NELFA Gene (Negative Elongation Factor Complex Member A)
Essential regulator of RNA polymerase II pausing and transcriptional elongation
Gene Information Card
| Symbol | NELFA |
|---|---|
| Full Name | Negative Elongation Factor Complex Member A |
| Gene Type | Protein coding |
| Chromosomal Location | 4p16.3 |
| NCBI Gene ID | 7469 ncbi.nlm.nih.gov/gene/7469 |
| Ensembl ID | ENSG00000138668 |
| UniProt ID | Q9H3P2 |
| OMIM ID | 606026 |
| HGNC ID | 12768 |
| Aliases | WHSC2, NELF-A, NELF-A/WHSC2 |
Description
NELFA encodes a component of the negative elongation factor (NELF) complex, which represses RNA polymerase II (Pol II) elongation by promoting promoter-proximal pausing. NELF-A is essential for proper transcriptional regulation of genes involved in development, cell cycle, and stress response. The protein contains a bipartite nuclear localization signal and interacts with other NELF subunits (NELF-B, NELF-C/D, NELF-E) to form the functional complex.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Wolf-Hirschhorn syndrome | NELFA is located in the Wolf-Hirschhorn syndrome critical region; haploinsufficiency contributes to the phenotype, including intellectual disability and growth delay. | OMIM #194190; NCBI Gene |
| Multiple myeloma | NELFA is fused to NSD2 (WHSC1) in t(4;14) translocations, leading to overexpression of NSD2 and altered histone methylation. | COSMIC; PMID: 11526490 |
| Breast cancer | NELFA overexpression correlates with poor prognosis and may promote proliferation via transcriptional dysregulation. | NCBI Gene; PMID: 23455423 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 18.5 | High |
| Brain | 12.3 | Medium |
| Heart | 9.8 | Medium |
| Liver | 6.2 | Low |
| Kidney | 7.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.2 | Embryonic kidney; high expression |
| HeLa | 12.8 | Cervical carcinoma; moderate expression |
| K562 | 9.1 | Leukemia; low expression |
| MCF7 | 11.4 | Breast cancer; moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | <0.01% | Loss of start codon; predicted loss of function |
| c.325C>T (p.Arg109Trp) | Missense | <0.01% | Unknown significance; reported in ClinVar |
| t(4;14)(p16.3;q32) | Translocation | Rare in general population | Fusion with NSD2; associated with multiple myeloma |
Mutation functional classification
Loss of Function (LOF)
Haploinsufficiency in Wolf-Hirschhorn syndrome; start codon loss variants.
Gain of Function (GOF)
Not well characterized; overexpression in some cancers may act as oncogenic driver.
Dominant Negative (DN)
Not reported for NELFA.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Negative elongation factor (NELF) complex
• RNA polymerase II transcription elongation
• Transcriptional regulation by small RNAs
Protein Summary
NELF-A is a 526-amino acid protein (56 kDa) that forms the core of the NELF complex. It contains a central domain required for interaction with NELF-B and NELF-E, and a C-terminal region that binds RNA. NELF-A is essential for promoter-proximal pausing of Pol II, a key step in metazoan gene regulation. The protein is ubiquitously expressed with highest levels in testis and brain.
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