SOCS5 Gene

HGNC Family	SH2 domain containing
Name	suppressor of cytokine signaling 5
Description	The protein encoded by this gene contains a SH2 domain and a SOCS BOX domain. The protein thus belongs to the suppressor of cytokine signaling (SOCS) family, also known as STAT-induced STAT inhibitor (SSI) protein family. SOCS family members are known to be cytokine-inducible negative regulators of cytokine signaling. The specific function of this protein has not yet been determined. Two alternatively spliced transcript variants encoding an identical protein have been reported. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSOCS5 is a member of the suppressor of cytokine signaling family that plays a multifaceted role in modulating cytokine and growth factor signaling. In tumor–host interactions, for example, tumor‐derived miR‑9 reduces SOCS5 expression in endothelial cells, leading to excessive JAK–STAT activation and promoting angiogenesis, while SOCS5 itself is induced by EGF to drive EGFR degradation, thereby serving as a negative feedback regulator in receptor tyrosine kinase pathways. In allergic inflammation models, constitutive expression of SOCS5 curbs IL‑4–mediated Th2 responses, resulting in diminished eosinophil infiltration."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn various malignancies, SOCS5 functions in a context‐dependent manner. In hepatocellular and pancreatic carcinomas, altered SOCS5 levels have been linked to aberrant activation of the PI3K/Akt/mTOR and JAK/STAT pathways, thereby influencing cell migration, invasion, and metastasis. Furthermore, SOCS5 helps restrain viral replication by modulating EGFR activity in influenza‐infected airway epithelia and, conversely, its downregulation by miRNAs during Japanese encephalitis virus or pancreatic cancer infection can enhance pro‐viral and pro‐tumorigenic signaling. In cervical cancer and osteosarcoma, targeting by miRNAs (such as miR‑301a and miR‑18a‑5p) leads to dysregulated SOCS5 expression that perturbs autophagy and epithelial–mesenchymal transition, while direct binding of SOCS5 to JAK1/2 and to phosphorylated Shc‑1 further underscores its role as an inhibitor of both cytokine and growth factor signaling. Structural studies also reveal that although much of its N‑terminal region is disordered, a conserved segment may be critical for partner recognition."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "12"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nSOCS5 also exerts significant influence on immune regulation and is emerging as a key node in gene–environment interactions. In liver cancer, the lncRNA HAND2‑AS1 enhances SOCS5 expression through miRNA sponging, leading to subdued JAK–STAT signaling and decreased tumor cell proliferation. In chronic lymphocytic leukemia, increased SOCS5 decouples IL‑4 receptor signaling from STAT6 activation, thereby impairing dendritic cell differentiation and T‑cell responses. Coordinated transcriptional regulation with SOCS6 has been observed in certain thyroid and liver cancers, while epigenetic silencing of SOCS5 contributes to unchecked cytokine receptor signaling in T‑cell acute lymphoblastic leukemia. In chronic obstructive pulmonary disease, miR‑132–mediated targeting of SOCS5 modulates inflammatory cytokine production, and altered SOCS5 expression is also implicated in immune dysfunction in multiple sclerosis. Genetic studies further support a role for SOCS5 in disease predisposition; for instance, noncoding RNAs and polymorphic variants (including those affecting miRNA binding sites) in SOCS5 have been linked to regulation in endometrial carcinoma, hepatocellular carcinoma, cholangiocarcinoma, non–small cell lung cancer, and allergic conditions such as bronchial asthma, as well as in glioblastoma where high SOCS5 levels promote chemoresistance via Bcl‑2–driven autophagy. Moreover, in prostate cancer, resistin‐induced SOCS5 elevates mitogenic signaling, and specific single nucleotide polymorphisms in SOCS5 modify immune responses in ocular inflammatory disease and atopic disorders."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "13", "end_ref": "31"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Guanglei Zhuang, Xiumin Wu, Zhaoshi Jiang, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Resistin stimulates PC-3 prostate cancer cell growth through stimulation of SOCS3 and SOCS5 genes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Biol Med (Maywood) (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1177/15353702231191206"}], "href": "https://doi.org/10.1177/15353702231191206"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37646261"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37646261"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Yun-Xia Liu, Hong Wang, Xiao-Yan Peng, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "[Association of polymorphism Rs6737848 in the Socs5 gene with bronchial asthma]."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Vestn Ross Akad Med Nauk (2013)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24340963"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24340963"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Showkat Hussain, Roohi Rasool, Tabasum Shafi, et al. 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Synonyms	CIS6, CISH6, SOCS-5, CISH5
Proteins	SOCS5_HUMAN
NCBI Gene ID	9655
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

SOCS5 has 6,588 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 114 datasets.

Click the + buttons to view associations for SOCS5 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

SOCS5 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 SOCS5 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 SOCS5 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 SOCS5 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 SOCS5 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 SOCS5 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 SOCS5 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 SOCS5 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 SOCS5 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 SOCS5 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 SOCS5 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of SOCS5 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 SOCS5 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of SOCS5 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of SOCS5 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 SOCS5 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 SOCS5 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 SOCS5 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing SOCS5 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 SOCS5 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 SOCS5 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 SOCS5 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with SOCS5 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with SOCS5 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with SOCS5 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by SOCS5 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with SOCS5 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 SOCS5 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 SOCS5 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with SOCS5 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 SOCS5 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 SOCS5 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of SOCS5 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 SOCS5 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with SOCS5 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with SOCS5 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of SOCS5 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with SOCS5 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 SOCS5 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of SOCS5 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 SOCS5 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.