NOSIP
protein-codingnitric oxide synthase interacting protein, the group of Spliceosomal P complex|Spliceosomal C complex
Gene summary
The protein encoded by this gene may modulate the activity and localization of nitric oxide synthase (endothelial and neuronal) and thus nitric oxide production. Alternative splicing results in multiple transcript variants that encode the same protein. [provided by RefSeq, Aug 2012]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~34.8 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 NOSIP variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001270960.2. 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 | 0 | |||||
| missense | 41 | 41 | ||||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 46 | 0 | 0 | 46 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001257889.1 | 8 | MANE Select | |
| Ensembl | ENSP00000470034.1 | 8 | MANE Select | |
| RefSeq | NP_001350578.1 | 8 | Standard | |
| RefSeq | NP_001426151.1 | 8 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Metabolism of nitric oxide
- NOSIP mediated eNOS trafficking
- eNOS activation and regulation
- Metabolism
Biological Process
- multicellular organism development
- protein ubiquitination
- negative regulation of catalytic activity
- regulation of nitric-oxide synthase activity
- negative regulation of nitric-oxide synthase activity
Molecular Function
- RNA binding
- protein binding
- ubiquitin protein ligase activity
Cellular Component
- Golgi membrane
- nucleus
- cytoplasm
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000391853
- Coding exons
- 8
- Length
- 34552
- Individuals with no LoFs
- 125666
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 40
- Defined
- 125706
- p
- 0.000159
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.11 | 129 | 217 | 0.596 | 0.0000155 | 1908 |
| Missense (PolyPhen) | 19 | 54.46 | 0.34888 | 498 | ||
| Synonymous | 1.98 | 69 | 93.4 | 0.739 | 0.00000675 | 615 |
| Loss of Function | 1.38 | 10 | 15.9 | 0.627 | 9.13e-7 | 164 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00033 | 0.00031 | rare |
| Latino/Admixed American | 0.00024 | 0.00020 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0.000047 | 0.000046 | rare |
| European (Non-Finnish) | 0.00011 | 0.00011 | rare |
| South Asian | 0.00040 | 0.00039 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: E3 ubiquitin-protein ligase that is essential for proper development of the forebrain, the eye, and the face. Catalyzes monoubiquitination of serine/threonine-protein phosphatase 2A (PP2A) catalytic subunit PPP2CA/PPP2CB (By similarity). Negatively regulates nitric oxide production by inducing NOS1 and NOS3 translocation to actin cytoskeleton and inhibiting their enzymatic activity (PubMed:11149895, PubMed:15548660, PubMed:16135813). {ECO:0000250|UniProtKB:Q9D6T0, ECO:0000269|PubMed:11149895, ECO:0000269|PubMed:15548660, ECO:0000269|PubMed:16135813}.;
Recessive Scores
- pRec
- 0.111
Intolerance Scores
- LoFtool
- 0.592
- RVIS EVS
- -0.34
- RVIS percentile EVS
- 30.07
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.934
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |