NELFA Gene

Name	negative elongation factor complex member A
Description	This gene is expressed ubiquitously with higher levels in fetal than in adult tissues. It encodes a protein sharing 93% sequence identity with the mouse protein. Wolf-Hirschhorn syndrome (WHS) is a malformation syndrome associated with a hemizygous deletion of the distal short arm of chromosome 4. This gene is mapped to the 165 kb WHS critical region, and may play a role in the phenotype of the WHS or Pitt-Rogers-Danks syndrome. The encoded protein is found to be capable of reacting with HLA-A2-restricted and tumor-specific cytotoxic T lymphocytes, suggesting a target for use in specific immunotherapy for a large number of cancer patients. This protein has also been shown to be a member of the NELF (negative elongation factor) protein complex that participates in the regulation of RNA polymerase II transcription elongation. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNELFA, a key subunit of the negative elongation factor (NELF) complex, is instrumental in regulating RNA polymerase II activity by enforcing promoter‐proximal pausing and coordinating co‐transcriptional mRNA processing. Its unique features—including a small region with similarity to the hepatitis delta antigen—are critical for binding to RNAP II and establishing the pause that ensures synchronized gene expression. In addition, NELF participates in the 3′ end processing of replication‐dependent histone mRNAs by interacting with factors such as the nuclear cap binding complex and histone stem–loop binding protein, and it is enriched at histone gene loci within distinct intranuclear foci sometimes overlapping with Cajal bodies."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn response to cellular cues and stress, regulatory modifications of NELFA modulate its activity. Under stressful conditions, NELF—including its NELFA component—rapidly forms nuclear condensates after undergoing dephosphorylation and SUMOylation; this condensation bolsters its recruitment to gene promoters to enforce transcriptional downregulation. Moreover, upon growth factor stimulation, ERK directly phosphorylates NELF-A, triggering its dissociation from paused RNA polymerase II and thereby facilitating the release of immediate–early genes from transcriptional arrest."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its canonical role in transcriptional regulation, NELFA has broader implications in cellular homeostasis and disease. Haploinsufficiency of the WHSC2 gene, which encodes NELF-A, has been linked to aberrant chromatin reorganization, delayed cell-cycle progression, and impaired DNA replication as observed in Wolf–Hirschhorn syndrome. In parallel, emerging research has uncovered a noncoding role for NELFA mRNA: by interacting with Rad17 in the nucleus, it modulates the formation of protein complexes necessary for efficient DNA damage response and repair. These multifaceted activities underscore NELFA’s critical importance in ensuring proper gene expression control, genomic stability, and appropriate cellular responses to stress, with significant consequences for development and tumorigenesis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "9"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Takashi Narita, Yuki Yamaguchi, Keiichi Yano, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human transcription elongation factor NELF: identification of novel subunits and reconstitution of the functionally active complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.23.6.1863-1873.2003"}], "href": "https://doi.org/10.1128/MCB.23.6.1863-1873.2003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12612062"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12612062"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Takashi Narita, Tetsu M C Yung, Junichi Yamamoto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NELF interacts with CBC and participates in 3' end processing of replication-dependent histone mRNAs."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2007.04.011"}], "href": "https://doi.org/10.1016/j.molcel.2007.04.011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17499042"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17499042"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Tetsu M C Yung, Takashi Narita, Toshiharu Komori, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cellular dynamics of the negative transcription elongation factor NELF."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Cell Res (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yexcr.2009.02.013"}], "href": "https://doi.org/10.1016/j.yexcr.2009.02.013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19245807"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19245807"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Seychelle M Vos, David Pöllmann, Livia Caizzi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Architecture and RNA binding of the human negative elongation factor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Elife (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7554/eLife.14981"}], "href": "https://doi.org/10.7554/eLife.14981"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27282391"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27282391"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Prashant Rawat, Marc Boehning, Barbara Hummel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Stress-induced nuclear condensation of NELF drives transcriptional downregulation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2021.01.016"}], "href": "https://doi.org/10.1016/j.molcel.2021.01.016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33548202"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33548202"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Seina Ohe, Yuji Kubota, Kiyoshi Yamaguchi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ERK-mediated NELF-A phosphorylation promotes transcription elongation of immediate-early genes by releasing promoter-proximal pausing of RNA polymerase II."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-022-35230-4"}], "href": "https://doi.org/10.1038/s41467-022-35230-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36463234"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36463234"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Claudia Kerzendorfer, Femke Hannes, Rita Colnaghi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterizing the functional consequences of haploinsufficiency of NELF-A (WHSC2) and SLBP identifies novel cellular phenotypes in Wolf-Hirschhorn syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/dds033"}], "href": "https://doi.org/10.1093/hmg/dds033"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22328085"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22328085"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Ewa Gutmajster, Anna Rokicka "}, {"type": "b", "children": [{"type": "t", "text": "[Genetic determination of Wolf-Hirschhorn syndrome ]."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Wiad Lek (2002)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12715353"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12715353"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Jiancheng Xu, Guangchao Wang, Wei Gong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The noncoding function of NELFA mRNA promotes the development of oesophageal squamous cell carcinoma by regulating the Rad17-RFC2-5 complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Oncol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/1878-0261.12619"}], "href": "https://doi.org/10.1002/1878-0261.12619"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31845510"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31845510"}]}]}]}
Synonyms	P/OKCL.15, WHSC2, NELF-A
Proteins	NELFA_HUMAN
NCBI Gene ID	7469
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

NELFA has 5,790 functional associations with biological entities spanning 7 categories (molecular profile, functional term, phrase or reference, chemical, 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 NELFA from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

NELFA 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 NELFA gene relative to other tissues from the Allen Brain Atlas Adult Human 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 NELFA 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 NELFA 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 NELFA 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 NELFA 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 NELFA 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 NELFA 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 NELFA gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of NELFA 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 NELFA gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with NELFA 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 NELFA gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of NELFA 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 NELFA 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 NELFA 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 NELFA gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing NELFA protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing NELFA protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing NELFA 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 NELFA 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 NELFA 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 NELFA protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing NELFA protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of NELFA gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with NELFA gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with NELFA gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with NELFA gene/protein from the curated CTD Gene-Disease Associations dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with NELFA 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 NELFA 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 NELFA gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with NELFA 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 NELFA 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 NELFA gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of NELFA 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 NELFA from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with NELFA gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with NELFA 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 NELFA gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with NELFA 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 NELFA from the GeneSigDB Published Gene Signatures dataset.