NELFA negative elongation factor complex member A [Homo sapiens (human)] - Gene

Summary

Official Symbol: NELFAprovided by HGNC
Official Full Name: negative elongation factor complex member Aprovided by HGNC
Primary source: HGNC:HGNC:12768
See related: Ensembl:ENSG00000185049 MIM:606026; AllianceGenome:HGNC:12768
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: WHSC2; NELF-A; P/OKcl.15
Summary: 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]
Expression: Ubiquitous expression in testis (RPKM 9.8), ovary (RPKM 6.6) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 4p16.3

Exon count:: 12

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	4	NC_000004.12 (1982723..2008974, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	4	NC_060928.1 (1981232..2007492, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	4	NC_000004.11 (1984450..2010701, complement)

Chromosome 4 - NC_000004.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

ERK-mediated NELF-A phosphorylation promotes transcription elongation of immediate-early genes by releasing promoter-proximal pausing of RNA polymerase II.
Title: ERK-mediated NELF-A phosphorylation promotes transcription elongation of immediate-early genes by releasing promoter-proximal pausing of RNA polymerase II.
Stress-induced nuclear condensation of NELF drives transcriptional downregulation.
Title: Stress-induced nuclear condensation of NELF drives transcriptional downregulation.
The noncoding function of NELFA mRNA promotes the development of oesophageal squamous cell carcinoma by regulating the Rad17-RFC2-5 complex.
Title: The noncoding function of NELFA mRNA promotes the development of oesophageal squamous cell carcinoma by regulating the Rad17-RFC2-5 complex.
A positively charged face of NELF-AC is involved in RNA binding, whereas the opposite face of the NELF-AC subcomplex binds NELF-B. NELF-B is predicted to form a HEAT repeat fold, also binds RNA in vivo, and anchors the subunit NELF-E, which is confirmed to bind RNA in vivo.
Title: Architecture and RNA binding of the human negative elongation factor.
These studies allow us to position the actions of two new modulators of GR-regulated transactivation, NELF-A and NELF-B, relative to other factors in the overall gene induction sequence.
Title: A conserved protein motif is required for full modulatory activity of negative elongation factor subunits NELF-A and NELF-B in modifying glucocorticoid receptor-regulated gene induction properties.
data show that NELF subunits exhibit highly specific subcellular localizations, such as in NELF bodies or in midbodies, and some shuttle actively between the nucleus and cytoplasm; loss of NELF from cells can lead to enlarged and/or multiple nuclei
Title: Cellular dynamics of the negative transcription elongation factor NELF.
haploinsufficiency of SLBP and/or WHSC2 (NELF-A) contributes to several novel cellular phenotypes of WHS.
Title: Characterizing the functional consequences of haploinsufficiency of NELF-A (WHSC2) and SLBP identifies novel cellular phenotypes in Wolf-Hirschhorn syndrome.
Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
Negative elongation factor (NELF) is a four subunit transcription factor. Our results point to a surprising role of NELF in the 3' end processing of histone mRNAs and suggest that NELF is a new factor that coordinates mRNA processing in transcription
Title: NELF interacts with CBC and participates in 3' end processing of replication-dependent histone mRNAs.
connection between the syndrome phenotype and cytogenetic abnormalities, through gradual shortening of the length of the critical region WHSCR (finally up to 165 kb), and sequencing it, at least 2 genes (WHSC1 and WHSC2) were identified.
Title: [Genetic determination of Wolf-Hirschhorn syndrome ].

Submit: New GeneRIF Correction See all GeneRIFs (11)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Copy number response

Description
Copy number response Haploinsufficency No evidence available (Last evaluated 2012-09-06) ClinGen Genome Curation Page Triplosensitivity No evidence available (Last evaluated 2012-09-06) ClinGen Genome Curation Page

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Tat	tat	NELF represses HIV-1 transcription by pausing the RNA polymerase II complex	PubMed
	tat	NELF associates with HIV-1 Tat as part of the HIV-1 transcription elongation complex	PubMed
	tat	WHSC2 is hypothesized to function as a transcriptional repressor and has been shown to be downregulated by HIV-1 Tat	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-59825 (e-PCR)
- UniSTS:45888

WHSC2_8727 (e-PCR)
- UniSTS:468172

G20233 (e-PCR)
- UniSTS:68602

A005A46 (e-PCR)
- UniSTS:68603

SHGC-67592 (e-PCR)
- UniSTS:14334

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables chromatin binding	IEA Inferred from Electronic Annotation more info
enables molecular adaptor activity	IDA Inferred from Direct Assay more info	PubMed
enables molecular adaptor activity	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in negative regulation of transcription elongation by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of transcription elongation by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of protein modification process	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of transcription by RNA polymerase II	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
part_of NELF complex	IBA Inferred from Biological aspect of Ancestor more info
part_of NELF complex	IDA Inferred from Direct Assay more info	PubMed
part_of NELF complex	IPI Inferred from Physical Interaction more info	PubMed
located_in cytosol	IDA Inferred from Direct Assay more info
located_in nuclear body	IDA Inferred from Direct Assay more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in nucleoplasm	TAS Traceable Author Statement more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: negative elongation factor A

Names: wolf-Hirschhorn syndrome candidate 2 protein

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.