PTDSS1 Gene

Name	phosphatidylserine synthase 1
Description	The protein encoded by this gene catalyzes the formation of phosphatidylserine from either phosphatidylcholine or phosphatidylethanolamine. Phosphatidylserine localizes to the mitochondria-associated membrane of the endoplasmic reticulum, where it serves a structural role as well as a signaling role. Defects in this gene are a cause of Lenz-Majewski hyperostotic dwarfism. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2014]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPhosphatidylserine synthase 1 (PSS1), encoded by PTDSS1, is an integral endoplasmic reticulum enzyme that catalyzes the conversion of phosphatidylcholine—and, to a lesser extent, phosphatidylethanolamine—into phosphatidylserine (PS). In normal cells, PSS1 activity is finely tuned by feedback inhibition exerted by its product, PS. However, missense mutations in PTDSS1 abolish this regulation, leading to gain‐of‐function effects characterized by unrestrained PS synthesis. This dysregulation is directly implicated in Lenz‐Majewski syndrome (LMS), a rare disorder marked by a constellation of craniofacial, skeletal, dental, and cutaneous anomalies, as well as intellectual disability."}, {"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 core synthetic activity, aberrant PSS1 function perturbs overall cellular lipid homeostasis. Novel studies have identified PTDSS1 as a potential susceptibility gene for Autism Spectrum Disorders, suggesting that imbalances in phospholipid metabolism might underlie broader neurodevelopmental disturbances. In cells expressing mutant PSS1, uncontrolled PS synthesis alters the levels of phosphatidylinositol 4‐phosphate (PI4P)—a key molecule in lipid trafficking and membrane signaling—which in turn disrupts the coupling between PS production and its transport. Moreover, the aberrant lipid profile is linked to extracellular matrix defects seen in cutis laxa phenotypes, further expanding the clinical spectrum associated with PTDSS1 dysregulation."}, {"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": "\nExperimental efforts to model PTDSS1 dysfunction have further illuminated its physiological roles. Transposon‐mediated transgenesis in zebrafish, aimed at recapitulating the human pathology, encountered challenges such as transgene silencing and viability issues, highlighting the enzyme’s critical role in skeletal development. In parallel, alanine‐scanning mutagenesis and epitope mapping have delineated the enzyme’s membrane topology, revealing that its key catalytic residues reside in the ER lumen while regulatory domains localize to the cytosolic leaflet—thereby explaining the mechanism of PS-mediated feedback inhibition. Complementary studies in osteoclasts have demonstrated that uncontrolled PS synthesis impairs podosome dynamics and cell fusion, potentially accounting for the osteosclerotic features observed in LMS patients."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Shiho Tomohiro, Ayako Kawaguti, Yukiyo Kawabe, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Purification and characterization of human phosphatidylserine synthases 1 and 2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20081597"}], "href": "https://doi.org/10.1042/BJ20081597"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19014349"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19014349"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Sérgio B Sousa, Dagan Jenkins, Estelle Chanudet, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Gain-of-function mutations in the phosphatidylserine synthase 1 (PTDSS1) gene cause Lenz-Majewski syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.2829"}], "href": "https://doi.org/10.1038/ng.2829"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24241535"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24241535"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Jihane Soueid, Silva Kourtian, Nadine J Makhoul, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RYR2, PTDSS1 and AREG genes are implicated in a Lebanese population-based study of copy number variation in autism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep19088"}], "href": "https://doi.org/10.1038/srep19088"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26742492"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26742492"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Mira Sohn, Pavlina Ivanova, H Alex Brown, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lenz-Majewski mutations in PTDSS1 affect phosphatidylinositol 4-phosphate metabolism at ER-PM and ER-Golgi junctions."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1525719113"}], "href": "https://doi.org/10.1073/pnas.1525719113"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27044099"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27044099"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Juliette Piard, James Lespinasse, Marketa Vlckova, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cutis laxa and excessive bone growth due to de novo mutations in PTDSS1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet A (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.a.38604"}], "href": "https://doi.org/10.1002/ajmg.a.38604"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29341480"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29341480"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Marian Seda, Emma Peskett, Charalambos Demetriou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Analysis of transgenic zebrafish expressing the Lenz-Majewski syndrome gene "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "PTDSS1"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " in skeletal cell lineages."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "F1000Res (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.12688/f1000research.17314.1"}], "href": "https://doi.org/10.12688/f1000research.17314.1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31231513"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31231513"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Non Miyata, Osamu Kuge "}, {"type": "b", "children": [{"type": "t", "text": "Topology of phosphatidylserine synthase 1 in the endoplasmic reticulum membrane."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Protein Sci (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/pro.4182"}], "href": "https://doi.org/10.1002/pro.4182"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34516042"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34516042"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Sari Sugahara, Yuki Ishino, Koki Sawada, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Disease-related PSS1 mutant impedes the formation and function of osteoclasts."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Lipid Res (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jlr.2023.100443"}], "href": "https://doi.org/10.1016/j.jlr.2023.100443"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37714410"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37714410"}]}]}]}
Synonyms	PSSA, LMHD
Proteins	PTSS1_HUMAN
NCBI Gene ID	9791
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

PTDSS1 has 8,624 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 138 datasets.

Click the + buttons to view associations for PTDSS1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

PTDSS1 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by PTDSS1 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of PTDSS1 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 PTDSS1 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 PTDSS1 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 PTDSS1 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 PTDSS1 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 PTDSS1 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 PTDSS1 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 PTDSS1 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 PTDSS1 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 PTDSS1 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of PTDSS1 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 PTDSS1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with PTDSS1 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with PTDSS1 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 PTDSS1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of PTDSS1 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 PTDSS1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with PTDSS1 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with PTDSS1 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of PTDSS1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing PTDSS1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing PTDSS1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing PTDSS1 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 PTDSS1 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 PTDSS1 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 PTDSS1 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 PTDSS1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with PTDSS1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with PTDSS1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of PTDSS1 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 PTDSS1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving PTDSS1 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with PTDSS1 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 PTDSS1 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 PTDSS1 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 PTDSS1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with PTDSS1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for PTDSS1 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at PTDSS1 gene from the ENCODE Histone Modification Site Profiles dataset.