NOSTRIN
protein-codingnitric oxide synthase trafficking, the group of F-BAR domain containing
Gene summary
Nitric oxide (NO) is a potent mediator in biologic processes such as neurotransmission, inflammatory response, and vascular homeostasis. NOSTRIN binds the enzyme responsible for NO production, endothelial NO synthase (ENOS; MIM 163729), and triggers the translocation of ENOS from the plasma membrane to vesicle-like subcellular structures, thereby attenuating ENOS-dependent NO production.[supplied by OMIM, Apr 2004]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~79.0 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 NOSTRIN variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001039724.4. 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 | 1 | 1 | ||||
| missense | 41 | 3 | 2 | 46 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 45 | 3 | 2 | 50 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001034813.2 | 16 | MANE Select | |
| Ensembl | ENSP00000318921.7 | 16 | MANE Select | |
| RefSeq | NP_001165102.1 | 17 | Standard | |
| RefSeq | NP_001165103.1 | 15 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| nostrin | Danio rerio | Structure: endothelial tip cell Quality: decreased length abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Metabolism of nitric oxide
- NOSTRIN mediated eNOS trafficking
- eNOS activation and regulation
- Metabolism
Biological Process
- endocytosis
- negative regulation of transcription, DNA-templated
- regulation of nitric-oxide synthase activity
Molecular Function
- DNA binding
- protein binding
Cellular Component
- cytoskeleton
- plasma membrane
- nuclear speck
- endocytic vesicle membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000444448
- Coding exons
- 17
- Length
- 78976
- Individuals with no LoFs
- 124731
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 64
- Defined
- 124795
- p
- 0.000256
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.644 | 247 | 277 | 0.891 | 0.0000131 | 3718 |
| Missense (PolyPhen) | 66 | 76.63 | 0.86129 | 1152 | ||
| Synonymous | -0.0703 | 103 | 102 | 1.01 | 0.00000533 | 966 |
| Loss of Function | 1.11 | 28 | 35.1 | 0.798 | 0.00000168 | 456 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00019 | 0.00019 | rare |
| Latino/Admixed American | 0.00015 | 0.00012 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00028 | 0.00028 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00035 | 0.00033 | rare |
| South Asian | 0.00043 | 0.00042 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Multivalent adapter protein which may decrease NOS3 activity by inducing its translocation away from the plasma membrane. {ECO:0000269|PubMed:12446846, ECO:0000269|PubMed:16234328, ECO:0000269|PubMed:16807357}.;
Recessive Scores
- pRec
- 0.0789
Intolerance Scores
- LoFtool
- 0.971
- RVIS EVS
- 1.29
- RVIS percentile EVS
- 93.8
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.800
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |