NSRP1
protein-codingnuclear speckle splicing regulatory protein 1, the group of MicroRNA protein coding host genes
Gene summary
Enables mRNA binding activity. Involved in developmental process and regulation of alternative mRNA splicing, via spliceosome. Located in nuclear speck. Part of ribonucleoprotein complex. [provided by Alliance of Genome Resources, Jul 2025]
- CCDC55
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~71.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0859275
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0859275
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0859275
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0859275
Submitter: ClinGen
*NSRP1* was first reported in relation to autosomal recessive neurodevelopmental disorder with spasticity, seizures, and brain abnormalities in 2021 (Calame et al., PMID: 34385670). Individuals with variants in *NSRP1* can present with features such as global developmental delay apparent in infancy, axial hypotonia, peripheral spasticity, and early-onset seizures of various types and severity. Other phenotypes can include delayed walking or inability to walk and impaired intellectual development with poor or absent speech. Five variants (frameshift, nonsense,missense) that have been reported in 4 probands in 2 publications (PMIDs: 34385670, 38808951) are included in this curation. The mechanism of pathogenicity is reported to be loss of function (PMID: 34385670). In summary, there is moderate evidence to support this gene-disease relationship between *NSRP1* and autosomal recessive neurodevelopmental disorder with spasticity, seizures, and brain abnormalities. While more evidence is needed to establish this relationship definitively, no convincing contradictory evidence has been reported. This classification was approved by the ClinGen Cerebral Palsy Gene Curation Expert Panel on December 16, 2024 (SOP Version 11).
Clinical Genomic Database (CGD)
Manifestation: Craniofacial; Neurologic
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to NSRP1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_032141.4. 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 | 4 | 5 | |||
| missense | 67 | 5 | 72 | |||
| nonsense | 2 | 1 | 3 | 6 | ||
| start loss | 1 | 1 | ||||
| frameshift | 3 | 1 | 1 | 5 | ||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 5 | 2 | 73 | 9 | 0 | 89 |
Highest pathogenic variant AF is 0.0000061992055
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_115517.1 | 7 | MANE Select | |
| Ensembl | ENSP00000247026.5 | 7 | MANE Select | |
| RefSeq | NP_001248396.1 | 5 | Standard | |
| Ensembl | ENSP00000378303.4 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- regulation of alternative mRNA splicing, via spliceosome
- mRNA processing
- RNA splicing
- developmental process
Molecular Function
- RNA binding
- mRNA binding
- protein binding
Cellular Component
- nucleus
- nucleoplasm
- nuclear speck
- ribonucleoprotein complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000247026
- Coding exons
- 7
- Length
- 70955
- Individuals with no LoFs
- 125701
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 44
- Defined
- 125745
- p
- 0.000175
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.147 | 273 | 280 | 0.975 | 0.0000137 | 3751 |
| Missense (PolyPhen) | 43 | 64.558 | 0.66607 | 905 | ||
| Synonymous | -0.475 | 102 | 96.1 | 1.06 | 0.00000463 | 909 |
| Loss of Function | 3.16 | 8 | 25.1 | 0.319 | 0.00000125 | 356 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00037 | 0.00037 | rare |
| Latino/Admixed American | 0.00014 | 0.00014 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0.00012 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00019 | 0.00018 | rare |
| South Asian | 0.00030 | 0.00029 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: RNA-binding protein that mediates pre-mRNA alternative splicing regulation. {ECO:0000269|PubMed:21296756}.;
Intolerance Scores
- RVIS EVS
- 0.42
- RVIS percentile EVS
- 77.16
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- N
- Indispensability score
- 0.114
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |