SMAP1 Gene

HGNC Family	ArfGAPs
Name	small ArfGAP 1
Description	The protein encoded by this gene is similar to the mouse stromal membrane-associated protein-1. This similarity suggests that this human gene product is also a type II membrane glycoprotein involved in the erythropoietic stimulatory activity of stromal cells. Alternate splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSMAP1 functions as a GTPase‐activating protein (GAP) that specifically inactivates Arf6, a small GTPase critical for actin remodeling and membrane trafficking. In this context, SMAP1 regulates clathrin‐dependent endocytosis by binding directly to the clathrin heavy chain via its clathrin-box motif, and its GAP domain is essential for controlling the internalization of transferrin receptors. Evidence also indicates that SMAP1 shares overlapping roles with its related isoform SMAP2, as the presence of either protein is sufficient for proper transferrin endocytosis, while their combined loss impairs this process."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its canonical role in endocytosis, SMAP1 has been implicated in the regulation of cancer cell behavior. In microsatellite instable colorectal cancers, loss‐of-function mutations in SMAP1—often resulting from frameshift events in a coding repeat region—lead to reduced transcript levels and protein instability. Functionally, restoration of SMAP1 in deficient cell models has been associated with decreased cell proliferation, clonogenicity, and invasiveness, as well as modulation of epithelial-to-mesenchymal transition markers. Moreover, SMAP1 appears to act redundantly with tight junction proteins, such as Pals1, to regulate Arf6 and downstream Rac1 activity; concomitant reduction of both proteins intensifies cell migration and invasion, correlating with poorer patient survival."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition, genome-wide association studies have identified SMAP1 as a novel susceptibility locus for pediatric venous thromboembolism. Single nucleotide polymorphisms within the SMAP1 gene region have reached genome-wide significance, underscoring its potential contribution to vascular pathology and highlighting the need for further functional studies to elucidate the molecular mechanisms by which SMAP1 variants predispose to disease."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Kenji Tanabe, Tetsuo Torii, Waka Natsume, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel GTPase-activating protein for ARF6 directly interacts with clathrin and regulates clathrin-dependent endocytosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.e04-08-0683"}], "href": "https://doi.org/10.1091/mbc.e04-08-0683"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15659652"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15659652"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Nobuhide Kobayashi, Shunsuke Kon, Yuji Henmi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Arf GTPase-activating protein SMAP1 promotes transferrin receptor endocytosis and interacts with SMAP2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2014.09.108"}], "href": "https://doi.org/10.1016/j.bbrc.2014.09.108"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25281535"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25281535"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "F Sangar, A-S Schreurs, C Umaña-Diaz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Involvement of small ArfGAP1 (SMAP1), a novel Arf6-specific GTPase-activating protein, in microsatellite instability oncogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2013.211"}], "href": "https://doi.org/10.1038/onc.2013.211"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23752192"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23752192"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Julia Harms, Simona Mareike Lüttgenau, Christin Emming, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pals1 functions in redundancy with SMAP1 to inhibit Arf6 in order to prevent Rac1-dependent colorectal cancer cell migration and invasion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Gene Ther (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41417-022-00570-2"}], "href": "https://doi.org/10.1038/s41417-022-00570-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36494580"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36494580"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Frank Rühle, Anika Witten, Andrei Barysenka, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Rare genetic variants in SMAP1, B3GAT2, and RIMS1 contribute to pediatric venous thromboembolism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2016-07-728840"}], "href": "https://doi.org/10.1182/blood-2016-07-728840"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28011674"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28011674"}]}]}]}
Synonyms	SMAP-1
Proteins	SMAP1_HUMAN
NCBI Gene ID	60682
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

SMAP1 has 5,206 functional associations with biological entities spanning 8 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 103 datasets.

Click the + buttons to view associations for SMAP1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

SMAP1 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 SMAP1 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 SMAP1 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 SMAP1 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 SMAP1 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 SMAP1 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 SMAP1 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 SMAP1 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 SMAP1 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 SMAP1 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 SMAP1 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 SMAP1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of SMAP1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of SMAP1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing SMAP1 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of SMAP1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing SMAP1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing SMAP1 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing SMAP1 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 SMAP1 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 SMAP1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with SMAP1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with SMAP1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with SMAP1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with SMAP1 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of SMAP1 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 SMAP1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with SMAP1 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with SMAP1 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 SMAP1 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 SMAP1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with SMAP1 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 SMAP1 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 SMAP1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of SMAP1 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 SMAP1 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with SMAP1 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with SMAP1 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 SMAP1 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with SMAP1 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 SMAP1 from the GeneSigDB Published Gene Signatures dataset.