NIPA1 Gene

Name	non imprinted in Prader-Willi/Angelman syndrome 1
Description	This gene encodes a magnesium transporter that associates with early endosomes and the cell surface in a variety of neuronal and epithelial cells. This protein may play a role in nervous system development and maintenance. Multiple transcript variants encoding different isoforms have been found for this gene. Mutations in this gene have been associated with autosomal dominant spastic paraplegia 6. [provided by RefSeq, Nov 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNIPA1 is a highly conserved gene located in the 15q11–q13 region that encodes a membrane protein characterized by nine transmembrane domains. Initially identified among several genes in the Prader–Willi/Angelman region, NIPA1 is nonimprinted and is expressed in a broad range of tissues, with particularly high levels in neuronal tissues. Its predicted structure suggests that it may function as a receptor or transporter, a concept first raised in analyses of the genomic interval and later supported by studies finding dominant‐negative mutations in families with autosomal dominant hereditary spastic paraplegia (HSP)."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}, {"type": "p", "children": [{"type": "t", "text": "\nFunctional studies have further delineated NIPA1’s role at the cellular level. Electrophysiological analyses in Xenopus oocytes demonstrated that NIPA1 mediates electrogenic, voltage‐dependent magnesium (Mg²⁺) uptake, with its trafficking between the plasma membrane and early endosomes being modulated by ambient Mg²⁺ concentrations. In parallel, biochemical investigations revealed that NIPA1 interacts with the type II bone morphogenetic protein receptor (BMPRII) to promote receptor endocytosis and lysosomal degradation, thereby inhibiting BMP signaling—a pathway known to be essential for axonal maintenance. Disruption of these activities, either by mutation or aberrant trafficking, has been implicated in the pathogenesis of HSP."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}, {"type": "p", "children": [{"type": "t", "text": "\nMutations in NIPA1 have been firmly linked to neurodegenerative phenotypes. In multiple independent studies, missense alterations (such as G106R) and de novo mutations have been shown to cause autosomal dominant HSP, with mutant proteins displaying abnormal intracellular trafficking, accumulation in the endoplasmic reticulum, and consequent endoplasmic reticulum stress leading to neuronal apoptosis. Moreover, expansions in the polyalanine repeat region of NIPA1 have been associated with an increased risk for amyotrophic lateral sclerosis (ALS) and modulate disease severity, although the extent of this association remains under active investigation. Recent work has also uncovered a regulatory role for a long noncoding RNA (NIPA1-SO) that interacts with transcription factors to fine-tune NIPA1 expression and downstream BMPRII signaling in vascular and leukemic cells, thereby broadening the functional spectrum of NIPA1 beyond classical neurodegeneration. Co-occurrence studies in ALS cohorts further support a contributory—albeit modest—role for NIPA1 genetic variability in complex motor neuron disease susceptibility."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "15"}]}, {"type": "t", "text": ""}]}]}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "J-H Chai, D P Locke, J M Greally, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of four highly conserved genes between breakpoint hotspots BP1 and BP2 of the Prader-Willi/Angelman syndromes deletion region that have undergone evolutionary transposition mediated by flanking duplicons."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1086/378816"}], "href": "https://doi.org/10.1086/378816"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14508708"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14508708"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Shirley Rainier, Jing-Hua Chai, Debra Tokarz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NIPA1 gene mutations cause autosomal dominant hereditary spastic paraplegia (SPG6)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1086/378817"}], "href": "https://doi.org/10.1086/378817"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14508710"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14508710"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Angela Goytain, Rochelle M Hines, Alaa El-Husseini, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NIPA1(SPG6), the basis for autosomal dominant form of hereditary spastic paraplegia, encodes a functional Mg2+ transporter."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M610314200"}], "href": "https://doi.org/10.1074/jbc.M610314200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17166836"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17166836"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Hilda T H Tsang, Thomas L Edwards, Xinnan Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The hereditary spastic paraplegia proteins NIPA1, spastin and spartin are inhibitors of mammalian BMP signalling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddp324"}], "href": "https://doi.org/10.1093/hmg/ddp324"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19620182"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19620182"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Johanna A Reed, Phillip A Wilkinson, Heema Patel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel NIPA1 mutation associated with a pure form of autosomal dominant hereditary spastic paraplegia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurogenetics (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10048-004-0209-9"}], "href": "https://doi.org/10.1007/s10048-004-0209-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15711826"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15711826"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Hylke M Blauw, Wouter van Rheenen, Max Koppers, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NIPA1 polyalanine repeat expansions are associated with amyotrophic lateral sclerosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/dds064"}], "href": "https://doi.org/10.1093/hmg/dds064"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22378146"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22378146"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Jiali Zhao, Dawn S Matthies, Emmanuel J Botzolakis, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hereditary spastic paraplegia-associated mutations in the NIPA1 gene and its Caenorhabditis elegans homolog trigger neural degeneration in vitro and in vivo through a gain-of-function mechanism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/JNEUROSCI.4668-08.2008"}], "href": "https://doi.org/10.1523/JNEUROSCI.4668-08.2008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19091982"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19091982"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Gijs H P Tazelaar, Annelot M Dekker, Joke J F A van Vugt, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of NIPA1 repeat expansions with amyotrophic lateral sclerosis in a large international cohort."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurobiol Aging (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neurobiolaging.2018.09.012"}], "href": "https://doi.org/10.1016/j.neurobiolaging.2018.09.012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30342764"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30342764"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Shi Guo Liu, Jian Jun Zhao, Mao You Zhuang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Clinical and genetic study of SPG6 mutation in a Chinese family with hereditary spastic paraplegia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurol Sci (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jns.2007.09.024"}], "href": "https://doi.org/10.1016/j.jns.2007.09.024"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17928003"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17928003"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Peter Hedera "}, {"type": "b", "children": [{"type": "t", "text": "Recurrent de novo c.316G>A mutation in NIPA1 hotspot."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurol Sci (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jns.2013.09.015"}], "href": "https://doi.org/10.1016/j.jns.2013.09.015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24075313"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24075313"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Min Jiang, Yu Song, Mei-Xia Ren, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LncRNA NIPA1-SO confers atherosclerotic protection by suppressing the transmembrane protein NIPA1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Adv Res (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jare.2023.01.017"}], "href": "https://doi.org/10.1016/j.jare.2023.01.017"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36736696"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36736696"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Jinliang Chen, Chunling Li, Renhui Zhan, et al. 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Synonyms	FSP3, SPG6, SLC57A1
Proteins	NIPA1_HUMAN
NCBI Gene ID	123606
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

NIPA1 has 5,373 functional associations with biological entities spanning 9 categories (molecular profile, organism, disease, phenotype or trait, functional term, phrase or reference, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 106 datasets.

Click the + buttons to view associations for NIPA1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

NIPA1 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 NIPA1 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 NIPA1 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 NIPA1 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 NIPA1 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 NIPA1 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 NIPA1 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of NIPA1 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 NIPA1 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 NIPA1 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 NIPA1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with NIPA1 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 NIPA1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of NIPA1 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 NIPA1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with NIPA1 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with NIPA1 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of NIPA1 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing NIPA1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with NIPA1 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 NIPA1 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 NIPA1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with NIPA1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with NIPA1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with NIPA1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of NIPA1 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 NIPA1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving NIPA1 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving NIPA1 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with NIPA1 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 NIPA1 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 NIPA1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with NIPA1 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 NIPA1 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 NIPA1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of NIPA1 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 NIPA1 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with NIPA1 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with NIPA1 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 NIPA1 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of NIPA1 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.