SEMA4C Gene

HGNC Family	Semaphorins (SEMA), Immunoglobulin superfamily domain containing
Name	sema domain, immunoglobulin domain (Ig), transmembrane domain (TM) and short cytoplasmic domain, (semaphorin) 4C
Description	Predicted to enable chemorepellent activity; neuropilin binding activity; and semaphorin receptor binding activity. Involved in muscle cell differentiation and positive regulation of stress-activated MAPK cascade. Located in extracellular space. [provided by Alliance of Genome Resources, Mar 2025]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSEMA4C is emerging as a pivotal mediator of epithelial–mesenchymal transition (EMT) and chemoresistance in a variety of malignancies. In several studies, downregulation of SEMA4C—often mediated by microRNAs such as miR‑125b, miR‑138, miR‑25‑3p, and miR‑31‑3p—has been shown to reverse EMT phenotypes in paclitaxel‐resistant breast cancer, non–small‐cell lung cancer, and cisplatin‐resistant cervical cancer cells. In addition, SEMA4C is essential for TGF‑β1–induced p38 MAPK activation, a signal cascade that further promotes the EMT process."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its modulation by microRNAs, high SEMA4C expression has been directly linked to aggressive tumor behavior and poor clinical outcomes. Overexpression of SEMA4C in breast, colorectal, and osteosarcoma models correlates with enhanced cellular proliferation, aberrant cytokinesis, disrupted cell polarity, and increased invasion and metastasis. These changes are accompanied by upregulation of mesenchymal marker genes and activation of survival pathways that contribute to resistance against standard therapies."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nSEMA4C also functions within a complex signaling network through interactions with its receptor PlexinB2 and other regulatory proteins. Signaling via SEMA4C triggers downstream effectors such as NF‑κB, RhoA, and AKT, which further promote oncogenic processes. Moreover, binding partners such as Erbin can interfere with SEMA4C-driven EMT, indicating that modulation of SEMA4C interactions may offer novel therapeutic avenues. In parallel, emerging evidence suggests that semaphorins, including SEMA4C, may play roles in immune regulation, underscoring their multifunctional significance in both cancer and other diseases."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Rui Zeng, Min Han, Yun Luo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Role of Sema4C in TGF-β1-induced mitogen-activated protein kinase activation and epithelial-mesenchymal transition in renal tubular epithelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nephrol Dial Transplant (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/ndt/gfq619"}], "href": "https://doi.org/10.1093/ndt/gfq619"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20959347"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20959347"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Qingling Yang, Yangyang Wang, Xiaohui Lu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MiR-125b regulates epithelial-mesenchymal transition via targeting Sema4C in paclitaxel-resistant breast cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.3065"}], "href": "https://doi.org/10.18632/oncotarget.3065"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25605244"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25605244"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Jiefang Li, Qinrong Wang, Ruiling Wen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MiR-138 inhibits cell proliferation and reverses epithelial-mesenchymal transition in non-small cell lung cancer cells by targeting GIT1 and SEMA4C."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Mol Med (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/jcmm.12666"}], "href": "https://doi.org/10.1111/jcmm.12666"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26283050"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26283050"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Jing Song, Yue Li "}, {"type": "b", "children": [{"type": "t", "text": "miR-25-3p reverses epithelial-mesenchymal transition via targeting Sema4C in cisplatin-resistance cervical cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Sci (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/cas.13104"}], "href": "https://doi.org/10.1111/cas.13104"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27743413"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27743413"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Li Jing, Wang Bo, Feng Yourong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sema4C mediates EMT inducing chemotherapeutic resistance of miR-31-3p in cervical cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-019-54177-z"}], "href": "https://doi.org/10.1038/s41598-019-54177-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31776419"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31776419"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "HuiJuan Liu, Hui Ye, Xinzheng Li "}, {"type": "b", "children": [{"type": "t", "text": "Effect of microrna-138 on epithelial-Mesenchymal transition and invasion of breast cancer cells by targeting semaphorin 4C."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Bioengineered (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/21655979.2021.2000733"}], "href": "https://doi.org/10.1080/21655979.2021.2000733"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34747314"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34747314"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Sreeharsha Gurrapu, Emanuela Pupo, Giulia Franzolin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sema4C/PlexinB2 signaling controls breast cancer cell growth, hormonal dependence and tumorigenic potential."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Differ (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41418-018-0097-4"}], "href": "https://doi.org/10.1038/s41418-018-0097-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29555978"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29555978"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Jie Yang, Zhen Zeng, Long Qiao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Semaphorin 4C Promotes Macrophage Recruitment and Angiogenesis in Breast Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer Res (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1541-7786.MCR-18-0933"}], "href": "https://doi.org/10.1158/1541-7786.MCR-18-0933"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31308149"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31308149"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Branden A Smeester, Nicholas J Slipek, Emily J Pomeroy, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SEMA4C is a novel target to limit osteosarcoma growth, progression, and metastasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41388-019-1041-x"}], "href": "https://doi.org/10.1038/s41388-019-1041-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31582836"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31582836"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Lilan Yang, Yayuan Yu, Zhenfang Xiong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Downregulation of SEMA4C Inhibit Epithelial-Mesenchymal Transition (EMT) and the Invasion and Metastasis of Cervical Cancer Cells via Inhibiting Transforming Growth Factor-beta 1 (TGF-β1)-Induced Hela cells p38 Mitogen-Activated Protein Kinase (MAPK) Activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Med Sci Monit (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.12659/MSM.918123"}], "href": "https://doi.org/10.12659/MSM.918123"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31951596"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31951596"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Yufang Hou, Weiqi Wang, Zifan Zeng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "High SEMA4C expression promotes the epithelial-mesenchymal transition and predicts poor prognosis in colorectal carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Aging (Albany NY) (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/aging.104038"}], "href": "https://doi.org/10.18632/aging.104038"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33177246"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33177246"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Qiao-Dan Zhou, Yong Ning, Rui Zeng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Erbin interacts with Sema4C and inhibits Sema4C-induced epithelial-mesenchymal transition in HK2 cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Huazhong Univ Sci Technolog Med Sci (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11596-013-1179-7"}], "href": "https://doi.org/10.1007/s11596-013-1179-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24142719"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24142719"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Misagh Rajabinejad, Gelayol Asadi, Sedigheh Ranjbar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Semaphorin 4A, 4C, and 4D: Function comparison in the autoimmunity, allergy, and cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.gene.2020.144637"}], "href": "https://doi.org/10.1016/j.gene.2020.144637"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32244055"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32244055"}]}]}]}
Synonyms	M-SEMA-F, SEMAI, SEMACL1
Proteins	SEM4C_HUMAN
NCBI Gene ID	54910
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

SEMA4C has 6,853 functional associations with biological entities spanning 8 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) extracted from 111 datasets.

Click the + buttons to view associations for SEMA4C from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

SEMA4C 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 SEMA4C 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 SEMA4C 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 SEMA4C 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 SEMA4C 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 SEMA4C 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 SEMA4C 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 SEMA4C 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 SEMA4C 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 SEMA4C 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 SEMA4C gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of SEMA4C 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 SEMA4C gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with SEMA4C 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 SEMA4C gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of SEMA4C 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 SEMA4C 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 SEMA4C gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of SEMA4C gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing SEMA4C protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing SEMA4C protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with SEMA4C 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 SEMA4C 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 SEMA4C gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with SEMA4C gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with SEMA4C gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with SEMA4C gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of SEMA4C 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 SEMA4C 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 SEMA4C 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 SEMA4C 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 SEMA4C gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with SEMA4C 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 SEMA4C 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 SEMA4C gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of SEMA4C 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 SEMA4C from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of SEMA4C gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with SEMA4C 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 SEMA4C from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of SEMA4C gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.