CERS2 Gene

HGNC Family	Homeoboxes
Name	ceramide synthase 2
Description	This gene encodes a protein that has sequence similarity to yeast longevity assurance gene 1. Mutation or overexpression of the related gene in yeast has been shown to alter yeast lifespan. The human protein may play a role in the regulation of cell growth. Alternatively spliced transcript variants encoding the same protein have been described. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Ceramide synthase 2 (CERS2) is a critical enzyme in sphingolipid metabolism that catalyzes the synthesis of very long‐chain ceramides (predominantly C22–C24), which are essential for establishing the proper acyl chain composition of cellular membranes. Comprehensive studies have demonstrated that CERS2 expression and activity govern diverse cellular functions by modulating membrane structure, signal transduction, and cellular stress responses. For instance, genetic ablation or knockdown of CERS2 in mice leads to a striking depletion of very long‐chain ceramides that is accompanied by compensatory increases in shorter chain species (e.g., C16‐ceramide), perturbing membrane fluidity, altering mitochondrial function (including complex IV activity), and triggering oxidative stress, apoptosis, autophagy, and unfolded protein responses."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition, further studies in CerS2‐null and gene‐trapped mice have revealed that loss of CERS2 impacts critical physiological processes such as myelin maintenance in the nervous system, liver homeostasis, and even tumorigenesis through altered cell proliferation and apoptosis, with some models developing hepatocellular carcinoma or showing myelin degeneration."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n CERS2 activity is subject to regulatory modifications such as phosphorylation and deacetylation, which modulate its catalytic efficiency and ensure that the production of very long‐chain ceramides is tightly coordinated with broader lipid metabolic networks and membrane biophysical properties."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, in cancer models, modulation of CERS2 expression has been implicated in regulating tumor cell invasion and chemoresistance by affecting extracellular acidity and the activity of proton pumps such as the V‐ATPase. Elevated CERS2 levels have been correlated with less aggressive phenotypes in certain cancers, suggesting that precise control of sphingolipid chain length is also important for maintaining cellular homeostasis in neoplastic conditions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings underscore the multifaceted role of CERS2 in maintaining the proper balance of ceramide species that is required for membrane integrity, signal regulation, and the prevention of pathologies ranging from neurodegeneration and liver disease to cancer. As such, CERS2 represents a potential therapeutic target for intervention in metabolic, neurological, and oncologic disorders.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Elad L Laviad, Lee Albee, Irene Pankova-Kholmyansky, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterization of ceramide synthase 2: tissue distribution, substrate specificity, and inhibition by sphingosine 1-phosphate."}]}, {"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.M707386200"}], "href": "https://doi.org/10.1074/jbc.M707386200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18165233"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18165233"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Suryaprakash Raichur, Siew Tein Wang, Puck Wee Chan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CerS2 haploinsufficiency inhibits β-oxidation and confers susceptibility to diet-induced steatohepatitis and insulin resistance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Metab (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cmet.2014.09.015"}], "href": "https://doi.org/10.1016/j.cmet.2014.09.015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25295789"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25295789"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Silke Imgrund, Dieter Hartmann, Hany Farwanah, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Adult ceramide synthase 2 (CERS2)-deficient mice exhibit myelin sheath defects, cerebellar degeneration, and hepatocarcinomas."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M109.031971"}], "href": "https://doi.org/10.1074/jbc.M109.031971"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19801672"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19801672"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yael Pewzner-Jung, Hyejung Park, Elad L Laviad, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A critical role for ceramide synthase 2 in liver homeostasis: I. alterations in lipid metabolic pathways."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M109.077594"}], "href": "https://doi.org/10.1074/jbc.M109.077594"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20110363"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20110363"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Yael Pewzner-Jung, Ori Brenner, Svantje Braun, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A critical role for ceramide synthase 2 in liver homeostasis: II. insights into molecular changes leading to hepatopathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M109.077610"}], "href": "https://doi.org/10.1074/jbc.M109.077610"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20110366"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20110366"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Hila Zigdon, Aviram Kogot-Levin, Joo-Won Park, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ablation of ceramide synthase 2 causes chronic oxidative stress due to disruption of the mitochondrial respiratory chain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M112.402719"}], "href": "https://doi.org/10.1074/jbc.M112.402719"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23283968"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23283968"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Stefka D Spassieva, Thomas D Mullen, Danyelle M Townsend, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Disruption of ceramide synthesis by CerS2 down-regulation leads to autophagy and the unfolded protein response."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20090699"}], "href": "https://doi.org/10.1042/BJ20090699"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19728861"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19728861"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Liana C Silva, Oshrit Ben David, Yael Pewzner-Jung, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ablation of ceramide synthase 2 strongly affects biophysical properties of membranes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Lipid Res (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1194/jlr.M022715"}], "href": "https://doi.org/10.1194/jlr.M022715"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22231783"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22231783"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Takayuki Sassa, Taisuke Hirayama, Akio Kihara "}, {"type": "b", "children": [{"type": "t", "text": "Enzyme Activities of the Ceramide Synthases CERS2-6 Are Regulated by Phosphorylation in the C-terminal Region."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M115.695858"}], "href": "https://doi.org/10.1074/jbc.M115.695858"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26887952"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26887952"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Sergei A Novgorodov, Christopher L Riley, Jarryd A Keffler, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SIRT3 Deacetylates Ceramide Synthases: IMPLICATIONS FOR MITOCHONDRIAL DYSFUNCTION AND BRAIN INJURY."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M115.668228"}], "href": "https://doi.org/10.1074/jbc.M115.668228"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26620563"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26620563"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Shao-hua Fan, Yan-yan Wang, Jun Lu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CERS2 suppresses tumor cell invasion and is associated with decreased V-ATPase and MMP-2/MMP-9 activities in breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biochem (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcb.24978"}], "href": "https://doi.org/10.1002/jcb.24978"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25213553"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25213553"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Julia Barthelmes, Anika Männer de Bazo, Yael Pewzner-Jung, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lack of ceramide synthase 2 suppresses the development of experimental autoimmune encephalomyelitis by impairing the migratory capacity of neutrophils."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Brain Behav Immun (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbi.2015.02.010"}], "href": "https://doi.org/10.1016/j.bbi.2015.02.010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25697397"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25697397"}]}]}]}
Synonyms	SP260, TMSG1, LASS2
Proteins	CERS2_HUMAN
NCBI Gene ID	29956
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

CERS2 has 6,667 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 126 datasets.

Click the + buttons to view associations for CERS2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

CERS2 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 CERS2 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 CERS2 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 CERS2 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 CERS2 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 CERS2 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 CERS2 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 CERS2 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 CERS2 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 CERS2 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 CERS2 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of CERS2 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 CERS2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with CERS2 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with CERS2 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 CERS2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of CERS2 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 CERS2 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 CERS2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing CERS2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing CERS2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing CERS2 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 CERS2 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	cellular components co-occuring with CERS2 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 CERS2 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 CERS2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with CERS2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with CERS2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of CERS2 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 CERS2 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with CERS2 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with CERS2 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 CERS2 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 CERS2 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 CERS2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with CERS2 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 CERS2 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 CERS2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of CERS2 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 CERS2 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with CERS2 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.