ARL6IP1 Gene

Name	ADP-ribosylation factor-like 6 interacting protein 1
Description	This gene belongs to the ARL6ip family and encodes a transmembrane protein that is predominantly localized to intracytoplasmic membranes. It is highly expressed in early myeloid progenitor cells and thought to be involved in protein transport, membrane trafficking, or cell signaling during hematopoietic maturation. Mutations in this gene are associated with spastic paraplegia 61 (SPG61). Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2015]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ARL6IP1 is an endoplasmic reticulum (ER)–resident membrane protein characterized by reticulon‐like short hairpin transmembrane domains that enable it to shape high‐curvature ER tubules and stabilize the ER network (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Its anti‐apoptotic function has been demonstrated in cancer models where ARL6IP1 modulates the expression and activity of key apoptotic regulators—including caspases and p53—to protect cells from chemotherapeutic stress, as observed in cervical cancer cells (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " In addition, ARL6IP1 can interact with addicsin to indirectly enhance EAAC1‐mediated glutamate transport in a protein kinase C–dependent manner, thereby influencing neurotransmitter regulation (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Its critical role in ER shaping is also essential for neuronal integrity; loss‐of‐function mutations in ARL6IP1 are linked to severe neurodegenerative conditions such as hereditary spastic paraplegia, with studies in both human patients and Drosophila models revealing that disruption of ARL6IP1 leads to fragmented ER, altered lipid homeostasis, and impaired mitochondrial network organization in long motor axons (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Moreover, ARL6IP1 plays developmental roles; in zebrafish, for example, it is required for proper cell cycle exit and differentiation of retinal progenitor cells as well as for normal ocular, cardiac, and fin‐bud formation (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " ARL6IP1’s direct binding to bioactive compounds such as conophylline further implicates it in modulating cellular differentiation—including the maturation of insulin‐producing beta‐cells—and in the regulation of osteoclastogenesis via effects on transcription factors like CREB, c‐Fos, and NFATc1 (see."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "10"}]}, {"type": "t", "text": " Finally, emerging evidence also points to roles for ARL6IP1 in systemic stress responses, as it has been identified as a genetic marker associated with thermoregulation in cattle and its expression in spinal dorsal horn neurons is modulated in the context of cancer‐induced bone pain (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yasunori Yamamoto, Asuka Yoshida, Naoyuki Miyazaki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Arl6IP1 has the ability to shape the mammalian ER membrane in a reticulon-like fashion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20131186"}], "href": "https://doi.org/10.1042/BJ20131186"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24262037"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24262037"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Fengjie Guo, Yalin Li, Yan Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ARL6IP1 mediates cisplatin-induced apoptosis in CaSki cervical cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncol Rep (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/or_00000783"}], "href": "https://doi.org/10.3892/or_00000783"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20372863"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20372863"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Saori Akiduki, Mitsushi J Ikemoto "}, {"type": "b", "children": [{"type": "t", "text": "Modulation of the neural glutamate transporter EAAC1 by the addicsin-interacting protein ARL6IP1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M801570200"}], "href": "https://doi.org/10.1074/jbc.M801570200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18684713"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18684713"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Salma M Wakil, Safa Alhissi, Haya Al Dossari, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Truncating ARL6IP1 variant as the genetic cause of fatal complicated hereditary spastic paraplegia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Med Genet (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12881-019-0851-6"}], "href": "https://doi.org/10.1186/s12881-019-0851-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31272422"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31272422"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Dwayne J Byrne, M Elena Garcia-Pardo, Nelson B Cole, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Liver X receptor-agonist treatment rescues degeneration in a Drosophila model of hereditary spastic paraplegia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Acta Neuropathol Commun (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s40478-022-01343-6"}], "href": "https://doi.org/10.1186/s40478-022-01343-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35346366"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35346366"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Hsing-Yen Huang, Jeng-Ting Liu, Hong-Young Yan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Arl6ip1 plays a role in proliferation during zebrafish retinogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cells Tissues Organs (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1159/000331589"}], "href": "https://doi.org/10.1159/000331589"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22269635"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22269635"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Hsing-Yen Huang, En-Sheng Dai, Jeng-Ting Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The embryonic expression patterns and the knockdown phenotypes of zebrafish ADP-ribosylation factor-like 6 interacting protein gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Dyn (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/dvdy.21832"}], "href": "https://doi.org/10.1002/dvdy.21832"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19097054"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19097054"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Masahiro Kuroda, Shintaro Funasaki, Tsuyoshi Saitoh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Determination of topological structure of ARL6ip1 in cells: identification of the essential binding region of ARL6ip1 for conophylline."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.febslet.2013.09.017"}], "href": "https://doi.org/10.1016/j.febslet.2013.09.017"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24076029"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24076029"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Eriko Suzuki, Hideki Ogura, Kuniki Kato, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Preparation of conophylline affinity nano-beads and identification of a target protein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Bioorg Med Chem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bmc.2009.07.062"}], "href": "https://doi.org/10.1016/j.bmc.2009.07.062"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19679484"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19679484"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Naoki Koide, Yuichiro Kondo, Erdenezaya Odkhuu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inhibition of receptor activator of nuclear factor-κB ligand- or lipopolysaccharide-induced osteoclast formation by conophylline through downregulation of CREB."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Immunol Lett (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.imlet.2014.04.006"}], "href": "https://doi.org/10.1016/j.imlet.2014.04.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24792671"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24792671"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "S Dikmen, X-z Wang, M S Ortega, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Single nucleotide polymorphisms associated with thermoregulation in lactating dairy cows exposed to heat stress."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Anim Breed Genet (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/jbg.12176"}], "href": "https://doi.org/10.1111/jbg.12176"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26198991"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26198991"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Hou-Sheng Deng, Long-Sheng Xu, Hua-Dong Ni, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Proteomic profiling reveals Arl6ip-1 as a candidate target in cancer-induced bone pain rat model after oxycodone treatment."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurosci Lett (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neulet.2019.01.045"}], "href": "https://doi.org/10.1016/j.neulet.2019.01.045"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30708128"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30708128"}]}]}]}
Synonyms	SPG61, ARMER, ARL6IP
Proteins	AR6P1_HUMAN
NCBI Gene ID	23204
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

ARL6IP1 has 9,014 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 104 datasets.

Click the + buttons to view associations for ARL6IP1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

ARL6IP1 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 ARL6IP1 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 ARL6IP1 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 ARL6IP1 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 ARL6IP1 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 ARL6IP1 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 ARL6IP1 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 ARL6IP1 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 ARL6IP1 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 ARL6IP1 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 ARL6IP1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with ARL6IP1 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with ARL6IP1 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 ARL6IP1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of ARL6IP1 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 ARL6IP1 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 ARL6IP1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing ARL6IP1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing ARL6IP1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with ARL6IP1 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 ARL6IP1 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 ARL6IP1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with ARL6IP1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of ARL6IP1 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 ARL6IP1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving ARL6IP1 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving ARL6IP1 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with ARL6IP1 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 ARL6IP1 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 ARL6IP1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with ARL6IP1 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 ARL6IP1 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 ARL6IP1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of ARL6IP1 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 ARL6IP1 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of ARL6IP1 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with ARL6IP1 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 ARL6IP1 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of ARL6IP1 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 ARL6IP1 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 ARL6IP1 gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset.