NRF1
protein-codingnuclear respiratory factor 1
Gene summary
This gene encodes a protein that homodimerizes and functions as a transcription factor which activates the expression of some key metabolic genes regulating cellular growth and nuclear genes required for respiration, heme biosynthesis, and mitochondrial DNA transcription and replication. The protein has also been associated with the regulation of neurite outgrowth. Alternative splicing results in multiple transcript variants. Confusion has occurred in bibliographic databases due to the shared symbol of NRF1 for this gene and for "nuclear factor (erythroid-derived 2)-like 1" which has an official symbol of NFE2L1. [provided by RefSeq, May 2014]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~145.4 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 NRF1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005011.5. 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 | 3 | 3 | 7 | ||
| missense | 24 | 24 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 2 | 2 | ||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 27 | 3 | 3 | 33 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005002.3 | 10 | MANE Select | |
| Ensembl | ENSP00000376924.1 | 10 | MANE Select | |
| RefSeq | NP_001035199.1 | 10 | Standard | |
| RefSeq | NP_001280092.1 | 11 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| nrf1 | Danio rerio | Structure: photoreceptor cell Quality: apoptotic abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Huntington,s disease - Homo sapiens (human)
- Apelin signaling pathway - Homo sapiens (human)
- Energy Metabolism
- Mitochondrial biogenesis
- Simplified Interaction Map Between LOXL4 and Oxidative Stress Pathway
Biological Process
- generation of precursor metabolites and energy
- regulation of transcription by RNA polymerase II
- mitochondrion organization
- positive regulation of transcription by RNA polymerase II
Molecular Function
- RNA polymerase II proximal promoter sequence-specific DNA binding
- RNA polymerase II core promoter sequence-specific DNA binding
- core promoter sequence-specific DNA binding
- DNA-binding transcription activator activity, RNA polymerase II-specific
- protein binding
Cellular Component
- nucleus
- nucleoplasm
- cytosol
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000393232
- Coding exons
- 10
- Length
- 145368
- Individuals with no LoFs
- 125514
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 2
- Defined
- 125516
- p
- 0.00000797
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 4.51 | 83 | 305 | 0.272 | 0.0000180 | 3225 |
| Missense (PolyPhen) | 17 | 81.846 | 0.20771 | 786 | ||
| Synonymous | 0.747 | 110 | 120 | 0.913 | 0.00000790 | 1048 |
| Loss of Function | 4.46 | 1 | 25.1 | 0.0399 | 0.00000114 | 277 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.0000088 | 0.0000088 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Transcription factor that activates the expression of the EIF2S1 (EIF2-alpha) gene. Links the transcriptional modulation of key metabolic genes to cellular growth and development. Implicated in the control of nuclear genes required for respiration, heme biosynthesis, and mitochondrial DNA transcription and replication.;
Intolerance Scores
- LoFtool
- 0.0375
- RVIS EVS
- -0.45
- RVIS percentile EVS
- 24
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 1.00
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |