GAS6 Gene

Name	growth arrest-specific 6
Description	This gene encodes a gamma-carboxyglutamic acid (Gla)-containing protein thought to be involved in the stimulation of cell proliferation. This gene is frequently overexpressed in many cancers and has been implicated as an adverse prognostic marker. Elevated protein levels are additionally associated with a variety of disease states, including venous thromboembolic disease, systemic lupus erythematosus, chronic renal failure, and preeclampsia. [provided by RefSeq, Aug 2014]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Growth arrest‐specific gene 6 (GAS6) is a vitamin K–dependent ligand that binds to and activates members of the TAM family of receptor tyrosine kinases—most notably AXL and MER—in a highly context‐dependent manner. In cancer, GAS6 binding to AXL has been shown to promote oncogenic signaling events that drive epithelial–mesenchymal transition, enhance survival and proliferation, and contribute to therapeutic resistance as well as metastatic dissemination (for example."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In the tumor microenvironment, GAS6 participates in autocrine and paracrine loops that influence not only tumor cell behavior but also critical stromal processes such as endothelial recruitment and angiogenesis; in this setting, shedding of TAM receptors and competition for GAS6 can modulate the extent of endothelial cell activation and metastatic colonization."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its roles in cancer, GAS6 is a pivotal mediator in immune regulation and tissue homeostasis. Binding of GAS6 to MER or AXL on phagocytes enhances the recognition and clearance of apoptotic cells via bridging to phosphatidylserine, a process that not only ensures efficient efferocytosis but also limits inflammatory cytokine production—thereby contributing to an anti‐inflammatory milieu."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In addition, GAS6 has been implicated in vascular biology; for instance, its interaction with AXL on platelets can amplify aggregation signals, thereby influencing thrombosis, while restoration of the GAS6–AXL pathway has been associated with protection against vascular calcification in smooth muscle cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n GAS6 also plays a central role in mediating viral entry. For example, in the context of Zika virus infection, GAS6 acts as a bridging molecule that links viral particles—bearing exposed phosphatidylserine—to AXL receptors on glial cells, thereby facilitating viral internalization."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Structural studies have further elucidated the molecular details of the GAS6–AXL interaction, identifying distinct binding sites that are essential for productive receptor dimerization and downstream signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, GAS6 functions as a multifunctional ligand that regulates diverse cellular processes—including proliferation, survival, migration, and immune modulation—by activating TAM receptors. Its activities have significant implications for cancer progression, thrombosis, immune homeostasis, and even viral pathogenesis, making the GAS6–TAM axis an attractive target for therapeutic intervention."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Zhenfeng Zhang, Jae Cheol Lee, Luping Lin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Activation of the AXL kinase causes resistance to EGFR-targeted therapy in lung cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.2330"}], "href": "https://doi.org/10.1038/ng.2330"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22751098"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22751098"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Christine Gjerdrum, Crina Tiron, Torill Høiby, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Axl is an essential epithelial-to-mesenchymal transition-induced regulator of breast cancer metastasis and patient survival."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0909333107"}], "href": "https://doi.org/10.1073/pnas.0909333107"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20080645"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20080645"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Kim J Png, Nils Halberg, Mitsukuni Yoshida, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A microRNA regulon that mediates endothelial recruitment and metastasis by cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature10661"}], "href": "https://doi.org/10.1038/nature10661"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22170610"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22170610"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Fiorenza Lotti, Awad M Jarrar, Rish K Pai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Chemotherapy activates cancer-associated fibroblasts to maintain colorectal cancer-initiating cells by IL-17A."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Med (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1084/jem.20131195"}], "href": "https://doi.org/10.1084/jem.20131195"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24323355"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24323355"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Lawrence Fourgeaud, Paqui G Través, Yusuf Tufail, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TAM receptors regulate multiple features of microglial physiology."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature17630"}], "href": "https://doi.org/10.1038/nature17630"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27049947"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27049947"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Federica Alciato, Pier Paolo Sainaghi, Daniele Sola, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TNF-alpha, IL-6, and IL-1 expression is inhibited by GAS6 in monocytes/macrophages."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Leukoc Biol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1189/jlb.0909610"}], "href": "https://doi.org/10.1189/jlb.0909610"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20103767"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20103767"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "A Angelillo-Scherrer, P de Frutos, C Aparicio, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Deficiency or inhibition of Gas6 causes platelet dysfunction and protects mice against thrombosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Med (2001)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/84667"}], "href": "https://doi.org/10.1038/84667"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11175853"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11175853"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Peter Vajkoczy, Pjotr Knyazev, Andrea Kunkel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dominant-negative inhibition of the Axl receptor tyrosine kinase suppresses brain tumor cell growth and invasion and prolongs survival."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0510923103"}], "href": "https://doi.org/10.1073/pnas.0510923103"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16585512"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16585512"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Laurent Meertens, Athena Labeau, Ophelie Dejarnac, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Axl Mediates ZIKA Virus Entry in Human Glial Cells and Modulates Innate Immune Responses."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2016.12.045"}], "href": "https://doi.org/10.1016/j.celrep.2016.12.045"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28076778"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28076778"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Kouki Morizono, Yiming Xie, Tove Olafsen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The soluble serum protein Gas6 bridges virion envelope phosphatidylserine to the TAM receptor tyrosine kinase Axl to mediate viral entry."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Host Microbe (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.chom.2011.03.012"}], "href": "https://doi.org/10.1016/j.chom.2011.03.012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21501828"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21501828"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Takako Sasaki, Pjotr G Knyazev, Naomi J Clout, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural basis for Gas6-Axl signalling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.emboj.7600912"}], "href": "https://doi.org/10.1038/sj.emboj.7600912"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16362042"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16362042"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Isabel Ben-Batalla, Alexander Schultze, Mark Wroblewski, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Axl, a prognostic and therapeutic target in acute myeloid leukemia mediates paracrine crosstalk of leukemia cells with bone marrow stroma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2013-03-491431"}], "href": "https://doi.org/10.1182/blood-2013-03-491431"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23982172"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23982172"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Wen-I Tsou, Khanh-Quynh N Nguyen, Daniel A Calarese, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Receptor tyrosine kinases, TYRO3, AXL, and MER, demonstrate distinct patterns and complex regulation of ligand-induced activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M114.569020"}], "href": "https://doi.org/10.1074/jbc.M114.569020"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25074926"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25074926"}]}]}]}
Synonyms	AXSF, AXLLG
Proteins	GAS6_HUMAN
NCBI Gene ID	2621
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

GAS6 has 12,026 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 GAS6 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

GAS6 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 GAS6 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 GAS6 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 GAS6 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 GAS6 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 GAS6 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 GAS6 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 GAS6 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 GAS6 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 GAS6 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 GAS6 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of GAS6 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 GAS6 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with GAS6 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with GAS6 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 GAS6 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of GAS6 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 GAS6 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 GAS6 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing GAS6 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 GAS6 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing GAS6 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing GAS6 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing GAS6 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 GAS6 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 GAS6 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 GAS6 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 GAS6 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with GAS6 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with GAS6 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with GAS6 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of GAS6 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 GAS6 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DGIdb Drug Targets 2026	interacting drugs for GAS6 protein from the DGIdb Drug Targets 2026 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with GAS6 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 GAS6 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 GAS6 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with GAS6 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 GAS6 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 GAS6 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of GAS6 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.