PPIP5K2 Gene

Name	diphosphoinositol pentakisphosphate kinase 2
Description	This gene encodes a member of the histidine acid phosphatase family of proteins. Despite containing a histidine acid phosphatase domain, the encoded protein functions as an inositol pyrophosphate kinase, and is thought to lack phosphatase activity. This kinase activity is the mechanism by which the encoded protein synthesizes high-energy inositol pyrophosphates, which act as signaling molecules that regulate cellular homeostasis and other processes. This gene may be associated with autism spectrum disorder in human patients. [provided by RefSeq, Sep 2016]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPPIP5K2 is a highly conserved, multifunctional enzyme belonging to the inositol pyrophosphate kinase family. Structural and kinetic studies have shown that it possesses bifunctional kinase/phosphatase activities that interconvert 5‑diphosphoinositol pentakisphosphate (5‑InsP7) and 1‑InsP7/InsP8, employing an unprecedented ratchet‐like mechanism that facilitates intramolecular substrate transfer despite considerable steric and electrostatic challenges. Detailed biochemical analyses further reveal that PPIP5K2’s catalytic efficiency is robust against fluctuations in cellular ATP/ADP ratios, and that it contains regulatory motifs such as a nuclear localization signal that may control its compartmentalization and function in response to changes in extracellular inorganic phosphate levels."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "PPIP5K2 function is critical for tissue homeostasis. In the inner ear, a pathogenic PPIP5K2 variant that reduces phosphatase activity while concomitantly augmenting its kinase function has been linked to degeneration of cochlear outer hair cells and consequent sensorineural hearing loss. Similarly, genetic studies in keratoconus patients and corresponding mouse models support a key role for PPIP5K2 in normal corneal structure and function, with altered enzyme activity contributing to corneal thinning and irregularity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "Beyond its metabolic and homeostatic roles, PPIP5K2 also exerts influence over nuclear processes. In colorectal cancer cells, for instance, stimulus-induced dephosphorylation of PPIP5K2 promotes its translocation to the nucleus where it acts as a novel scaffold protein by binding and recruiting key DNA repair factors such as RPA70. This activity facilitates homologous recombination repair, enhances cell survival under genotoxic stress, and identifies PPIP5K2 as a potential therapeutic target in malignancies characterized by DNA repair defects."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Huanchen Wang, J R Falck, Traci M Tanaka Hall, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural basis for an inositol pyrophosphate kinase surmounting phosphate crowding."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Chem Biol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nchembio.733"}], "href": "https://doi.org/10.1038/nchembio.733"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22119861"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22119861"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jeremy D Weaver, Huanchen Wang, Stephen B Shears "}, {"type": "b", "children": [{"type": "t", "text": "The kinetic properties of a human PPIP5K reveal that its kinase activities are protected against the consequences of a deteriorating cellular bioenergetic environment."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biosci Rep (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BSR20120115"}], "href": "https://doi.org/10.1042/BSR20120115"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23240582"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23240582"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Sheila T Yong, Hoai-Nghia Nguyen, Jae H Choi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of a functional nuclear translocation sequence in hPPIP5K2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Cell Biol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12860-015-0063-7"}], "href": "https://doi.org/10.1186/s12860-015-0063-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26084399"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26084399"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Chunfang Gu, Hoai-Nghia Nguyen, Alexandre Hofer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Significance of the Bifunctional Kinase/Phosphatase Activities of Diphosphoinositol Pentakisphosphate Kinases (PPIP5Ks) for Coupling Inositol Pyrophosphate Cell Signaling to Cellular Phosphate Homeostasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M116.765743"}], "href": "https://doi.org/10.1074/jbc.M116.765743"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28126903"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28126903"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Yi An, Henning J Jessen, Huanchen Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dynamics of Substrate Processing by PPIP5K2, a Versatile Catalytic Machine."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Structure (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.str.2019.03.007"}], "href": "https://doi.org/10.1016/j.str.2019.03.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30956131"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30956131"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Rizwan Yousaf, Chunfang Gu, Zubair M Ahmed, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in Diphosphoinositol-Pentakisphosphate Kinase PPIP5K2 are associated with hearing loss in human and mouse."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Genet (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pgen.1007297"}], "href": "https://doi.org/10.1371/journal.pgen.1007297"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29590114"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29590114"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Mariam Lofty Khaled, Yelena Bykhovskaya, Chunfang Gu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PPIP5K2 and PCSK1 are Candidate Genetic Contributors to Familial Keratoconus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-019-55866-5"}], "href": "https://doi.org/10.1038/s41598-019-55866-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31852976"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31852976"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Chen-Hui Cao, Han Ling, Kai Han, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PPIP5K2 promotes colorectal carcinoma pathogenesis through facilitating DNA homologous recombination repair."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41388-021-02052-5"}], "href": "https://doi.org/10.1038/s41388-021-02052-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34645979"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34645979"}]}]}]}
Synonyms	HISPPD1, VIP2, DFNB100, IP7K2, CFAP160
Proteins	VIP2_HUMAN
NCBI Gene ID	23262
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

PPIP5K2 has 4,431 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 107 datasets.

Click the + buttons to view associations for PPIP5K2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

PPIP5K2 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 PPIP5K2 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 PPIP5K2 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 PPIP5K2 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 PPIP5K2 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 PPIP5K2 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 PPIP5K2 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 PPIP5K2 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of PPIP5K2 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 PPIP5K2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with PPIP5K2 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with PPIP5K2 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 PPIP5K2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of PPIP5K2 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 PPIP5K2 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 PPIP5K2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing PPIP5K2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing PPIP5K2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing PPIP5K2 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with PPIP5K2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with PPIP5K2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with PPIP5K2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by PPIP5K2 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving PPIP5K2 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with PPIP5K2 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with PPIP5K2 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 PPIP5K2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with PPIP5K2 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 PPIP5K2 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 PPIP5K2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of PPIP5K2 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 PPIP5K2 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with PPIP5K2 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of PPIP5K2 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with PPIP5K2 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing PPIP5K2 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of PPIP5K2 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.
	GEO Signatures of Differentially Expressed Genes for Gene Perturbations	gene perturbations changing expression of PPIP5K2 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
	GEO Signatures of Differentially Expressed Genes for Kinase Perturbations	kinase perturbations changing expression of PPIP5K2 gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset.
	GEO Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of PPIP5K2 gene from the GEO Signatures of Differentially Expressed Genes for Small Molecules dataset.
	GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations	transcription factor perturbations changing expression of PPIP5K2 gene from the GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations dataset.