NOS1
protein-codingnitric oxide synthase 1, the group of PDZ domain containing
Gene summary
The protein encoded by this gene belongs to the family of nitric oxide synthases, which synthesize nitric oxide from L-arginine. Nitric oxide is a reactive free radical, which acts as a biologic mediator in several processes, including neurotransmission, and antimicrobial and antitumoral activities. In the brain and peripheral nervous system, nitric oxide displays many properties of a neurotransmitter, and has been implicated in neurotoxicity associated with stroke and neurodegenerative diseases, neural regulation of smooth muscle, including peristalsis, and penile erection. This protein is ubiquitously expressed, with high level of expression in skeletal muscle. Multiple transcript variants that differ in the 5' UTR have been described for this gene but the full-length nature of these transcripts is not known. Additionally, alternatively spliced transcript variants encoding different isoforms (some testis-specific) have been found for this gene.[provided by RefSeq, Feb 2011]
- NOS
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~244.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0019635
Submitter: Orphanet
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to NOS1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000620.5. 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 | 38 | 12 | 50 | |||
| missense | 164 | 13 | 3 | 180 | ||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 170 | 51 | 15 | 236 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000611.1 | 28 | MANE Select | |
| Ensembl | ENSP00000320758.6 | 28 | MANE Select | |
| RefSeq | NP_001191142.1 | 25 | Standard | |
| RefSeq | NP_001191143.1 | 25 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| nos1 | Danio rerio | Structure: motor neuron Quality: decreased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Relaxin signaling pathway - Homo sapiens (human)
- Arginine and proline metabolism - Homo sapiens (human)
- Long-term depression - Homo sapiens (human)
- Phagosome - Homo sapiens (human)
- Alzheimer,s disease - Homo sapiens (human)
Biological Process
- response to hypoxia
- regulation of sodium ion transport
- arginine catabolic process
- nitric oxide biosynthetic process
- striated muscle contraction
Molecular Function
- NADPH-hemoprotein reductase activity
- nitric-oxide synthase activity
- protein binding
- calmodulin binding
- FMN binding
Cellular Component
- photoreceptor inner segment
- nucleus
- nucleoplasm
- cytoplasm
- mitochondrion
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000338101
- Coding exons
- 29
- Length
- 244029
- Individuals with no LoFs
- 124790
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 10
- Defined
- 124800
- p
- 0.0000401
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.68 | 587 | 898 | 0.654 | 0.0000550 | 9621 |
| Missense (PolyPhen) | 177 | 373.88 | 0.47341 | 3849 | ||
| Synonymous | -0.960 | 394 | 371 | 1.06 | 0.0000249 | 2894 |
| Loss of Function | 7.23 | 8 | 76.1 | 0.105 | 0.00000408 | 822 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000047 | 0.000046 | rare |
| European (Non-Finnish) | 0.000037 | 0.000035 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0.00017 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In the brain and peripheral nervous system, NO displays many properties of a neurotransmitter. Probably has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such SRR.;
Recessive Scores
- pRec
- 0.612
Intolerance Scores
- LoFtool
- 0.306
- RVIS EVS
- -1.01
- RVIS percentile EVS
- 8.21
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.981
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |