SACM1L Gene

Name	SAC1 suppressor of actin mutations 1-like (yeast)
Description	This gene encodes an integral membrane protein, which is localized to the endoplasmic reticulum, and functions as a phosphoinositide phosphatase that hydrolyzes phosphatidylinositol 3-phosphate, phosphatidylinositol 4-phosphate, and phosphatidylinositol 3,5-bisphosphate. Deletion of this gene in mouse results in preimplantation lethality. Other studies suggest that this gene is also involved in the organization of golgi membranes and mitotic spindles. Alternatively spliced transcript variants have been found for this gene. A C-terminally extended isoform is also predicted to be produced by the use of an alternative in-frame, downstream translation termination codon via a stop codon readthrough mechanism.[provided by RefSeq, Dec 2017]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSACM1L, the mammalian homolog of the yeast SAC1 gene, encodes an integral membrane protein with phosphatidylinositol-4-phosphate (PI4P) phosphatase activity that localizes predominantly to the endoplasmic reticulum and Golgi apparatus. Its fundamental role in controlling PI4P levels is critical for maintaining phosphoinositide homeostasis, which in turn impacts diverse cellular processes including secretory trafficking, Golgi organization, and the regulation of mitotic spindle dynamics. Studies in yeast and murine models reveal that loss of SACM1L function causes pleiotropic defects such as inositol auxotrophy, secretory pathway defects, and even preimplantation lethality due to mitotic errors."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAt the mechanistic level, SACM1L function is tightly coupled with membrane trafficking events. In mammalian cells, its recycling between the Golgi and ER is modulated by coat protein complexes: COPI‐mediated retrieval requires a specific KXKXX motif, while export from the ER into COPII vesicles depends on interactions with 14-3-3 proteins recognizing a defined sorting signal. Moreover, at endoplasmic reticulum–trans-Golgi network (TGN) contact sites, the adaptor protein FAPP1 recruits SACM1L in trans to regulate local PI4P consumption, thereby controlling lipid-dependent processes such as cargo exit from the Golgi. Despite these critical interactions, perturbations in SACM1L distribution appear to have only a limited direct effect on the activity of other lipid transfer proteins like OSBP."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its housekeeping roles in lipid metabolism, SACM1L has emerged as an important host factor in viral infections. During replication of positive-strand RNA viruses such as Aichi virus, SACM1L is co-opted as part of a cholesterol transport machinery that facilitates the formation of replication organelles through direct interactions with viral and host proteins. Similarly, in the context of Hepatitis B virus, SACM1L modulation leads to altered intracellular PI4P pools, which in turn disrupts the trafficking and envelopment of viral proteins, ultimately impairing virus assembly and release."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Holger M Rohde, Fei Ying Cheong, Gerlinde Konrad, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The human phosphatidylinositol phosphatase SAC1 interacts with the coatomer I complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M307983200"}], "href": "https://doi.org/10.1074/jbc.M307983200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14527956"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14527956"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Yang Liu, Malika Boukhelifa, Emily Tribble, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Sac1 phosphoinositide phosphatase regulates Golgi membrane morphology and mitotic spindle organization in mammals."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.e07-12-1290"}], "href": "https://doi.org/10.1091/mbc.e07-12-1290"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18480408"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18480408"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Kanika Bajaj Pahuja, Jinzhi Wang, Anastasia Blagoveshchenskaya, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Phosphoregulatory protein 14-3-3 facilitates SAC1 transport from the endoplasmic reticulum."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1509119112"}], "href": "https://doi.org/10.1073/pnas.1509119112"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26056309"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26056309"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Mark Charman, Asako Goto, Neale D Ridgway "}, {"type": "b", "children": [{"type": "t", "text": "Oxysterol-binding protein recruitment and activity at the endoplasmic reticulum-Golgi interface are independent of Sac1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Traffic (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/tra.12491"}], "href": "https://doi.org/10.1111/tra.12491"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28471037"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28471037"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Rossella Venditti, Maria Chiara Masone, Laura Rita Rega, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The activity of Sac1 across ER-TGN contact sites requires the four-phosphate-adaptor-protein-1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.201812021"}], "href": "https://doi.org/10.1083/jcb.201812021"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30659099"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30659099"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Kumiko Ishikawa-Sasaki, Shigeo Nagashima, Koki Taniguchi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Model of OSBP-Mediated Cholesterol Supply to Aichi Virus RNA Replication Sites Involving Protein-Protein Interactions among Viral Proteins, ACBD3, OSBP, VAP-A/B, and SAC1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Virol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/JVI.01952-17"}], "href": "https://doi.org/10.1128/JVI.01952-17"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29367253"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29367253"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Mirela-Andreea Popescu, David Patriche, Mihaela-Olivia Dobrica, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sac1 phosphatidylinositol 4-phosphate phosphatase is a novel host cell factor regulating hepatitis B virus particles assembly and release."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS J (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/febs.16575"}], "href": "https://doi.org/10.1111/febs.16575"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35816160"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35816160"}]}]}]}
Synonyms	SAC1
Proteins	SAC1_HUMAN
NCBI Gene ID	22908
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

SACM1L has 7,144 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 120 datasets.

Click the + buttons to view associations for SACM1L from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

SACM1L 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 SACM1L 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 SACM1L 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 SACM1L 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 SACM1L 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 SACM1L 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 SACM1L 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 SACM1L 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 SACM1L 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 SACM1L 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 SACM1L gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of SACM1L 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 SACM1L gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with SACM1L protein from the CCLE Cell Line Proteomics dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of SACM1L gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of SACM1L 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 SACM1L 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 SACM1L gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing SACM1L 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 SACM1L gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing SACM1L protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of SACM1L gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with SACM1L gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with SACM1L gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with SACM1L gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with SACM1L gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DGIdb Drug Targets 2026	interacting drugs for SACM1L protein from the DGIdb Drug Targets 2026 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with SACM1L gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with SACM1L gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DisGeNET Gene-Disease Associations	diseases associated with SACM1L gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with SACM1L 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 SACM1L 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 SACM1L gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of SACM1L 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 SACM1L from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with SACM1L gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with SACM1L 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 SACM1L gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with SACM1L 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 SACM1L from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of SACM1L gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.