NOX5
protein-codingNADPH oxidase 5, the group of EF-hand domain containing
Gene summary
Enables proton channel activity and superoxide-generating NADPH oxidase activity. Involved in several processes, including endothelial cell proliferation; positive regulation of reactive oxygen species metabolic process; and superoxide anion generation. Located in endoplasmic reticulum and plasma membrane. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~48.1 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 NOX5 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_024505.4. 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 | 2 | 2 | ||||
| missense | 120 | 7 | 3 | 130 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 120 | 9 | 4 | 133 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_078781.3 | 16 | MANE Select | |
| Ensembl | ENSP00000373518.3 | 16 | MANE Select | |
| RefSeq | NP_001171708.1 | 16 | Standard | |
| Ensembl | ENSP00000455703.1 | 6 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Detoxification of Reactive Oxygen Species
- Cellular responses to stress
- Cellular responses to external stimuli
Biological Process
- angiogenesis
- endothelial cell proliferation
- apoptotic process
- defense response
- cell population proliferation
Molecular Function
- calcium ion binding
- proton channel activity
- superoxide-generating NADPH oxidase activity
- heme binding
- flavin adenine dinucleotide binding
Cellular Component
- endoplasmic reticulum membrane
- plasma membrane
- integral component of membrane
- NADPH oxidase complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000388866
- Coding exons
- 16
- Length
- 132220
- Individuals with no LoFs
- 124088
- Homozygous LoFs
- 57
- Heterozygous LoFs
- 1603
- Defined
- 125748
- p
- 0.00662
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.838 | 406 | 456 | 0.890 | 0.0000263 | 4983 |
| Missense (PolyPhen) | 120 | 135.23 | 0.88735 | 1652 | ||
| Synonymous | 0.396 | 182 | 189 | 0.963 | 0.0000112 | 1523 |
| Loss of Function | -0.552 | 40 | 36.4 | 1.10 | 0.00000163 | 391 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.088 | 0.088 | notable |
| Latino/Admixed American | 0.0041 | 0.0040 | notable |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00055 | 0.00054 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00087 | 0.00086 | rare |
| South Asian | 0.00095 | 0.00091 | rare |
| Other | 0.0031 | 0.0031 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Calcium-dependent NADPH oxidase that generates superoxide. Also functions as a calcium-dependent proton channel and may regulate redox-dependent processes in lymphocytes and spermatozoa. May play a role in cell growth and apoptosis. Isoform v2 and isoform v5 are involved in endothelial generation of reactive oxygen species (ROS), proliferation and angiogenesis and contribute to endothelial response to thrombin. {ECO:0000269|PubMed:11483596, ECO:0000269|PubMed:12686516, ECO:0000269|PubMed:17275676}.;
Recessive Scores
- pRec
- 0.766
Intolerance Scores
- LoFtool
- 0.113
- RVIS EVS
- 1.58
- RVIS percentile EVS
- 95.79
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.311
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |