SHMT1 Gene

Name	serine hydroxymethyltransferase 1 (soluble)
Description	This gene encodes the cytosolic form of serine hydroxymethyltransferase, a pyridoxal phosphate-containing enzyme that catalyzes the reversible conversion of serine and tetrahydrofolate to glycine and 5,10-methylene tetrahydrofolate. This reaction provides one-carbon units for synthesis of methionine, thymidylate, and purines in the cytoplasm. This gene is located within the Smith-Magenis syndrome region on chromosome 17. A pseudogene of this gene is located on the short arm of chromosome 1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nCytosolic serine hydroxymethyltransferase 1 (SHMT1) is a key enzyme in folate‐dependent one‐carbon metabolism that catalyzes the reversible conversion of serine and tetrahydrofolate (THF) into glycine and 5,10‐methylene THF—a reaction fundamental to the synthesis of nucleotide precursors. By providing one‐carbon units, SHMT1 directs folate flux toward de novo thymidylate (dTMP) synthesis rather than S-adenosylmethionine (SAM) production, thereby maintaining the balance between DNA synthesis and methylation reactions. This enzymatic function is reflected in its central role in replenishing the one‐carbon pool necessary for DNA replication and repair, as originally characterized in studies of its basic biochemistry."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}, {"type": "p", "children": [{"type": "t", "text": "\nSHMT1 is not only essential for its metabolic conversion but is also subject to intricate regulatory mechanisms. During S-phase, SHMT1 undergoes SUMOylation and nuclear translocation along with thymidylate synthase (TYMS) and dihydrofolate reductase (DHFR) to enable localized dTMP synthesis. This compartmentation acts as a metabolic switch that prioritizes nucleotide production over methylation reactions. Notably, studies have shown that loss of SHMT1 can be partially compensated by an alternative cytoplasmic/nuclear isoform derived from the SHMT2 gene, underscoring a built-in functional redundancy that influences cell viability and contributes to the physiological tolerance of certain genetic polymorphisms."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its central metabolic role, SHMT1 is emerging as a critical factor in cancer biology. In lung cancer, for example, SHMT1 is found to be overexpressed, and its knockdown leads to cell cycle arrest and p53-dependent apoptosis due to uracil misincorporation during DNA replication. Structurally, SHMT1 exists as a stable tetramer independent of its cofactor pyridoxal 5'-phosphate (PLP), a property that differentiates it from the mitochondrial isoform SHMT2, which undergoes ligand-dependent oligomerization. In addition, the presence of aberrant (truncated) forms of SHMT1 in plasma has been observed in patients with breast and ovarian cancers, raising the potential for its use as a biomarker."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "7"}]}]}]}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "S G Heil, N M Van der Put, E T Waas, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Is mutated serine hydroxymethyltransferase (SHMT) involved in the etiology of neural tube defects?"}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Genet Metab (2001)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1006/mgme.2001.3175"}], "href": "https://doi.org/10.1006/mgme.2001.3175"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11386852"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11386852"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Katherine Herbig, En-Pei Chiang, Ling-Ru Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cytoplasmic serine hydroxymethyltransferase mediates competition between folate-dependent deoxyribonucleotide and S-adenosylmethionine biosyntheses."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M205000200"}], "href": "https://doi.org/10.1074/jbc.M205000200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12161434"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12161434"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Collynn F Woeller, Donald D Anderson, Doletha M E Szebenyi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Evidence for small ubiquitin-like modifier-dependent nuclear import of the thymidylate biosynthesis pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M702526200"}], "href": "https://doi.org/10.1074/jbc.M702526200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17446168"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17446168"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Donald D Anderson, Patrick J Stover "}, {"type": "b", "children": [{"type": "t", "text": "SHMT1 and SHMT2 are functionally redundant in nuclear de novo thymidylate biosynthesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0005839"}], "href": "https://doi.org/10.1371/journal.pone.0005839"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19513116"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19513116"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "A Paone, M Marani, A Fiascarelli, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SHMT1 knockdown induces apoptosis in lung cancer cells by causing uracil misincorporation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/cddis.2014.482"}], "href": "https://doi.org/10.1038/cddis.2014.482"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25412303"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25412303"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Giorgio Giardina, Paolo Brunotti, Alessio Fiascarelli, et al. "}, {"type": "b", "children": [{"type": "t", "text": "How pyridoxal 5'-phosphate differentially regulates human cytosolic and mitochondrial serine hydroxymethyltransferase oligomeric state."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS J (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/febs.13211"}], "href": "https://doi.org/10.1111/febs.13211"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25619277"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25619277"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Marta Lomnytska, Anna Dubrovska, Ulf Hellman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Increased expression of cSHMT, Tbx3 and utrophin in plasma of ovarian and breast cancer patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Cancer (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ijc.21332"}], "href": "https://doi.org/10.1002/ijc.21332"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16049973"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16049973"}]}]}]}
Synonyms	CSHMT, SHMT
Proteins	GLYC_HUMAN
NCBI Gene ID	6470
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

SHMT1 has 8,781 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 133 datasets.

Click the + buttons to view associations for SHMT1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

SHMT1 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 SHMT1 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 SHMT1 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 SHMT1 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 SHMT1 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 SHMT1 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 SHMT1 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 SHMT1 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 SHMT1 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 SHMT1 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 SHMT1 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of SHMT1 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 SHMT1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with SHMT1 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 SHMT1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of SHMT1 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 SHMT1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing SHMT1 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 SHMT1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing SHMT1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing SHMT1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing SHMT1 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with SHMT1 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 SHMT1 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 SHMT1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with SHMT1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with SHMT1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with SHMT1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of SHMT1 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 SHMT1 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 SHMT1 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 SHMT1 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 SHMT1 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 SHMT1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with SHMT1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for SHMT1 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at SHMT1 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 SHMT1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of SHMT1 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 SHMT1 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with SHMT1 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.