KDM5C Gene

HGNC Family	X-linked mental retardation, Chromatin-modifying enzymes, Zinc fingers
Name	lysine (K)-specific demethylase 5C
Description	This gene is a member of the SMCY homolog family and encodes a protein with one ARID domain, one JmjC domain, one JmjN domain and two PHD-type zinc fingers. The DNA-binding motifs suggest this protein is involved in the regulation of transcription and chromatin remodeling. Mutations in this gene have been associated with X-linked cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2009]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n KDM5C (also known as JARID1C) is a Jumonji C (JmjC) domain‐containing histone demethylase that specifically targets trimethylated lysine 4 on histone H3 (H3K4me3), converting it into di‐ and monomethylated states. In doing so, KDM5C contributes to the fine‐tuning of chromatin structure and gene transcription by erasing a mark generally associated with active promoters, thereby influencing transcriptional repression and cellular differentiation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the context of cancer, particularly clear cell renal cell carcinoma (ccRCC), loss-of-function mutations in KDM5C have been identified and are associated with altered levels of H3K4me3 and aberrant gene expression. In VHL-deficient ccRCC cells, KDM5C is implicated in modulating the transcriptional output of hypoxia-inducible factor (HIF) by downregulating H3K4 trimethylation at the promoters of certain HIF-responsive genes. Such epigenetic alterations appear to suppress the expression of genes with potential tumor-suppressive roles, thereby influencing tumor progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its role in cancer, KDM5C activity is critical for proper neuronal development and survival. Its enzymatic function in reducing H3K4me3 levels has been linked to the regulation of neuronal gene expression, and mutations in KDM5C are associated with X-linked mental retardation. Loss or impairment of its demethylase activity disrupts normal chromatin remodeling and gene expression programs in neurons, ultimately affecting dendritic development and cell survival."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, KDM5C functions as an H3K4me3 demethylase that plays a pivotal role in regulating transcription through chromatin modification. Its activity is essential for maintaining appropriate gene expression patterns in both normal neuronal development and in suppressing tumor growth in ccRCC, with its mutational inactivation contributing to disease pathogenesis by perturbing epigenetic homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ignacio Varela, Patrick Tarpey, Keiran Raine, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature09639"}], "href": "https://doi.org/10.1038/nature09639"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21248752"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21248752"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Gillian L Dalgliesh, Kyle Furge, Chris Greenman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature08672"}], "href": "https://doi.org/10.1038/nature08672"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20054297"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20054297"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Shigeki Iwase, Fei Lan, Peter Bayliss, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The X-linked mental retardation gene SMCX/JARID1C defines a family of histone H3 lysine 4 demethylases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2007.02.017"}], "href": "https://doi.org/10.1016/j.cell.2007.02.017"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17320160"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17320160"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "X Niu, T Zhang, L Liao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The von Hippel-Lindau tumor suppressor protein regulates gene expression and tumor growth through histone demethylase JARID1C."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2011.266"}], "href": "https://doi.org/10.1038/onc.2011.266"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21725364"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21725364"}]}]}]}
Synonyms	SMCX, MRXSJ, MRX13, XE169, MRXSCJ, DXS1272E, MRXJ, JARID1C
Proteins	KDM5C_HUMAN
NCBI Gene ID	8242
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

KDM5C has 7,561 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 128 datasets.

Click the + buttons to view associations for KDM5C from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

KDM5C 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 KDM5C 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 KDM5C 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 KDM5C 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 KDM5C 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 KDM5C 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 KDM5C 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 KDM5C 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 KDM5C 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 KDM5C 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 KDM5C gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of KDM5C 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 KDM5C gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with KDM5C 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 KDM5C gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of KDM5C 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 KDM5C 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 KDM5C gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with KDM5C gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of KDM5C 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 KDM5C gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing KDM5C protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with KDM5C 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 KDM5C 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 KDM5C gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with KDM5C gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with KDM5C gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with KDM5C gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with KDM5C gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of KDM5C 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 KDM5C gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DGIdb Drug Targets 2026	interacting drugs for KDM5C protein from the DGIdb Drug Targets 2026 dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving KDM5C gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with KDM5C 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 KDM5C 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 KDM5C gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with KDM5C 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 KDM5C 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 KDM5C gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of KDM5C 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 KDM5C from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.