro‐survival signaling in inflammatory and fibrotic lung environments, and acts as a barrier to oncogenic transformation. Maintaining proper INPP4A function is therefore critical for neural homeostasis, for limiting inflammatory airway remodeling, and for suppressing tumor progression (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "4"}, {"type": "fg_f", "ref": "2"}, {"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Junko Sasaki, Satoshi Kofuji, Reietsu Itoh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The PtdIns(3,4)P(2) phosphatase INPP4A is a suppressor of excitotoxic neuronal death."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature09023"}], "href": "https://doi.org/10.1038/nature09023"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20463662"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20463662"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Ruth Sheffer, Odeya Bennett-Back, Barak Yaacov, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hindbrain malformation and myoclonic seizures associated with a deleterious mutation in the INPP4A gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurogenetics (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10048-014-0428-7"}], "href": "https://doi.org/10.1007/s10048-014-0428-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25338135"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25338135"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Sara Banihashemi, Maryam Tahmasebi-Birgani, Javad Mohammadiasl, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Whole exome sequencing identified a novel nonsense INPP4A mutation in a family with intellectual disability."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Med Genet (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ejmg.2020.103846"}], "href": "https://doi.org/10.1016/j.ejmg.2020.103846"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31978615"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31978615"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Jyotirmoi Aich, Ulaganathan Mabalirajan, Tanveer Ahmad, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Resveratrol attenuates experimental allergic asthma in mice by restoring inositol polyphosphate 4 phosphatase (INPP4A)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int Immunopharmacol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.intimp.2012.08.017"}], "href": "https://doi.org/10.1016/j.intimp.2012.08.017"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22986054"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22986054"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Chuyong Lin, Aibin Liu, Jinrong Zhu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-508 sustains phosphoinositide signalling and promotes aggressive phenotype of oesophageal squamous cell carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms5620"}], "href": "https://doi.org/10.1038/ncomms5620"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25099196"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25099196"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Weiguo Zhang, Bin Qiao, Junli Fan "}, {"type": "b", "children": [{"type": "t", "text": "Overexpression of miR-4443 promotes the resistance of non-small cell lung cancer cells to epirubicin by targeting INPP4A and regulating the activation of JAK2/STAT3 pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pharmazie (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1691/ph.2018.8313"}], "href": "https://doi.org/10.1691/ph.2018.8313"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30001772"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30001772"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Ying Huang, Wenfeng Xiao, Xiuli Jiang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-935 acts as a prognostic marker and promotes cell proliferation, migration, and invasion in colorectal cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Biomark (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3233/CBM-190183"}], "href": "https://doi.org/10.3233/CBM-190183"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31524145"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31524145"}]}]}]}
Synonyms	INPP4, TVAS1
Proteins	INP4A_HUMAN
NCBI Gene ID	3631
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

INPP4A has 6,326 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 129 datasets.

Click the + buttons to view associations for INPP4A from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

INPP4A Gene

Functional Associations

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

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of INPP4A 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 INPP4A gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of INPP4A gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of INPP4A 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 INPP4A 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 INPP4A 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 INPP4A 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 INPP4A 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 INPP4A gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of INPP4A gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of INPP4A 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 INPP4A gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with INPP4A protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with INPP4A 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 INPP4A gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of INPP4A 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 INPP4A gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of INPP4A gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of INPP4A gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing INPP4A protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing INPP4A protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with INPP4A 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 INPP4A protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of INPP4A gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with INPP4A gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with INPP4A gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with INPP4A gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of INPP4A protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by INPP4A gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with INPP4A 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 INPP4A 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 INPP4A gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with INPP4A 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 INPP4A 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 INPP4A gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of INPP4A 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 INPP4A from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with INPP4A gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with INPP4A 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 INPP4A gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.