PPFIA4 Gene

HGNC Family	Sterile alpha motif (SAM) domain containing (SAMD)
Name	protein tyrosine phosphatase, receptor type, f polypeptide (PTPRF), interacting protein (liprin), alpha 4
Description	PPFIA4, or liprin-alpha-4, belongs to the liprin-alpha gene family. See liprin-alpha-1 (LIP1, or PPFIA1; MIM 611054) for background on liprins.[supplied by OMIM, Mar 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPPFIA4, which encodes Liprin‑α14, has emerged as a multifunctional adaptor protein with potential roles in both cardiac and cancer biology. In studies of early‐onset atrial fibrillation, genetic analyses in Korean patients have pointed to PPFIA4 as part of a novel susceptibility locus, suggesting that alterations in this gene may influence cardiac electrical remodeling and arrhythmogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the cancer arena, Liprin‑α14 expression is highly responsive to hypoxic conditions. In renal cell carcinomas and pancreatic cancer, its gene promoter is directly activated by hypoxia‑inducible factor 1α (HIF‑1α), leading to increased gene expression; this upregulation is accompanied by changes in cellular adhesion, including reductions in E‑cadherin and β‑catenin levels when Liprin‑α14 is suppressed. Furthermore, under conditions of environmental stress such as nickel chloride exposure, specific isoforms of Liprin‑α14 interact with the cytoplasmic domain of receptor protein tyrosine phosphatase‑LAR, thereby enhancing its phosphatase activity and reducing overall tyrosine phosphorylation. These findings highlight Liprin‑α14 as a key modulator in cell–cell adhesion and signal transduction under hypoxic or toxic conditions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "2", "end_ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its roles in structural and signaling dynamics, emerging evidence suggests a link between PPFIA4 and cancer metabolism. Preliminary data indicate an association with the regulation of glycolysis in cancer cells, as reported in the context of esophageal cancer; this, alongside its involvement in the hypoxic tumor microenvironment that can influence responses to chemotherapeutic agents in small‑cell lung cancer, points to a multifaceted role for PPFIA4 in tumor progression and treatment resistance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ji-Young Lee, Tae-Hoon Kim, Pil-Sung Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Korean atrial fibrillation network genome-wide association study for early-onset atrial fibrillation identifies novel susceptibility loci."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur Heart J (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/eurheartj/ehx213"}], "href": "https://doi.org/10.1093/eurheartj/ehx213"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28460022"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28460022"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Sandra Mattauch, Martin Sachs, Jürgen Behrens "}, {"type": "b", "children": [{"type": "t", "text": "Liprin-α4 is a new hypoxia-inducible target gene required for maintenance of cell-cell contacts."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Cell Res (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yexcr.2010.06.022"}], "href": "https://doi.org/10.1016/j.yexcr.2010.06.022"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20599943"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20599943"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Akio Yamasaki, Kazunori Nakayama, Akira Imaizumi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Liprin-α4 as a Possible New Therapeutic Target for Pancreatic Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Anticancer Res (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.21873/anticanres.12122"}], "href": "https://doi.org/10.21873/anticanres.12122"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29187440"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29187440"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Kathrin Kiok, Hong Sun, Hailey Clancy, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Liprin-α4 is required for nickel induced receptor protein tyrosine phosphatase-leukocyte antigen related receptor F (RPTP-LAR) activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0022764"}], "href": "https://doi.org/10.1371/journal.pone.0022764"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21829649"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21829649"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Hideya Onishi, Akio Yamasaki, Katsuya Nakamura, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Liprin-α4 as a New Therapeutic Target for SCLC as an Upstream Mediator of HIF1α."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Anticancer Res (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.21873/anticanres.13227"}], "href": "https://doi.org/10.21873/anticanres.13227"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30842147"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30842147"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Yingying He, Dingyu Lu, Hao Cheng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PPFIA4 Promotes Proliferation, Migration and Glycolysis of Esophageal Cancer Cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ann Clin Lab Sci (2023)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38182152"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38182152"}]}]}]}
Proteins	LIPA4_HUMAN
NCBI Gene ID	8497
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

PPFIA4 has 4,858 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 112 datasets.

Click the + buttons to view associations for PPFIA4 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

PPFIA4 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 PPFIA4 gene relative to other tissues from the Allen Brain Atlas Adult Human 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 PPFIA4 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 RNA-seq	tissue samples with high or low expression of PPFIA4 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 PPFIA4 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 PPFIA4 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 PPFIA4 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 PPFIA4 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 PPFIA4 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of PPFIA4 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 PPFIA4 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with PPFIA4 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 PPFIA4 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of PPFIA4 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 PPFIA4 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 PPFIA4 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 PPFIA4 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing PPFIA4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing PPFIA4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing PPFIA4 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	cellular components co-occuring with PPFIA4 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 PPFIA4 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 PPFIA4 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with PPFIA4 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with PPFIA4 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with PPFIA4 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with PPFIA4 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 PPFIA4 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 PPFIA4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with PPFIA4 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 PPFIA4 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 PPFIA4 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of PPFIA4 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 PPFIA4 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with PPFIA4 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with PPFIA4 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 PPFIA4 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with PPFIA4 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 PPFIA4 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of PPFIA4 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 PPFIA4 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.