NELFA
protein-codingnegative elongation factor complex member A, the group of Negative elongation factor complex members|MicroRNA protein coding host genes
Gene 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]
- WHSC2
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~59.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to NELFA variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005663.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 28 | 5 | 34 | ||
| missense | 67 | 5 | 3 | 75 | ||
| nonsense | 0 | |||||
| start loss | 1 | 1 | ||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 71 | 33 | 8 | 112 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005654.4 | 11 | MANE Select | |
| Ensembl | ENSP00000372335.4 | 11 | MANE Select | |
| Ensembl | ENSP00000330311.4 | 2 | Standard | |
| Ensembl | ENSP00000396996.1 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Initiation of transcription and translation elongation at the HIV-1 LTR
- Disease
- Formation of the HIV-1 Early Elongation Complex
- Gene expression (Transcription)
- Formation of HIV-1 elongation complex containing HIV-1 Tat
Biological Process
- transcription by RNA polymerase II
- transcription elongation from RNA polymerase II promoter
- multicellular organism development
- negative regulation of transcription elongation from RNA polymerase II promoter
Molecular Function
- protein binding
Cellular Component
- nucleoplasm
- cytosol
- nuclear body
- NELF complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000382882
- Coding exons
- 11
- Length
- 59190
- Individuals with no LoFs
- 125735
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 13
- Defined
- 125748
- p
- 0.0000517
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.82 | 256 | 352 | 0.727 | 0.0000227 | 3417 |
| Missense (PolyPhen) | 55 | 109.49 | 0.50234 | 975 | ||
| Synonymous | -2.17 | 213 | 176 | 1.21 | 0.0000137 | 1142 |
| Loss of Function | 3.29 | 6 | 23.0 | 0.260 | 0.00000124 | 256 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.000064 | 0.000062 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Essential component of the NELF complex, a complex that negatively regulates the elongation of transcription by RNA polymerase II. The NELF complex, which acts via an association with the DSIF complex and causes transcriptional pausing, is counteracted by the P-TEFb kinase complex. The NELF complex is involved in HIV-1 latency possibly involving recruitment of PCF11 to paused RNA polymerase II. In vitro, the NELFA:NELFCD subcomplex binds to ssDNA and ssRNA in a sequence- and structure-dependent manner. Probably required to interact with the RNA polymerase II complex. {ECO:0000269|PubMed:10199401, ECO:0000269|PubMed:12563561, ECO:0000269|PubMed:12612062, ECO:0000305}.;
Recessive Scores
- pRec
- 0.146
Intolerance Scores
- RVIS EVS
- -1.11
- RVIS percentile EVS
- 6.83
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |