SAMD8 Gene

HGNC Family	Sterile alpha motif (SAM) domain containing (SAMD)
Name	sterile alpha motif domain containing 8
Description	Predicted to enable ceramide cholinephosphotransferase activity and sphingomyelin synthase activity. Involved in ceramide biosynthetic process and regulation of ceramide biosynthetic process. Located in cytosol and endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Mar 2025]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSAMD8, also known as SMSr, is an endoplasmic reticulum–resident enzyme that plays a pivotal role during sphingolipid biosynthesis by channeling ceramides into the production of ceramide phosphoethanolamine (CPE). This activity prevents excessive ceramide accumulation in the ER, which would otherwise mislocalize to mitochondria and trigger a mitochondrial pathway of apoptotic cell death. In this way, SAMD8 is essential for monitoring and maintaining ceramide homeostasis and thus serves as a critical suppressor of ceramide-mediated apoptosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its CPE synthase function, SAMD8 exhibits a range of alternative catalytic activities. Highly purified enzyme preparations have revealed that SAMD8 possesses phosphatidic acid phosphatase and phospholipase C activities, generating diacylglycerol (DG) from substrates including phosphatidylethanolamine, phosphatidic acid, and phosphatidylinositol. Moreover, its activity and anti‐apoptotic function are tightly linked to its N-terminal sterile α-motif (SAM domain), which is required not only for full catalytic suppression of ceramide-induced cell death but also for mediating specific protein–protein interactions—such as with diacylglycerol kinase δ—to engage novel DG/PA signaling pathways. Notably, during apoptotic stimulation, SAMD8 is cleaved by caspase‑6 at a conserved site downstream of its SAM domain, underscoring its integration into cellular death-signaling networks."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "2", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nRecent in vivo studies further reveal that modulation of SAMD8/PE-PLC activity has significant implications for broader aspects of physiology. In models of nonalcoholic fatty liver disease (NAFLD), inhibition or genetic deficiency of SAMD8 leads to phosphatidylethanolamine accumulation that attenuates steatosis, nonalcoholic steatohepatitis, and even fibrosis. These findings suggest that, besides its role in ceramide homeostasis and apoptotic control, SAMD8 is an important regulator of lipid metabolism whose dysregulation may contribute to metabolic and fibrotic liver disorders."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Fikadu G Tafesse, Ana M Vacaru, Elleke F Bosma, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sphingomyelin synthase-related protein SMSr is a suppressor of ceramide-induced mitochondrial apoptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.138933"}], "href": "https://doi.org/10.1242/jcs.138933"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24259670"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24259670"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Birol Cabukusta, Niclas T Nettebrock, Matthijs Kol, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ceramide phosphoethanolamine synthase SMSr is a target of caspase-6 during apoptotic cell death."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biosci Rep (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BSR20170867"}], "href": "https://doi.org/10.1042/BSR20170867"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28659495"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28659495"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Chiaki Murakami, Fumio Sakane "}, {"type": "b", "children": [{"type": "t", "text": "Sphingomyelin synthase-related protein generates diacylglycerol via the hydrolysis of glycerophospholipids in the absence of ceramide."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jbc.2021.100454"}], "href": "https://doi.org/10.1016/j.jbc.2021.100454"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33621517"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33621517"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Masataka Furuta, Chiaki Murakami, Yuki Numagami, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Diacylglycerol kinase ζ interacts with sphingomyelin synthase 1 and sphingomyelin synthase-related protein via different regions."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Open Bio (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/2211-5463.13628"}], "href": "https://doi.org/10.1002/2211-5463.13628"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37166445"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37166445"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Yeun-Po Chiang, Zhiqiang Li, Mulin He, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sphingomyelin synthase-related protein SMSr is a phosphatidylethanolamine phospholipase C that promotes nonalcoholic fatty liver disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jbc.2023.105162"}], "href": "https://doi.org/10.1016/j.jbc.2023.105162"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37586586"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37586586"}]}]}]}
Synonyms	HEL-177, SMSR
Proteins	SAMD8_HUMAN
NCBI Gene ID	142891
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

SAMD8 has 5,283 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 107 datasets.

Click the + buttons to view associations for SAMD8 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

SAMD8 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 SAMD8 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 SAMD8 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 SAMD8 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 SAMD8 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 SAMD8 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 SAMD8 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of SAMD8 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 SAMD8 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 SAMD8 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with SAMD8 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 SAMD8 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of SAMD8 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 SAMD8 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 SAMD8 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing SAMD8 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing SAMD8 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with SAMD8 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 SAMD8 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 SAMD8 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with SAMD8 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with SAMD8 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with SAMD8 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of SAMD8 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 SAMD8 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 SAMD8 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 SAMD8 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 SAMD8 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 SAMD8 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with SAMD8 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 SAMD8 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 SAMD8 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of SAMD8 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 SAMD8 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with SAMD8 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 SAMD8 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of SAMD8 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 SAMD8 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 SAMD8 gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset.
	GEO Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of SAMD8 gene from the GEO Signatures of Differentially Expressed Genes for Small Molecules dataset.
	GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations	transcription factor perturbations changing expression of SAMD8 gene from the GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations dataset.